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HOME > Diabetes Metab J > Volume 36(5); 2012 > Article
Review
Obesity and Metabolic Syndrome Clinical Relevance of Adipokines
Matthias Blüher
Diabetes & Metabolism Journal 2012;36(5):317-327.
DOI: https://doi.org/10.4093/dmj.2012.36.5.317
Published online: October 18, 2012
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Department of Medicine, University of Leipzig, Leipzig, Germany.

corresp_icon Corresponding author: Matthias Blüher. Department of Medicine, University of Leipzig, Liebigstr. 20, D-04103 Leipzig, Germany. bluma@medizin.uni-leipzig.de

Copyright © 2012 Korean Diabetes Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • The incidence of obesity has increased dramatically during recent decades. Obesity increases the risk for metabolic and cardiovascular diseases and may therefore contribute to premature death. With increasing fat mass, secretion of adipose tissue derived bioactive molecules (adipokines) changes towards a pro-inflammatory, diabetogenic and atherogenic pattern. Adipokines are involved in the regulation of appetite and satiety, energy expenditure, activity, endothelial function, hemostasis, blood pressure, insulin sensitivity, energy metabolism in insulin sensitive tissues, adipogenesis, fat distribution and insulin secretion in pancreatic β-cells. Therefore, adipokines are clinically relevant as biomarkers for fat distribution, adipose tissue function, liver fat content, insulin sensitivity, chronic inflammation and have the potential for future pharmacological treatment strategies for obesity and its related diseases. This review focuses on the clinical relevance of selected adipokines as markers or predictors of obesity related diseases and as potential therapeutic tools or targets in metabolic and cardiovascular diseases.
It is widely accepted that obesity and abdominal fat distribution contribute to the individual risk for type 2 diabetes, dyslipidemia, fatty liver disease, chronic subclinical inflammation, hypertension, and cardiovascular disease [1-3]. Dissection of the molecular mechanisms underlying obesity and its relationship to metabolic and cardiovascular diseases are essential for developing new strategies for prevention and treatment of these disorders. However, we are only at the beginning to understand the mechanistic link between obesity and its associated metabolic and vascular diseases. In the past two decades, advances in obesity research have led to the recognition that adipose tissue is an active endocrine organ that secretes more than 600 bioactive factors termed adipokines [4]. Adipokines play important roles in the regulation of appetite and satiety control, fat distribution, insulin sensitivity and insulin secretion, energy expenditure, inflammation, blood pressure, hemostasis, and endothelial function [5-11]. In an autocrine and paracrine manner, adipokines contribute to the modulation of adipogenesis, immune cell migration into adipose tissue, adipocyte metabolism and function [5,6]. Most importantly, adipokines have significant systemic effects on target organs including the brain, liver, muscle, vasculature, heart and pancreatic β-cells (Fig. 1) [5,6]. The adipokine secretion pattern reflects adipose tissue function and seems to be important for determining the individual risk to develop metabolic and cardiovascular comorbidities of obesity [1,3-6]. When adipose tissue inflammation and dysfunction have developed, adipokine secretion is significantly changed towards a diabetogenic, proinflammatory, and atherogenic pattern [1,3-6].
In 1987, adipose tissue was identified as a major site for sex steroid metabolism [8] and production of adipsin, an endocrine factor that is negatively correlated with obesity in rodents [9]. The discovery of leptin as an adipokine [7] further stimulated the discovery of new adipose tissue derived signals [3-5]. Since then, the search for novel adipokines, but more importantly the molecular characterization of newly identified adipokines with unknown function represents a major topic in obesity research. Secretion of adipokines (e.g., leptin, chemerin, monocyte-chemotactic-protein-1 [MCP-1], retinol-binding-protein-4 [RBP4]) may either closely reflect body fat mass and body weight dynamic or be related to other factors including adipose tissue function or dietary pattern (e.g., adiponectin, fetuin-A, C-reactive protein [CRP], progranulin, vaspin) [10,11].
However, there remains a major challenge to characterize the function, mode of action and molecular targets for the growing list of newly identified adipokines. Recently, 44 novel adipokines with unknown function have been identified using and unbiased protein profiling approach of the secretome of primary human adipocytes [12,13]. Among the more of 600 putative adipokines [4], there are molecules which play a role inflammatory response including interleukins (IL)-1, -6, -8, -10, tumour necrosis factor alpha (TNFα), transforming growth factor β (TGFβ), interferon-γ, CRP, plasminogen activator inhibitor-1, and chemerin (Table 1). Several adipokines including RBP4, chemerin, vaspin, fetuin-A, omentin, and fatty acid binding protein 4 have been associated with insulin resistance and fatty liver disease (Table 1), whereas adiponectin positively correlates with insulin sensitivity [reviewed in 3,5]. Other adipokines may cause or reflect adverse fat distribution including RBP4 [14], dipeptidyl peptidase-4 (DPP-4) [15], chemerin [16,17], apelin [reviewed in 18], vaspin [19,20], endocannabinoids [21], fetuin-A [22], omentin [23], and progranulin [24] (Table 1) [5]. Adipokines may represent the link between obesity and hypertension (e.g., angiotensinogen), endothelial function (e.g., omentin, apelin), hemostasis (e.g., fibrinogen), immune cell infiltration in adipose tissue (e.g., MCP-1, progranulin and macrophage inflammatory protein-1α) [3-5]. For several adipokines including resistin, visfatin/PBEF/Nampt, progranulin, fractalkine the clinical relevance of altered serum concentrations is either not clear or controversial [3-5]. The role of the adipokines leptin and adiponectin as mediators linking increased fat mass and/or impaired adipose tissue function to metabolic and cardiovascular diseases has been extensively characterized during the past years [25-29]. In addition to the discussion of these classical adipokines, this review focuses on the clinical importance of more recently identified adipokines [3-5,14-17,22-24,30] as biomarkers and therapeutic tools or targets for obesity related diseases.
Leptin was discovered in 1994 as the protein product of the ob gene mutation, which causes extreme obesity in the ob/ob mouse model [7]. The importance of altered leptin signalling for the development of obesity and diabetes is further supported by the discovery that a mutation in the leptin receptor gene causes obesity and diabetes in db/db mice [reviewed in 25]. Leptin is almost exclusively secreted from adipocytes, controls food intake and energy expenditure and has atherogenic and growth properties [25]. Leptin decreases orexigenic and increases anorexigenic peptide synthesis in the hypothalamus thereby decreasing appetite [25]. Obesity is associated with increased leptin serum concentrations, which potentially contribute to the development of insulin resistance and the metabolic syndrome [25]. Interestingly, exogenous administration of leptin does not significantly influence appetite and body weight in obese patients, a phenomenon which has been attributed to central leptin resistance [26]. It has been suggested that leptin exerts insulin sensitizing effects by increasing fatty acid oxidation and decreasing triglyceride storage in muscle [25]. In addition to the effects of leptin on insulin sensitivity, there may be a direct link between high circulating leptin concentrations and increased cardiovascular risk [1,5,25]. Leptin may enhance platelet aggregation and arterial thrombosis, promote angiogenesis, impair arterial distensibility and induce proliferation and migration of vascular smooth muscle cells [25].
In addition, to its potential role as mediator of insulin resistance, leptin has been identified as an important regulator of β-cell mass and cell survival [31]. Studies in the leptin receptor-deficient Zucker diabetic fatty (ZDF) rats reveal that the reduction in β-cell mass is primarily due to increased rate of β-cell death and not related to proliferation [32].
Adiponectin has been discovered in 1995 and was originally named Acrp30 [33]. Several groups identified this protein in a different context and referred to it as adipoQ [34], and apM1 [35], until the consensus name 'adiponectin' found widespread acceptance [36]. Since its discovery, several different functions have been found for adiponectin. There is consensus that adiponectin generally exerts insulin sensitising, anti-inflammatory and anti-apoptotic actions on a number of different cell types [36]. Consistent with these properties, adiponectin release from adipocytes is down-regulated under adverse metabolic conditions, resulting in reduced circulating adiponectin levels [36]. Furthermore, adiponectin expression and secretion increase upon improved insulin sensitivity and weight loss [36]. Insulin-sensitizing TZDs probably mediate part of their effect via adiponectin since they increase plasma concentrations of this adipokine in both, subjects with normal insulin sensitivity and type 2 diabetes in vivo [36]. In contrast, various hormones associated with insulin resistance and obesity including catecholamines, insulin, glucocorticoids, TNFα and IL-6 down-regulate adiponectin expression and secretion in fat cells in vitro [37]. Besides its peripheral effects, adiponectin acts in the brain to increase energy expenditure and cause weight loss [3,5,36].
The role of adiponectin as an endogenous insulin sensitizer was discovered using experimental down-regulation of the adiponectin gene in knockout mice [29]. Two independent studies demonstrate impaired insulin sensitivity in adiponectin knockout mice as compared to wild type controls [29, reviewed in 36]. In mice with transgenic overexpression, adiponectin was shown to have anti-obesity effects due to enhanced energy expenditure and impairment of adipocyte differentiation [38].
The effects of adiponectin on glucose homeostasis may be mediated both via effects on peripheral insulin sensitivity and insulin secretion [31]. Adiponectin plays a direct role in improving insulin sensitivity on the whole body level [36]. One mechanism how adiponectin directly improves insulin sensitivity is that the globular C-terminal fragment reduces glucose levels by increasing fatty acid combustion in myocytes [reviewed in 36]. Moreover, adiponectin exerts significnant anti-inflammatory effects [36]. In addition, adiponectin improves insulin sensitivity by paracrine action in fat cells [37] and most likely also in hepatocytes [36]. Potential effects of adiponectin on insulin secretion in β-cells, has been examined in several recent studies [31,36]. Transgenic ob/ob mice overexpressing the globular domain of adiponectin have increased insulin sensitivity and increased insulin secretion independently of body weight compared to control mice [39]. These results suggest that adiponectin has in addition to its insulin-sensitizing properties protective effects on β-cells [31]. Adiponectin is able to mitigate the apoptotic effects of either palmitate- or ceramide-induced cell death-an effect that may critically depend on the formation of the downstream conversion product of ceramide, sphingosine-1 phosphate in β-cells in vitro [36]. Further in vivo studies in C57BL/6 mice demonstrated that systemic adiponectin administration results in increased insulin secretion [40]. Adiponectin has additional anti-atherogenic effects and low adiponectin serum concentrations are associated with increased risk for cardiovascular disease [36]. Endothelium dependent vasoreactivity is impaired in people with low adiponectin levels, which could contribute to the development of hypertension in visceral obese individuals [36]. In addition, it has been suggested that adiponectin protects plaque rupture by the inhibition of matrix metalloproteinase function [41], because adiponectin increases the expression of tissue inhibitor of metalloproteinase in macrophages and selectively suppresses endothelial cell apoptosis [41].
Leptin as therapy of lipodystrophy and leptin deficiency
Adipokines may be clinically relevant both as therapeutic tools or targets in the treatment of obesity and its related diseases. The clinical use of leptin is an example how basic adipokine research may be translated into novel treatment concepts. Although chronic leptin administration does not significantly reduce body weight in common human obesity, exogenous leptin can significantly improve insulin resistance, glucose and lipid metabolism when endogenous leptin levels are low such as in patients with lipodystrophy [26]. Moreover, in rare cases of genetically-based leptin deficiency in morbidly-obese patients, leptin treatment is able to rescue the morbidly obese phenotype [27]. In women with hypothalamic amenorrhea, recombinant leptin therapy improved reproductive, thyroid, and growth hormone axes, as well as markers of bone formation [28]. Taken together, leptin can serve as a model that adipokines can be successfully used in the treatment of diseases.
DPP-4: an adipokine target
Another example for the role adipokines in the treatment of metabolic diseases has been recently provided by the discovery, that adipose tissue secretes DPP-4 [15]. DPP-4 is a 766 amino acid membrane-associated, serine-protease enzyme [42]. The enzyme is widely detected in numerous tissues such as kidney, liver, intestine, spleen, lymphocytic organs, placenta, adrenal glands, and vascular endothelium [42]. Increased DPP-4 expression and secretion from adipose tissue in obesity may impair insulin sensitivity in an autocrine and paracrine fashion [15]. Lamers et al. [15] further demonstrated that DPP-4 release significantly correlates with adipocyte size, suggesting that DPP-4 may be involved in linking adipose tissue to impaired glucose homeostasis. Increased DPP-4 activity and serum concentrations in obesity may serve as a model how altered adipokine secretion may be successfully used as therapeutic target in the treatment of obesity related diseases.
Inhibition of DPP-4 is now a well-established therapeutic principle to lower hyperglycemia in patients with type 2 diabetes. The glucose lowering properties of DPP-4 inhibitors are due to the mechanism that under normal physiological conditions, DPP-4 rapidly degrades glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) [42]. Nutrient intake stimulates the release of the incretin hormones GIP and GLP-1 into the circulation [42]. Important functions of both incretins include potentiating glucose-dependent insulin secretion from pancreatic β-cells and inhibiting glucagon secretion, which in turn reduces hepatic gluconeogenesis [42]. The effect of incretins is significantly reduced in patients with type 2 diabetes and contributes to impaired insulin secretion and chronic hyperglycemia [42].
IL-1β as an adipokine target
Adipose tissue expresses and releases IL-1β [43]. IL-1β is a proinflammatory cytokine which has been proposed to play a role in inflammatory pancreatic β-cell destruction leading to type 1 diabetes [44]. IL-1β inhibits the function and promotes the apoptosis of β-cells [44]. The blockade of IL-1 with a recombinant human IL-1-receptor antagonist (anakinra) has been shown to improve glycemia and β-cell function and reduced markers of systemic inflammation in a double-blind, parallel-group clinical trial involving 70 patients with type 2 diabetes [44]. Therefore IL-1β represents a model that in addition to the direct use of adipokines as therapeutic strategy, adipokines may be indirectly used as target molecules for the treatment of obesity comorbidities.
However, for most adipokines, effects of acute and chronic treatment have only been tested in the context of animal studies and there is no clinical application yet. Among several adipokines with a potential for future use as pharmacological treatment strategy, apelin and vaspin have been recently extensively studied [18-20].
Apelin
Apelin is an adipokine which plays a role in the regulation of glucose homeostasis and may contribute to the link between increased adipose tissue mass and obesity related metabolic diseases [18]. Apelin, a 36 amino-acid peptide endogenous ligand of the G-protein-coupled receptor APJ receptor, has been identified in a variety of tissues, including central nervous system with high expression in the hypothalamus, stomach, heart, skeletal muscle, and white adipose tissue [reviewed in 18]. Apelin serum concentration was shown to be higher in patients with obesity and insulin resistance [18]. Recently, higher apelin serum concentrations were found to be associated with liver cirrhosis both in rats and humans [18]. Moreover, treatment of rats with cirrhosis with an apelin receptor antagonist showed diminished hepatic fibrosis and loss of ascites suggesting the hepatic apelin system as a novel therapeutic target in liver disease [45]. Apelin serum concentrations correlate with hyperinsulinemia and obesity, suggesting that apelin may be another adipokine mediator of impaired adipose tissue function in obesity [18]. Interestingly, apelin administration has been shown to have glucose-lowering effects associated with enhanced glucose utilization in skeletal muscle and fat [46]. Moreover, apelin restored glucose tolerance and increased glucose utilization in obese and insulin-resistant mouse models [46]. Collectively, data obtained from apelin treatment in different rodent models indicate that apelin influences glucose homeostasis and may contribute to the link between increased adipose tissue mass and obesity related metabolic and inflammatory diseases [18].
Vaspin
Visceral adipose tissue-derived serpin (vaspin) gained a lot of attention since it has been identified as a member of serine protease inhibitor family, which was expressed in visceral adipose tissue of Otsuka Long-Evans Tokushima Fatty (OLETF) rats at the age when obesity and insulin plasma concentrations reach a peak [19]. We found vaspin expression in adipose tissue [47], stomach and rodent pancreatic islets [48], however the mechanisms how vaspin secretion may be linked to deterioration of glucose metabolism and insulin sensitivity are not entirely understood. In OLETF rats, tissue expression of vaspin and its serum levels decrease with worsening of diabetes and body weight loss at 50 weeks and could be normalized with insulin or pioglitazone treatment [19]. Administration of vaspin to obese mice improves glucose tolerance, insulin sensitivity and altered gene expression of candidate genes for insulin resistance [19]. Moreover, we could recently show that treatment of different mouse models with recombinant vaspin leads to sustained glucose lowering and reduction of food intake [48], suggesting vaspin as a treatment target for future pharmacological therapies of obesity and its related metabolic diseases.
Adipokines have a potential clinical relevance as biomarkers for fat mass, fat distribution, adipose tissue function, liver fat content, insulin sensitivity, and subclinical chronic inflammation associated with metabolic diseases. As a prominent example, circulating leptin levels are highly correlated with adipose tissue mass, and can thus be used as a surrogate for changes in the amount of adipose tissue [3,10,11]. Leptin may be one example for additional adipokines that signal the functional status of adipose tissue to other tissues and frequently reflect weight changes. Using an unbiased proteomics approach, we recently detected differential abundance of proteins associated with fat mass for antithrombin-III, clusterin, complement C3 and complement C3b, pigment epithelium-derived factor, RBP4, serum amyloid P, and vitamin-D binding protein [49].
In clinical practice measurement of adipokines which only reflect weight changes will not improve individual therapeutic decisions. However, there is a need in the monitoring of weight loss therapies for novel biomarkers, which predict how successful an individual can loose weight, which weight loss strategy may be the best and weight regain. In addition, there is no biomarker which distinguishes whether weight regain during diet interventions is due to diet failure or occurs despite healthy dieting. Adipokine biomarkers may also be promising candidates to predict the individual weight loss outcome with regard to improved cardiovascular function, insulin sensitivity, inflammation, liver function and steatosis, and adipose tissue function. In line with this, we recently described two distinct adipokine biomarker patterns [11] among 322 participants of the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT) of low-fat, Mediterranean or low-carbohydrate diets for weight loss [50]. One pattern includes biomarkers (insulin, triglycerides, leptin, chemerin, MCP-1, and RBP4) whose dynamics tightly correspond to changes in body weight [11], whereas a different pattern was observed for adiponectin, high density lipoprotein cholesterol, hsCRP, fetuin-A, progranulin, and vaspin. The latter pattern reflected lifestyle factors such as physical activity and healthier diet beyond simple associations with body fat mass [11].
Fat distribution
The search for adipokines which are exclusively expressed in distinct fat depots has not revealed a specific fat depot marker so far. However, there are several candidate adipokines, for which circulating levels strongly correlate with visceral fat distribution. Circulating biomarkers for abdominal visceral fat accumulation include adiponectin, RBP4, vaspin, chemerin, progranulin, omentin, fetuin-A and others [30]. We and others have recently shown that adiponectin serum concentration negatively correlates with visceral fat mass [30], whereas RBP4 [51], vaspin [20], chemerin [17], fetuin-A [22], omentin [23], and progranulin [24] are predictors of increased visceral fat distribution.
As a potential marker for visceral fat mass, visfatin, which has been previously identified as a protein involved in B-cell maturation (pre-B colony enhancing factor), caught much attention, because it was suggested to be exclusively expressed in visceral adipose tissue and have insulin mimetic effects [5]. With several subsequent studies it became clear that visfatin is expressed in many cells and tissues and represents the enzyme nicotinamide phosphoribosyltransferase (Nampt, EC 2.4.2.12) [52]. Although visfatin/PBEF/Nampt is clearly not exclusively expressed in visceral fat [52], a positive correlation between visceral adipose tissue visfatin/PBEF/Nampt gene expression and body mass index (BMI), was supported by a number of subsequent studies demonstrating that plasma visfatin levels in humans correlate with obesity and visceral fat mass [52].
We have recently extended the original finding that vaspin expression is higher in visceral depots of OLETF rats [19] by demonstrating fat depot-specific vaspin expression in obese individuals [47]. Elevated vaspin serum concentrations are associated with obesity, impaired insulin sensitivity and fitness level [20]. Analyses of vaspin serum concentrations in the 2-year DIRECT study [50] further revealed vaspin as a novel biomarker for a continuous beneficial response to switching to healthier dietary patterns [11].
RBP4 is predominantly secreted from the liver, but also expressed in adipocytes [14]. However, increased RBP4 serum concentrations have been shown to be the result of increased RBP4 expression in visceral adipose tissue of patients with insulin resistance [51]. RBP4 has gained a lot of attention after the first notion that it is elevated in the serum of insulin resistant humans and mice and that increased RBP4 serum concentrations are associated with obesity, insulin resistance, and abdominal fat distribution [14,51]. Therefore, increased RBP4 serum concentrations might causally link (visceral) obesity to insulin resistance and its associated metabolic diseases. We recently showed that RBP4 serum concentration patterns closely follow the body weight pattern in response to different diet regimens, suggesting that RBP4 rather reflect than cause changes in body weight and glucose homeostasis [11].
Analyses of chemerin concentrations in portal, hepatic and systemic venous blood revealed that visceral fat is not a major site of chemerin release, and elevated systemic levels of chemerin in obesity and type 2 diabetes seem to be associated with inflammation rather than BMI [17]. We recently postulated an important role of chemerin in the initiation of adipose tissue inflammation and dysfunction and suggested that reduced adipose tissue chemerin expression may contribute to improved insulin sensitivity and subclinical inflammation beyond significant weight loss [17].
Progranulin is a secreted protein with important functions in several processes, including immune response and embryonic development [53]. In adipose tissue, progranulin is secreted both from adipocytes and infiltrating macrophages [24]. We recently found that elevated progranulin serum concentrations are associated with visceral obesity, elevated plasma glucose, and dyslipidemia [24]. Taken together, adipokine serum concentrations may serve as biomarkers for visceral fat mass and could therefore be clinically important to avoid expensive direct measurement of visceral fat mass using magnetic resonance imaging scans.
Adipose tissue inflammation and dysfunction
Adipose tissue dysfunction and ectopic fat accumulation belong to the early abnormalities in the development of obesity and seem to be important factors determining the individual risk to develop metabolic and cardiovascular comorbidities of obesity [1,3-6]. With the development of adipose tissue dysfunction, adipokine secretion is significantly altered. These changes in adipokine secretion are very likely to link impaired adipose tissue function to insulin resistance and cardiovascular disease [1,3-6]. Hotamisligil et al. [54] first discovered the existence of an inflammatory state involving adipose tissue and its potential role in obesity by demonstrating the secretion of TNFα by the adipose tissue [54]. TNFα expression increases in adipocytes of obese animals, and the neutralisation of TNFα by a TNFα soluble antibody leads to an improvement of insulin sensitivity [54]. These observations exhibit the existence of a strong link between a proinflammatory cytokine, produced and secreted by adipose tissue, and the development of insulin resistance associated with obesity progression. These findings opened a new field of research in the domain of inflammation and obesity [1,3-6].
In addition to adipocytes, macrophages in human adipose tissue may contribute to enhance the obesity-related 'low-grade' chronic inflammation [3]. Various observations support the hypothesis of a potential deleterious role for adipose-infiltrated macrophages in the pathogenesis of obesity-associated diseases [3]. Indeed, increased number of macrophages in adipose tissue might cause increased systemic concentrations of pro-inflammatory cytokines. The action of these inflammatory molecules may represent the molecular link between adipose tissue and the metabolic, cardiovascular or even hepatic complications of obesity. In particular, increased levels of TNFα, IL-6, progranulin and MCP-1, produced by activated macrophages may directly contribute to the mechanisms of change in the insulin sensitivity in different adipose depots [3]. Due to the significant overlap between visceral fat distribution and adipose tissue inflammation, which is typically more pronounced in omental compared to subcutaneous fat [3], the same factors which may predict visceral fat mass are predictors of adipose tissue inflammation. Such molecules include MCP-1 [55,56], chemerin [17], omentin [23], progranulin [24], and others. Noteworthy, disruption of MCP1 action by knockout of either MCP1 or its receptor CC chemokine receptor 2 is associated with protection against insulin resistance further supporting the notion that increased adipose tissue macrophage infiltration may causally link obesity with insulin resistance [55,56]. In addition, we recently found that progranulin may contribute to immune cell attraction into adipose tissue and could therefore be a novel marker of chronic inflammation in obesity and type 2 diabetes. Progranulin closely reflects omental adipose tissue macrophage infiltration and improved insulin sensitivity after physical training significantly reduces elevated circulating progranulin in patients with type 2 diabetes [24].
Insulin sensitivity and glucose homeostasis
Obesity does not necessarily translate into increased risk for comorbidities and ~15% of obese individuals do not develop obesity associated disorders [30]. Therefore the pathogenic link between increased adipose tissue mass and higher risk for obesity related disorders including impaired insulin sensitivity is not necessarily directly related to fat mass. Adipose tissue dysfunction and ectopic fat accumulation seem to be important factors determining the individual risk to develop insulin resistance as comorbidity of obesity. To identify adipokines, which are independently of body fat mass are associated with impaired insulin sensitivity, we systematically characterized paired samples from abdominal subcutaneous and intraabdominal omental adipose tissue of insulin sensitive obese individuals compared with BMI-, age-, and gender-matched insulin resistant obese individuals without significant comorbidities including type 2 diabetes [30]. Increased circulating concentrations of RBP4 [14,51], vaspin [20], MCP-1 [55,56], visfatin/PBEF/Nampt [52], chemerin [17], progranulin [24] and fetuin-A [22] and decreased adiponectin serum concentrations [36] have been shown to be associated with either insulin resistance, obesity or both. However, it has been difficult to dissect the effects of obesity and insulin resistance on increased serum concentrations of these molecules. Comparison of insulin sensitive versus insulin resistant obese patients provided new evidence for a significant body fat mass independent role for adiponectin, chemerin, progranulin, RBP4 and fetuin-A in the development or at least as markers of insulin resistant obesity [30]. Among those markers, adiponectin has been shown to be a sensitive biomarker for insulin sensitivity in extensive studies [36]. In addition to these potential biomarkers of insulin resistance, increased activity of circulating DPP-4 derived from adipose tissue expression may impair insulin sensitivity in an autocrine and paracrine fashion [15]. Resistin has originally been suggested as an adipokine upregulated during weight gain, impairing insulin sensitivity, and linking insulin resistance with obesity in mice [57]. A recent large study involving the Framingham offspring cohort confirmed a significant relationship between insulin resistance and circulating resistin in humans, but found that this relationship was not independent of BMI [58].
A relationship between RBP4, insulin resistance and impaired glucose homeostasis has been first reported in mice lacking glucose transporter 4 in adipose tissue and has been subsequently confirmed in human cohorts [14,51]. These mice exhibit significantly higher RBP4 serum concentrations as their control littermates [59]. The effects of RBP4 are mediated through retinol-dependent or retinol-independent mechanisms [59]. It has been demonstrated that RBP4 can induce the retinoid-regulated gene encoding the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK), increase basal glucose production, and reduce insulin action to suppress glucose production in hepatocytes in vitro [59]. Recombinant RBP4 treatment in mice causes an impaired suppression of hepatic glucose production in response to maximal insulin concentrations [59] providing another mechanistic link between RBP4 induced insulin resistance, which might lead to increased fat accumulation [51].
Adipose tissue is an active endocrine organ, which produces a number of bioactive molecules, so called adipokines. Altered adipokine secretion may represent a link between adipose tissue dysfunction in obesity and metabolic and cardiovascular obesity-related disorders. Adipokines are important modulators of glucose metabolism, because they may primarily contribute to adverse fat distribution (e.g., chemerin, RBP4), altered appetite and satiety (e.g., leptin, vaspin), impaired insulin sensitivity (e.g., adiponectin, leptin, RBP4) or insulin secretion (e.g., leptin, adiponectin), and to inflammation (e.g., resistin, IL-6, TNFα, MCP-1, chemerin, progranulin). Functional characterization of newly identified adipokines which may link obesity to glucose homeostasis represents a main research focus. The identification of adipokine related mechanisms will be a prerequisit for translation into novel pharmacological treatment approaches of obesity, insulin resistance and type 2 diabetes.
Acknowledgements
This work was supported by the Kompetenznetz Adipositas (Competence Network for Obesity) funded by the Federal Ministry of Education and Research (FKZ 01GI0829).

No potential conflict of interest relevant to this article was reported.

  • 1. Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature 2006;444:875-880. ArticlePubMedPDF
  • 2. LeRoith D, Novosyadlyy R, Gallagher EJ, Lann D, Vijayakumar A, Yakar S. Obesity and type 2 diabetes are associated with an increased risk of developing cancer and a worse prognosis: epidemiological and mechanistic evidence. Exp Clin Endocrinol Diabetes 2008;116(Suppl 1):S4-S6. ArticlePubMed
  • 3. Bluher M. Adipose tissue dysfunction in obesity. Exp Clin Endocrinol Diabetes 2009;117:241-250. ArticlePubMed
  • 4. Lehr S, Hartwig S, Sell H. Adipokines: a treasure trove for the discovery of biomarkers for metabolic disorders. Proteomics Clin Appl 2012;6:91-101. ArticlePubMedPDF
  • 5. Bluher M. Do adipokines link obesity to its related metabolic and cardiovascular diseases? Clin Lipidol 2010;5:95-107.Article
  • 6. Bays HE. "Sick fat," metabolic disease, and atherosclerosis. Am J Med 2009;122(1 Suppl):S26-S37. ArticlePubMed
  • 7. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425-432. ArticlePubMedPDF
  • 8. Siiteri PK. Adipose tissue as a source of hormones. Am J Clin Nutr 1987;45(1 Suppl):277-282. ArticlePubMed
  • 9. Flier JS, Cook KS, Usher P, Spiegelman BM. Severely impaired adipsin expression in genetic and acquired obesity. Science 1987;237:405-408. ArticlePubMed
  • 10. Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 2000;21:697-738. ArticlePubMed
  • 11. Bluher M, Rudich A, Kloting N, Golan R, Henkin Y, Rubin E, Schwarzfuchs D, Gepner Y, Stampfer MJ, Fiedler M, Thiery J, Stumvoll M, Shai I. Two patterns of adipokine and other biomarker dynamics in a long-term weight loss intervention. Diabetes Care 2012;35:342-349. ArticlePubMedPMCPDF
  • 12. Lehr S, Hartwig S, Lamers D, Famulla S, Muller S, Hanisch FG, Cuvelier C, Ruige J, Eckardt K, Ouwens DM, Sell H, Eckel J. Identification and validation of novel adipokines released from primary human adipocytes. Mol Cell Proteomics 2012;11:M111.010504ArticlePubMed
  • 13. Dahlman I, Elsen M, Tennagels N, Korn M, Brockmann B, Sell H, Eckel J, Arner P. Functional annotation of the human fat cell secretome. Arch Physiol Biochem 2012;118:84-91. ArticlePubMed
  • 14. Graham TE, Yang Q, Bluher M, Hammarstedt A, Ciaraldi TP, Henry RR, Wason CJ, Oberbach A, Jansson PA, Smith U, Kahn BB. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med 2006;354:2552-2563. ArticlePubMed
  • 15. Lamers D, Famulla S, Wronkowitz N, Hartwig S, Lehr S, Ouwens DM, Eckardt K, Kaufman JM, Ryden M, Muller S, Hanisch FG, Ruige J, Arner P, Sell H, Eckel J. Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome. Diabetes 2011;60:1917-1925. ArticlePubMedPMCPDF
  • 16. Wittamer V, Franssen JD, Vulcano M, Mirjolet JF, Le Poul E, Migeotte I, Brezillon S, Tyldesley R, Blanpain C, Detheux M, Mantovani A, Sozzani S, Vassart G, Parmentier M, Communi D. Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids. J Exp Med 2003;198:977-985. ArticlePubMedPMCPDF
  • 17. Chakaroun R, Raschpichler M, Kloting N, Oberbach A, Flehmig G, Kern M, Schon MR, Shang E, Lohmann T, Dressler M, Fasshauer M, Stumvoll M, Bluher M. Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity. Metabolism 2012;61:706-714. ArticlePubMed
  • 18. Castan-Laurell I, Dray C, Attane C, Duparc T, Knauf C, Valet P. Apelin, diabetes, and obesity. Endocrine 2011;40:1-9. ArticlePubMedPDF
  • 19. Hida K, Wada J, Eguchi J, Zhang H, Baba M, Seida A, Hashimoto I, Okada T, Yasuhara A, Nakatsuka A, Shikata K, Hourai S, Futami J, Watanabe E, Matsuki Y, Hiramatsu R, Akagi S, Makino H, Kanwar YS. Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity. Proc Natl Acad Sci U S A 2005;102:10610-10615. ArticlePubMedPMC
  • 20. Youn BS, Kloting N, Kratzsch J, Lee N, Park JW, Song ES, Ruschke K, Oberbach A, Fasshauer M, Stumvoll M, Bluher M. Serum vaspin concentrations in human obesity and type 2 diabetes. Diabetes 2008;57:372-377. ArticlePubMedPDF
  • 21. Bluher M, Engeli S, Kloting N, Berndt J, Fasshauer M, Batkai S, Pacher P, Schon MR, Jordan J, Stumvoll M. Dysregulation of the peripheral and adipose tissue endocannabinoid system in human abdominal obesity. Diabetes 2006;55:3053-3060. ArticlePubMedPMCPDF
  • 22. Stefan N, Hennige AM, Staiger H, Machann J, Schick F, Krober SM, Machicao F, Fritsche A, Haring HU. Alpha2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes Care 2006;29:853-857. PubMed
  • 23. Schaffler A, Neumeier M, Herfarth H, Furst A, Scholmerich J, Buchler C. Genomic structure of human omentin, a new adipocytokine expressed in omental adipose tissue. Biochim Biophys Acta 2005;1732:96-102. ArticlePubMed
  • 24. Youn BS, Bang SI, Kloting N, Park JW, Lee N, Oh JE, Pi KB, Lee TH, Ruschke K, Fasshauer M, Stumvoll M, Bluher M. Serum progranulin concentrations may be associated with macrophage infiltration into omental adipose tissue. Diabetes 2009;58:627-636. ArticlePubMedPMCPDF
  • 25. Ahima RS, Flier JS. Leptin. Annu Rev Physiol 2000;62:413-437. ArticlePubMed
  • 26. Savage DB, O'Rahilly S. Leptin: a novel therapeutic role in lipodystrophy. J Clin Invest 2002;109:1285-1286. ArticlePubMedPMC
  • 27. Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, Hughes IA, McCamish MA, O'Rahilly S. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999;341:879-884. ArticlePubMed
  • 28. Welt CK, Chan JL, Bullen J, Murphy R, Smith P, DePaoli AM, Karalis A, Mantzoros CS. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med 2004;351:987-997. ArticlePubMed
  • 29. Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci U S A 2001;98:2005-2010. ArticlePubMedPMC
  • 30. Kloting N, Fasshauer M, Dietrich A, Kovacs P, Schon MR, Kern M, Stumvoll M, Bluher M. Insulin-sensitive obesity. Am J Physiol Endocrinol Metab 2010;299:E506-E515. ArticlePubMed
  • 31. Lee YH, Magkos F, Mantzoros CS, Kang ES. Effects of leptin and adiponectin on pancreatic beta-cell function. Metabolism 2011;60:1664-1672. ArticlePubMed
  • 32. Pick A, Clark J, Kubstrup C, Levisetti M, Pugh W, Bonner-Weir S, Polonsky KS. Role of apoptosis in failure of beta-cell mass compensation for insulin resistance and beta-cell defects in the male Zucker diabetic fatty rat. Diabetes 1998;47:358-364. ArticlePubMedPDF
  • 33. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 1995;270:26746-26749. ArticlePubMed
  • 34. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 1996;271:10697-10703. ArticlePubMed
  • 35. Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem Biophys Res Commun 1996;221:286-289. ArticlePubMed
  • 36. Turer AT, Scherer PE. Adiponectin: mechanistic insights and clinical implications. Diabetologia 2012;55:2319-2326. ArticlePubMedPDF
  • 37. Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R. Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun 2002;290:1084-1089. ArticlePubMed
  • 38. Bauche IB, El Mkadem SA, Pottier AM, Senou M, Many MC, Rezsohazy R, Penicaud L, Maeda N, Funahashi T, Brichard SM. Overexpression of adiponectin targeted to adipose tissue in transgenic mice: impaired adipocyte differentiation. Endocrinology 2007;148:1539-1549. ArticlePubMed
  • 39. Yamauchi T, Kamon J, Waki H, Imai Y, Shimozawa N, Hioki K, Uchida S, Ito Y, Takakuwa K, Matsui J, Takata M, Eto K, Terauchi Y, Komeda K, Tsunoda M, Murakami K, Ohnishi Y, Naitoh T, Yamamura K, Ueyama Y, Froguel P, Kimura S, Nagai R, Kadowaki T. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem 2003;278:2461-2468. ArticlePubMed
  • 40. Okamoto M, Ohara-Imaizumi M, Kubota N, Hashimoto S, Eto K, Kanno T, Kubota T, Wakui M, Nagai R, Noda M, Nagamatsu S, Kadowaki T. Adiponectin induces insulin secretion in vitro and in vivo at a low glucose concentration. Diabetologia 2008;51:827-835. ArticlePubMedPDF
  • 41. Kobayashi H, Ouchi N, Kihara S, Walsh K, Kumada M, Abe Y, Funahashi T, Matsuzawa Y. Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin. Circ Res 2004;94:e27-e31. ArticlePubMedPMC
  • 42. Nauck MA. Incretin-based therapies for type 2 diabetes mellitus: properties, functions, and clinical implications. Am J Med 2011;124(1 Suppl):S3-S18. ArticlePubMed
  • 43. Sopasakis VR, Nagaev I, Smith U. Cytokine release from adipose tissue of nonobese individuals. Int J Obes (Lond) 2005;29:1144-1147. ArticlePubMedPDF
  • 44. Larsen CM, Faulenbach M, Vaag A, Volund A, Ehses JA, Seifert B, Mandrup-Poulsen T, Donath MY. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med 2007;356:1517-1526. ArticlePubMed
  • 45. Principe A, Melgar-Lesmes P, Fernandez-Varo G, del Arbol LR, Ros J, Morales-Ruiz M, Bernardi M, Arroyo V, Jimenez W. The hepatic apelin system: a new therapeutic target for liver disease. Hepatology 2008;48:1193-1201. ArticlePubMed
  • 46. Dray C, Knauf C, Daviaud D, Waget A, Boucher J, Buleon M, Cani PD, Attane C, Guigne C, Carpene C, Burcelin R, Castan-Laurell I, Valet P. Apelin stimulates glucose utilization in normal and obese insulin-resistant mice. Cell Metab 2008;8:437-445. ArticlePubMed
  • 47. Kloting N, Berndt J, Kralisch S, Kovacs P, Fasshauer M, Schon MR, Stumvoll M, Bluher M. Vaspin gene expression in human adipose tissue: association with obesity and type 2 diabetes. Biochem Biophys Res Commun 2006;339:430-436. ArticlePubMed
  • 48. Kloting N, Kovacs P, Kern M, Heiker JT, Fasshauer M, Schon MR, Stumvoll M, Beck-Sickinger AG, Bluher M. Central vaspin administration acutely reduces food intake and has sustained blood glucose-lowering effects. Diabetologia 2011;54:1819-1823. ArticlePubMedPDF
  • 49. Oberbach A, Bluher M, Wirth H, Till H, Kovacs P, Kullnick Y, Schlichting N, Tomm JM, Rolle-Kampczyk U, Murugaiyan J, Binder H, Dietrich A, von Bergen M. Combined proteomic and metabolomic profiling of serum reveals association of the complement system with obesity and identifies novel markers of body fat mass changes. J Proteome Res 2011;10:4769-4788. ArticlePubMed
  • 50. Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, Greenberg I, Golan R, Fraser D, Bolotin A, Vardi H, Tangi-Rozental O, Zuk-Ramot R, Sarusi B, Brickner D, Schwartz Z, Sheiner E, Marko R, Katorza E, Thiery J, Fiedler GM, Bluher M, Stumvoll M, Stampfer MJ. Dietary Intervention Randomized Controlled Trial (DIRECT) Group. Weight loss with a low-carbohydrate, mediterranean, or low-fat diet. N Engl J Med 2008;359:229-241. ArticlePubMed
  • 51. Kloting N, Graham TE, Berndt J, Kralisch S, Kovacs P, Wason CJ, Fasshauer M, Schon MR, Stumvoll M, Bluher M, Kahn BB. Serum retinol-binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass. Cell Metab 2007;6:79-87. ArticlePubMed
  • 52. Berndt J, Kloting N, Kralisch S, Kovacs P, Fasshauer M, Schon MR, Stumvoll M, Bluher M. Plasma visfatin concentrations and fat depot-specific mRNA expression in humans. Diabetes 2005;54:2911-2916. ArticlePubMedPDF
  • 53. Tolkatchev D, Malik S, Vinogradova A, Wang P, Chen Z, Xu P, Bennett HP, Bateman A, Ni F. Structure dissection of human progranulin identifies well-folded granulin/epithelin modules with unique functional activities. Protein Sci 2008;17:711-724. ArticlePubMedPMC
  • 54. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993;259:87-91. ArticlePubMed
  • 55. Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, Kitazawa S, Miyachi H, Maeda S, Egashira K, Kasuga M. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 2006;116:1494-1505. ArticlePubMedPMC
  • 56. Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, Vaddi K, Charo I, Leibel RL, Ferrante AW Jr. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 2006;116:115-124. ArticlePubMed
  • 57. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA. The hormone resistin links obesity to diabetes. Nature 2001;409:307-312. ArticlePubMedPDF
  • 58. Hivert MF, Sullivan LM, Fox CS, Nathan DM, D'Agostino RB Sr, Wilson PW, Meigs JB. Associations of adiponectin, resistin, and tumor necrosis factor-alpha with insulin resistance. J Clin Endocrinol Metab 2008;93:3165-3172. PubMedPMC
  • 59. Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, Kotani K, Quadro L, Kahn BB. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 2005;436:356-362. ArticlePubMedPDF
  • 60. Lamounier-Zepter V, Look C, Alvarez J, Christ T, Ravens U, Schunck WH, Ehrhart-Bornstein M, Bornstein SR, Morano I. Adipocyte fatty acid-binding protein suppresses cardiomyocyte contraction: a new link between obesity and heart disease. Circ Res 2009;105:326-334. PubMed
Fig. 1
Effects of adipokines. Adipokines regulate adipogenesis, adipocyte metabolism, immune cell migration into adipose tissue via autocrine and paracrine signalling. In addition, adipokines have endocrine/systemic effects on appetite and satiety control, regulation of energy expenditure and activity, influence insulin sensitivity and energy metabolism in insulin sensitive tissues, such as liver, muscle and fat as well as insulin secretion in pancreatic β-cells. IL, interleukin; TNFα, tumour necrosis factor alpha; MCP-1, monocyte-chemotactic-protein-1; FABP4, fatty acid binding protein 4; RBP4, retinol-binding-protein-4.
dmj-36-317-g001.jpg
Table 1
Relevance of selected adipokines as biomarkers or therapeutic tools
dmj-36-317-i001.jpg

RBP4, retinol-binding-protein-4; DPP-4, dipeptidyl peptidase-4; IL, interleukin; MCP-1, monocyte-chemotactic-protein-1; FABP4, fatty acid binding protein 4.

aDemonstrated in animal models only.

Figure & Data

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    Citations to this article as recorded by  
    • Omentin roles in physiology and pathophysiology: an up-to-date comprehensive review
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      Arşiv Kaynak Tarama Dergisi.2024; 33(1): 71.     CrossRef
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      Advances in Clinical Medicine.2024; 14(04): 2647.     CrossRef
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      Biomedicines.2024; 12(8): 1882.     CrossRef
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      JAMA Network Open.2024; 7(9): e2436157.     CrossRef
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      Ruiqiang Li, Xiaoyi Lin, Tingyu Lu, Jiao Wang, Ying Wang, Lin Xu
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      The FEBS Journal.2023; 290(3): 620.     CrossRef
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      Clinical Endocrinology.2023; 98(2): 141.     CrossRef
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      British Journal of Dermatology.2023; 188(3): 320.     CrossRef
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      Proceedings of the National Academy of Sciences.2022;[Epub]     CrossRef
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      Frontiers in Immunology.2022;[Epub]     CrossRef
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      Pamela A. Nono Nankam, Manuel Cornely, Nora Klöting, Matthias Blüher
      Frontiers in Endocrinology.2022;[Epub]     CrossRef
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      Nutrients.2022; 15(1): 37.     CrossRef
    • Leptin and Adiponectin Concentrations Independently Predict Future Accumulation of Visceral Fat in Nondiabetic Japanese Americans
      Sun Ok Song, Seung Jin Han, Steven E. Kahn, Donna L. Leonetti, Wilfred Y. Fujimoto, Edward J. Boyko
      Obesity.2021; 29(1): 233.     CrossRef
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      Bareket Daniel, Ariela Livne, Guy Cohen, Shirin Kahremany, Shlomo Sasson
      Endocrinology.2021;[Epub]     CrossRef
    • Visfatin level and gestational diabetes mellitus: a systematic review and meta-analysis
      Yong-Kuan Jiang, Hai-Yan Deng, Zeng-Yong Qiao, Fang-Xiao Gong
      Archives of Physiology and Biochemistry.2021; 127(5): 468.     CrossRef
    • Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer
      Yetirajam Rajesh, Devanand Sarkar
      International Journal of Molecular Sciences.2021; 22(4): 2163.     CrossRef
    • Contribution of Adipose Tissue Oxidative Stress to Obesity-Associated Diabetes Risk and Ethnic Differences: Focus on Women of African Ancestry
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      Antioxidants.2021; 10(4): 622.     CrossRef
    • Retinol-binding protein 4 in obesity and metabolic dysfunctions
      Pamela A. Nono Nankam, Matthias Blüher
      Molecular and Cellular Endocrinology.2021; 531: 111312.     CrossRef
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      Radzisław Mierzyński, Elżbieta Poniedziałek-Czajkowska, Dominik Dłuski, Maciej Kamiński, Agnieszka Mierzyńska, Bożena Leszczyńska-Gorzelak, Antonio Schiattarella
      Journal of Diabetes Research.2021; 2021: 1.     CrossRef
    • A systematic literature review on obesity: Understanding the causes & consequences of obesity and reviewing various machine learning approaches used to predict obesity
      Mahmood Safaei, Elankovan A. Sundararajan, Maha Driss, Wadii Boulila, Azrulhizam Shapi'i
      Computers in Biology and Medicine.2021; 136: 104754.     CrossRef
    • Does a Vegetarian Diet Affect the Levels of Myokine and Adipokine in Prepubertal Children?
      Jadwiga Ambroszkiewicz, Joanna Gajewska, Joanna Mazur, Witold Klemarczyk, Grażyna Rowicka, Mariusz Ołtarzewski, Małgorzata Strucińska, Magdalena Chełchowska
      Journal of Clinical Medicine.2021; 10(17): 3995.     CrossRef
    • Characteristics of Selected Adipokines in Ascites and Blood of Ovarian Cancer Patients
      Marcin Wróblewski, Karolina Szewczyk-Golec, Iga Hołyńska-Iwan, Joanna Wróblewska, Alina Woźniak
      Cancers.2021; 13(18): 4702.     CrossRef
    • Nutrition as Prevention Factor of Gestational Diabetes Mellitus: A Narrative Review
      Radzisław Mierzyński, Elżbieta Poniedziałek-Czajkowska, Maciej Sotowski, Magdalena Szydełko-Gorzkowicz
      Nutrients.2021; 13(11): 3787.     CrossRef
    • The myokine meteorin‐like (metrnl) improves glucose tolerance in both skeletal muscle cells and mice by targeting AMPKα2
      Jung Ok Lee, Won Seok Byun, Min Ju Kang, Jeong Ah Han, Jiyoung Moon, Min‐Jeong Shin, Ho Jun Lee, Ji Hyung Chung, Jin‐Seok Lee, Chang‐Gue Son, Kwon‐Ho Song, Tae Woo Kim, Eun‐Soo Lee, Hong Min Kim, Choon Hee Chung, Kevin R. W. Ngoei, Naomi X. Y. Ling, Jonat
      The FEBS Journal.2020; 287(10): 2087.     CrossRef
    • Plasma Adipsin as a Biomarker and Its Implication in Type 2 Diabetes Mellitus


      Gebrehiwot Gebremedhin Tafere, Dawit Zewdu Wondafrash, Kaleab Alemayehu Zewdie, Brhane Teklebrhan Assefa, Muluken Altaye Ayza
      Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2020; Volume 13: 1855.     CrossRef
    • Low-dose naltrexone rescues inflammation and insulin resistance associated with hyperinsulinemia
      Abhinav Choubey, Khyati Girdhar, Aditya K. Kar, Shaivya Kushwaha, Manoj Kumar Yadav, Debabrata Ghosh, Prosenjit Mondal
      Journal of Biological Chemistry.2020; 295(48): 16359.     CrossRef
    • Association between Adipokines and Biomarkers of Alzheimer’s Disease: A Cross-Sectional Study
      Liliana Letra, Paulo Matafome, Tiago Rodrigues, Diana Duro, Raquel Lemos, Inês Baldeiras, Miguel Patrício, Miguel Castelo-Branco, Gina Caetano, Raquel Seiça, Isabel Santana
      Journal of Alzheimer's Disease.2019; 67(2): 725.     CrossRef
    • Role of adiponectin and its target receptors to control deposition of fat in obesity related disorders
      souravh Bais, Nilesh J. Patel
      Obesity Medicine.2019; 16: 100148.     CrossRef
    • Circulatory Omentin-1 levels but not genetic variants influence the pathophysiology of Type 2 diabetes
      Nirali Rathwa, Roma Patel, Sayantani Pramanik Palit, Shahnawaz D. Jadeja, Mahendra Narwaria, A.V. Ramachandran, Rasheedunnisa Begum
      Cytokine.2019; 119: 144.     CrossRef
    • Roles of omental and bone marrow adipocytes in tumor biology
      Yoon Jin Cha, Ja Seung Koo
      Adipocyte.2019; 8(1): 304.     CrossRef
    • Genetic susceptibility of Iraqis for obesity and type 2 diabetes: LEPR gene polymorphisms
      Maysoon K. Almyah, Adnan Issa Al-Badran
      Gene Reports.2019; 15: 100386.     CrossRef
    • New Insights into Adipokines as Potential Biomarkers for Type-2 Diabetes Mellitus
      Marta Olivera-Santa Catalina, Pedro C. Redondo, Maria P. Granados, Carlos Cantonero, Jose Sanchez-Collado, Letizia Albarran, Jose J. Lopez
      Current Medicinal Chemistry.2019; 26(22): 4119.     CrossRef
    • Impact of Intragastric Balloon Treatment on Adipokines, Cytokines, and Metabolic Profile in Obese Individuals
      Marcella Rodrigues Guedes, Ricardo José Fittipaldi-Fernandez, Cristina Fajardo Diestel, Márcia Regina Simas Torres Klein
      Obesity Surgery.2019; 29(8): 2600.     CrossRef
    • The cross-talk between adipokines and miRNAs in health and obesity-mediated diseases
      Ahmad Ghasemi, Seyed Isaac Hashemy, Mohsen Azimi-Nezhad, Alireza Dehghani, Jafar Saeidi, Mahnaz Mohtashami
      Clinica Chimica Acta.2019; 499: 41.     CrossRef
    • Minor lipids profiling in subcutaneous and epicardial fat tissue using LC/MS with an optimized preanalytical phase
      Petra Tomášová, Martina Čermáková, Helena Pelantová, Marek Vecka, Helena Kratochvílová, Michal Lipš, Jaroslav Lindner, Blanka Šedivá, Martin Haluzík, Marek Kuzma
      Journal of Chromatography B.2019; 1113: 50.     CrossRef
    • Impact of body weight gain on hepatic metabolism and hepatic inflammatory cytokines in comparison of Shetland pony geldings and Warmblood horse geldings
      Carola Schedlbauer, Dominique Blaue, Martin Gericke, Matthias Blüher, Janine Starzonek, Claudia Gittel, Walter Brehm, Ingrid Vervuert
      PeerJ.2019; 7: e7069.     CrossRef
    • Lipid classes in adipose tissues and liver differ between Shetland ponies and Warmblood horses
      Stephanie Adolph, Carola Schedlbauer, Dominique Blaue, Axel Schöniger, Claudia Gittel, Walter Brehm, Herbert Fuhrmann, Ingrid Vervuert, Juan J. Loor
      PLOS ONE.2019; 14(3): e0207568.     CrossRef
    • Effects of Probiotic Yogurt on Serum Omentin-1, Adropin, and Nesfatin-1 Concentrations in Overweight and Obese Participants Under Low-Calorie Diet
      Mitra Zarrati, Mahsa Raji Lahiji, Eisa Salehi, Bahareh Yazdani, Elham Razmpoosh, Raheleh Shokouhi Shoormasti, Farzad Shidfar
      Probiotics and Antimicrobial Proteins.2019; 11(4): 1202.     CrossRef
    • Placental expressions and serum levels of adiponectin, visfatin, and omentin in GDM
      Xaynaly Souvannavong-Vilivong, Chantacha Sitticharoon, Roongrit Klinjampa, Issarawan Keadkraichaiwat, Chanakarn Sripong, Saimai Chatree, Rungnapa Sririwichitchai, Tripop Lertbunnaphong
      Acta Diabetologica.2019; 56(10): 1121.     CrossRef
    • Angiotensin-(1-7), Adipokines and Inflammation
      Deborah de Farias Lelis, Daniela Fernanda de Freitas, Amanda Souto Machado, Thaísa Soares Crespo, Sérgio Henrique Sousa Santos
      Metabolism.2019; 95: 36.     CrossRef
    • Recent advances in biosensor technology in assessment of early diabetes biomarkers
      Armin Salek-Maghsoudi, Faezeh Vakhshiteh, Raheleh Torabi, Shokoufeh Hassani, Mohammad Reza Ganjali, Parviz Norouzi, Morteza Hosseini, Mohammad Abdollahi
      Biosensors and Bioelectronics.2018; 99: 122.     CrossRef
    • Potential role of microRNAs in the regulation of adipocytes liposecretion and adipose tissue physiology
      Giulia Maurizi, Lucia Babini, Lucio Della Guardia
      Journal of Cellular Physiology.2018; 233(12): 9077.     CrossRef
    • Metabolomic and lipidomic analysis of the effect of pioglitazone on hepatic steatosis in a rat model of obese Type 2 diabetes
      Hyekyung Yang, Dong Ho Suh, Dae Hee Kim, Eun Sung Jung, Kwang‐Hyeon Liu, Choong Hwan Lee, Cheol‐Young Park
      British Journal of Pharmacology.2018; 175(17): 3610.     CrossRef
    • Implications of circulating Meteorin-like (Metrnl) level in human subjects with type 2 diabetes
      Hye Soo Chung, Soon Young Hwang, Ju Hee Choi, Hyun Jung Lee, Nam Hoon Kim, Hye Jin Yoo, Ji-A Seo, Sin Gon Kim, Nan Hee Kim, Sei Hyun Baik, Kyung Mook Choi
      Diabetes Research and Clinical Practice.2018; 136: 100.     CrossRef
    • Anti-Inflammatory and Pro-Inflammatory Adipokine Profiles in Children on Vegetarian and Omnivorous Diets
      Jadwiga Ambroszkiewicz, Magdalena Chełchowska, Grażyna Rowicka, Witold Klemarczyk, Małgorzata Strucińska, Joanna Gajewska
      Nutrients.2018; 10(9): 1241.     CrossRef
    • Adipokine profile as a novel screening method for cardiometabolic disease: Help or hindrance?
      Ivana Veljić, Marija Polovina, Jelena P Seferović, Petar M Seferović
      European Journal of Preventive Cardiology.2018; 25(14): 1543.     CrossRef
    • Adipocytes and intestinal epithelium dysfunctions linking obesity to inflammation induced by high glycemic index pellet-diet in Wistar rats
      Anna Beatriz Santana Luz, Júlia Braga dos Santos Figueredo, Bianca Damásio Pereira Dantas Salviano, Ana Júlia Felipe Camelo Aguiar, Luiza Gabriella Soares Dantas Pinheiro, Matheus Felipe Dantas Krause, Christina da Silva Camillo, Fernando Vagner Lobo Ladd
      Bioscience Reports.2018;[Epub]     CrossRef
    • The effect of diet, adiposity, and weight loss on the secretion of incretin hormones in cats
      K.E. McCool, A.J. Rudinsky, V.J. Parker, C.O. Herbert, C. Gilor
      Domestic Animal Endocrinology.2018; 62: 67.     CrossRef
    • Carnosine Supplementation Improves Serum Resistin Concentrations in Overweight or Obese Otherwise Healthy Adults: A Pilot Randomized Trial
      Estifanos Baye, Jozef Ukropec, Maximilian P. J. De Courten, Aya Mousa, Timea Kurdiova, Josphin Johnson, Kirsty Wilson, Magdalena Plebanski, Giancarlo Aldini, Barbara Ukropcova, Barbora De Courten
      Nutrients.2018; 10(9): 1258.     CrossRef
    • Metabolic syndrome alters expression of insulin signaling-related genes in swine mesenchymal stem cells
      Sabena M. Conley, Xiang-Yang Zhu, Alfonso Eirin, Hui Tang, Amir Lerman, Andre J. van Wijnen, Lilach O. Lerman
      Gene.2018; 644: 101.     CrossRef
    • Changes in Omentin Levels and Its mRNA Expression in Epicardial Adipose Tissue in Patients Undergoing Elective Cardiac Surgery: the Influence of Type 2 Diabetes and Coronary Heart Disease
      Z. MATLOCH, H. KRATOCHVÍLOVÁ, A. CINKAJZLOVÁ, M. LIPŠ, P. KOPECKÝ, M. POŘÍZKA, D. HALUZÍKOVÁ, J. LINDNER, M. MRÁZ, J. KLOUČKOVÁ, Z. LACINOVÁ, M. HALUZÍK
      Physiological Research.2018; : 881.     CrossRef
    • Apport du tissu adipeux et de la fraction vasculaire stromale en chirurgie de la main
      I. Nseir, F. Delaunay, C. Latrobe, A. Bonmarchand, D. Coquerel-Beghin, I. Auquit-Auckbur
      Revue de Chirurgie Orthopédique et Traumatologique.2017; 103(6): 643.     CrossRef
    • Specific Strains of Lactic Acid Bacteria Differentially Modulate the Profile of Adipokines In Vitro
      Emanuel Fabersani, María Claudia Abeijon-Mukdsi, Romina Ross, Roxana Medina, Silvia González, Paola Gauffin-Cano
      Frontiers in Immunology.2017;[Epub]     CrossRef
    • Use of adipose tissue and stromal vascular fraction in hand surgery
      I. Nseir, F. Delaunay, C. Latrobe, A. Bonmarchand, D. Coquerel-Beghin, I. Auquit-Auckbur
      Orthopaedics & Traumatology: Surgery & Research.2017; 103(6): 927.     CrossRef
    • Investigating the role of adipokines in chronic migraine
      Elisa Rubino, Alessandro Vacca, Flora Govone, Annalisa Gai, Silvia Boschi, Milena Zucca, Paola De Martino, Salvatore Gentile, Lorenzo Pinessi, Innocenzo Rainero
      Cephalalgia.2017; 37(11): 1067.     CrossRef
    • Life in the fat lane: seasonal regulation of insulin sensitivity, food intake, and adipose biology in brown bears
      K. S. Rigano, J. L. Gehring, B. D. Evans Hutzenbiler, A. V. Chen, O. L. Nelson, C. A. Vella, C. T. Robbins, H. T. Jansen
      Journal of Comparative Physiology B.2017; 187(4): 649.     CrossRef
    • Predictors of leptin concentration and association with cardiovascular risk in patients with coronary artery disease: results from the AtheroGene study
      Christoph Bickel, Renate B. Schnabel, Tanja Zeller, Karl J. Lackner, Hans J. Rupprecht, Stefan Blankenberg, Christoph Sinning, Dirk Westermann
      Biomarkers.2017; 22(3-4): 210.     CrossRef
    • Omentin-A Novel Adipokine in Respiratory Diseases
      Yan Zhou, Bo Zhang, Caixia Hao, Xiaoting Huang, Xiaohong Li, Yanhong Huang, Ziqiang Luo
      International Journal of Molecular Sciences.2017; 19(1): 73.     CrossRef
    • Exercise training lowers serum chemerin concentration in obese children
      F. Zehsaz, N. Farhangi, M. Ghahramani
      Science & Sports.2017; 32(1): 39.     CrossRef
    • MicroRNAs and adipocytokines: Promising biomarkers for pharmacological targets in diabetes mellitus and its complications
      Mohamad Reza Ashoori, Mohammad Rahmati-Yamchi, Alireza Ostadrahimi, Sedigheh Fekri Aval, Nosratollah Zarghami
      Biomedicine & Pharmacotherapy.2017; 93: 1326.     CrossRef
    • Adiponectin, Leptin, and Leptin Receptor in Obese Patients with Type 2 Diabetes Treated with Insulin Detemir
      Paweł Olczyk, Robert Koprowski, Katarzyna Komosinska-Vassev, Agnieszka Jura-Półtorak, Katarzyna Winsz-Szczotka, Kornelia Kuźnik-Trocha, Łukasz Mencner, Alicja Telega, Diana Ivanova, Krystyna Olczyk
      Molecules.2017; 22(8): 1274.     CrossRef
    • C1q/TNF-related protein-9 inhibits cytokine-induced vascular inflammation and leukocyte adhesiveness via AMP-activated protein kinase activation in endothelial cells
      Chang Hee Jung, Min Jung Lee, Yu Mi Kang, Yoo La Lee, So Mi Seol, Hae Kyeong Yoon, Sang-Wook Kang, Woo Je Lee, Joong-Yeol Park
      Molecular and Cellular Endocrinology.2016; 419: 235.     CrossRef
    • Effects of high glucose on caveolin-1 and insulin signaling in 3T3-L1 adipocytes
      Sara Palacios-Ortega, Maider Varela-Guruceaga, J. Alfredo Martínez, Carlos de Miguel, Fermín I. Milagro
      Adipocyte.2016; 5(1): 65.     CrossRef
    • The Impact of Organokines on Insulin Resistance, Inflammation, and Atherosclerosis
      Kyung Mook Choi
      Endocrinology and Metabolism.2016; 31(1): 1.     CrossRef
    • Molecular Pathogenesis of NASH
      Alessandra Caligiuri, Alessandra Gentilini, Fabio Marra
      International Journal of Molecular Sciences.2016; 17(9): 1575.     CrossRef
    • Association Between Long-term Exposure to Air Pollution and Biomarkers Related to Insulin Resistance, Subclinical Inflammation, and Adipokines
      Kathrin Wolf, Anita Popp, Alexandra Schneider, Susanne Breitner, Regina Hampel, Wolfgang Rathmann, Christian Herder, Michael Roden, Wolfgang Koenig, Christa Meisinger, Annette Peters
      Diabetes.2016; 65(11): 3314.     CrossRef
    • Anti-inflammatory effects of sucrose-derived oligosaccharides produced by a constitutive mutant L. mesenteroides B-512FMCM dextransucrase in high fat diet-fed mice
      Min-Gyung Kang, Hee Jae Lee, Jae-Young Cho, Kanghwa Kim, Soo Jin Yang, Doman Kim
      Biochemical and Biophysical Research Communications.2016; 477(3): 350.     CrossRef
    • UV-induced inhibition of adipokine production in subcutaneous fat aggravates dermal matrix degradation in human skin
      Eun Ju Kim, Yeon Kyung Kim, Min-Kyoung Kim, Sungsoo Kim, Jin Yong Kim, Dong Hun Lee, Jin Ho Chung
      Scientific Reports.2016;[Epub]     CrossRef
    • Adipokines in health and disease
      Mathias Fasshauer, Matthias Blüher
      Trends in Pharmacological Sciences.2015; 36(7): 461.     CrossRef
    • Les cellules stromales mésenchymateuses du tissu adipeux : historique, isolement, propriétés immunomodulatrices et perspectives cliniques
      N. Bertheuil, B. Chaput, C. Ménard, A. Varin, I. Garrido, J.L. Grolleau, L. Sensébé, E. Watier, K. Tarte
      Annales de Chirurgie Plastique Esthétique.2015; 60(2): 94.     CrossRef
    • Oncostatin M Modulation of Lipid Storage
      Carrie Elks, Jacqueline Stephens
      Biology.2015; 4(1): 151.     CrossRef
    • Adiposité, hypoxie et apnées du sommeil : de l’obésité au syndrome métabolique
      P. Böhme, P. Corbonnois, L. Duchesne, D. Quilliot, O. Ziegler
      Obésité.2015; 10(3): 204.     CrossRef
    • ADIPOQ and IL6 variants are associated with a pro-inflammatory status in obeses with cardiometabolic dysfunction
      Raquel de Oliveira, Tamiris Invencioni Moraes, Alvaro Cerda, Mario Hiroyuki Hirata, Cristina Moreno Fajardo, Marcela Correia Sousa, Egidio Lima Dorea, Márcia Martins Silveira Bernik, Rosario Dominguez Crespo Hirata
      Diabetology & Metabolic Syndrome.2015;[Epub]     CrossRef
    • Extensive weight loss reveals distinct gene expression changes in human subcutaneous and visceral adipose tissue
      Adil Mardinoglu, John T. Heiker, Daniel Gärtner, Elias Björnson, Michael R. Schön, Gesine Flehmig, Nora Klöting, Knut Krohn, Mathias Fasshauer, Michael Stumvoll, Jens Nielsen, Matthias Blüher
      Scientific Reports.2015;[Epub]     CrossRef
    • Involvement of resveratrol in crosstalk between adipokine adiponectin and hepatokine fetuin-A in vivo and in vitro
      Hee Jae Lee, Yunsook Lim, Soo Jin Yang
      The Journal of Nutritional Biochemistry.2015; 26(11): 1254.     CrossRef
    • Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes
      Hee Jae Lee, Young-Shick Hong, Woojin Jun, Soo Jin Yang
      Journal of Medicinal Food.2015; 18(11): 1207.     CrossRef
    • Inverse Relationship between Serum Lipoxin A4 Level and the Risk of Metabolic Syndrome in a Middle-Aged Chinese Population
      Dan Yu, Zhiye Xu, Xueyao Yin, Fenping Zheng, Xihua Lin, Qianqian Pan, Hong Li, Liqing Yu
      PLOS ONE.2015; 10(11): e0142848.     CrossRef
    • Autophagy in adipose tissue of patients with obesity and type 2 diabetes
      J. Kosacka, M. Kern, N. Klöting, S. Paeschke, A. Rudich, Y. Haim, M. Gericke, H. Serke, M. Stumvoll, I. Bechmann, M. Nowicki, M. Blüher
      Molecular and Cellular Endocrinology.2015; 409: 21.     CrossRef
    • Autocrine/Paracrine Function of Globular Adiponectin: Inhibition of Lipid Metabolism and Inflammatory Response in 3T3-L1 Adipocytes
      Yulia Lazra, Alona Falach, Lital Frenkel, Konstantin Rozenberg, Sanford Sampson, Tovit Rosenzweig
      Journal of Cellular Biochemistry.2015; 116(5): 754.     CrossRef
    • From leptin to other adipokines in health and disease: Facts and expectations at the beginning of the 21st century
      Matthias Blüher, Christos S. Mantzoros
      Metabolism.2015; 64(1): 131.     CrossRef
    • Serum adiponectin levels in patients with acute coronary syndromes: Serial changes and relation to infarct size
      Hadeel Alkofide, Gordon S Huggins, Robin Ruthazer, Joni R Beshansky, Harry P Selker
      Diabetes and Vascular Disease Research.2015; 12(6): 411.     CrossRef
    • Peripheral Signals Mediate the Beneficial Effects of Gastric Surgery in Obesity
      Silvia Barja-Fernández, Cintia Folgueira, Cecilia Castelao, Rosaura Leis, Felipe F. Casanueva, Luisa M. Seoane
      Gastroenterology Research and Practice.2015; 2015: 1.     CrossRef
    • Association of serum omentin-1 concentrations with the presence and severity of preeclampsia
      Haiping Liu, Jianfeng Wu, Haiyu Wang, Lianbing Sheng, Ning Tang, Yunfei Li, Tianyu Hao
      Annals of Clinical Biochemistry: International Journal of Laboratory Medicine.2015; 52(2): 245.     CrossRef
    • Asthma and metabolic syndrome: Current knowledge and future perspectives
      Laura Serafino-Agrusa
      World Journal of Clinical Cases.2015; 3(3): 285.     CrossRef
    • CILAIR-Based Secretome Analysis of Obese Visceral and Subcutaneous Adipose Tissues Reveals Distinctive ECM Remodeling and Inflammation Mediators
      Arturo Roca-Rivada, Susana Belen Bravo, Diego Pérez-Sotelo, Jana Alonso, Ana Isabel Castro, Iván Baamonde, Javier Baltar, Felipe F. Casanueva, María Pardo
      Scientific Reports.2015;[Epub]     CrossRef
    • Leptin of dermal adipose tissue is differentially expressed during the hair cycle and contributes to adipocyte‐mediated growth inhibition of anagen‐phase vibrissa hair
      Chao‐Chun Yang, Hamm‐Ming Sheu, Pei‐Lun Chung, Chung‐Hsing Chang, Yau‐Sheng Tsai, Michael W. Hughes, Tai‐Lan Tuan, Lynn L. H. Huang
      Experimental Dermatology.2015; 24(1): 57.     CrossRef
    • Association of serum C1q/TNF-Related Protein-9 (CTRP9) concentration with visceral adiposity and metabolic syndrome in humans
      Y-C Hwang, S Woo Oh, S-W Park, C-Y Park
      International Journal of Obesity.2014; 38(9): 1207.     CrossRef
    • Adipocyte dysfunction, inflammation and metabolic syndrome
      Nora Klöting, Matthias Blüher
      Reviews in Endocrine and Metabolic Disorders.2014; 15(4): 277.     CrossRef
    • Implications of C1q/TNF-related protein-3 (CTRP-3) and progranulin in patients with acute coronary syndrome and stable angina pectoris
      Kyung Mook Choi, Soon Young Hwang, Ho Chel Hong, Hae Yoon Choi, Hye Jin Yoo, Byung-Soo Youn, Sei Hyun Baik, Hong Seog Seo
      Cardiovascular Diabetology.2014;[Epub]     CrossRef
    • Serum Concentrations and Subcutaneous Adipose Tissue mRNA Expression of Omentin in Morbid Obesity and Type 2 Diabetes Mellitus: the Effect of Very-Low-Calorie Diet, Physical Activity and Laparoscopic Sleeve Gastrectomy
      M. URBANOVÁ, I. DOSTÁLOVÁ, P. TRACHTA, J. DRÁPALOVÁ, P. KAVÁLKOVÁ, D. HALUZÍKOVÁ, M. MATOULEK, Z. LACINOVÁ, M. MRÁZ, M. KASALICKÝ, M. HALUZÍK
      Physiological Research.2014; : 207.     CrossRef
    • Impact of Visceral Fat on Skeletal Muscle Mass and Vice Versa in a Prospective Cohort Study: The Korean Sarcopenic Obesity Study (KSOS)
      Tae Nyun Kim, Man Sik Park, Ja Young Ryu, Hae Yoon Choi, Ho Cheol Hong, Hye Jin Yoo, Hyun Joo Kang, Wook Song, Seok Won Park, Sei Hyun Baik, Anne B. Newman, Kyung Mook Choi, Rozalyn M. Anderson
      PLoS ONE.2014; 9(12): e115407.     CrossRef
    • Links Between Ectopic Fat and Vascular Disease in Humans
      Soo Lim, James B. Meigs
      Arteriosclerosis, Thrombosis, and Vascular Biology.2014; 34(9): 1820.     CrossRef
    • Circulating levels of adipokines in Parkinson's disease
      Natália Pessoa Rocha, Paula Luciana Scalzo, Izabela Guimarães Barbosa, Mariana Soares de Sousa, Isabela Boechat Morato, Érica Leandro Marciano Vieira, Paulo Pereira Christo, Helton José Reis, Antônio Lúcio Teixeira
      Journal of the Neurological Sciences.2014; 339(1-2): 64.     CrossRef
    • Das Fettgewebe – ein endokrines Organ
      M. Blüher
      Der Internist.2014; 55(6): 687.     CrossRef
    • The prediction role of indexes of circulating adipokines for common anthropometric and nutritional characteristics of obesity in the obese Central European population
      Julie Bienertová-Vašků, Jan Novák, Filip Zlámal, Martin Forejt, Soňa Havlenová, Aneta Jackowská, Josef Tomandl, Marie Tomandlová, Zbyněk Šplíchal, Anna Vašků
      Eating Behaviors.2014; 15(2): 244.     CrossRef
    • Das Fettgewebe – ein endokrines Organ
      M. Blüher
      Humanmedizin kompakt.2014;[Epub]     CrossRef
    • An exploratory investigation of links between changes in adipokines and quality of life in individuals undergoing weight loss interventions: Possible implications for cancer research
      Faina Linkov, Lora E. Burke, Marina Komaroff, Robert P. Edwards, Anna Lokshin, Mindi A. Styn, Eugene Tseytlin, Kyle E. Freese, Dana H. Bovbjerg
      Gynecologic Oncology.2014; 133(1): 67.     CrossRef
    • Adipose tissue and its role in organ crosstalk
      T. Romacho, M. Elsen, D. Röhrborn, J. Eckel
      Acta Physiologica.2014; 210(4): 733.     CrossRef
    • Adipokines – removing road blocks to obesity and diabetes therapy
      Matthias Blüher
      Molecular Metabolism.2014; 3(3): 230.     CrossRef
    • Relationship Between Retinol-Binding Protein-4/Adiponectin and Leptin/Adiponectin Ratios with Insulin Resistance and Inflammation
      Ishwarlal Jialal, Beverley Adams-Huet, Frank Duong, Gerred Smith
      Metabolic Syndrome and Related Disorders.2014; 12(4): 227.     CrossRef
    • Metabolically Healthy Obesity—Does it Exist?
      Patchaya Boonchaya-anant, Caroline M. Apovian
      Current Atherosclerosis Reports.2014;[Epub]     CrossRef
    • Strong correlations between circulating chemerin levels and lipoprotein subfractions in nondiabetic obese and nonobese subjects
      Hajnalka Lőrincz, Mónika Katkó, Mariann Harangi, Sándor Somodi, Krisztina Gaál, Péter Fülöp, György Paragh, Ildikó Seres
      Clinical Endocrinology.2014; 81(3): 370.     CrossRef
    • Physical inactivity, insulin resistance, and the oxidative-inflammatory loop
      A. Gratas-Delamarche, F. Derbré, S. Vincent, J. Cillard
      Free Radical Research.2014; 48(1): 93.     CrossRef
    • Oncostatin M Is Produced in Adipose Tissue and Is Regulated in Conditions of Obesity and Type 2 Diabetes
      David Sanchez-Infantes, Ursula A. White, Carrie M. Elks, Ron F. Morrison, Jeffrey M. Gimble, Robert V. Considine, Anthony W. Ferrante, Eric Ravussin, Jacqueline M. Stephens
      The Journal of Clinical Endocrinology & Metabolism.2014; 99(2): E217.     CrossRef
    • Bright light enhances the efficiency of physical activity in combination with a restrictive diet
      Boris B. Pinkhasov, Vera G. Selyatitskaya, Ani R. Karapetyan
      Health.2014; 06(03): 202.     CrossRef
    • Impact of obesity on cardiovascular health
      Marzena Chrostowska, Anna Szyndler, Michał Hoffmann, Krzysztof Narkiewicz
      Best Practice & Research Clinical Endocrinology & Metabolism.2013; 27(2): 147.     CrossRef
    • The GH/IGF-1 axis in obesity: pathophysiology and therapeutic considerations
      Darlene E. Berryman, Camilla A. M. Glad, Edward O. List, Gudmundur Johannsson
      Nature Reviews Endocrinology.2013; 9(6): 346.     CrossRef
    • Phosphodiesterase 5 as target for adipose tissue disorders
      Giovani Colombo, Maria Daniela H. Périco Colombo, Leonardo De Lucca Schiavon, Armando José d’Acampora
      Nitric Oxide.2013; 35: 186.     CrossRef
    • Resistance Training for Diabetes Prevention and Therapy: Experimental Findings and Molecular Mechanisms
      Barbara Strasser, Dominik Pesta
      BioMed Research International.2013; 2013: 1.     CrossRef
    • Adipose tissue dysfunction contributes to obesity related metabolic diseases
      Matthias Blüher
      Best Practice & Research Clinical Endocrinology & Metabolism.2013; 27(2): 163.     CrossRef
    • Importance of adipokines in glucose homeostasis
      Matthias Blüher
      Diabetes Management.2013; 3(5): 389.     CrossRef
    • Association of Glypican-4 With Body Fat Distribution, Insulin Resistance, and Nonalcoholic Fatty Liver Disease
      H. J. Yoo, S. Y. Hwang, G. J. Cho, H. C. Hong, H. Y. Choi, T. G. Hwang, S. M. Kim, Matthias Blüher, Byung-Soo Youn, S. H. Baik, K. M. Choi
      The Journal of Clinical Endocrinology & Metabolism.2013; 98(7): 2897.     CrossRef
    • Association of Serum Adiponectin, Leptin, and Resistin Concentrations with the Severity of Liver Dysfunction and the Disease Complications in Alcoholic Liver Disease
      Beata Kasztelan-Szczerbinska, Agata Surdacka, Maria Slomka, Jacek Rolinski, Krzysztof Celinski, Agata Smolen, Mariusz Szczerbinski
      Mediators of Inflammation.2013; 2013: 1.     CrossRef
    • RLIP76 Protein Knockdown Attenuates Obesity Due to a High-fat Diet
      Sharad S. Singhal, James Figarola, Jyotsana Singhal, Marpadga A. Reddy, Xueli Liu, David Berz, Rama Natarajan, Sanjay Awasthi
      Journal of Biological Chemistry.2013; 288(32): 23394.     CrossRef
    • Tumor Necrosis Factor-α as a Predictor for the Development of Nonalcoholic Fatty Liver Disease: A 4-Year Follow-Up Study
      Yun Yong Seo, Yong Kyun Cho, Ji-Cheol Bae, Mi Hae Seo, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee
      Endocrinology and Metabolism.2013; 28(1): 41.     CrossRef
    • Adipose Tissue Dysfunction in Nascent Metabolic Syndrome
      Andrew A. Bremer, Ishwarlal Jialal
      Journal of Obesity.2013; 2013: 1.     CrossRef

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      Clinical Relevance of Adipokines
      Diabetes Metab J. 2012;36(5):317-327.   Published online October 18, 2012
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    Clinical Relevance of Adipokines
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    Fig. 1 Effects of adipokines. Adipokines regulate adipogenesis, adipocyte metabolism, immune cell migration into adipose tissue via autocrine and paracrine signalling. In addition, adipokines have endocrine/systemic effects on appetite and satiety control, regulation of energy expenditure and activity, influence insulin sensitivity and energy metabolism in insulin sensitive tissues, such as liver, muscle and fat as well as insulin secretion in pancreatic β-cells. IL, interleukin; TNFα, tumour necrosis factor alpha; MCP-1, monocyte-chemotactic-protein-1; FABP4, fatty acid binding protein 4; RBP4, retinol-binding-protein-4.
    Clinical Relevance of Adipokines
    Table 1 Relevance of selected adipokines as biomarkers or therapeutic tools

    RBP4, retinol-binding-protein-4; DPP-4, dipeptidyl peptidase-4; IL, interleukin; MCP-1, monocyte-chemotactic-protein-1; FABP4, fatty acid binding protein 4.

    aDemonstrated in animal models only.

    Blüher M. Clinical Relevance of Adipokines. Diabetes Metab J. 2012;36(5):317-327.
    DOI: https://doi.org/10.4093/dmj.2012.36.5.317.

    Diabetes Metab J : Diabetes & Metabolism Journal
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