SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat

Dongyeop Lee; Dae-Eun Jeong; Heehwa G Son; Yasuyo Yamaoka; Hyunmin Kim; Keunhee Seo; Abdul Aziz Khan; Tae-Young Roh; Dae Won Moon; Youngsook Lee; Seung-Jae V Lee

doi:10.1101/gad.266304.115

SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat

Genes Dev. 2015 Dec 1;29(23):2490-503. doi: 10.1101/gad.266304.115.

Authors

Affiliations

¹ Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea;
² Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, South Korea;
³ Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea;
⁴ Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea;
⁵ Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea; Information Technology Convergence Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea; School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.

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: C. elegans; MDT-15; SREBP; aging; fat; glucose.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging / drug effects
Aging / genetics*
Aging / metabolism
Animals
Caenorhabditis elegans / drug effects
Caenorhabditis elegans / enzymology
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Diet
Dietary Sucrose / pharmacology
Enzyme Induction / drug effects
Fatty Acid Desaturases / genetics
Fatty Acids / metabolism*
Gene Expression Regulation, Developmental / drug effects
Genome-Wide Association Study
Glucose / metabolism
Glucose / pharmacology
Glucose / toxicity
RNA Interference
Sterol Regulatory Element Binding Proteins / genetics
Sterol Regulatory Element Binding Proteins / metabolism*
Transcription Factors / genetics
Transcription Factors / metabolism*

Substances

Caenorhabditis elegans Proteins
Dietary Sucrose
Fatty Acids
MDT-15 protein, C elegans
Sterol Regulatory Element Binding Proteins
Transcription Factors
Fatty Acid Desaturases
Glucose