Sex difference in effects of intermittent heat exposure on hepatic lipid and glucose metabolisms

Global climate warming has drawn worldwide attention. However, the health impact of heat exposure is still controversial. This study aimed to explore the exact effects and sex differential vulnerability under intermittent heat exposure (IHE) patterns and tried to elucidate the potential mechanisms by which IHE modulated hepatic lipid and glucose homeostasis. Both female and male C57BL/6 N mice were randomly allocated to control group (22 ± 1 °C) or intermittent heat group (37 ± 1 °C for 6 h) for 9 consecutive days followed by 4-day recovery at 22 ± 1 °C in a whole-body exposure chamber. Male mice, but not female, being influenced by IHE with decreased body weight, improved insulin sensitivity and glucose tolerance. Next, the levels of hepatic triglyceride (TG) were decreased and free fatty acid (FFA) increased in male mice exposed to intermittent heat, accompanied with upregulated expression of anti-oxidative enzymes in the liver. In addition, IHE led to enhanced lipid catabolism in male mice by inducing fatty acid uptake, lipid lipolysis, mitochondrial/peroxisomal fatty acid oxidation and lipid export. And glycolysis and glucose utilization were induced by IHE in male mice as well. Mechanically, heat shock protein 70 (HSP70)/insulin receptor substrate 1 (IRS1)/AMPKα pathways were activated in response to IHE. These findings provide new evidence that IHE sex-dependently enhanced the metabolism of lipid and glucose in male mice through HSP70/IRS1/AMPKα signaling.