Adipogenesis, lipogenesis and lipolysis is stimulated by mild but not severe hypoxia in 3T3-L1 cells

作者：Weiszenstein Martin; Musutova Martina; Plihalova Andrea; Westlake Katerina; Elkalaf Moustafa; Koc Michal; Prochazka Antonin; Pala Jan; Gulati Sumeet; Trnka Jan; Polak Jan^*

来源：Biochemical and Biophysical Research Communications, 2016, 478(2): 727-732.

DOI：10.1016/j.bbrc.2016.08.015

• Adipocytes
• Lipolysis
• Gene expression
• Hypoxia
• Lipogenesis
• Differentiation

In-vitro investigation of the effects of hypoxia is limited by physical laws of gas diffusion and cellular O-2 consumption, making prolonged exposures to stable O-2 concentrations impossible. Using a gas permeable cultureware, chronic effects of mild and severe hypoxia on triglyceride accumulation, lipid droplet size distribution, spontaneous lipolysis and gene expression of adipocyte-specific markers were assessed. 3T3-L1 cells were differentiated under 20%, 4% or 1% O-2 using a gas-permeable cultureware. Triglyceride accumulation, expression of genes characteristic for advanced adipocyte differentiation and involvement of key lipogenesis enzymes were assessed after exposures. Lipogenesis increased by 375% under mild hypoxia, but dropped by 43% in severe hypoxia. Mild, but not severe, hypoxia increased formation of large lipid droplets 6.4 fold and strongly induced gene expression of adipocyte-specific markers. Spontaneous lipolysis increased by 488% in mild, but only by 135% in severe hypoxia. Inhibition of ATP-dependent citrate lyase suppressed hypoxia-induced lipogenesis by 81% and 85%. Activation of HIF inhibited lipogenesis by 59%. Mild, but not severe, hypoxia stimulates lipolysis and promotes adipocyte differentiation, probably through excess of acetyl-CoA originating from tricarboxylic acid cycle independently of HIF activation.

• 出版日期2016-9-16