Genomics · Nov 4, 2026

Exercise mode and intensity interact to shape brain-region-specific transcriptional adaptation in obese mice

By Yang B, Li L, Fei Q et al.

Obesity impairs brain health, yet how exercise mode and intensity influence region-specific molecular responses remains unclear. Male C57BL/6 J mice high-fat-diet induced obesity underwent 12 weeks of moderate- or high-intensity aerobic or resistance training. RNA sequencing was subsequently performed on the hippocampus, cerebral cortex and cerebellum. Obesity was associated with distinct transcriptional alterations across these regions, with no FDR-significant differentially expressed genes shared by all three. Factorial analysis identified significant effects of exercise mode, intensity, and their interaction. For most genes showing a significant Mode × Intensity interaction, increasing exercise intensity produced opposite transcriptional responses under aerobic and resistance conditions. Joint analysis across brain regions further identified significant Mode × Intensity × Region effects, with the clearest differences observed in comparisons involving the hippocampus. Overall, exercise-induced transcriptional adaptation in the obese brain did not follow a uniform intensity-dependent pattern, but varied according to exercise mode, intensity, and brain region.

doi.org/10.1016/j.ygeno.2026.111341Open accessPubMed 42982205Interventions