Inhibiting serotonin signaling through HTR2B in visceral adipose tissue improves obesity-related insulin resistance

Insulin resistance is a cornerstone of obesity-related complications such as type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease. A high rate of lipolysis is known to be associated with insulin resistance, and inhibiting adipose tissue lipolysis improves obesity-related insulin resistance. Here, we demonstrate that inhibition of serotonin (5-hydroxytryptamine [5-HT]) signaling through serotonin receptor 2B (HTR2B) in adipose tissues ameliorates insulin resistance by reducing lipolysis in visceral adipocytes. Chronic high-fat diet (HFD) feeding increased Htr2b expression in epididymal white adipose tissue, resulting in increased HTR2B signaling in visceral white adipose tissue. Moreover, HTR2B expression in white adipose tissue was increased in obese humans and positively correlated with metabolic parameters. We further found that adipocyte-specific Htr2b-knockout mice are resistant to HFD-induced insulin resistance, visceral adipose tissue inflammation, and hepatic steatosis. Enhanced 5-HT signaling through HTR2B directly activated lipolysis through phosphorylation of hormone-sensitive lipase in visceral adipocytes. Moreover, treatment with a selective HTR2B antagonist attenuated HFD-induced insulin resistance, visceral adipose tissue inflammation, and hepatic steatosis. Thus, adipose HTR2B signaling could be a potential therapeutic target for treatment of obesity-related insulin resistance.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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Introduction Non-alcoholic fatty liver disease (NAFLD), a disorder characterised by pathological accumulation of non-visible free fatty acids and visible triglyceride in hepatocytes, is on the rise globally in both adult and paediatric populations.1 Evidence suggests that 20%–50% of the European Union and US populations exhibit features of NAFLD,2 driven by higher rates of obesity, insulin resistance and type 2 diabetes, and metabolic syndrome.3 Additionally, recognition of a growing number of patients with ‘lean NAFLD’ who are not obese, but have high levels of visceral fat, diets high in fats and carboh...
Source: Journal of Clinical Pathology - Category: Pathology Authors: Tags: Open access Viewpoint Source Type: research
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide, affecting at least a quarter of the global adult population. It is rapidly becoming one of the most common indications for liver transplantation in Western countries. NAFLD is widely considered as the hepatic manifestation of the metabolic syndrome. It is particularly common among patients with type 2 diabetes and obesity. Nonetheless, emerging data suggest that NAFLD is present in a significant proportion of lean individuals. In a systematic review and meta-analysis of 93 studies (involving over 10 million individuals), Ye e...
Source: Gut - Category: Gastroenterology Authors: Tags: Gut Commentary Source Type: research
Adv Exp Med Biol. 2021;1328:37-57. doi: 10.1007/978-3-030-73234-9_4.ABSTRACTNoncommunicable diseases (NCDs) are one of the major public health concerns globally. Most of the NCDs including insulin resistance, metabolic syndrome, type 2 diabetes mellitus, fatty liver disease, and coronary heart disease are related to obesity and are called obesity-related NCDs (OR-NCDs). However, adipocytes can reduce OR-NCDs by secreting adiponectin. Adiponectin has an inverse relationship with body fat. Obese people have impairment in differentiating pre-adipocytes to adipocytes, the process facilitated by adiponectin. Adiponectin directl...
Source: Advances in Experimental Medicine and Biology - Category: Research Authors: Source Type: research
J Obes Metab Syndr. 2021 Dec 20. doi: 10.7570/jomes21063. Online ahead of print.ABSTRACTChildhood obesity has been increasing steadily in recent decades, and severe childhood obesity has emerged as a major public health problem both nationally and internationally. A current concern is that lockdown due to the coronavirus disease 2019 (COVID-19) pandemic could exacerbate the spread of childhood obesity and increase the gap in obesity risk. Recent research results indicate the aggravation of obesity after school closures. The consequences of severe childhood obesity are more devastating than those of mild to moderate obesity...
Source: Atherosclerosis - Category: Cardiology Authors: Source Type: research
CONCLUSIONS: MicroRNAs seem to be promising prognostic markers for diagnosis of endothelial dysfunction, non-alcoholic fatty liver disease, type 2 diabetes, metabolic syndrome and insulin resistance in children.PMID:34918493 | DOI:10.1111/ijpo.12880
Source: Atherosclerosis - Category: Cardiology Authors: Source Type: research
ConclusionsMicroRNAs seem to be promising prognostic markers for diagnosis of endothelial dysfunction, non-alcoholic fatty liver disease, type 2 diabetes, metabolic syndrome and insulin resistance in children.
Source: Pediatric Obesity - Category: Eating Disorders & Weight Management Authors: Tags: REVIEW ARTICLE Source Type: research
Metabolic Syndrome and Related Disorders, Ahead of Print.
Source: Metabolic Syndrome and Related Disorders - Category: Endocrinology Authors: Source Type: research
J Nutr Sci Vitaminol (Tokyo). 2021;67(5):292-300. doi: 10.3177/jnsv.67.292.ABSTRACTMetabolic syndrome (MS) is a combination of risk factors related to the development of mainly type 2 diabetes mellitus, cardiovascular disease (CVD) and nonalcoholic fatty liver disease (NAFLD). Its prevalence has increased worldwide, and healthcare systems will face major challenges in addressing this problem. The aim of this work was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on insulin resistance (IR) and obesity associated with MS in Wistar rats. The experimental design consisted of three groups of sucrose-induced MS rats...
Source: Journal of Nutritional Science and Vitaminology - Category: Nutrition Authors: Source Type: research
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