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

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

Cell Reports (Apr 2023)

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

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

Affiliations

Pasquale Nigro: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
Maria Vamvini: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA; Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Jiekun Yang: Computational Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA
Tiziana Caputo: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA; Computational Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA
Li-Lun Ho: Computational Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA
Nicholas P. Carbone: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
Danae Papadopoulos: Computational Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA
Royce Conlin: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
Jie He: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
Michael F. Hirshman: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
Joseph D. White: Department of Pharmacology and Toxicology, East Carolina University, Greenville, NC, USA
Jacques Robidoux: Department of Pharmacology and Toxicology, East Carolina University, Greenville, NC, USA
Robert C. Hickner: Department of Pharmacology and Toxicology, East Carolina University, Greenville, NC, USA; Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, FL, USA
Søren Nielsen: The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Bente K. Pedersen: The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Manolis Kellis: Computational Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA
Roeland J.W. Middelbeek: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA; Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Laurie J. Goodyear: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 4
p. 112392

Abstract

Read online

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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

About the journal

Abstract

Keywords