Paper
Paper
Exercise training and cold exposure are physiological stimuli that both improve systemic glucose metabolism, but the mechanisms are not well understood. Here, we tested the hypothesis that adaptations to inguinal white adipose tissue (iWAT) are critical for the beneficial effects of exercise-trained and cold-exposed iWAT on metabolism. First, we utilized an iWAT transplantation model. Male donor mice were sedentary, exercise trained by voluntary wheel running, or cold exposed (5°C) for 11 days (n=5/group). Transplanting iWAT from exercised into sedentary mice enhanced glucose tolerance, yet cold-exposed iWAT had no effect, suggesting unique adaptations to trained iWAT that confer beneficial effects on glucose homeostasis. To determine exercise-specific effects on iWAT, quantitative proteomic profiling (QPP) of iWAT was done from sedentary, trained, and cold-exposed mice. Cold down-regulated >2,000 proteins in iWAT, but also resulted in a protein signature of enhanced mitochondrial biogenesis, energy production, and fatty acid metabolism. Training also regulated protein expression, but interestingly only training-specific proteins (>50 proteins), and not cold proteins, were inversely correlated with fasting glucose. This suggests that training results in fundamental changes in iWAT that mediate systemic glucose homeostasis, consistent with the transplantation glucose tolerance data. Training also upregulated iWAT extracellular space and vesicle transport proteins. Consistent with this finding, isolation of adipocyte-derived EVs from sedentary and trained mice revealed a significant increase in EV release from trained adipocytes. In sum, exercise training facilitates the release of iWAT-derived molecules, fostering inter-tissue communication. We define the unique exercise training- and cold exposure-induced iWAT proteomes, revealing distinct mechanisms for the beneficial effects of these interventions on metabolic health. Disclosure M. Vamvini: None. P. Nigro: None. K.I. Stanford: None. M.F. Hirshman: None. R.J. Middelbeek: Research Support; Novo Nordisk. L. Goodyear: None. Funding This work was supported by NIH grant (R01DK099511, R01DK101043 (to L.J.G.)), (T32DK00726042, F32DK12643201) and Joslin DRC (P30 DK36836) Pilot and Feasibility Program award (to M.V.), K23DK114550 (to R.J.W.M), and the Joslin Diabetes Center DRC (P30 DK36836).