Attenuation of obesity and related metabolic disorders by the individual or combination treatment with IL-2/anti-IL-2 complex and hyperbaric oxygen

Obesity is the disease accumulating excessive fat in the body. The prevalence of obesity and related metabolic disorders is increasing every year worldwide. Immunologically, obesity is a chronic low-grade inflammatory state with the increase of M1 macrophages and decrease of regulatory T cells (Tregs). IL-2/anti-IL-2 complex (IL-2C) and hyperbaric oxygen (HBO) are known to expand Tregs in vivo and suppress inflammation. Therefore, in this study, IL-2C and HBO were investigated for the preventive effect of obesity and related metabolic disorders. Male C57BL/6 mice were fed with a high-fat diet (HFD) for 16 weeks, and counterparts were fed with a low-fat diet (LFD). At the end of the experiment, the body weight gain and impaired glucose metabolism, elevated levels of insulin and total cholesterol induced by HFD were improved by the individual or combination treatment with Il-2C and HBO. Histological examination of the epididymal white adipose tissue showed adipocyte hypertrophy and many crown-like structures in the HFD control groups. In addition, the liver showed the progression of non-alcoholic fatty liver disease (NAFLD) in the HFD control groups, but it was significantly improved by the individual or combination treatment with IL-2C and HBO. As for the underlying mechanism, inflammation induced by obesity was decreased, and HIF-1α expression by adipocyte hypertrophy was also reduced by the individual or combination treatment with IL-2C and HBO. In addition, adipose tissue browning was activated in brown and inguinal adipose tissue, and the expression of UCP-1 involved in the thermogenesis was increased by the individual or combination treatment with IL-2C and HBO. Overall, these results suggested that IL-2C and HBO might be a new promising immunotherapy for the treatment of obesity and related metabolic disorders by regulation of inflammation and activation of adipose tissue browning.