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SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat
- SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat
- Lee, D[Lee, Dongyeop]; Jeong, DE[Jeong, Dae-Eun]; Son, HG[Son, Heehwa G.]; Yamaoka, Y[Yamaoka, Yasuyo]; Kim, H[Kim, Hyunmin]; Seo, K[Seo, Keunhee]; Khan, AA[Khan, Abdul Aziz]; Roh, TY[Roh, Tae-Young]; Moon, DW[Moon, Dae Won]; Lee, Y[Lee, Youngsook]; Lee, SJV[Lee, Seung-Jae V.]
- DGIST Authors
- Kim, H[Kim, Hyunmin]; Moon, DW[Moon, Dae Won]
- Issue Date
- Genes and Development, 29(23), 2490-2503
- Article Type
- Aging; C. Elegans; Caenorhabditis Elegans; Controlled Study; Endocytosis; Fat; Genetic Screening; Glucose; Glucose Intake; Glucotoxicity; Glycolysis; Lifespan; MDT-15; Metabolite; Non-Human; Priority Journal; Saturated Fatty Acid; SREBP; Sterol Regulatory Element Binding Protein; Transcription Factor; Transcription Factor MDT15; Unclassified Drug; Unsaturated Fatty Acid; Upregulation
- 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. © 2015 Lee et al.
- Cold Spring Harbor Laboratory Press
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