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other·preclinical research, endocrinology, biomedical research, cardiology·PMC10374102

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

Cell reports · 18 authors, 9 centres

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The PRDM16 transcriptional complex was shown to be necessary for these adaptations and for adipocyte beiging.

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The PRDM16 transcriptional complex was shown to be necessary for these adaptations and for adipocyte beiging. The study also observed a shift in adipocyte subpopulations, with training increasing insulin-sensitive adipocytes and reducing stressed/hypertrophic adipocytes. Limitations include the use of only male mice in the primary animal experiments and the use of a spatial transcriptomics platform that detects mRNA in cell clusters rather than individual cells.

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preclinical research

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ORIGINAL PAPER

PMC10374102

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

Cell reports

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ABSTRACT

SUMMARY 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.

CITATION EXPORT

Pasquale Nigro, Maria Vamvini, Jiekun Yang et al.. Exercise training remodels inguinal white adipose tissue through adaptations in innervation, vascularization, and the extracellular matrix. Cell reports. (2023). https://doi.org/10.1016/j.celrep.2023.112392

AUTHORS

18 · 9 CENTRES

Pasquale Nigro, Maria Vamvini, Jiekun Yang, Tiziana Caputo, Li-Lun Ho, Nicholas P. Carbone, Danae Papadopoulos, Royce Conlin, Jie He, Michael F. Hirshman, Joseph D. White, Jacques Robidoux, Robert C. Hickner, Søren Nielsen, Bente K. Pedersen, Manolis Kellis, Roeland J.W. Middelbeek, Laurie J. Goodyear

1Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
2Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
3Computational Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA
4Department of Pharmacology and Toxicology, East Carolina University, Greenville, NC, USA
5Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, FL, USA
6The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
7These authors contributed equally
8Senior author
9Lead contact