Role of brown adipose tissue (BAT) in energy balance

虽然BAT在维持体温方面的作用是明确的，但BAT对体重调节的作用还不清楚。 Rothwell和Stock（Nature，1979）表明，高脂肪饮食过度喂养啮齿动物会刺激BAT，这表明BAT在限制体重增加方面的作用。 然而，BAT具有这一功能的观点远未被普遍接受。 二零一四财政年度的进展包括以下各项： 我们发表了间歇性冷暴露（4 ℃，每周三次，每次1至8小时）对喂食高脂肪饮食的C57 BL/6 J小鼠的影响。冷暴露增加代谢率约两倍，在挑战和激活棕色脂肪。作为回应，食物摄入量增加，以完全补偿增加的能量消耗;因此，小鼠体重或肥胖没有减少。尽管肥胖没有改变，但冷处理的小鼠在葡萄糖稳态方面表现出短暂的改善。大麻素受体-1反向激动剂AM 251的施用引起体重减轻和葡萄糖稳态的改善，但当与冷暴露结合时没有显示出进一步的改善。这些数据表明，间歇性冷暴露导致葡萄糖稳态的短暂的、有意义的改善，但当与AM 251组合时没有协同作用。由于在冷暴露期间能量消耗显著增加，因此在冷暴露期间将食物摄入与代谢需求分离的药物可以实现体重减轻和进一步的代谢改善。

While the role of BAT in maintaining body temperature is unambiguous, BATs contribution to body weight regulation is not well understood. Rothwell and Stock (Nature, 1979) showed that overfeeding rodents a high fat diet stimulated BAT, suggesting a role for BAT in limiting weight gain. However, the idea that BAT has this function is far from universally accepted. Progress in FY2014 includes the following: We published the effects of intermittent cold exposure (4 C for one to eight hours three times a week) on C57BL/6J mice fed a high fat diet. Cold exposure increased metabolic rate approximately twofold during the challenge and activated brown fat. In response, food intake increased to compensate fully for the increased energy expenditure; thus, the mice showed no reduction in body weight or adiposity. Despite the unchanged adiposity, the cold-treated mice showed transient improvements in glucose homeostasis. Administration of the cannabinoid receptor-1 inverse agonist AM251 caused weight loss and improvements in glucose homeostasis, but showed no further improvements when combined with cold exposure. These data suggest that intermittent cold exposure causes transient, meaningful improvements in glucose homeostasis, but without synergy when combined with AM251. Since energy expenditure is significantly increased during cold exposure, a drug that dissociates food intake from metabolic demand during cold exposure may achieve weight loss and further metabolic improvements.