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Basic Research
Multiple Roles of Sirtuin 6 in Adipose Tissue Inflammation
Eun Ju Bae, Byung-Hyun Park
Diabetes Metab J. 2023;47(2):164-172.   Published online January 12, 2023
DOI: https://doi.org/10.4093/dmj.2022.0270
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  • 4 Web of Science
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AbstractAbstract PDFPubReader   ePub   
Adipose tissue (AT) inflammation is strongly associated with obesity-induced insulin resistance. When subjected to metabolic stress, adipocytes become inflamed and secrete a plethora of cytokines and chemokines, which recruit circulating immune cells to AT. Although sirtuin 6 (Sirt6) is known to control genomic stabilization, aging, and cellular metabolism, it is now understood to also play a pivotal role in the regulation of AT inflammation. Sirt6 protein levels are reduced in the AT of obese humans and animals and increased by weight loss. In this review, we summarize the potential mechanism of AT inflammation caused by impaired action of Sirt6 from the immune cells’ point of view. We first describe the properties and functions of immune cells in obese AT, with an emphasis on discrete macrophage subpopulations which are central to AT inflammation. We then highlight data that links Sirt6 to functional phenotypes of AT inflammation. Importantly, we discuss in detail the effects of Sirt6 deficiency in adipocytes, macrophages, and eosinophils on insulin resistance or AT browning. In our closing perspectives, we discuss emerging issues in this field that require further investigation.

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  • The Role of Increased Expression of Sirtuin 6 in the Prevention of Premature Aging Pathomechanisms
    Adrianna Dzidek, Olga Czerwińska-Ledwig, Małgorzata Żychowska, Wanda Pilch, Anna Piotrowska
    International Journal of Molecular Sciences.2023; 24(11): 9655.     CrossRef
  • Exploring the Influence of Age, Gender and Body Mass Index on Colorectal Cancer Location
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Original Article
Pathophysiology
Low-Frequency Intermittent Hypoxia Suppresses Subcutaneous Adipogenesis and Induces Macrophage Polarization in Lean Mice
Yan Wang, Mary Yuk Kwan Lee, Judith Choi Wo Mak, Mary Sau Man Ip
Diabetes Metab J. 2019;43(5):659-674.   Published online April 23, 2019
DOI: https://doi.org/10.4093/dmj.2018.0196
  • 4,408 View
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  • 4 Web of Science
  • 6 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   
Background

The relationship between obstructive sleep apnoea (OSA) and metabolic disorders is complex and highly associated. The impairment of adipogenic capacity in pre-adipocytes may promote adipocyte hypertrophy and increase the risk of further metabolic dysfunction. We hypothesize that intermittent hypoxia (IH), as a pathophysiologic feature of OSA, may regulate adipogenesis by promoting macrophage polarization.

Methods

Male C57BL/6N mice were exposed to either IH (240 seconds of 10% O2 followed by 120 seconds of 21% O2, i.e., 10 cycles/hour) or intermittent normoxia (IN) for 6 weeks. Stromal-vascular fractions derived from subcutaneous (SUB-SVF) and visceral (VIS-SVF) adipose tissues were cultured and differentiated. Conditioned media from cultured RAW 264.7 macrophages after air (Raw) or IH exposure (Raw-IH) were incubated with SUB-SVF during adipogenic differentiation.

Results

Adipogenic differentiation of SUB-SVF but not VIS-SVF from IH-exposed mice was significantly downregulated in comparison with that derived from IN-exposed mice. IH-exposed mice compared to IN-exposed mice showed induction of hypertrophic adipocytes and increased preferential infiltration of M1 macrophages in subcutaneous adipose tissue (SAT) compared to visceral adipose tissue. Complementary in vitro analysis demonstrated that Raw-IH media significantly enhanced inhibition of adipogenesis of SUB-SVF compared to Raw media, in agreement with corresponding gene expression levels of differentiation-associated markers and adipogenic transcription factors.

Conclusion

Low frequency IH exposure impaired adipogenesis of SAT in lean mice, and macrophage polarization may be a potential mechanism for the impaired adipogenesis.

Citations

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  • Obstructive sleep apnea hypopnea syndrome and vascular lesions: An update on what we currently know
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    Shuiming Guo, Lei Dong, Junhua Li, Yuetao Chen, Ying Yao, Rui Zeng, Nelli Shushakova, Hermann Haller, Gang Xu, Song Rong
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Reviews
Pathophysiology
Role of NO/VASP Signaling Pathway against Obesity-Related Inflammation and Insulin Resistance
Yu Mi Kang, Francis Kim, Woo Je Lee
Diabetes Metab J. 2017;41(2):89-95.   Published online November 15, 2016
DOI: https://doi.org/10.4093/dmj.2017.41.2.89
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AbstractAbstract PDFPubReader   

Obesity has quickly become a worldwide pandemic, causing major adverse health outcomes such as dyslipidemia, type 2 diabetes mellitus, cardiovascular disease and cancers. Obesity-induced insulin resistance is the key for developing these metabolic disorders, and investigation to understand the molecular mechanisms involved has been vibrant for the past few decades. Of these, low-grade chronic inflammation is suggested as a critical concept in the development of obesity-induced insulin resistance, and the anti-inflammatory effect of nitric oxide (NO) signaling has been reported to be linked to improvement of insulin resistance in multiple organs involved in glucose metabolism. Recently, a body of evidence suggested that vasodilatory-stimulated phosphoprotein (VASP), a downstream mediator of NO signaling plays a crucial role in the anti-inflammatory effect and improvement of peripheral insulin resistance. These preclinical studies suggest that NO/VASP signaling could be an ideal therapeutic target in the treatment of obesity-related metabolic dysfunction. In this review, we introduce studies that investigated the protective role of NO/VASP signaling against obesity-related inflammation and insulin resistance in various tissues.

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Resistin in Rodents and Humans
Hyeong Kyu Park, Rexford S. Ahima
Diabetes Metab J. 2013;37(6):404-414.   Published online December 12, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.6.404
  • 5,741 View
  • 54 Download
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AbstractAbstract PDFPubReader   

Obesity is characterized by excess accumulation of lipids in adipose tissue and other organs, and chronic inflammation associated with insulin resistance and an increased risk of type 2 diabetes. Obesity, type 2 diabetes, and cardiovascular diseases are major health concerns. Resistin was first discovered as an adipose-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents. Adipocyte-derived resistin is increased in obese rodents and strongly related to insulin resistance. However, in contrast to rodents, resistin is expressed and secreted from macrophages in humans and is increased in inflammatory conditions. Some studies have also suggested an association between increased resistin levels and insulin resistance, diabetes and cardiovascular disease. Genetic studies have provided additional evidence for a role of resistin in insulin resistance and inflammation. Resistin appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and formation of foam cells. Indeed, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with coronary artery disease and ischemic stroke. There is also growing evidence that elevated resistin is associated with the development of heart failure. This review will focus on the biology of resistin in rodents and humans, and evidence linking resistin with type 2 diabetes, atherosclerosis, and cardiovascular disease.

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  • The dynamics of human bone marrow adipose tissue in response to feeding and fasting
    Pouneh K. Fazeli, Miriam A. Bredella, Gisela Pachon-Peña, Wenxiu Zhao, Xun Zhang, Alexander T. Faje, Megi Resulaj, Sai P. Polineni, Tara M. Holmes, Hang Lee, Elizabeth K. O’Donnell, Ormond A. MacDougald, Mark C. Horowitz, Clifford J. Rosen, Anne Klibanski
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  • Measurement of Plasma Resistin Concentrations in Horses with Metabolic and Inflammatory Disorders
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  • Alteration of gut microbiota affects expression of adiponectin and resistin through modifying DNA methylation in high-fat diet-induced obese mice
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  • Adipokines: New Potential Therapeutic Target for Obesity and Metabolic, Rheumatic, and Cardiovascular Diseases
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  • Proteomic profile of patients with atrial fibrillation undergoing cardiac surgery†
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  • The effect of a garlic supplement on the pro-inflammatory adipocytokines, resistin and tumor necrosis factor-alpha, and on pain severity, in overweight or obese women with knee osteoarthritis
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  • Resistin and NGAL are associated with inflammatory response, endothelial activation and clinical outcomes in sepsis
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    Ulrik Lausten-Thomsen, Michael Christiansen, Paula Louise Hedley, Tenna Ruest Haarmark Nielsen, Cilius Esmann Fonvig, Oluf Pedersen, Torben Hansen, Jens-Christian Holm
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  • Differences in Mean Levels of Maternal Resistin Serum between Early Onset Preeclampsia (EOPE) and Late Onset Preeclampsia (LOPE)
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  • Secret talk between adipose tissue and central nervous system via secreted factors—an emerging frontier in the neurodegenerative research
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  • Uncovering Factors Related to Pancreatic Beta-Cell Function
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  • Local and serum levels of adipokines in patients with obesity after periodontal therapy: one‐year follow‐up
    Tiago Eduardo Dias Gonçalves, Glaucia Santos Zimmermann, Luciene Cristina Figueiredo, Monique de Carvalho Souza, Daniele Ferreira da Cruz, Marta Ferreira Bastos, Hélio Doyle Pereira da Silva, Poliana Mendes Duarte
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  • The effect of a preparation of minerals, vitamins and trace elements on the cardiac gene expression pattern in male diabetic rats
    Márta Sárközy, Gergő Szűcs, Márton Pipicz, Ágnes Zvara, Katalin Éder, Veronika Fekete, Csilla Szűcs, Judit Bárkányi, Csaba Csonka, László G. Puskás, Csaba Kónya, Péter Ferdinandy, Tamás Csont
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    A. T. Teplyakov, Sh. D. Akhmedov, T. Ye. Suslova, А. V. Andriyanova, A. V. Kuznetsova, N. V. Protopopova, V. V. Kalyuzhin, O. N. Nasanova
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  • The Effects of a Single Developmentally Entrained Pulse of Testosterone in Female Neonatal Mice on Reproductive and Metabolic Functions in Adult Life
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    Karine Maria Martins Bezerra Carvalho, José Delano Barreto Marinho Filho, Tiago Sousa de Melo, Ana Jérsia Araújo, Josiane da Silva Quetz, Maria do Perpétuo Socorro Saldanha da Cunha, Karina Moura de Melo, Armenio Andre de Carvalho Almeida da Silva, Adrian
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    Qingda Hu, Huanran Tan, David M. Irwin, Marc Robinson-Rechavi
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    Shirley Guzmán, Silvia Marin, Anibal Miranda, Vitaly A Selivanov, Josep J Centelles, Romain Harmancey, Fatima Smih, Annie Turkieh, Yves Durocher, Antonio Zorzano, Philippe Rouet, Marta Cascante
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Diabetes Metab J : Diabetes & Metabolism Journal