2. Academic Validation
  3. An isocaloric moderately high-fat diet extends lifespan in male rats and Drosophila

An isocaloric moderately high-fat diet extends lifespan in male rats and Drosophila

  • Cell Metab. 2021 Mar 2;33(3):581-597.e9. doi: 10.1016/j.cmet.2020.12.017.
Dan Shi 1,  TianShu Han 1,  Xia Chu 1,  Huimin Lu 1,  Xue Yang 1,  TianQi Zi 1,  YanHe Zhao 1,  XinYue Wang 1,  ZhiPeng Liu 1,  JingQi Ruan 1,  Xin Liu 1,  Hua Ning 1,  MaoQing Wang 1,  Zhen Tian 1,  Wei Wei 1,  Yue Sun 1,  YinLing Li 1,  Rui Guo 1,  Yu Wang 1,  Fan Ling 1,  Yue Guan 1,  Da Shen 2,  YuCun Niu 3,  Ying Li 4,  ChangHao Sun 5
Affiliations

Affiliations

  • 1 National Key Discipline Laboratory, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, P.R. China.
  • 2 Gene Regulatory Laboratory, School of Medicine, Tsinghua University, Beijing 100084, China.
  • 3 National Key Discipline Laboratory, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, P.R. China. Electronic address: niuyucun@163.com.
  • 4 National Key Discipline Laboratory, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, P.R. China. Electronic address: liying_helen@163.com.
  • 5 National Key Discipline Laboratory, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, P.R. China. Electronic address: changhaosun2002@163.com.
PMID: 33440166 DOI: 10.1016/j.cmet.2020.12.017
Abstract

The health effect of dietary fat has been one of the most vexing issues in the field of nutrition. Few animal studies have examined the impact of high-fat diets on lifespan by controlling energy intake. In this study, we found that compared to a normal diet, an isocaloric moderately high-fat diet (IHF) significantly prolonged lifespan by decreasing the profiles of free fatty acids (FFAs) in serum and multiple tissues via downregulating FFA anabolism and upregulating catabolism pathways in rats and flies. Proteomics analysis in rats identified PPRC1 as a key protein that was significantly upregulated by nearly 2-fold by IHF, and among the FFAs, only palmitic acid (PA) was robustly and negatively associated with the expression of PPRC1. Using PPRC1 transgenic RNAi/overexpression flies and in vitro experiments, we demonstrated that IHF significantly reduced PA, which could upregulate PPRC1 through PPARG, resulting in improvements in oxidative stress and inflammation and prolonging the lifespan.

Keywords

PPRC1; isocaloric moderately high-fat diet; lifespan; palmitic acid.

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