Chronic Transient Hypoxia Alleviates High Fat Diet-Induced Obesity and Fatty Liver in C57 Mice by Upregulating Epinephrine Levels and Activation of AMPK

Background According to epidemiologic studies, it was found that people living in high altitude areas have a lower prevalence of obesity and diabetes, and the main environmental differences between high altitude areas and plain areas are temperature and oxygen concentration. In this study, we investigated the effect of chronic transient hypoxia on obesity and fatty liver caused by high-fat diet in mice. Methods Put the mice under 10% oxygen concentration for 1 hour every day, this method is different from high altitude hypoxia and will not cause a series of acute altitude sicknesses. Intraperitoneal injection of epinephrine or propranolol was employed to examine the effect of chronic transient hypoxia on HFD-induced obesity, hyperglycemia and hepatic lipid accumulation. Results It showed that chronic transient hypoxia environment reduces the weight of mice and improve glucose tolerance, reduce the fat content of mice and alleviate fatty liver, reduces liver fat synthesis, promotes the expression M2 phenotype of macrophage genes in liver and thermogenic genes in brown fat. Furthermore, we showed that blocking the rise of epinephrine will compromise the chronic transient hypoxia environment beneficial ability to obesity and fatty liver, diminished expression of the liver AMPK phosphorylation and CD206. Conclusions These results suggest that chronic transient hypoxia activation of AMPK, induction of M2 type macrophage marker CD206 expression in the liver leads to significant weight loss and remission the severity of fatty liver through the adrenergic system.