Brown adipose tissue regulates glucose homeostasis and insulin sensitivity
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
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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Research Article Metabolism

Brown adipose tissue regulates glucose homeostasis and insulin sensitivity

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 2

BAT transplantation ameliorates high-fat diet–induced insulin resistance and has dose-dependent effects on glucose tolerance.

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BAT transplantation ameliorates high-fat diet–induced insulin resistance...
(A–C) Mice were fed a high-fat diet (HF) for 18 weeks, with BAT transplanted after 6 weeks. (A) Body weight, (B) GTT AUC, and (C) GTT curve at 12 weeks after transplantation. Data are mean ± SEM. n = 6/group; *P < 0.05. For comparison, chow-fed, sham-operated mice from a separate cohort of animals are indicated with a dashed line (n = 17). (D–F) Mice received transplants of 0.1 g BAT or 0.4 g BAT or were sham operated. (D) Body weight, (E) GTT AUC, and (F) GTT curve at 12 weeks after transplantation. Data are mean ± SEM. n = 13–14/group; *P < 0.05, **P < 0.01, #P < 0.001 compared with sham.