Obesity increases the risks for a wide variety of serious diseases, including Type II diabetes, cardiovascular disease, stroke, and certain cancers. While obesity is a largely preventable disease, more than one third of adults in the United States are obese. Increased exercise and dietary changes, especially caloric restriction, remain the most common obesity treatments. Such lifestyle modifications, however, require constant vigilance, which limits their therapeutic success. Limiting food consumption to discreet periods during the day has shown promise in reducing diet-induced metabolic disorders in mice. An exciting new report in Cell Metabolism (Chaix et al. 2014) illustrates the efficacy of time-restricted feeding in preventing and mitigating diet-induced obesity and metabolic disorders in mice without caloric restriction.
TRF protects against weight gain without affecting caloric intake
Time-restricted feeding (TRF) of C57BL/6J (000664) mice during a 9-hour window of the dark cycle (when mice are most active and eating) for 12 weeks significantly reduced body weight gain on different diets as compared to ad libitum feeding (ALF). TRF mice fed a high fat diet (HFD) gained less than half as much weight as ALF mice (26% vs. 65% weight gain after 12 weeks, respectively). When fed a high fat, high sucrose diet (HFSD), the TRF mice gained half as much weight (21%) compared to ALF mice (42%). As the TRF duration for C57BL/6J mice fed the HFD increased to 12- and 15-hour windows, the amount of weight gain also increased in a near linear fashion (from 26% for 9-hour TRF to 43% for 15-hour TRF). For all of these cohorts, fat mass accumulation accounted for all of the weight gain; lean mass was comparable between each cohort. Additionally, caloric intake remained constant regardless of diet or feeding regimen. These data reveal that TRF protects mice against diet-dependent weight gain without affecting food consumption.
Pleiotropic, beneficial TRF effects
In addition to preventing weight gain in mice, TRF significantly impacted a wide range of high fat diet-induced Type II diabetes and cardiovascular disease phenotypes/risk factors. TRF benefits included:
- Decreased fasting blood glucose and insulin levels
- Improved glucose tolerance
- Decreased serum leptin and increased serum adiponectin levels
- Reduced liver and serum triglycerides
- Decreased cholesterol
- Increased coordination and endurance
To mimic occasional dietary lapses, HFD-fed mice were switched from TRF (9-hour) for 5 days to ALF for 2 days (5T2A). Remarkably, the weight gain of the 5T2A mice was nearly identical to that for 9-hour TRF mice (29% vs. 26%). The 5TA2 regimen, also, conferred all of the pleiotropic beneficial effects of 9-hr TRF alone (see above). Further, TRF showed some lasting effects following complete interruption: for example, when C57BL/6J mice were maintained on TRF for 26 weeks, then switched to ALF for 12 weeks, they gained approximately 2/3 less weight than mice maintained on ALF for the entire 38 weeks. They also displayed lower triglycerides, lower fasting insulin, and improved physical endurance. TRF-derived benefits to improved glucose tolerance, however, were lost by 4 weeks after the switch to ALF.
Therapeutic potential of TRF
ALF C57BL/6J mice maintained on HFD for 13 weeks or 26 weeks, then switched to TRF for 12 weeks lost 5% and 12% of their body weight, respectively, following the switch while consuming the same amount of calories. In contrast, mice maintained on ALF for the entire 25 or 38 weeks gained 24.8% and 10.6% body weight, respectively, during the 12 weeks after the switch point. Surprisingly, 4 weeks following the change to TRF, glucose tolerance significantly improved. The transition from ALF to TRF also:
- Prevented further accumulation of liver and serum triglycerides
- Lowered fasting glucose and insulin
- Increased endurance
These exciting results demonstrate the multiple beneficial effects of time restricted eating on the development of obesity and obesity-related disease risk factors. They also confirm the potential for TRF as a therapeutic treatment in the fight against obesity that does not require concomitant dietary nutritional changes or calorie restriction.