한빛사 논문
Won Gun Choi1, Wonsuk Choi1,2, Tae Jung Oh3, Hye-Na Cha4, Inseon Hwang1, Yun Kyung Lee5, Seung Yeon Lee1, Hyemi Shin1, Ajin Lim1, Dongryeol Ryu6, Jae Myoung Suh1, So-Young Park4,*, Sung Hee Choi3,5,* and Hail Kim1,*
1Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST, Daejeon, South Korea. 2Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, South Korea. 3Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea. 4Department of Physiology, College of Medicine, Yeungnam University, Daegu, South Korea. 5Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea. 6Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, South Korea
Authorship note: WGC, WC, and TJO contributed equally to this work.
*Address correspondence to: Hail Kim, Graduate School of Medical Science and Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, South Korea. Or to: Sung Hee Choi, Department of Internal Medicine, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Seongnam 13620, South Korea. Or to: So-Young Park, Department of Physiology, College of Medicine, Yeungnam University, 170 Hyunchoongro, Namgu, Daegu 42415, South Korea.
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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