Long-term voluntary exercise partially reverses obesity-associated transcriptomic remodeling in brown adipose tissue.

Authors

Takuya Sakurai, Eriko Nozaki, Tetsuya Iwawa

Published in

Metabolism open. Volume 32. Pages 100504. Epub Oct 06, 2026.

Abstract

Although exercise may counteract some changes caused by obesity-induced functional and molecular remodeling of brown adipose tissue (BAT), the extent to which long-term voluntary exercise reverses obesity-associated BAT transcriptional changes remains unclear.
Male C57BL/6J mice were assigned to the control, high-fat diet (HFD), or HFD plus voluntary exercise (HFD + VE) groups for four months (n = 4 per group). Interscapular BAT transcriptomic profiles were analyzed using the Clariom S Mouse Array. Differential expression was explored using eBayes ANOVA, and transcript clusters with an absolute fold change >2, a nominal P value < 0.05, and a mean log2 signal intensity ≥8 in the group with higher expression were selected for exploratory analyses. FDR-adjusted P values were additionally examined to account for multiple testing. Gene Ontology enrichment analysis was performed using DAVID.
Using the prespecified exploratory criteria (absolute fold change >2, nominal P < 0.05, and mean log2 signal intensity ≥8 in the group with higher expression), 579 transcript clusters differed between the control and HFD groups. In the HFD versus HFD + VE comparison, 89 transcript clusters met these exploratory criteria; 74 showed lower expression and 15 showed higher expression with VE. None of the 89 transcript clusters remained significant at FDR <0.05 after genome-wide multiple-testing correction. GO enrichment analysis nevertheless identified coordinated immune/inflammatory and muscle contraction-related biological processes, several of which remained significant after FDR correction for GO-term testing.
Long-term voluntary exercise was associated with transcriptomic changes that opposed a subset of HFD-associated alterations, particularly immune and inflammatory signatures. A restricted contractile/Ca2+-related transcriptional signature was also identified, although the transcriptomic data alone do not establish altered Ca2+ signaling. These exploratory findings highlight the need for further investigation of the cellular and signaling mechanisms underlying exercise-associated BAT remodeling.

PMID:
42893232
Bibliographic data and abstract were imported from PubMed on 18 Oct 2026.

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