Circadian Phase Determines Tissue-Specific Adaptations to Long-Term Exercise in Obese Mice

Area of Science:

• Metabolic adaptations
• Circadian biology
• Exercise physiology

Background:

• Exercise and circadian rhythms are closely linked.
• The impact of long-term exercise timing on metabolic adaptations in obesity is not well understood.

Purpose of the Study:

• To investigate time-of-day-dependent metabolic adaptations to long-term exercise in obese mice.
• To explore the effects of exercise timing on lipid metabolism and hepatic oxidative capacity.

Main Methods:

• Male C57BL/6 mice on a high-fat diet underwent 8 weeks of treadmill training during either the early rest (ZT3) or early active (ZT15) phase.
• Sedentary controls were maintained.
• Plasma triglycerides and glucose, liver, and epididymal white adipose tissue (EPI) were analyzed post-fasting.

Main Results:

• Active-phase exercise (ZT15) significantly reduced plasma triglycerides compared to sedentary and rest-phase exercised mice.
• Rest-phase exercise (ZT3) showed lower hepatic triglyceride content and reduced lipid accumulation compared to ZT15.
• Exercise suppressed lipogenesis (Fasn expression) in EPI, while hepatic Cpt1a expression indicated enhanced oxidative capacity, particularly in ZT3-trained mice.

Conclusions:

• Long-term exercise elicits phase-dependent adaptations in lipid metabolism.
• Active-phase exercise promotes lipid mobilization and reduces plasma triglycerides.
• Rest-phase exercise enhances hepatic oxidative capacity, suggesting a 'tissue × time' framework for optimizing exercise timing in metabolic disorders.