RRC ID 53435
Author Lee D, Jeong DE, Son HG, Yamaoka Y, Kim H, Seo K, Khan AA, Roh TY, Moon DW, Lee Y, Lee SJ.
Title SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat.
Journal Genes Dev
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.
Volume 29(23)
Pages 2490-503
Published 2015-12-1
DOI 10.1101/gad.266304.115
PII 29/23/2490
PMID 26637528
PMC PMC4691952
MeSH 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*
IF 9.527
Times Cited 46
C.elegans tm2182 tm3410 tm5782 tm420