TY - JOUR
T1 - A novel role for subcutaneous adipose tissue in exercise-induced improvements in glucose homeostasis
AU - Stanford, Kristin I.
AU - Middelbeek, Roeland J.W.
AU - Townsend, Kristy L.
AU - Lee, Min Young
AU - Takahashi, Hirokazu
AU - So, Kawai
AU - Hitchcox, Kristen M.
AU - Markan, Kathleen R.
AU - Hellbach, Katharina
AU - Hirshman, Michael F.
AU - Tseng, Yu Hua
AU - Goodyear, Laurie J.
N1 - Funding Information:
Acknowledgments. The authors thank Dr. Mary-Elizabeth Patti and Katelyn Hughes (Joslin Diabetes Center) for helpful discussion and Maura Mulvey, Allen Clermont, Alevtina Pinkhasov, Zhen Fu, and Geetha Sankaranarayan (Joslin Diabetes Research Center Physiology, Advanced Microscopy, and Complex Assay Cores) for technical assistance. Funding. This work was supported by National Institutes of Health grants T32-DK-07260 (to K.I.S., K.L.T., and K.R.M.), F32-DK-091996 (to K.L.T.), F32-DK-091048 (to K.I.S.), R01-DK-077097 (to Y.-H.T.), R01-DK-099511 and R21-DK-091764 (to L.J.G.), and 5P30-DK-36836 (to Diabetes Research and Endocrinology Research Center, Joslin Diabetes Center). K.I.S. was also supported by the Mary K. Iacocca Fellowship. R.J.W.M. and M.-Y.L. were supported by a mentor-based fellowship (7-08-MN-18) awarded to L.J.G. from the American Diabetes Association. Complete microarray data were submitted to the National Institutes of Health database concurrently with acceptance of the manuscript as per requirements. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. K.I.S. designed the research, performed the experiments, analyzed the data, and wrote the paper. R.J.W.M., M.-Y.L., H.T., K.S., K.M.H., K.R.M., and K.H. performed the experiments. K.L.T. and M.F.H. performed the experiments and analyzed the data. Y.-H.T. analyzed the data. L.J.G. designed the research, analyzed the data, and wrote the paper. L.J.G. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Publisher Copyright:
© 2015 by the American Diabetes Association.
PY - 2015/6
Y1 - 2015/6
N2 - 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 posttransplantation, mice receiving scWAT from exercisetrained 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 exercisetrained 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.
AB - 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 posttransplantation, mice receiving scWAT from exercisetrained 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 exercisetrained 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.
UR - http://www.scopus.com/inward/record.url?scp=84940707952&partnerID=8YFLogxK
U2 - 10.2337/db14-0704
DO - 10.2337/db14-0704
M3 - Article
C2 - 25605808
AN - SCOPUS:84940707952
SN - 0012-1797
VL - 64
SP - 2002
EP - 2014
JO - Diabetes
JF - Diabetes
IS - 6
ER -