Adipogenesis, lipogenesis and lipolysis is stimulated by mild but not severe hypoxia in 3T3-L1 cells
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
27498031
DOI
10.1016/j.bbrc.2016.08.015
PII: S0006-291X(16)31270-0
Knihovny.cz E-resources
- Keywords
- Adipocytes, Differentiation, Gene expression, Hypoxia, Lipogenesis, Lipolysis,
- MeSH
- Acetyl Coenzyme A metabolism MeSH
- Adipogenesis drug effects genetics MeSH
- ATP Citrate (pro-S)-Lyase genetics metabolism MeSH
- Cell Differentiation drug effects MeSH
- 3T3-L1 Cells MeSH
- Citric Acid Cycle drug effects genetics MeSH
- Diacylglycerol O-Acyltransferase genetics metabolism MeSH
- Hypoxia-Inducible Factor 1, alpha Subunit genetics metabolism MeSH
- Cell Hypoxia MeSH
- Oxygen pharmacology MeSH
- Lipid Droplets chemistry drug effects MeSH
- Lipogenesis drug effects genetics MeSH
- Lipolysis drug effects genetics MeSH
- Mice MeSH
- Perilipin-1 genetics metabolism MeSH
- Fatty Acid-Binding Proteins genetics metabolism MeSH
- Gene Expression Regulation drug effects MeSH
- Signal Transduction MeSH
- Sterol Esterase genetics metabolism MeSH
- Triglycerides metabolism MeSH
- Adipocytes cytology drug effects metabolism MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acetyl Coenzyme A MeSH
- ATP Citrate (pro-S)-Lyase MeSH
- DGAT2 protein, mouse MeSH Browser
- Diacylglycerol O-Acyltransferase MeSH
- Fabp4 protein, mouse MeSH Browser
- Hypoxia-Inducible Factor 1, alpha Subunit MeSH
- HIF1A protein, human MeSH Browser
- Oxygen MeSH
- Perilipin-1 MeSH
- Plin1 protein, mouse MeSH Browser
- Fatty Acid-Binding Proteins MeSH
- Sterol Esterase MeSH
- Triglycerides MeSH
In-vitro investigation of the effects of hypoxia is limited by physical laws of gas diffusion and cellular O2 consumption, making prolonged exposures to stable O2 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% O2 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.
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