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 and Laurie J.
Goodyear
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.