Reversal of Obesity and Metabolic Disorders by Exercise in High-Fat Diet-Induced Obese C57BL/6 Mice

Obesity has become a major global health challenge. The rising prevalence of overweight and obesity in several countries has been described as a global pandemic. The objective of this study was to examine whether 13 weeks of moderate aerobic exercise performed in the fed-state could reverse metabolic disorders associated with obesity in a C57BL/6 female mice fed diets high in saturated or unsaturated fats. A total of 31 female C57BL/6 five weeks old mice were randomly assigned to three groups: a normal fat diet (NFD) group, a high saturated fat diet group (HSFD), or a high unsaturated fat diet group (HUSFD). Mice were fed their respective diets for 13 weeks after which exercise regimen was undertaken. Mice fed the high fat diets were further subdivided into sedentary and exercise groups (13 weeks exercise). Mice fed the NFD continued on the same diet without exercise treatment. Glucose, lipid profile, and glucagon-like peptide-1 (GLP-1) levels were analyzed after 13 weeks of diet induction, and at the end of the study. Intraperitoneal glucose tolerance tests were carried out after 12 weeks of the diet induction, and at 25th week of the study. 13 weeks of feeding the HFD caused obesity among experimental groups as compared to NFD group which maintained normal body weight. Glucose levels were significantly higher in the fed the high fat diet (HFD) groups (168.6±3.2 and 167.25±2.2) than that in the NFD group (123.86±2.9, P 0.001). Similarly, TC, TG and HDL levels were significantly higher in the HFD groups than that in the controls; whereas, GLP-1 levels were significantly reduced in the HSFD and HUSFD groups as compared to the controls (6.46±0.3, 7.97±1.2, and 10.56±0.3; respectively, P 0.001). GLP-1 levels were significantly higher in the HUSFD than that in the NFD group (P 0.001). Mice in the groups fed the HFD gained significantly more body weight than that in the NFD group and became glucose intolerant (P 0.001). Exercise for 13 weeks resulted in decreased both hypertriglyceridemia (P 0.01) and hyperglycemia (P 0.001) observed in the sedentary groups. It also significantly reduced body mass index (P 0.001) and feed efficiency (P 0.05). While GLP-1 levels were significantly lower in the sedentary HFD groups than that in the NFD group, GLP-1 levels in the HFD exercise subgroups were significantly higher than that in the NFD group. Glucose intolerance was improved in the HFD exercise subgroups as compared to the sedentary counterparts and the NFD group. Exercise had no effect (P 0.05) on serum levels of total cholesterol and high density lipoprotein in mice fed the HFD. In conclusion, exercise reverses obesity and certain metabolic disorders resulting from long-term feeding of HFD regardless of the need for dietary modification; these beneficial effects of exercise could be mediated by a significant increase in GLP-1 levels following weight loss. This study therefore may support that exercise is an effective treatment for obesity.