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.

膳食脂肪对健康的影响一直是营养领域最令人头疼的问题之一。很少有动物研究通过控制能量摄入来检查高脂肪饮食对寿命的影响。在这项研究中，我们发现与正常饮食相比，等热量中高脂饮食 (IHF) 通过下调 FFA 合成代谢和上调分解代谢途径来降低血清和多个组织中游离脂肪酸 (FFA) 的分布，从而显着延长寿命在老鼠和苍蝇中。大鼠蛋白质组学分析确定 PPRC1 是一种关键蛋白，IHF 显着上调近 2 倍，在 FFA 中，只有棕榈酸 (PA) 与 PPRC1 的表达呈强负相关。使用 PPRC1 转基因 RNAi/过表达苍蝇和体外实验表明，IHF 显着降低 PA，可通过 PPARG 上调 PPRC1，从而改善氧化应激和炎症并延长寿命。