Biotin augments acetyl CoA carboxylase 2 gene expression in the hypothalamus, leading to the suppression of food intake in mice
Biotin augments acetyl CoA carboxylase 2 gene expression in the hypothalamus, leading to the suppression of food intake in mice
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DOI：
10.1016/j.bbrc.2016.04.152
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发表时间：
2016-07-29
影响因子：
3.1
通讯作者：
Shiozawa, Kota
中科院分区：
文献类型：
--
作者：
Sone, Hideyuki;Kamiyama, Shin;Shiozawa, Kota
众所周知，生物素通过增加胰岛β细胞的功能和改善外周胰岛素敏感性来预防糖尿病的发展。然而，它的抗肥胖作用如。厌食效应仍有待阐明。乙酰辅酶A羧化酶(ACC)是一种依赖生物素的酶，有两种亚型(ACC1和ACC2)，催化乙酰辅酶A合成丙二酰辅酶A。在下丘脑，ACC2增加丙二酰辅酶A的产生，丙二酰辅酶A是饱腹感的信号。在这项研究中，我们研究了生物素是否增加了下丘脑ACC2基因的表达，并抑制了过量生物素摄入的食物摄入量。生物素显著减少了食物的摄入量，但包括葡萄糖、胃促生长素和瘦素在内的食欲血浆调节因子没有受到影响。另一方面，生物素在下丘脑显著积聚，促进ACC2基因的表达，但不改变ACC1、丙二酰辅酶A脱羧酶(丙二酰辅酶A降解酶)和AMP激活的蛋白激酶α2(ACC抑制酶)的基因表达。这些发现有力地表明，生物素通过上调下丘脑ACC2基因的表达来加强对食欲的抑制。生物素的这种作用可能有助于通过生物素治疗预防糖尿病。(C)2016 Elsevier Inc.保留所有权利。
It is known that biotin prevents the development of diabetes by increasing the functions of pancreatic beta-cells and improving insulin sensitivity in the periphery. However, its anti-obesity effects such as. anorectic effects remain to be clarified. Acetyl CoA carboxylase (ACC), a biotin-dependent enzyme, has two isoforms (ACC1 and ACC2) and serves to catalyze the reaction of acetyl CoA to malonyl CoA. In the hypothalamus, ACC2 increases the production of malonyl CoA, which acts as a satiety signal. In this study, we investigated whether biotin increases the gene expression of ACC2 in the hypothalamus and suppresses food intake in mice administered excessive biotin. Food intake was significantly decreased by biotin, but plasma regulators of appetite, including glucose, ghrelin, and leptin, were not affected. On the other hand, biotin notably accumulated in the hypothalamus and enhanced ACC2 gene expression there, but it did not change the gene expression of ACC1, malonyl CoA decarboxylase (a malonyl CoA-degrading enzyme), and AMP-activated protein kinase alpha-2 (an ACC-inhibitory enzyme). These findings strongly suggest that biotin potentiates the suppression of appetite by upregulating ACC2 gene expression in the hypothalamus. This effect of biotin may contribute to the prevention of diabetes by biotin treatment. (C) 2016 Elsevier Inc. All rights reserved.