Presentation/Session Information

Session Information

Session Title: Physiology: Aging and Stress I Session Type: Parallel
Session Location: Grand Horizon Ballroom Session Time: Thu, Jun 25 8:30AM - 11:30AM

Presentation Information

Program Number: 27 Presentation Time: 9:30AM - 9:42AM

Presentation Content

SBP-1 and MDT-15 moderate the life-shortening effect of glucose by promoting fat conversion.Dongyeop Lee 1, Dae-Eun Joeng 1, Heehwa G. Son 1, Yasuyo Yamaoka 4, Hyunmin Kim 5, Keunhee Seo 1, Abdul Aziz Khan 4, Tae-Young Roh 1,4, Dae Won Moon 5, Youngsook Lee 1,4, Seung-Jae V. Lee 1,2,3. 1)Department of Life sciences; 2)ITCE; 3)I-BIO; 4)IBB, Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea; 5)Department of New Biology, DGIST, Daegu, South Korea

Abnormal glucose metabolism is linked to many age-related diseases. Several studies including ours have shown that glucose-enriched diets shorten the lifespan of C. elegans (1, 2, 3). Here, we sought to identify genes that mediate the effects of dietary glucose on lifespan. We performed a genome-wide RNAi screen using a glucose-responsive GFP transgenic C. elegans. The level of GFP expression was reproducibly increased by 170 RNAi clones and decreased by 43 RNAi clones. We then examined the effects of these RNAi clones on lifespan upon glucose-rich diet feeding. Knock down of mdt-15/mediator 15 significantly enhanced the life-shortening effect of glucose-rich diets. MDT-15 regulates lipid metabolism and stress resistance by acting as a co-regulator of transcription factors, SBP-1 (4), NHR-49 (5), and SKN-1 (6, 7). We showed that genetic inhibition of sbp-1 enhanced the toxic effects of glucose on lifespan but knockdown of nhr-49 or skn-1 did not. Conversely, gain-of-function mutation of mdt-15 or overexpression of sbp-1 restored normal lifespan in glucose-fed conditions. These data suggest that MDT-15 and SBP-1 protect worms from the glucose toxicity. Next, we performed mRNA sequencing to identify functionally important downstream effectors of MDT-15 and SBP-1. Glucose-rich diet feeding induced several fatty acid desaturases in an mdt-15- and sbp-1-dependent manner. Fatty acid desaturases are enzymes that convert saturated fatty acids (SFAs) to unsaturated fatty acids (UFAs). By using GC/MS analysis, we found that SFAs were accumulated in glucose-fed mdt-15(RNAi) and sbp-1(RNAi) animals. We showed that glucose-induced shortened lifespan was further decreased by SFA feeding, while being suppressed by overexpression of fatty acid desaturases. Thus, MDT-15 and SBP-1 appear to moderate the lifespan-shortening effects of glucose by promoting fat conversion through regulating fatty acid desaturases. Our study will lead to better understanding of the relationship between glucose and lipid metabolism in lifespan regulation at the organismal level. (1) Schulz et al., 2007 (2) Schlotterer et al., 2009 (3) Lee et al., 2009 (4) Yang et al., 2006 (5) Taubert et al., 2006 (6) Goh et al., 2014 (7) Pang et al., 2014.




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