Contrasting effects of acute versus chronic intermittent hypoxia on leptin secretion in differentiated human adipocytes – Implications for sleep apnea

Abstract

Obstructive sleep apnea (OSA) is a common sleep disorder associated with repetitive episodes of nocturnal intermittent hypoxia (IH), obesity and elevated leptin. Newly diagnosed OSA patients have a history of significant recent weight gain. While IH is implicated in OSA pathophysiology, the factors contributing to weight gain in OSA are not completely understood. Leptin is an adipokine with a central role in energy homeostasis and appetite control. Increases in leptin suppress appetite, while decreases in leptin increase appetite and may consequently cause weight gain. Using an in vitro approach, we examined the role of acute and chronic IH exposure on leptin secretion in differentiated human white preadipocytes. We show that acute 24-h exposure to IH and sustained hypoxia both increased leptin secretion, compared to normoxic controls (p = 0.01). In contrast, chronic repetitive IH exposure for 7 days decreased leptin secretion, compared to normoxic controls (p = 0.02). The decrease in leptin secretion during chronic IH exposure suggests a mechanism which may contribute to increased appetite and thereby predispose patients with untreated OSA to weight gain and obesity in early stages. As obesity progresses, leptin levels likely rise secondary to the increase in body fat. Elevated leptin levels in patients with longstanding OSA may be indicative of increased fat mass and not a consequence of IH-mediated effects on adipocytes.

Keywords

• Hypoxia
• Adipocytes
• Leptin
• Sleep apnea