TY - JOUR
T1 - Brown adipose tissue regulates glucose homeostasis and insulin sensitivity
AU - Stanford, Kristin I.
AU - Middelbeek, Roeland J.W.
AU - Townsend, Kristy L.
AU - An, Ding
AU - Nygaard, Eva B.
AU - Hitchcox, Kristen M.
AU - Markan, Kathleen R.
AU - Nakano, Kazuhiro
AU - Hirshman, Michael F.
AU - Tseng, Yu Hua
AU - Goodyear, Laurie J.
PY - 2013/1/2
Y1 - 2013/1/2
N2 - Brown adipose tissue (BAT) is known to function in the dissipation of chemical energy in response to cold or excess feeding, and also has the capacity to modulate energy balance. To test the hypothesis that BAT is fundamental to the regulation of glucose homeostasis, we transplanted BAT from male donor mice into the visceral cavity of age- and sex-matched recipient mice. By 8-12 weeks following transplantation, recipient mice had improved glucose tolerance, increased insulin sensitivity, lower body weight, decreased fat mass, and a complete reversal of high-fat diet-induced insulin resistance. Increasing the quantity of BAT transplanted into recipient mice further improved the metabolic effects of transplantation. BAT transplantation increased insulin-stimulated glucose uptake in vivo into endogenous BAT, white adipose tissue (WAT), and heart muscle but, surprisingly, not skeletal muscle. The improved metabolic profile was lost when the BAT used for transplantation was obtained from Il6-knockout mice, demonstrating that BAT-derived IL-6 is required for the profound effects of BAT transplantation on glucose homeostasis and insulin sensitivity. These findings reveal a previously under-appreciated role for BAT in glucose metabolism.
AB - Brown adipose tissue (BAT) is known to function in the dissipation of chemical energy in response to cold or excess feeding, and also has the capacity to modulate energy balance. To test the hypothesis that BAT is fundamental to the regulation of glucose homeostasis, we transplanted BAT from male donor mice into the visceral cavity of age- and sex-matched recipient mice. By 8-12 weeks following transplantation, recipient mice had improved glucose tolerance, increased insulin sensitivity, lower body weight, decreased fat mass, and a complete reversal of high-fat diet-induced insulin resistance. Increasing the quantity of BAT transplanted into recipient mice further improved the metabolic effects of transplantation. BAT transplantation increased insulin-stimulated glucose uptake in vivo into endogenous BAT, white adipose tissue (WAT), and heart muscle but, surprisingly, not skeletal muscle. The improved metabolic profile was lost when the BAT used for transplantation was obtained from Il6-knockout mice, demonstrating that BAT-derived IL-6 is required for the profound effects of BAT transplantation on glucose homeostasis and insulin sensitivity. These findings reveal a previously under-appreciated role for BAT in glucose metabolism.
UR - http://www.scopus.com/inward/record.url?scp=84873854027&partnerID=8YFLogxK
U2 - 10.1172/JCI62308
DO - 10.1172/JCI62308
M3 - Article
C2 - 23221344
AN - SCOPUS:84873854027
SN - 0021-9738
VL - 123
SP - 215
EP - 223
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 1
ER -