Intermittent Hypoxia Stimulates Lipolysis, But Inhibits Differentiation and De Novo Lipogenesis in 3T3-L1 Cells
Abstract
Exposure to intermittent hypoxia (IH) may play a role in the development of metabolic impairments in the context of obstructive sleep apnea syndrome, probably by elevated plasma levels of free fatty acids. Employing gas-permeable cultureware to grow differentiated human and mouse adipocytes , we directly studied the effects of pericellular oxygen fluctuations on key adipocyte metabolic functions-spontaneous lipolytic rates, triglyceride accumulation, lipogenesis, and expression of adipocyte-specific marker genes. 3T3-L1 fibroblasts and human subcutaneous preadipocytes were differentiated under conditions that induced repetitive pericellular-oxygen cycles IH between 1% O (5 min) and 16% O (5 min), continuously for 14 days or under control conditions.
Chemicals were used to inhibit the flux of acetyl-CoA from glycolysis (alfa-cyano-4-hydroxy cinnamate) or the tricarboxylic acid cycle (SB204990), or to stimulate the flux of acetyl-CoA from pyruvate to the lipogenic pool. Lipolytic rate, intracellular lipids, and expression of adipocyte differentiation markers were assessed and -test or ANOVA were used to find significant differences.
The rate of lipolysis increased by 211% in 3T3-L1 cells and by 39% in obese human adipocytes. Exposure to IH reduced intracellular lipid stores by 37% and reduced the expression of adipocyte differentiation markers.
Pharmacological stimulation or inhibition of lipogenesis did not modify the intracellular lipid content under IH. Pericellular oxygen fluctuations directly stimulated lipolysis, but did not increase lipogenesis from endogenous substrates.
Similarly, IH hampered adipocyte differentiation from precursors.