Exercise training and cold exposure are very different physiological stimuli; yet both improve systemic metabolic health and have pronounced effects on the gene expression profile of subcutaneous white adipose tissue (scWAT). To test whether adaptations to scWAT mediate the beneficial effects of exercise training and cold exposure on glucose tolerance, we used a transplantation model. Donor mice were males and either sedentary, exercise trained (voluntary wheel running), or cold exposed (5°C) for 11 days. scWAT from donors was transplanted into sedentary recipients and mice were studied nine days later (n=3-5/group). Mice transplanted with scWAT from trained, but not cold-exposed mice, had improved glucose tolerance compared to mice transplanted with sedentary scWAT, suggesting unique adaptations to trained scWAT that confer beneficial effects on glucose homeostasis. To determine exercise-specific effects on scWAT, we performed quantitative proteomic profiling (QPP) of scWAT from another cohort of sedentary, trained and cold-exposed mice. Exercise training significantly increased 300 proteins and decreased 182 proteins, whereas cold increased 956 and decreased 2096. Interestingly, exercise uniquely upregulated 171 proteins. GO analysis revealed that a high percentage of these exercise-specific upregulated proteins were located in the extracellular exosome (36%) and extracellular region (22%). In contrast, the majority of the cold-specific upregulated proteins (64%) were located in mitochondrial-related structures. QPP of scWAT secretome using conditioned media revealed 14 unique exercise-induced upregulated proteins, localized exclusively to the extracellular exosome. Exercise training, but not cold, results in adaptions to scWAT that improve glucose tolerance. These results also reveal that there are dramatically different molecular signatures and pathways regulated by these two potent metabolic stimuli.
M. Vamvini: None. P. Nigro: None. K.I. Stanford: None. M.F. Hirshman: Stock/Shareholder; Self; Abbott Laboratories, AbbVie Inc., Amgen, Colgate-Palmolive, Eli Lilly and Company, Medtronic. R. Middelbeek: None. L.J. Goodyear: None.