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
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.
