Time-restricted feeding restores metabolic flexibility in adult mice with excess adiposity

Authors: Yan, Lin; RUST, BRET M - Former ARS Employee; PALMER, DANIEL - University Of North Dakota

Submitted to: Frontiers in Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/23/2024
Publication Date: 2/15/2024
Citation: Yan, L., Rust, B., Palmer, D. 2024. Time-restricted feeding restores metabolic flexibility in adult mice with excess adiposity. Frontiers in Nutrition. 11:1-14. https://doi.org/10.3389/fnut.2024.1340735.
DOI: https://doi.org/10.3389/fnut.2024.1340735

Interpretive Summary: Obesity is prevalent with the adult population in the U.S., over 30 percent of adults are over-weight and 40 percent of adults are obese. The estimated medical cost of obesity in the U.S. was over 170 billion in 2019. Lifestyle changes in modern world (for example, irregular mealtime and energy dense diets) contribute to obesity and its related metabolic disorders. In this study, we investigated effects of the time-restricted feeding on metabolism in adult obese mice, in which mice had free access to their diets for 12 hours in the dark phase of the day (the active phase for rodents). Compared to mice with un-restricted feeding of a high-fat diet, time-restricted feeding of the same high-fat diet did not decrease food intake and body fat mass, but it restored metabolic rhythms which was dampened in mice with unrestricted feeding of the high-fat diet. Furthermore, the restoration of metabolic rhythms was accompanied with improvement in insulin sensitivity and decreases of cholesterol in blood and triacylglycerol in liver in mice with time-restricted feeding. Findings from this study showed that fixed mealtime, such as time-restricted feeding, improved metabolism in adult obese mice. This improvement was not through the reduction in body fat mass but rather the restoration of metabolic rhythms and metabolic homeostasis. It indicates that restriction of mealtime to the active phase of the day may improve metabolic health in adults with obesity.

Technical Abstract: Obesity is prevalent with the adult population in the U.S. Erratic eating behavior and energy-dense diets are environmental contributors to obesity. This study tested the hypothesis that time-restricted feeding (TRF) improves metabolic homeostasis in adult mice with excess adiposity. Male C57BL/6NHsd mice were first fed a control or a high-fat diet (HFD) for 12 weeks to establish body adiposity. After 12 weeks, the control mice remained on the same diet ad libitum, whereas the HFD-fed mice were assigned to 2 groups, either HFD ad libitum or TRF of the HFD in the dark phase for another 12 weeks. There were no differences in energy intake and body fat mass between the TRF and HFD groups. The TRF restored rhythmic oscillations of respiratory exchange ratio (RER) flattened by the HFD with the greater RER amplitude in the dark phase. Improvements in insulin sensitivity and decreases in plasma cholesterol and hepatic triacylglycerol occurred in TRF mice. Compared to the HFD, TRF decreased transcription of circadian genes Per1 and Per2 and genes encoding lipid metabolism (Acaca, Fads1 Fads2, Fasn, Scd1, and Srebf1) in liver. Metabolomic analysis showed that TRF altered amino acid metabolism considerably when compared to the HFD. This included alterations in aminoacyl-tRNA-biosynthesis, glutathione metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In conclusion, TRF improved metabolic homeostasis in adult mice with excess adiposity. This improvement was not through the reduction in body fat mass but the restoration of metabolic flexibility.