| Autor: |
Choi WG; Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST, Daejeon, South Korea., Choi W; Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST, Daejeon, South Korea.; Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, South Korea., Oh TJ; Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea., Cha HN; Department of Physiology, College of Medicine, Yeungnam University, Daegu, South Korea., Hwang I; Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST, Daejeon, South Korea., Lee YK; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea., Lee SY; Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST, Daejeon, South Korea., Shin H; Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST, Daejeon, South Korea., Lim A; Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST, Daejeon, South Korea., Ryu D; Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, South Korea., Suh JM; Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST, Daejeon, South Korea., Park SY; Department of Physiology, College of Medicine, Yeungnam University, Daegu, South Korea., Choi SH; Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea., Kim H; Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST, Daejeon, South Korea. |
| Abstrakt: |
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. |
