Deficiency of the basic helix-loop-helix transcription factor DEC1 prevents obesity induced by a high-fat diet in mice
Deficiency of the basic helix-loop-helix transcription factor DEC1 prevents obesity induced by a high-fat diet in mice
复制标题
DOI：
10.1111/gtc.12607
复制
发表时间：
2018-08-01
期刊：
影响因子：
2.1
通讯作者：
Kato, Yukio
中科院分区：
文献类型：
--
作者：
Noshiro, Mitsuhide;Kawamoto, Takeshi;Kato, Yukio
肥胖症是发达国家的一个主要公共卫生问题，其原因是食物摄入量增加和能量消耗减少，并且通常与脂质代谢异常有关。在这里，我们表明，DEC 1，一个基本的螺旋-环-螺旋转录因子，在调节小鼠棕色脂肪组织（BAT），这是产热的主要网站的脂质消耗中起着重要的作用。纯合子Dec 1缺失减弱高脂饮食诱导的肥胖、脂肪细胞肥大、脂肪体积和肝脂肪变性。此外，DEC 1缺乏增加体温在白天和增强解偶联蛋白1的表达，产热的关键因素，和各种脂肪分解相关基因在肩胛间BAT。体外实验表明，DEC 1通过直接结合RXR α抑制过氧化物酶体增殖物激活受体γ和类维生素A X受体α（RXR α）的异二聚体诱导的各种脂解相关基因的表达。这些观察结果表明，由DEC 1缺乏引起的BAT中的脂解增强导致脂质消耗增加，从而减少脂肪组织和肝脏中的脂质积累。因此，DEC 1可以作为抑制脂质消耗的节能因子，这可能与控制肥胖有关。
Obesity is a major public health problem in developed countries resulting from increased food intake and decreased energy consumption and usually associated with abnormal lipid metabolism. Here, we show that DEC1, a basic helix-loop-helix transcription factor, plays an important role in the regulation of lipid consumption in mouse brown adipose tissue (BAT), which is the major site of thermogenesis. Homozygous Dec1 deletion attenuated high-fat-diet-induced obesity, adipocyte hypertrophy, fat volume and hepatic steatosis. Furthermore, DEC1 deficiency increased body temperature during daytime and enhanced the expression of uncoupler protein 1, a key factor of thermogenesis, and various lipolysis-related genes in interscapular BAT. In vitro experiments suggested that DEC1 suppresses the expression of various lipolysis-related genes induced by the heterodimer of peroxisome proliferator-activated receptor gamma and retinoid X receptor alpha (RXR alpha ) through direct binding to RXRa. These observations suggest that enhanced lipolysis in BAT caused by DEC1 deficiency leads to an increase in lipid consumption, thereby decreasing lipid accumulation in adipose tissues and the liver. Thus, DEC1 may serve as an energy-saving factor that suppresses lipid consumption, which may be relevant to managing obesity.