Sex- and age-dependent outcomes of 9-hour time-restricted feeding of a Western high-fat high-sucrose diet in C57BL/6J mice

Time-restricted feeding (TRF) is a nutritional intervention wherein food intake is limited to a consistent 8- to 10-h daily window without changes in nutritional quality or quantity. TRF can prevent and treat diet-induced obesity (DIO) and associated metabolic disease in young male mice fed an obesogenic diet, the gold standard preclinical model for metabolic disease research. Because age and sex are key biological variables affecting metabolic disease pathophysiology and response to therapies, we assessed their impact on TRF benefits by subjecting young 3-month-old or middle-aged 12-month-old male and female mice to ad libitum or TRF of a Western diet. We show that most of the benefits of TRF are age-independent but are sex-dependent. TRF protects both sexes against fatty liver and glucose intolerance while body weight benefits are observed only in males. We also find that TRF imparts performance benefits and increases survival to sepsis in both sexes. [Display omitted] •TRF protects against body weight gain in young and old male mice but not in female mice•TRF protects from fatty liver regardless of sex or age•TRF preserves whole-body glucose regulation in males and females irrespective of age•TRF extends muscle performance, motor coordination, and survival to sepsis in old mice Chaix et al. show that time-restricted feeding (TRF) can improve metabolic functions in an age-independent but sex-dependent manner. While TRF of a Western diet blunted weight gain and adipose tissue inflammation in males only, it protected against fatty liver disease and glucose intolerance in both sexes.