Exercise Training Remodels Adipocyte-Specific Extracellular Matrix Proteins and Alters Innervation and Vascularization in Inguinal White Adipose Tissue (iWAT)

Abstract: Inguinal subcutaneous white adipose tissue (iWAT) is essential for conferring the beneficial effects of exercise training on metabolic health. Training alters adipocyte function, yet how the structural components of iWAT respond to training is not known. Using multi-omics approaches, we show that training in male mice results in iWAT remodeling, decreasing extracellular matrix (ECM) deposition, and increasing vascularization and innervation. We find adipose stem cells (ASC) to be the main ECM contributors and show an exercise-induced shift from hypertrophic to insulin sensitive adipocyte subpopulations. We demonstrate a critical role of the PRDM16 transcriptional complex in training-induced tissue remodeling, and propose a link between PRDM16 and neuronal growth regulator1 (NEGR1) in regulating neuritogenesis in trained iWAT. Combined, the major cellular and structural adaptations to iWAT induced by exercise training give rise to a remarkably flexible and multitasking tissue with a key role in modulating metabolic health.