Voluntary exercise ameliorates obesity and related metabolic disorders by promoting browning of visceral adipose tissue.

OBJECTIVE

This study aims to investigate whether voluntary exercise alleviates obesity-induced metabolic disorders by promoting visceral adipose tissue (VAT) browning and to explore its potential mechanisms.

METHODS

Thirty male C57BL/6J mice were fed a normal diet (ND) or high-fat diet (HFD) for 8 weeks. Obese HFD mice were then divided into sedentary (HFD) or voluntary wheel running (HFD + VWR) groups and switched to standard diet for 4 weeks. VWR mice had access to unlocked running wheels; HFD controls had locked wheels.

RESULTS

Voluntary exercise significantly reduced obesity-associated metabolic disturbances compared to HFD controls, including decreased body weight, fat mass, serum insulin, triglycerides (TG), total cholesterol (T-CHO), and hepatic lipid accumulation. Crucially, voluntary exercise enhanced VAT browning, evidenced by upregulated UCP1 and PPAR-γ protein expression, as well as increased mRNA levels of beige adipocyte-specific markers TMEM26 and CD137. Additionally, VWR significantly upregulated the protein expression of the exercise-responsive factor FGF21 in VAT. Mechanistically, the observed browning phenotype was accompanied by alterations in the PI3K/AKT/mTOR signaling axis, characterized by enhanced PI3K/AKT activity and reduced mTOR phosphorylation, though the causal relationship remains to be established.

CONCLUSIONS

Voluntary exercise mitigates obesity and metabolic dysfunction, may be associated with the regulation of VAT browning, potentially involving the PI3K/AKT/mTOR signaling axis, thus enhancing insulin sensitivity and reducing lipid accumulation. Unlike forced exercise, it is low-stress and self-regulated, offering a mechanistic reference for understanding exercise-induced adipose remodeling.