Type I collagen reduces lipid accumulation during adipogenesis of preadipocytes 3T3-L1 via the YAP-mTOR-autophagy axis |
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| Affiliation: | 1. Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China;2. Department of Chemistry and Life Science, School of Advanced Engineering, Kogakuin University, 2665-1, Nakanomachi, Hachioji, Tokyo 192-0015, Japan;3. Nippi Research Institute of Biomatrix, Ibaraki 302-0017, Japan;4. Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development Liaoning Province, Liaoning, China;1. Univ. Grenoble Alpes, Inserm, LBFA, U1055, UFR STAPS, Grenoble, France;2. LBEPS, Univ Evry, IRBA, Université Paris Saclay, Evry, France;3. Aix Marseille Univ, CNRS, CRMBM, Marseille, France;4. Univ. Grenoble Alpes, Inserm, HP2, U1042, Grenoble, France;5. Univ. Grenoble Alpes, Inserm, LBFA, U1055, CHU Grenoble Alpes, Grenoble, France;6. Univ. Grenoble Alpes, Inserm, LBFA, U1055, Grenoble, France;1. Department of Molecular and Cell Biology and Biochemistry, Basic Veterinary Science, Faculty of Veterinary Medicine, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-0065, Japan;2. Laboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan;3. Education and Research Center for Fermentation Studies, Faculty of Agriculture, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-0065, Japan;1. Departments of Medicine and Physiology and Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, Canada;2. Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada;3. Maccabi Healthcare Services, Endocrinology Division, Tel Aviv, Israel;1. Laboratory of Animal Morphology, Graduate School of Bioagricultural Sciences, Nagoya University, Tokai National Higher Education and Research System, Nagoya, Aichi, Japan;2. Laboratory of Marine Life Science and Genetics, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi, Japan;1. College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China;2. Sanya Institute of Nanjing Agricultural University, Sanya, Hainan 572024, China;3. College of Animal Science, Fujian Agriculture & Forestry University, Fuzhou, Fujian 350002, China |
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| Abstract: | The extracellular matrix (ECM) regulates cell behavior through signal transduction and provides a suitable place for cell survival. As one of the major components of the extracellular matrix, type I collagen is involved in regulating cell migration, proliferation and differentiation. We present a system in which 3T3-L1 preadipocyte cells are induced for adipogenic differentiation on type I collagen coated dishes. Our previous study has found that type I collagen inhibits adipogenic differentiation via YAP activation. Here we further reveal that type I collagen inactivates autophagy by up-regulating mTOR activity via the YAP pathway. Under collagen-coating conditions, co-localization of lysosomes with mTOR was increased and the level of downstream protein p-S6K was elevated, accompanied by a decrease in the level of autophagy. Autophagy is negatively correlated with adipogenesis under type I collagen coating. Through the YAP-autophagy axis, type I collagen improves glycolipid metabolism accompanied by increased mitochondrial content, enhanced glucose uptake, reduced release of free fatty acids (FFAs) and decreased intracellular lipid accumulation. Our findings provide insight into the strategy for dealing with obesity: Type I collagen or the drugs with inhibitory effects on autophagy or YAP, have a potential to accelerate the energy metabolism of adipose tissue, so as to better maintain the homeostasis of glucose and lipids in the body, which can be used for achieving weight loss. |
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