Exercise training remodels inguinal white adipose tissue through adaptations in innervation, vascularization, and the extracellular matrix

Cell Rep. 2023 Apr 25;42(4):112392. doi: 10.1016/j.celrep.2023.112392. Epub 2023 Apr 13.


Inguinal white adipose tissue (iWAT) is essential for the beneficial effects of exercise training on metabolic health. The underlying mechanisms for these effects are not fully understood, and here, we test the hypothesis that exercise training results in a more favorable iWAT structural phenotype. Using biochemical, imaging, and multi-omics analyses, we find that 11 days of wheel running in male mice causes profound iWAT remodeling including decreased extracellular matrix (ECM) deposition and increased vascularization and innervation. We identify adipose stem cells as one of the main contributors to training-induced ECM remodeling, show that the PRDM16 transcriptional complex is necessary for iWAT remodeling and beiging, and discover neuronal growth regulator 1 (NEGR1) as a link between PRDM16 and neuritogenesis. Moreover, we find that training causes a shift from hypertrophic to insulin-sensitive adipocyte subpopulations. Exercise training leads to remarkable adaptations to iWAT structure and cell-type composition that can confer beneficial changes in tissue metabolism.

Keywords: Adipo-Clear; CP: Metabolism; CP: Molecular biology; ECM; NEGR1; PRDM16; exercise; innervation; proteomics; spatial transcriptomics; vascularization; white adipose tissue.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acclimatization / physiology
  • Adaptation, Physiological / physiology
  • Adipose Tissue / metabolism
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, White* / metabolism
  • Animals
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity*
  • Transcription Factors / metabolism


  • Transcription Factors
  • NEGR1 protein, mouse
  • Cell Adhesion Molecules, Neuronal