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Inhibiting serotonin signaling through HTR2B in visceral adipose tissue improves obesity-related insulin resistance
- Source :
- J Clin Invest
- Publication Year :
- 2021
- Publisher :
- American Society for Clinical Investigation, 2021.
-
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.
- Subjects :
- Adult
Glycerol
Male
Serotonin
medicine.medical_specialty
Adipose Tissue, White
Lipolysis
Adipocytes, White
Adipose tissue
Type 2 diabetes
White adipose tissue
Intra-Abdominal Fat
Diet, High-Fat
Mice
Young Adult
Insulin resistance
Internal medicine
Receptor, Serotonin, 5-HT2B
Nonalcoholic fatty liver disease
Adipocytes
medicine
Animals
Humans
Insulin
Obesity
Phosphorylation
Epididymis
Inflammation
Mice, Knockout
business.industry
General Medicine
Middle Aged
medicine.disease
Mice, Inbred C57BL
Endocrinology
Adipose Tissue
Female
Insulin Resistance
Steatosis
Metabolic syndrome
business
Research Article
Signal Transduction
Subjects
Details
- ISSN :
- 15588238
- Volume :
- 131
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Investigation
- Accession number :
- edsair.doi.dedup.....a1069f3aa19f63bd740b878331e0dde1