Lipid synthesis is promoted by hypoxic adipocyte-derived exosomes in 3T3-L1 cells |
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Authors: | Soichi Sano Yasukatsu Izumi Takehiro Yamaguchi Takanori Yamazaki Masako Tanaka Masayuki Shiota Mayuko Osada-Oka Yasuhiro Nakamura Min Wei Hideki Wanibuchi Hiroshi Iwao Minoru Yoshiyama |
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Institution: | 1. Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan;2. Department of Pharmacology, Osaka City University Graduate School of Medicine, Osaka, Japan;3. Food Hygiene and Environmental Health, Kyoto Prefectural University, Graduate School of Life and Environmental Sciences, Kyoto, Japan;4. Department of Cardiology, Izumi Municipal Hospital, Izumi-Osaka, Japan;5. Department of Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan |
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Abstract: | Hypoxia occurs within adipose tissues as a result of adipocyte hypertrophy and is associated with adipocyte dysfunction in obesity. Here, we examined whether hypoxia affects the characteristics of adipocyte-derived exosomes. Exosomes are nanovesicles secreted from most cell types as an information carrier between donor and recipient cells, containing a variety of proteins as well as genetic materials. Cultured differentiated 3T3-L1 adipocytes were exposed to hypoxic conditions and the protein content of the exosomes produced from these cells was compared by quantitative proteomic analysis. A total of 231 proteins were identified in the adipocyte-derived exosomes. Some of these proteins showed altered expression levels under hypoxic conditions. These results were confirmed by immunoblot analysis. Especially, hypoxic adipocyte-released exosomes were enriched in enzymes related to de novo lipogenesis such as acetyl-CoA carboxylase, glucose-6-phosphate dehydrogenase, and fatty acid synthase (FASN). The total amount of proteins secreted from exosomes increased by 3–4-fold under hypoxic conditions. Moreover, hypoxia-derived exosomes promoted lipid accumulation in recipient 3T3-L1 adipocytes, compared with those produced under normoxic conditions. FASN levels were increased in undifferentiated 3T3-L1 cells treated with FASN-containing hypoxic adipocytes-derived exosomes. This is a study to characterize the proteomic profiles of adipocyte-derived exosomes. Exosomal proteins derived from hypoxic adipocytes may affect lipogenic activity in neighboring preadipocytes and adipocytes. |
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Keywords: | ACN acetonitrile ACC acetyl-CoA carboxylase FASN fatty acid synthase FBS fetal bovine serum G6PD glucose-6-phosphate dehydrogenase GAPDH glyceraldehyde-phosphate dehydrogenase Hsc70 heat shock cognate 71 kDa protein Hsp heat shock protein Hsp72 heat shock 71 kDa protein 1A HIF-1α hypoxia-inducible factor-1α WT wild-type |
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