Dongyeop Lee1,6, Dae-Eun Jeong1,6, Heehwa G. Son1, Yasuyo Yamaoka1, Hyunmin Kim2, Keunhee Seo1, Abdul Aziz Khan3, Tae-Young Roh1,3, Dae Won Moon2, Youngsook Lee1,3 and Seung-Jae V. Lee1,4,5
1Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea;
2Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, South Korea;
3Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea;
4Information Technology Convergence Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea;
5School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea
6 These authors contributed equally to this work.
Corresponding author : Seung-Jae V. Lee
Abstract
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.
Keywords : aging, glucose, fat, SREBP, MDT-15, C. elegans