期刊
GENES & DEVELOPMENT
卷 29, 期 23, 页码 2490-2503出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.266304.115
关键词
aging; glucose; fat; SREBP; MDT-15; C. elegans
资金
- National Research Foundation of Korea (NRF) grant - Korean government (Ministry of Science, ICT, and Future Planning) [NRF-2012R1A4A1028200, NRF-2013R1A1A2014754]
- Korean Health Technology R&D Project, Ministry of Health and Welfare [HI14C2337]
- Fostering Core Leaders of the Future Basic Science Program [NRF-2013H1A8A1003751]
- Global Frontier Project of the Advanced Biomass R&D Center - Korean government [ABC-2015M3A6A2065746]
- DGIST R&D Program - Korean government [15-BD-06]
Glucose-rich diets shorten the life spans of various organisms. However, the metabolic processes involved in this phenomenon remain unknown. Here, we show that sterol regulatory element-binding protein (SREBP) and mediator-15 (MDT-15) prevent the life-shortening effects of a glucose-rich diet by regulating fat-converting processes in Caenorhabditis elegans. Up-regulation of the SREBP/MDT-15 transcription factor complex was necessary and sufficient for alleviating the life-shortening effect of a glucose-rich diet. Glucose feeding induced key enzymes that convert saturated fatty acids (SFAs) to unsaturated fatty acids (UFAs), which are regulated by SREBP and MDT-15. Furthermore, SREBP/MDT-15 reduced the levels of SFAs and moderated glucose toxicity on life span. Our study may help to develop strategies against elevated blood glucose and free fatty acids, which cause glucolipotoxicity in diabetic patients.
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