Diabetes & Metabolism Journal

Review

Basic and Translational Research
Extracellular Vesicle-Mediated Network in the Pathogenesis of Obesity, Diabetes, Steatotic Liver Disease, and Cardiovascular Disease: Joonyub Lee, Won Gun Choi, Marie Rhee, Seung-Hwan Lee; Diabetes Metab J. 2025;49(3):348-367. Published online May 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0184

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Extracellular vesicles (EVs) are lipid bilayer-enclosed particles carrying bioactive cargo, including nucleic acids, proteins, and lipids, facilitating intercellular and interorgan communication. In addition to traditional mediators such as hormones, metabolites, and cytokines, increasing evidence suggests that EVs are key modulators in various physiological and pathological processes, particularly influencing metabolic homeostasis and contributing to the progression of cardiometabolic diseases. This review provides an overview of the most recent insights into EV-mediated mechanisms involved in the pathogenesis of obesity, insulin resistance, diabetes mellitus, steatotic liver disease, atherosclerosis, and cardiovascular disease. EVs play a critical role in modulating insulin sensitivity, glucose homeostasis, systemic inflammation, and vascular health by transferring functional molecules to target cells. Understanding the EV-mediated network offers potential for identifying novel biomarkers and therapeutic targets, providing opportunities for EV-based interventions in cardiometabolic disease management. Although many challenges remain, this evolving field highlights the need for further research into EV biology and its translational applications in cardiovascular and metabolic health.

Citations

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Postbiotics in Functional Foods: Microbial Derivatives Shaping Health, Immunity and Next‐Generation Nutrition
Alice Njolke Mafe, Javad Sharifi‐Rad, Daniela Calina, Ayobami Joshua Ogunyemi, Abiola O. Tubi
Food Frontiers.2026;[Epub] CrossRef
Decoding the Endocrine Code of Skeletal Muscle: Myokines, Exerkines, and Inter-Organ Crosstalk in Metabolic Health and Disease
Young-Sool Hah, Jeongyun Hwang, Seung-Jun Lee, Seung-Jin Kwag
Cells.2026; 15(4): 318. CrossRef
Extracellular Vesicles: Biology, Intercellular Communication and Therapeutic Potential in Diabetes
Swayam Prakash Srivastava, Lydia Herrmann, Eden Ozkan, Abhiram Kunamneni, Vinamra Swaroop, Geetika Nehra, Rohit Srivastava, Pratima Tripathi, Ken Inoki, Julie E. Goodwin
Advanced Therapeutics.2026;[Epub] CrossRef
Association between dyslipidemia and elevated liver enzymes: A cross-sectional study from the PERSIAN Guilan cohort study
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Molecular Signatures of Obesity-Associated Infertility in Polycystic Ovary Syndrome: The Emerging Role of Exosomal microRNAs and Non-Coding RNAs
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Genes.2025; 16(9): 1101. CrossRef
Molecular mechanisms linking adipose tissue-derived small extracellular vesicles/exosomes to the development or amelioration of obesity, insulin resistance, and diabetes-related complications
Linfeng Chen, Fatemeh Amraee, Sahar Sadegh-Nejadi, Mostafa Saberian, Seyed Arsalan Ghahari, Xiaolei Miao, Giuseppe Lisco, Reza Afrisham
European Journal of Medical Research.2025;[Epub] CrossRef
Mitochondria-Enriched Extracellular Vesicles (EVs) for Cardiac Bioenergetics Restoration: A Scoping Review of Preclinical Mechanisms and Source-Specific Strategies
Dhienda C. Shahannaz, Tadahisa Sugiura, Taizo Yoshida
International Journal of Molecular Sciences.2025; 26(22): 11052. CrossRef
A Comprehensive Insight Into the Roles of Exosomal circRNAs in Metabolic Syndrome
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Original Article

Basic and Translational Research
Serotonin Regulates Lipogenesis and Endoplasmic Reticulum Stress in Alcoholic Liver Disease: Inseon Hwang, Jung Eun Nam, Wonsuk Choi, Won Gun Choi, Eunji Lee, Hyeongseok Kim, Young-Ah Moon, Jun Yong Park, Hail Kim; Diabetes Metab J. 2025;49(4):798-811. Published online February 5, 2025; DOI: https://doi.org/10.4093/dmj.2024.0215

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Abstract PDF Supplementary Material PubReader ePub

Background
Serotonin (5-hydroxytryptamine [5-HT]) is a monoamine neurotransmitter that has various functions in central and peripheral tissues. While 5-HT is known to regulate various biological processes in liver, direct role of 5-HT and its receptors, especially 5-HT receptor 2A (HTR2A) and HTR2B, in development and progression of alcoholic liver disease (ALD) in vivo is not well understood.
Methods
Blood 5-HT level was measured from both human ALD patients and ethanol (EtOH) diet-fed mouse models. Gut-specific tryptophan hydroxylase 1 (Tph1) knockout mice, liver-specific Htr2a knockout mice, and liver-specific Htr2b knockout mice were fed with EtOH diet. Then we evaluated liver damage, hepatic steatosis, endoplasmic reticulum (ER) stress, and inflammation.
Results
Blood 5-HT concentrations are increased in both humans and mice with ALD. Both gut-specific Tph1 knockout and liver- specific Htr2a knockout mice are resistant to steatosis by down-regulating lipogenic pathways in liver of chronic EtOH diet-fed mice. Moreover, genetic inhibition of both gut-derived serotonin (GDS) synthesis and hepatic HTR2A signaling prevents ER stress in liver of chronic EtOH diet-fed mice. Additionally, we found that ablation of HTR2A signaling protects against disease progression by attenuating liver injury and inflammation in chronic plus binge EtOH diet-fed mice. Also, inhibiting HTR2A signaling ameliorates alcohol-induced liver injury and ER stress in an acute EtOH diet-fed mice model.
Conclusion
GDS directly regulates lipogenesis and ER stress via signaling through hepatic HTR2A in the context of ALD. Inhibiting HTR2A signaling protects against alcohol-induced steatosis, liver injury and disease progression in various ALD mouse models and may also provide a novel therapeutic strategy for ALD.

Citations

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Oxidative stress modulation in alcohol-related liver disease: From chinese botanical drugs to exercise-based interventions
Yuting Zhu, Yuqing Jia, Enming Zhang
Frontiers in Pharmacology.2025;[Epub] CrossRef
Lactoferrin alleviates non-alcoholic steatohepatitis via remodeling gut microbiota to regulate serotonin-related pathways
Li Ding, Jia-Ying Xu, Li-Li Zhang, Yan Liu, Kai-Tian Gu, Yan-Zi Liang, Khemayanto Hidayat, Zhongxiao Wan, Guo-Chong Chen, Li-Qiang Qin
Journal of Advanced Research.2025;[Epub] CrossRef

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