title: Lipid synthesis is promoted by hypoxic adipocyte-derived exosomes in 3T3-L1 cells.
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.
authors: Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Soichi
authors: S
authors: Sano
authors: Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan; Department of Pharmacology, Osaka City University Graduate School of Medicine, Osaka, Japan. Electronic address: izumi@msic.med.osaka-cu.ac.jp.
authors: Yasukatsu
authors: Y
authors: Izumi
authors: Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Takehiro
authors: T
authors: Yamaguchi
authors: Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Takanori
authors: T
authors: Yamazaki
authors: Department of Pharmacology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Masako
authors: M
authors: Tanaka
authors: Department of Pharmacology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Masayuki
authors: M
authors: Shiota
authors: Food Hygiene and Environmental Health, Kyoto Prefectural University, Graduate School of Life and Environmental Sciences, Kyoto, Japan.
authors: Mayuko
authors: M
authors: Osada-Oka
authors: Department of Cardiology, Izumi Municipal Hospital, Izumi-Osaka, Japan.
authors: Yasuhiro
authors: Y
authors: Nakamura
authors: Department of Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Min
authors: M
authors: Wei
authors: Department of Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Hideki
authors: H
authors: Wanibuchi
authors: Department of Pharmacology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Hiroshi
authors: H
authors: Iwao
authors: Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Minoru
authors: M
authors: Yoshiyama
mesh_terms: D041721:3T3-L1 Cells / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia; D055354:Exosomes / Q000201:enzymology / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D050155:Lipogenesis; D051379:Mice; D009765:Obesity / Q000097:blood / Q000378:metabolism; D020543:Proteome / Q000032:analysis / Q000378:metabolism
chemical_list: D020543:Proteome
keywords: Adipocytes; De novo lipogenesis; Exosome; Hypoxia; Proteomic analysis