4-week aerobic exercise training regulates systemic macrophage polarization in obese mice

Obesity is accompanied by chronic low-grade inflammation, largely driven by imbalances in macrophage polarization. While pro-inflammatory M1 macrophages accumulate in adipose tissue and circulation, contributing to insulin resistance and metabolic disruption, alternatively activated M2 macrophages exert anti-inflammatory and tissue-protective effects. Exercise is widely recognized as a non-pharmacological strategy to improve metabolic health; however, the extent to which short-term aerobic training influences systemic macrophage polarization in obesity is not fully understood. This study examined whether a 4-week aerobic exercise intervention alters systemic macrophage polarization in diet-induced obese mice and explored its role in attenuating obesity-related inflammation.

Male C57BL/6J mice (8 weeks old) were fed either a standard chow diet (Ch) or a high-fat diet (HF; 60% kcal from fat) for 12 weeks. Following obesity induction, HF-fed mice were assigned to either a sedentary (HF-Sed) or exercise-trained (HF-Exe) group. The training protocol involved treadmill running at moderate intensity, performed twice daily, 5 days per week, for 4 weeks. Plasma concentrations of M1-associated markers (TNF-α, IFN-γ , IL-1β, IL-6) and M2-associated markers (IL-10, Arg1, CD163) were measured by an enzyme-linked immunosorbent assay (ELISA). Statistical differences were analyzed using analysis of variance (ANOVA) with post hoc testing.

After 12 weeks of high-fat feeding, mice exhibited approximately 20% higher body weight than chow controls, confirming obesity induction. Four weeks of exercise training did not significantly reduce body weight but improved metabolic indices, including plasma glucose and insulin sensitivity. HF-Sed mice displayed elevated circulating M1 cytokines, whereas HF-Exe mice had significantly lower levels of IL-6, and TNF-α. Conversely, exercise enhanced M2-associated markers, including IL-10, Arg1, and CD163. Thus, aerobic training shifted systemic macrophage polarization away from a pro-inflammatory toward an anti-inflammatory profile, independent of substantial weight loss.

Short-term aerobic exercise is sufficient to promote M2 macrophage polarization and dampen systemic inflammation in obese mice. These findings underline the rapid immunomodulatory potential of exercise and support its role as an effective non-pharmacological approach to counteract obesity-related inflammation and metabolic dysfunction.