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

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.

Automated summary

Moderately high-fat diet can significantly prolong the lifespan of rats and flies by regulating the synthesis and breakdown pathways of free fatty acids. The study found that by reducing palmitic acid levels, the moderately high-fat diet can upregulate PPRC1, leading to improvements in oxidative stress and inflammation, ultimately prolonging lifespan.