Deficiency of the basic helix-loop-helix transcription factor DEC1 prevents obesity induced by a high-fat diet in mice

作者：Noshiro Mitsuhide; Kawamoto Takeshi^*; Nakashima Ayumu; Ozaki Noritsugu; Ueno Yoshinori; Saeki Masayumi; Honda Kiyomasa; Fujimoto Katsumi; Kato Yukio

来源：Genes to Cells, 2018, 23(8): 658-669.

DOI：10.1111/gtc.12607

• circadian rhythms
• DEC1
• energy homeostasis
• lipid metabolism
• obesity
• PPAR
• PPRE
• RXR
• thermogenesis
• UCP1

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.

• 出版日期2018-8