title: Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes.
abstract: BACKGROUND
  A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function.
  
  
  METHODS
  Differentiated 3T3-L1 adipocytes were incubated at 5% O2 for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC).
  
  
  RESULTS
  HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p<0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p<0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p<0.01).
  
  
  CONCLUSIONS
  We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via decreased glucose uptake and lipogenic protein expression and increased basal lipolysis. Such an hypoxia-induced decrease in lipogenesis may be an attractive therapeutic target against lipid-associated metabolic diseases.
authors.affiliation: Faculty of Sport & Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan. Electronic address: thashimo@fc.ritsumei.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Takumi
authors.initials: T
authors.lastname: Yokokawa
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Endo
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Iwanaka
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Higashida
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Taguchi
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism; D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D015687:Cell Hypoxia; D005947:Glucose / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D050155:Lipogenesis; D008066:Lipolysis; D051379:Mice; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000378:metabolism; D002787:Sterol Esterase / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*; D000217:Acyltransferases
chemical_list: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D002352:Carrier Proteins; D005947:Glucose; D008049:Lipase; D000070778:Perilipin-1; D010750:Phosphoproteins; D002787:Sterol Esterase; D014280:Triglycerides; C000602979:Plin1 protein, mouse; C492986:Abhd5 protein, mouse; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases
keywords: Glucose uptake; Lipid metabolism; Lipid-associated proteins; Lipogenesis; Lipolysis