Laboratory of Metabolic Control, Department of Health and Human Services, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland.
Ann N Y Acad Sci. 2013 Oct;1302(1):42-48. doi: 10.1111/nyas.12222. Epub 2013 Aug 2.
Brown adipose tissue (BAT) is classically activated by sympathetic nervous stimulation resulting from exposure to cold. Feeding a high-fat diet also induces development of brown fat, but is decreased by caloric restriction. Blood ketone bodies, which function as alternative energy substrates to glucose, are increased during caloric restriction. Here we discuss the unexpected observation that feeding an ester of ketone bodies to the mouse, which increases blood ketone body concentrations, results in an activation of brown fat. The mechanism of this activation of brown fat is similar to that occurring from cold exposure in that cyclic adenosine monophosphate (AMP) levels are increased as are levels of the transcription factor cyclic AMP-responsive element-binding protein, which is also increased by ketone ester feeding. Other effects of feeding ketone esters, in addition to their ability to induce brown fat, are discussed such as their ability to overcome certain aspects of insulin resistance and to ameliorate the accumulation of amyloid and phosphorylated tau protein in brain, and improve cognitive function, in a triple transgenic mouse model of Alzheimer's disease.
棕色脂肪组织（BAT）通常通过暴露于寒冷而受到交感神经刺激而被激活。高脂肪饮食也会诱导棕色脂肪的发育，但会被热量限制所减少。在热量限制期间，血液酮体作为葡萄糖的替代能量底物而增加。在这里，我们讨论了一个意外的观察结果，即给老鼠喂食酮体的酯，增加了血液酮体浓度，导致棕色脂肪的激活。这种棕色脂肪的激活机制类似于冷暴露时的情况，因为环腺苷酸（AMP）水平增加，转录因子环腺苷酸反应元件结合蛋白的水平也增加，而该蛋白也会因酮酯喂养而增加。除了诱导棕色脂肪的能力之外，酮酯的其他作用，如它们克服胰岛素抵抗某些方面的能力，以及减轻大脑中淀粉样蛋白和磷酸化 tau 蛋白的积累并改善认知功能，在阿尔茨海默病的三重转基因小鼠模型中也得到了讨论。
