Impact of time‐restricted feeding on metabolic health and adipose tissue metabolism in aged female mice with high‐fat diet‐induced obesity

Ageing increases the risk of obesity and related metabolic diseases, emphasizing the need to understand how dietary interventions influence metabolism and metabolic health in older populations. This study aimed to investigate the impact of time-restricted feeding (TRF) on energy balance, adipose tissue metabolism and overall metabolic health in aged female mice with high-fat diet (HFD)-induced obesity. A 10-week TRF regimen was implemented in aged female mice following 12 weeks of HFD exposure. Mice were either maintained on HFD ad libitum (HFD-AL) or subjected to TRF with HFD access restricted to a 10 h daily feeding window (HFD-TRF). Glucose and insulin tolerance tests, meal pattern and indirect calorimetry were measured during the regimen. We showed that TRF partially reversed HFD-induced weight gain and fat mass accumulation. In white adipose tissue TRF reduced average adipocyte size and increased the heterogeneity in adipocyte size distribution. TRF also led to increased VO₂ and VCO_2, along with a decreased respiratory efficiency ratio (RER) compared to the HFD-AL group, particularly during the light phase. Meal pattern analysis showed increased meal frequency during the feeding window in HFD-TRF mice relative to HFD-AL. Additionally TRF lowered fasting blood glucose and reduced liver lipid accumulation. At the molecular level TRF induced significant metabolic adaptations in adipose tissue, including upregulation of genes involved in adipogenesis and lipid cycling, as well as depot-specific alterations in mitochondrial oxidation and circadian rhythm gene expression. In conclusion TRF promotes beneficial metabolic adaptations and may serve as an effective dietary strategy to improve metabolic health in aged females. KEY POINTS: Time-restricted feeding (TRF) reduced body weight and fat mass, lowered blood glucose and decreased lipid accumulation in the liver. TRF also changed energy fuel utilization, increased metabolic activity of adipose tissue and altered the size and function of fat cells. Altered meal timing can trigger beneficial metabolic changes and suggests that TRF may help protect against obesity-related diseases during ageing.