Endocrine Abstracts

Obesity is a major health problem that is crucial in the pathogenesis of diabetes mellitus, cardiovascular diseases, and some types of cancer. Intermittent fasting is an eating pattern in which periods of fasting, lasting from 12 up to 36h, are alternated with periods of eating. Time restricted feeding (TRF) 16/8 is a type of intermittent fasting that is being used to lose weight and for treating metabolic disorders. Several studies in humans have shown a slight effect of TRF on body weight but more consistent effects on metabolic parameters. However, the molecular mechanisms by which these effects occur are poorly understood. We aimed to investigate if TRF 16/8 in mice reproduced the metabolic effects observed in human and tested if TRF 16/8 reduces inflammation in obese mice. We used C57BL/6J mice under a high fat diet for 12 weeks (60%KCal in fat) to develop obesity associated with glucose intolerance and fatty liver. Then we exposed the animals to TRF 16/8 (feeding in active phase) for 6 weeks. We found that TRF decreases body weight without changes in epididymal or subcutaneous fat, it reduces fasting glycemia, improves glucose tolerance, decreases liver weight, and decreases gut epithelial permeability. In addition, TRF increases blood ketone bodies, in particular l-hydroxybutyrate (BHB). These results show that 6 weeks of TRF are enough to produce metabolic improvements in obese mice. Since obesity is characterized by a low-grade inflammatory state and BHB may have anti-inflammatory effects, we propose that BHB induced by TRF has anti-inflammatory effects in the brain and periphery that explain why TRF improves metabolic parameters in obese mice.