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Brown adipose tissue regulates glucose homeostasis and insulin sensitivity
Kristin I. Stanford, … , Yu-Hua Tseng, Laurie J. Goodyear
Kristin I. Stanford, … , Yu-Hua Tseng, Laurie J. Goodyear
Published December 10, 2012
Citation Information: J Clin Invest. 2013;123(1):215-223. https://doi.org/10.1172/JCI62308.
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Research Article Metabolism

Brown adipose tissue regulates glucose homeostasis and insulin sensitivity

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Abstract

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.

Authors

Kristin I. Stanford, Roeland J.W. Middelbeek, Kristy L. Townsend, Ding An, Eva B. Nygaard, Kristen M. Hitchcox, Kathleen R. Markan, Kazuhiro Nakano, Michael F. Hirshman, Yu-Hua Tseng, Laurie J. Goodyear

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Figure 4

BAT transplantation increases circulating IL-6 and FGF21 concentrations, and Il6–/– mice do not show beneficial effects of BAT transplantation.

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BAT transplantation increases circulating IL-6 and FGF21 concentrations,...
(A–E) Mice underwent sham operation or transplantation with 0.1 or 0.4 g BAT and were studied 12 weeks after transplantation. (A) Serum FGF21 and (B) FGF21 protein levels in endogenous BAT, (C) FGF21 protein levels in liver, (D) serum IL-6, (E) and Il6 measured by qPCR in endogenous BAT. Data are mean ± SEM. n = 6–17/group; *P < 0.05 compared with sham. **P < 0.01. ***P < 0.001. (F–H) Mice underwent sham operation or transplantation with 0.1 g BAT from Il6–/– or Il6+/+ mice. (F) GTT AUC, (G) serum leptin, and (H) body weight. Data are mean ± SEM. *P < 0.05 compared with sham and mice receiving 0.1 g Il6–/– BAT. n = 4–8/group.

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