mTORC1 is Required for Brown Adipose Tissue Recruitment and Metabolic Adaptation to Cold.
mTORC1 is Required for Brown Adipose Tissue Recruitment and Metabolic Adaptation to Cold.
复制标题
DOI：
10.1038/srep37223
复制
发表时间：
2016-11-23
影响因子：
4.6
通讯作者：
Laplante M
中科院分区：
文献类型：
--
作者：
Labbé SM;Mouchiroud M;Caron A;Secco B;Freinkman E;Lamoureux G;Gélinas Y;Lecomte R;Bossé Y;Chimin P;Festuccia WT;Richard D;Laplante M
作为对寒冷的反应，棕色脂肪组织(BAT)增加其代谢率并扩大其质量以产生生存所需的热量，这一过程被称为BAT招募。雷帕霉素复合体1(MTORC1)的作用靶点控制着新陈代谢、细胞生长和增殖，但它在调节蝙蝠对慢性冷刺激反应中的招募作用尚不清楚。在这里，我们展示了寒冷会激活蝙蝠体内的mTORC1，这一效应依赖于交感神经系统。小鼠脂肪细胞特异性mTORC1的丢失完全阻止了寒冷诱导的BAT扩张，并严重损害了线粒体的生物发生。因此，mTORC1的丢失减少了氧气消耗，并在冷暴露时导致蝙蝠氧化代谢的严重缺陷。利用体内代谢成像、代谢组学和转录组学，我们发现mTORC1缺失会损害葡萄糖和脂肪的氧化，这种影响与三羧酸(TCA)循环活性的缺陷有关。这些分析还显示，在缺乏mTORC1的情况下，核苷酸合成存在严重缺陷。总体而言，这些发现证明了mTORC1在调节蝙蝠对寒冷的反应中的招募和新陈代谢方面发挥了重要作用。
In response to cold, brown adipose tissue (BAT) increases its metabolic rate and expands its mass to produce heat required for survival, a process known as BAT recruitment. The mechanistic target of rapamycin complex 1 (mTORC1) controls metabolism, cell growth and proliferation, but its role in regulating BAT recruitment in response to chronic cold stimulation is unknown. Here, we show that cold activates mTORC1 in BAT, an effect that depends on the sympathetic nervous system. Adipocyte-specific mTORC1 loss in mice completely blocks cold-induced BAT expansion and severely impairs mitochondrial biogenesis. Accordingly, mTORC1 loss reduces oxygen consumption and causes a severe defect in BAT oxidative metabolism upon cold exposure. Using in vivo metabolic imaging, metabolomics and transcriptomics, we show that mTORC1 deletion impairs glucose and lipid oxidation, an effect linked to a defect in tricarboxylic acid (TCA) cycle activity. These analyses also reveal a severe defect in nucleotide synthesis in the absence of mTORC1. Overall, these findings demonstrate an essential role for mTORC1 in the regulation of BAT recruitment and metabolism in response to cold.
登录
查看更多内容
影响因子：
7.4
作者：
Bird, Susan S.;Marur, Vasant R.;Sniatynski, Matthew J.;Greenberg, Heather K.;Kristal, Bruce S.
通讯作者：
Kristal, Bruce S.
影响因子：
16.6
作者：
Berbée JF;Boon MR;Khedoe PP;Bartelt A;Schlein C;Worthmann A;Kooijman S;Hoeke G;Mol IM;John C;Jung C;Vazirpanah N;Brouwers LP;Gordts PL;Esko JD;Hiemstra PS;Havekes LM;Scheja L;Heeren J;Rensen PC
通讯作者：
Rensen PC
影响因子：
2.1
作者：
FOSTER, DO;DEPOCAS, F;FRYDMAN, ML
通讯作者：
FRYDMAN, ML
影响因子：
6.5
作者：
Festuccia, William T.;Blanchard, Pierre-Gilles;Deshaies, Yves
通讯作者：
Deshaies, Yves
影响因子：
11.1
作者：
Albert V;Svensson K;Shimobayashi M;Colombi M;Muñoz S;Jimenez V;Handschin C;Bosch F;Hall MN
通讯作者：
Hall MN