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

Cell Rep. 2021 Aug 17;36(7):109543. doi: 10.1016/j.celrep.2021.109543.


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.

Keywords: aging; circadian rhythms; diet-induced obesity; endurance; fatty liver; motor coordination; sepsis; sex differences; time-restricted feeding; type 2 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / pathology
  • Adiposity
  • Aging / physiology*
  • Animals
  • Cholesterol / blood
  • Diet, High-Fat*
  • Dietary Sucrose / administration & dosage*
  • Fasting*
  • Fatty Liver / pathology
  • Female
  • Glucose / metabolism
  • Homeostasis
  • Inflammation / pathology
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscles / pathology
  • Organ Size
  • Sex Characteristics*
  • Weight Gain


  • Dietary Sucrose
  • Lipopolysaccharides
  • Cholesterol
  • Glucose