Low-frequency intermittent hypoxia promotes subcutaneous adipogenic differentiation

Abstract

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is associated with obesity and metabolic disorders. The mass and function of adipose tissue are largely dependent on adipogenesis. The impact of low-frequency IH on adipogenesis is unknown. Sprague-Dawley rats were subjected to IH (4 min for 10% O2 and 2 min for 21% O2) or intermittent normoxia (IN) for 6 weeks. The degree of adipogenic differentiation was evaluated by adipogenic transcriptional factors, adipocyte-specific proteins, and oily droplet production in both subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). Upregulation of proadipogenic markers (CEBPα, PPARγ, and FABP4) and downregulation of antiadipogenic markers CHOP in line with smaller size of adipocytes were found in IH-exposed SAT. In vitro experiments using human preadipocytes (HPAs) of subcutaneous lineage during differentiation phase, subjected to IH (1% O2 for 10 min and 21% O2 for 5 min; 5% CO2) or IN treatment, were done to investigate the insulin-like growth factor 1 receptor (IGF-1R)/Akt pathway in adipogenesis. IH promoted the accumulation of oily droplets and adipogenesis-associated markers. IGF-1R kinase inhibitor NVP-AEW541 attenuated the proadipogenic role in IH-exposed HPAs. In summary, relatively low frequency of IH may enhance adipogenesis preferentially in SAT.