title: SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat.
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.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea;
authors.forename: Dongyeop
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea;
authors.forename: Dae-Eun
authors.initials: DE
authors.lastname: Jeong
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea;
authors.forename: Heehwa G
authors.initials: HG
authors.lastname: Son
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea;
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Yamaoka
authors.affiliation: Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, South Korea;
authors.forename: Hyunmin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea;
authors.forename: Keunhee
authors.initials: K
authors.lastname: Seo
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea;
authors.forename: Abdul Aziz
authors.initials: AA
authors.lastname: Khan
authors.affiliation: 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;
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Roh
authors.affiliation: Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, South Korea;
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Moon
authors.affiliation: 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;
authors.forename: Youngsook
authors.initials: Y
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Seung-Jae V
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000375:Aging / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004032:Diet; D019422:Dietary Sucrose / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D044943:Fatty Acid Desaturases / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055106:Genome-Wide Association Study; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D034622:RNA Interference; D051779:Sterol Regulatory Element Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D019422:Dietary Sucrose; D005227:Fatty Acids; C571065:MDT-15 protein, C elegans; D051779:Sterol Regulatory Element Binding Proteins; D014157:Transcription Factors; D044943:Fatty Acid Desaturases; D005947:Glucose
keywords: C. elegans; MDT-15; SREBP; aging; fat; glucose