Reduced adipose tissue hypoxia as a potential mechanism by which exercise and/or low fat diet reduces inflammation in obese mice

摘要

Recent evidence from our lab suggests that, in high fat diet-induced (HFD, 45% fat) obese mice, moderate exercise, low fat diet (LFD, 10% fat), or their combination results in significant reductions in the visceral adipose tissue inflammation. Adipose tissue hypoxia, perhaps involving cell stress or death, has been suggested as one of the major initiating events inciting inflammation. Purpose- The purpose of the proposed study was to investigate adipose tissue hypoxia as a potential mechanism by which exercise and/or low fat diet might exert anti-inflammatory effects in adipose tissue. Methods- Male C57BL/6 mice (n=73) fed a 45% high fat diet for 6 weeks to induce obesity were randomly assigned to one of 4 groups: exercised (5 days/week, 40 min/day, 65-70% VO2 max) high fat diet or low fat diet or sedentary high fat diet or low fat diet for 12 weeks in a 2 x 2 design. In a subset of these mice (n=32), adipose tissue hypoxia was measured in epididymal fat pads using pimonidazole hydrochloride (injected intraperitonealy at a concentration of 60 mg/g body weight) and detected via ELISA. Results- Exercise and diet interventions had similar effects at attenuating body weight and epididymal fat pad weight gain as compared to a recent study from our lab where mice underwent the same interventions. There was a significant (F1,23=6.3; p=0.02) exercise x diet interaction such that adipose tissue hypoxia in the combined intervention was significantly less than all other groups with a tendency for low fat diet alone to be more efficacious than exercise alone. Conclusion- These circumstantial data suggest that adipose tissue hypoxia may be a potential mechanism by which both regular exercise and/or a low fat diet reduce adipose tissue inflammation and that exercise when combined with low fat diet provides a strong enough stimulus to reduce adipose tissue hypoxia.