Brown adipose tissue regulates glucose homeostasis and insulin sensitivity
Brown adipose tissue regulates glucose homeostasis and insulin sensitivity
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DOI：
10.1172/jci62308
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发表时间：
2013-01-01
影响因子：
15.9
通讯作者：
Goodyear, Laurie J.
中科院分区：
文献类型：
--
作者：
Stanford, Kristin I.;Middelbeek, Roeland J. W.;Goodyear, Laurie J.
众所周知，棕色脂肪组织 (BAT) 的功能是在寒冷或过量进食时消耗化学能，并且还具有调节能量平衡的能力。为了检验 BAT 对葡萄糖稳态调节至关重要的假设，我们将雄性供体小鼠的 BAT 移植到年龄和性别匹配的受体小鼠的内脏腔中。移植后 8-12 周，受体小鼠的葡萄糖耐量得到改善，胰岛素敏感性增加，体重减轻，脂肪量减少，并完全逆转高脂肪饮食诱导的胰岛素抵抗。增加移植到受体小鼠体内的BAT数量进一步改善了移植的代谢效果。 BAT 移植增加了体内胰岛素刺激的葡萄糖摄取，进入内源性 BAT、白色脂肪组织 (WAT) 和心肌，但令人惊讶的是，骨骼肌却没有增加。当用于移植的 BAT 从 Il6 敲除小鼠中获得时，改善的代谢特征消失，这表明 BAT 衍生的 IL-6 是 BAT 移植对葡萄糖稳态和胰岛素敏感性产生深远影响所必需的。这些发现揭示了 BAT 在葡萄糖代谢中的先前未被充分认识的作用。
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.