2025/02/22 by Stephen P. Ashcroft, Amy M. Ehrlich, Krzysztof Burek +4 · 1 voice
Medicine · Neuroscience · #Adipose Tissue and Metabolism #Circadian rhythm and melatonin #Dietary Effects on Health
paper · doi:10.1016/j.molmet.2025.102116
openalex publication_date 2025/02/22 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23
Exercise interventions represent an effective strategy to prevent and treat metabolic diseases and the time-of-day-dependent effects of exercise on metabolic outcomes are becoming increasingly apparent. We aimed to study the influence of time-restricted wheel running on whole-body energy and glucose homeostasis. Male, 8-week-old, C57BL/6NTac mice were fed either a 60% high-fat diet (HFD) or a 10% low-fat diet (LFD) for 4 weeks. Following this, mice were given access to a running wheel between zeitgeber time (ZT) 12–16 (early dark phase) or ZT 20-0 (late dark phase). Sedentary mice had access to a permanently locked wheel. Mice were housed under these conditions in metabolic chambers for 4 weeks in which LFD and HFD conditions were maintained. Following the exercise intervention, body composition and glucose tolerance were assessed. Wheel running during either the early or late dark phase resulted in metabolic improvements such as attenuation in body weight gain, enhanced glucose tolerance and reduced ectopic lipid deposition. However, late dark phase exercise resulted in a greater reduction in body weight gain, as well as enhanced metabolic flexibility and insulin sensitivity. Our data suggest that late dark phase versus early dark phase exercise confers greater metabolic adaptations in HFD-fed mice. • Exercise-timing promotes divergent metabolic adaptations in lean and obese mice. • Late dark phase exercise resulted in a greater reduction in body weight gain. • Late dark phase exercise promotes metabolic flexibility and insulin sensitivity. • Enhanced Pdk4 expression following late dark phase exercise.