The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon.
The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon.
复制标题
DOI：
10.1016/j.cmet.2011.02.018
复制
发表时间：
2011-05-04
期刊：
影响因子：
29
通讯作者：
Bultman SJ
中科院分区：
文献类型：
--
作者：
Donohoe DR;Garge N;Zhang X;Sun W;O'Connell TM;Bunger MK;Bultman SJ
微生物组正通过大规模测序工作进行特征分析，但尚不清楚它是以一种普遍的还是组织特异性的方式调节宿主代谢，也不清楚哪些细菌代谢物是重要的。在此，我们证明与其他组织相比，微生物群对结肠中的能量稳态有强烈影响。这种组织特异性是由于结肠细胞利用细菌产生的丁酸盐作为其主要能量来源。无菌小鼠的结肠细胞处于能量匮乏状态，并且参与中间代谢关键步骤（包括三羧酸循环）的酶的表达降低。因此，NADH/NAD⁺、氧化磷酸化和ATP水平显著下降，这导致AMPK激活、p27kip1磷酸化和自噬。当向无菌结肠细胞中添加丁酸盐时，它可挽救其线粒体呼吸的缺陷，并防止它们发生自噬。其机制是由于丁酸盐作为一种能量来源而非HDAC抑制剂起作用。
The microbiome is being characterized by large-scale sequencing efforts, yet it is not known whether it regulates host metabolism in a general versus tissue-specific manner or which bacterial metabolites are important. Here, we demonstrate that microbiota have a strong effect on energy homeostasis in the colon compared to other tissues. This tissue specificity is due to colonocytes utilizing bacterially-produced butyrate as their primary energy source. Colonocytes from germfree mice are in an energy-deprived state and exhibit decreased expression of enzymes that catalyze key steps in intermediary metabolism including the TCA cycle. Consequently, there is a marked decrease in NADH/NAD+, oxidative phosphorylation, and ATP levels, which results in AMPK activation, p27kip1 phosphorylation, and autophagy. When butyrate is added to germfree colonocytes, it rescues their deficit in mitochondrial respiration and prevents them from undergoing autophagy. The mechanism is due to butyrate acting as an energy source rather than as an HDAC inhibitor.
登录
查看更多内容
影响因子：
11.1
作者：
He C;Klionsky DJ
通讯作者：
Klionsky DJ
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
2.8
作者：
Diez-Gonzalez, F;Bond, DR;Russell, JB
通讯作者：
Russell, JB
影响因子：
29.4
作者：
Camp JG;Kanther M;Semova I;Rawls JF
通讯作者：
Rawls JF
影响因子：
4.2
作者：
Hinnebusch, BF;Meng, SF;Hodin, RA
通讯作者：
Hodin, RA