# Enhanced metabolic adaptations following late dark phase wheel running in high-fat diet-fed mice

## TL;DR

Exercising during the late dark phase improves metabolic health more than early dark phase in mice on a high-fat diet.

## Contribution

Late dark phase exercise shows greater metabolic benefits compared to early dark phase in high-fat diet-fed mice.

## Key findings

- Late dark phase exercise reduces body weight gain more effectively than early dark phase.
- Late dark phase exercise enhances metabolic flexibility and insulin sensitivity.
- Late dark phase exercise increases Pdk4 expression.

## Abstract

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.

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.