Recent studies demonstrate that exercise training causes pronounced changes in inguinal white adipose tissue (iWAT). While most of these studies have focused on adaptations related to enhanced lipolysis and beiging of adipocytes, other tissue remodeling processes include innervation and vascularization, and changes in collagen and glycoprotein-rich extracellular matrix (ECM), all critical for adipose tissue function. Here, we determined the effects of exercise training on these iWAT adaptations. Mice were housed in individual cages with (Trained) or without (Sedentary) access to running wheels for 11 days (n=8/group). Exercise training significantly increased: iWAT neuronal innervation assessed by immunolabeling of synaptophysin (2.2 fold; p<0.01) and tyrosine hydroxylase (2.3 fold; p<0.001); and vascularization as assessed by increased lectin staining (1.5 fold; p<0.01), Vegfa mRNA (1.5 fold; p<0.05) and Angpt2 mRNA (2.6 fold; p<0.05). Since decreases in ECM components have been suggested to allow for increased innervation and vascularization in tissues, we collected conditioned media from trained and sedentary iWAT to determine if adipocyte-specific ECM proteins are changed by training. Quantitative proteomic profiling using mass spec showed that exercise training significantly increased 23 proteins and decreased 32 proteins in the iWAT-conditioned media. Interestingly, pathway analysis revealed that 14 of the 32 downregulated proteins are adipocyte-specific ECM components [collagens (COL1A2,COL14A1), laminins (LAMA4, LAMB1, LAMB2), glycoproteins (NID1, NID2)] (p<0.001: FDR <0.001). These findings support the hypothesis that exercise training leads to remodeling of ECM, which in turn regulates increased innervation and vascularization, and could facilitate exercise-induced training effects on iWAT.
P. Nigro: None. M. Vamvini: None. R. Middelbeek: None. M.F. Hirshman: Stock/Shareholder; Self; Abbott Laboratories, AbbVie Inc., Amgen, Colgate-Palmolive, Eli Lilly and Company, Medtronic. L.J. Goodyear: None.