Palm oil-rich diet affects murine liver proteome and S-palmitoylome

Palmitic acid (C16:0) is the most abundant saturated fatty acid in animals serving as a substrate in lipid synthesis and β-oxidation, and in the modification of proteins called palmitoylation. The influence of dietary palmitic acid on protein palmitoylation in the context of metabolic processes remains largely unknown. In this study we performed high-throughput proteomic analyses of the liver membrane fraction in the mouse to examine the influence of a palm oil-rich diet on the level and S-palmitoylation of proteins. For this purpose, mice were fed for 4 or 12 weeks a diet containing 19.1% of palm oil in addition to 4% soybean oil (45% kcal from fat) while 4% soybean oil (10% kcal from fat) was the only fat source in the control diet. Liver functioning and pro-inflammatory responses of the liver and peritoneal macrophages as well as the input of protein S-palmitoylation to these aspects were assessed in parallel. We found that the diet rich in palm oil induced transient accumulation of C16:0 and C18:1 fatty acids in murine liver leading to changes of the level and S-palmitoylation of numerous proteins involved in liver metabolism and selected innate immune responses. The relatively mild negative impact of such diet on liver functioning can be attributed to a lower bioavailability of palm oil-derived C16:0 vs. that of C18:1 and the efficiency of mechanisms preventing liver injury, including dynamic protein S-palmitoylation.

棕榈酸（Palmitic acid, C16:0）是动物体内含量最为丰富的饱和脂肪酸，既可作为脂质合成与β-氧化的底物，也参与蛋白质的棕榈酰化修饰。目前学界对代谢过程中膳食棕榈酸对蛋白质棕榈酰化的影响仍知之甚少。本研究通过对小鼠肝脏膜组分开展高通量蛋白质组学分析，旨在探究高脂棕榈油膳食对蛋白质表达水平及S-棕榈酰化修饰的影响。实验中，实验组小鼠喂食含19.1%棕榈油与4%大豆油的饲料（脂肪供能占比45%），对照组仅以4%大豆油作为唯一脂肪来源（脂肪供能占比10%），喂养周期分别为4周和12周。本研究同时并行评估了小鼠肝脏功能、肝脏与腹腔巨噬细胞的促炎反应，以及蛋白质S-棕榈酰化修饰在上述过程中的作用。研究结果显示，高脂棕榈油膳食可诱导小鼠肝脏内C16:0与C18:1脂肪酸一过性蓄积，进而改变大量参与肝脏代谢与特定先天免疫应答的蛋白质的表达水平及S-棕榈酰化修饰状态。该膳食对肝脏功能的负面影响相对温和，这可归因于棕榈油来源的C16:0相较于C18:1具有更低的生物利用度，以及机体预防肝损伤的机制（包括动态蛋白质S-棕榈酰化修饰）的高效运作。