Abstract 11547: Intermittent Hypoxia Deteriorates Mesenchymal Cells Differentiating to Adipocytes: An in vitro Demonstration of Vicious Link of Obesity, Sleep Apnea and Increased Cardiovascular Risk
Objectives: Sleep-disordered breathing causing intermittent hypoxia (IH) is often associated with obesity, in which dysregulated differentiation/proliferation and dysfunction of mesenchymal fat cells, play important roles in developing cardiovascular diseases. We examined the impacts of IH on the 3T3-L1 cells which mimicked various life stages of adipocytes in progressive obesity.
Methods and Results: We applied IH, in which 21%O2 alternated with 1%O2, to 3T3-L1 cells before (as they were fibroblast-like preadipocytes), immediately after (differentiating adipocytes), or 8 days after (mature adipocytes) the induction of differentiation by 10 μg/ml insulin, 0.4 μg/ml dexamethasone, and 0.5 mM IBMX in DMEM containing 10% FBS, while control 3T3-L1 cells were similarly cultured and allowed to differentiate under normoxia. In preadipocytes, when they were still incapable of adiponectin secretion, dihydroethidium staining revealed that IH increased superoxide production, which was accompanied by increased secretion of IL-6 and vascular endothelial growth factor (VEGF) as assessed by ELISA. In differentiating adipocytes, IH markedly reduced adiponectin secretion by 80% but doubled IL-6 secretion. In mature adipocytes, IH reduced both adiponectin and IL-6 secretions as compared with controls.
Conclusions: Responses of mesenchymal fat cells at various stages of life to IH included increased oxidative stress and increased secretions of neovascular as well as proinflammatory mediators at early stages of their life, and diminished adiponectin secretion during differentiation and maturation. These results may provide the basis for understanding the mechanisms of increased cardiovascular risk in obese patients with sleep-disordered breathing.
- © 2012 by American Heart Association, Inc.