Noshiro Mitsuhide, Kawamoto Takeshi, Nakashima Ayumu, Ozaki Noritsugu, Ueno Toshinori, Saeki Masayumi, Honda Kiyomasa, Fujimoto Katsumi, Kato Yukio
Department of Dental and Medical Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Writing Center, Hiroshima University, Higashi-Hiroshima, Japan.
Genes Cells. 2018 Jul 3. doi: 10.1111/gtc.12607.
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 γ and retinoid X receptor α (RXRα) through direct binding to RXRα. 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.
肥胖是发达国家的一个主要公共卫生问题，其起因是食物摄入量增加和能量消耗减少，通常与脂质代谢异常有关。在此，我们表明DEC1（一种碱性螺旋-环-螺旋转录因子）在小鼠棕色脂肪组织（BAT，产热的主要部位）的脂质消耗调节中起重要作用。纯合子Dec1缺失减轻了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，DEC1缺乏在白天提高了体温，并增强了解偶联蛋白1（产热的关键因子）以及肩胛间BAT中各种脂解相关基因的表达。体外实验表明，DEC1通过直接结合视黄醇X受体α（RXRα）抑制由过氧化物酶体增殖物激活受体γ和视黄醇X受体α（RXRα）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，DEC1缺乏导致的BAT中脂解增强会导致脂质消耗增加，从而减少脂肪组织和肝脏中的脂质积累。因此，DEC1可能作为一种抑制脂质消耗的节能因子，这可能与肥胖管理相关。
