포도당 과량 섭취로 인한 예쁜 꼬마 선충의 수명 단축 효과를 막는 유전자 lpin-1의 규명

Abstract

Glucose is one of the most basic carbohydrates and essential energy source, which has close relationship with fat metabolism. Impaired glucose and fat metabolism are associated with many diseases, including diabetes, metabolic syndrome, and cardiovascular diseases. Furthermore, a high glucose diet shortens lifespan via altering fat metabolism in many organisms, including Caenorhabditis elegans. However, how glucose and fat metabolism regulate lifespan remains incompletely understood. In this study, we examined lifespan of enhancer RNAi clones from previous screen using glucose-responsive transgenic C. elegans (Lee et al., 2015). Here, we show that Lipin/LPIN-1, a phosphatidate phosphatase that contributes to glucose-to-TAG synthesis, prevents worms from the life-shortening effects of a glucose-rich diet in C. elegans. We found that genetic inhibition of lpin-1 increased the levels of fatty acid desatureases, fat-5 and fat-7 that elevate the level of unsaturated fatty acids (UFAs) compared to saturated fatty acids (SFAs). In addition, we identified lpin-1 as one of 7 enhancer RNAi clones from additional whole genome RNAi-screen using fat-5p::fat-5::gfp transgenic worms. To find mediator of the effects of LPIN-1 on regulating the life-shortening effects of a glucose-rich diet, we examined the lifespan of 7 enhancer RNAi clones on non-glucose and glucose-rich diets. These data suggest that cytb-5.1 may interact with LPIN-1 to prevent worms from the life-shortening effects of a glucose-rich diet.