A Novel Role for Subcutaneous Adipose Tissue in Exercise-Induced Improvements in Glucose Homeostasis

Abstract

Exercise training improves whole-body glucose homeostasis through effects largely attributed to adaptations in skeletal muscle; however, training also affects other tissues, including adipose tissue. To determine whether exercise-induced adaptations to adipose tissue contribute to training-induced improvements in glucose homeostasis, subcutaneous white adipose tissue (scWAT) from exercise-trained or sedentary donor mice was transplanted into the visceral cavity of sedentary recipients. Remarkably, 9 days post-transplantation, mice receiving scWAT from exercise-trained mice had improved glucose tolerance and enhanced insulin sensitivity compared with mice transplanted with scWAT from sedentary or sham-treated mice. Mice transplanted with scWAT from exercise-trained mice had increased insulin-stimulated glucose uptake in tibialis anterior and soleus muscles and brown adipose tissue, suggesting that the transplanted scWAT exerted endocrine effects. Furthermore, the deleterious effects of high-fat feeding on glucose tolerance and insulin sensitivity were completely reversed if high-fat–fed recipient mice were transplanted with scWAT from exercise-trained mice. In additional experiments, voluntary exercise training by wheel running for only 11 days resulted in profound changes in scWAT, including the increased expression of ∼1,550 genes involved in numerous cellular functions including metabolism. Exercise training causes adaptations to scWAT that elicit metabolic improvements in other tissues, demonstrating a previously unrecognized role for adipose tissue in the beneficial effects of exercise on systemic glucose homeostasis.

Exercise regulation of adipose tissue

“…26 Our work demonstrated that exercise training by voluntary running in a cage containing a wheel for only 11 d resulted in a marked upregulation of numerous beige adipocyte marker genes including Ucp1, Prdm16, Cidea, Elovl3, Pgc1a, Pparg, Cox8b, Dio2, otopetrin, and Tbx1. 21 The wheel cage-trained mice had dramatically increased UCP1 immunofluorescence and the presence of multilocular cells in the scWAT, all of which are consistent with the beiging of scWAT. 21 Thus, exercise training in rodents increases the presence of beige adipocytes in the subcutaneous adipose tissue depots.…”

“…21 The wheel cage-trained mice had dramatically increased UCP1 immunofluorescence and the presence of multilocular cells in the scWAT, all of which are consistent with the beiging of scWAT. 21 Thus, exercise training in rodents increases the presence of beige adipocytes in the subcutaneous adipose tissue depots.…”

“…19,20,[22][23][24] Importantly, many of these metabolic adaptations to adipose tissue can occur independently of significant weight loss 20 demonstrating that adipose tissue can be an important contributor to metabolic health, independent of changes in body weight. In addition, we have recently reported that transplantation of scWAT from exercise-trained mice into the visceral cavity of sedentary recipient mice results in improved glucose homeostasis in the recipient mice, 21 also demonstrating that training-induced changes in adipose tissue can have important metabolic effects on organism health.…”

“…[19][20][21][22][23][24] Exercise training-induced decreases in adipocyte size and lipid content, and increases in GLUT4 and PGC1a expression have been observed in both scWAT 20,23 and vWAT. 19,20,[22][23][24] Importantly, many of these metabolic adaptations to adipose tissue can occur independently of significant weight loss 20 demonstrating that adipose tissue can be an important contributor to metabolic health, independent of changes in body weight.…”

“…21,23,[25][26][27] In rodent studies, 3-4 weeks of exposure to an enriched environment, which included the presence of a running wheel, resulted in the emergence of beige cells in scWAT. [25][26][27] These beige cells were identified by an increase in multilocular adipocytes and an increase in Ucp1, Prdm16 and other markers of BAT or beiging.…”