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

Noshiro Mitsuhide

Kawamoto Takeshi

Nakashima Ayumu

Ozaki Noritsugu

Ueno Toshinori

Saeki Masayumi

Honda Kiyomasa

Fujimoto Katsumi

Kato Yukio

Genes to Cells

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.

circadian rhythms

DEC1

energy homeostasis

lipid metabolism

obesity

PPAR

PPRE

RXR

thermogenesis

UCP1

eng

Molecular Biology Society of Japan

Wiley

This is the peer reviewed version of the following article: Noshiro, M, Kawamoto, T, Nakashima, A, et al. Deficiency of the basic helix‐loop‐helix transcription factor DEC1 prevents obesity induced by a high‐fat diet in mice. Genes Cells. 2018; 23: 658– 669, which has been published in final form at https://doi.org/10.1111/gtc.12607. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

This is not the published version. Please cite only the published version. この論文は出版社版ではありません。引用の際には出版社版をご確認、ご利用ください。

[ISSN] 1356-9597

[ISSN] 1365-2443

[DOI] 10.1111/gtc.12607

[PMID] 29968353

[DOI] https://doi.org/10.1111/gtc.12607