ArticleThe Journal of clinical investigation2021
Inhibiting serotonin signaling through HTR2B in visceral adipose tissue improves obesity-related insulin resistance.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 58 citations in OpenAlex.
- Article
- Serotonin Signaling and Vascular Reactivity in Cardiometabolic Disease and Cardiac Surgery.Cells · 2026Review
- Long-term stability of the triglyceride-glucose index in cancer patient Cohort.Scientific reports · 2026Article
- Association of Visceral Fat Mass Index with Diabetes and Vascular Complications: NHANES 2011-2018 Cross-Sectional Study.Health data science · 2026Article
- Role of central and peripheral serotonin in liver physiology and diseases.Theranostics · 2026Review
- Tryptophan's Journey Through Pregnancy: The Role of Serotonin.International journal of tryptophan research : IJTR · 2026Review
- Cardiometabolic Index as a predictor of mortality in metabolic Dysfunction-Associated Steatotic Liver Disease.BMC gastroenterology · 2025Article
- Hyperinsulinemia-induced upregulation of adipocyte TPH2 contributes to peripheral serotonin production, metabolic dysfunction, and obesity.The Journal of clinical investigation · 2025Article
- Serotonin transporter deficiency, but not absence of platelet serotonin, impairs thrombus formation in a model of deep vein thrombosis.Research and practice in thrombosis and haemostasis · 2025Article
- Inhibition of serotonin-Htr2b signaling in skeletal muscle mitigates obesity-induced insulin resistance.Experimental & molecular medicine · 2025Article
- Serotonin signaling to regulate energy metabolism: a gut microbiota perspective.Life metabolism · 2025Review
- Short-term and long-term high-fat diet promote metabolic disorder through reprogramming mRNA mMicrobiome · 2025Article
- Gut Bacteria-Derived Tryptamine Ameliorates Diet-Induced Obesity and Insulin Resistance in Mice.International journal of molecular sciences · 2025Article
- Transcriptional regulation of adipocyte lipolysis by IRF2BP2.Science advances · 2025Article
- Review
- Loss of endothelial TRPC1 aggravates metabolic dysfunction in obesity via disrupting adipose tissue homeostasis.Frontiers in molecular biosciences · 2025Article
- Association of Metabolic Score for Visceral Fat (METS-VF) with Gout Risk in Patients with Hypertension and Hyperuricemia: A Multicenter Study Based on the Chinese Population.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Gut microbiota and its metabolites regulate insulin resistance: traditional Chinese medicine insights for T2DM.Frontiers in microbiology · 2025Review
- Obesity is associated with SHBG levels rather than blood lipid profiles in PCOS patients with insulin resistance.BMC endocrine disorders · 2024Article
- Targeting HTR2B suppresses nonfunctioning pituitary adenoma growth and sensitizes cabergoline treatment via inhibiting Gαq/PLC/PKCγ/STAT3 axis.Neuro-oncology · 2024Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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