Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis.
Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis.
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DOI：
10.1038/nchembio.1961
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发表时间：
2016-01
影响因子：
14.8
通讯作者：
Metallo CM
中科院分区：
文献类型：
--
作者：
Green CR;Wallace M;Divakaruni AS;Phillips SA;Murphy AN;Ciaraldi TP;Metallo CM
脂肪组织在调节碳水化合物和脂质稳态中发挥重要作用，但对脂肪细胞中氨基酸代谢的调节知之甚少。在这里，我们应用同位素示踪对前脂肪细胞和分化脂肪细胞进行了量化，以确定不同底物对三羧酸代谢和脂肪生成的贡献。与使用葡萄糖和谷氨酰胺生成乙酰辅酶A （AcCoA）的增殖细胞相反，分化的脂肪细胞增加了支链氨基酸（BCAA）分解代谢通量，因此来自培养基和/或蛋白质分解代谢的亮氨酸和异亮氨酸占脂肪源性AcCoA库的30%。中度钴胺素缺乏引起甲基丙二酸积累和奇链脂肪酸合成。补充B12减少了这些代谢物，并改变了进入线粒体的底物的平衡。最后，抑制BCAA分解代谢会损害脂肪生成。这些结果定量地强调了BCAA对脂肪细胞代谢的贡献，并提示BCAA分解代谢在脂肪细胞分化中起功能作用。
Adipose tissue plays important roles in regulating carbohydrate and lipid homeostasis, though less is known about the regulation of amino acid metabolism in adipocytes. Here we applied isotope tracing to pre–adipocytes and differentiated adipocytes to quantify the contributions of different substrates to tricarboxylic acid metabolism and lipogenesis. In contrast to proliferating cells that use glucose and glutamine for acetyl–coenzyme A (AcCoA) generation, differentiated adipocytes increased branched chain amino acid (BCAA) catabolic flux such that leucine and isoleucine from media and/or protein catabolism accounted for as much as 30% of lipogenic AcCoA pools. Medium cobalamin deficiency caused methylmalonic acid accumulation and odd–chain fatty acid synthesis. B12 supplementation reduced these metabolites and altered the balance of substrates entering mitochondria. Finally, inhibition of BCAA catabolism compromised adipogenesis. These results quantitatively highlight the contribution of BCAAs to adipocyte metabolism and suggest that BCAA catabolism plays a functional role in adipocyte differentiation.