| Description: |
Sleep apnea is a respiratory disease characterized by intermittent hypoxia (IH) due to repeated obstructions of the airways during sleep. Men and women after menopause are more likely to develop sleep apnea than women before menopause. In addition to disrupting sleep quality, sleep apnea is strongly associated with metabolic syndrome and type 2 diabetes, and the metabolic consequences of sleep apnea may vary according to sex or the hormonal status. We therefore used intact males, intact females, and ovariectomized (OVX) female mice to ask if IH induces sex‐specific metabolic responses and if endogenous female hormones prevent these effects. Within each group, mice were exposed to room air (RA) or IH (nadir 6% O 2 , 10 cycles/hour, 12 hours/day) during 2 weeks. Body weights were measured before and after the exposures to IH. At the end of the IH exposures, mice were fasted for 6 hours, a blood sample was drawn from the saphenous vein to measure fasting plasma glucose and insulin levels. We then performed intraperitoneal insulin or glucose tolerance tests to further assess glucose homeostasis. In distinct groups, we assessed liver levels of glycogen, triglycerides (TG), and expression levels of selected genes involved in glucose metabolism. In intact males, IH reduced weight gain, lowered the fasting levels of glucose and insulin in plasma, and slightly increased glucose tolerance. In intact females, the only effect of IH was a modest decrease of glucose tolerance. In OVX females, IH exposures reduced fasting glucose and insulin levels, induced insulin resistance, and led to a major glucose intolerance. In the liver, IH exposures slightly increased glycogen levels in males and OVX females and had a profound effect to decrease TG levels only in males. The expression levels of key liver glycolytic (LDH) and mitochondrial (Citrate synthase, PDH, PDK) genes were reduced by IH in males or in OVX females. We conclude that the metabolic consequences of IH exposures are sex specific. In females, endogenous ovarian ... |