Impacts of time-restricted feeding on middle-aged and old mice with obesity.

Time-restricted feeding is known to ameliorate obesity in young mice. However, evaluation of its effect in old age is still lacking. The current work aims to investigate the effects of time-restricted feeding on treating pre-existing obesity in old animals. The study utilized middle-aged and old high fat diet-induced obese mice and subjected them to 8 h daily time-restricted feeding. Aged obese mice did not lose fat mass but lost lean mass after 8 weeks of treatment. In addition, time-restricted feeding reduced adiposity in brown adipose tissue, reversed excessive hepatic lipid accumulation, and improved glucose homeostasis in middle-aged and old obese mice. Mechanistic studies show that these metabolic benefits were mediated by transcriptional downregulation of essential genes responsible for hepatic adipogenesis and adipose tissue chronic inflammation. These results demonstrate that time-restricted feeding improves metabolic health and has beneficial effects in combating diet-induced obesity in aged obese mice. KEY POINTS: Contrary to in young obese mice, in old obese mice time-restricted feeding did not significantly reduce body fat but decreased lean mass. Time-restricted feeding reduced adipose tissue inflammation, reversed fatty liver, and improved glucose homeostasis in aged mice with diet-induced obesity. Time-restricted feeding is effective in improving metabolic homeostasis in aged mice, but less effective in terms of reducing obesity. Future studies should investigate the underlying mechanism of how ageing impaired intermittent fasting induced fat loss.