TM4SF5 Knockout Protects Mice from Diet-Induced Obesity Partly by Regulating Autophagy in Adipose Tissue
| Autor: | Minsu Kim, Yeonho Son, Kyung-Min Kim, Je Kyung Seong, Jin Young Kim, Jung Weon Lee, Yun Hee Lee, Yoon Keun Cho, Hyeonyeong Im, Abhirup Saha, Juhyeong Han, Cheoljun Choi |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Endocrinology Diabetes and Metabolism Adipose tissue mTORC1 White adipose tissue Biology Mechanistic Target of Rapamycin Complex 1 Diet High-Fat Mice Downregulation and upregulation Brown adipose tissue Internal Medicine medicine Autophagy Lipolysis Animals Obesity Mice Knockout Membrane Proteins Cell biology medicine.anatomical_structure Metabolism Adipose Tissue Female Signal transduction Energy Metabolism Signal Transduction |
| Zdroj: | Diabetes |
| Popis: | Transmembrane 4 L six family member 5 (TM4SF5) functions as a sensor for lysosomal arginine levels and activates the mammalian target of rapamycin complex 1 (mTORC1). While the mTORC1 signaling pathway plays a key role in adipose tissue metabolism, the regulatory function of TM4SF5 in adipocytes remains unclear. In this study we aimed to establish a TM4SF5 knockout (KO) mouse model and investigated the effects of TM4SF5 KO on mTORC1 signaling–mediated autophagy and mitochondrial metabolism in adipose tissue. TM4SF5 expression was higher in inguinal white adipose tissue (iWAT) than in brown adipose tissue and significantly upregulated by a high-fat diet (HFD). TM4SF5 KO reduced mTORC1 activation and enhanced autophagy and lipolysis in adipocytes. RNA sequencing analysis of TM4SF5 KO mouse iWAT showed that the expression of genes involved in peroxisome proliferator–activated receptor α signaling pathways and mitochondrial oxidative metabolism was upregulated. Consequently, TM4SF5 KO reduced adiposity and increased energy expenditure and mitochondrial oxidative metabolism. TM4SF5 KO prevented HFD-induced glucose intolerance and inflammation in adipose tissue. Collectively, the results of our study demonstrate that TM4SF5 regulates autophagy and lipid catabolism in adipose tissue and suggest that TM4SF5 could be therapeutically targeted for the treatment of obesity-related metabolic diseases. |
| Databáze: | OpenAIRE |
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