高脂肪和/或高果糖摄入等因素导致过多的脂肪储存在肝脏形成非酒精性脂肪肝病（NAFLD），其全球发病率为25.2%，呈快速上升趋势。该文采用高糖高脂诱导NAFLD小鼠模型，研究了葛根素对NAFLD的干预作用。结果显示NAFLD小鼠体质量、肝指数分别下降13.7%、14.9%；H&E染色提示肝脏组织损伤减轻，脂肪空泡几乎消失；ELISA测定炎症因子TNF-α、IL-1β和IL-6浓度分别下降62.9%、60.5%和61.0%。采用LC-MS非靶向代谢组学分析NAFLD小鼠的肝脏代谢，结果表明葛根素提高代谢物L-蛋氨酸、L-丝氨酸、L-天冬酰胺、L-苯丙氨酸和氨基己二酸的水平，调控了半胱氨酸和蛋氨酸代谢，甘氨酸、丝氨酸和苏氨酸代谢和苯丙氨酸、酪氨酸和色氨酸生物合成等途径的紊乱；下调脂质代谢物油酸水平，促进鞘脂降解；并调节磷酸戊糖代谢、维生素代谢、嘌呤及嘧啶代谢途径的代谢物水平。因此，葛根素调控氨基酸代谢、脂质代谢等途径的紊乱，对高糖高脂饮食诱导的非酒精性脂肪肝发挥保护作用，为饮食调控脂肪代谢乃至脂肪肝奠定实验基础。

High fat and/or high fructose intakes lead to excessive fat storage in the liver, resulting in nonalcoholic fatty liver disease (NAFLD), whose global incidence rate is 25.2% and rising rapidly. In this study, the effects of puerarin intervention on NAFLD were investigated in a mouse model induced by high-fructose and high-fat diets. The results show that the body weight and liver index of NAFLD mice decreased by 13.7% and 14.9%, respectively; the H&E staining indicated that the liver tissue damage was mitigated and the fat vacuoles almost disappeared; and the concentrations of inflammatory factors TNF-α, IL-1β, and IL-6 decreased by 62.9%, 60.5% and 61.0%, respectively, as determined by ELISA. LC-MS non-targeted metabolomic analysis of liver metabolism in the NAFLD mice showed that puerarin increased the levels of metabolites L-methionine, L-serine, L-asparagine, L-phenylalanine, and aminoadipic acid; modulated the disturbances of cysteine and methionine metabolism pathways, glycine, serine, and threonine metabolism pathways, and phenylalanine, tyrosine and tryptophan biosynthesis pathways. In addition, puerarin down-regulated the levels of the lipid metabolite oleic acid and promoted the degradation of sphingolipids and regulated the levels of pentose phosphate metabolites, vitamin metabolites, and purine and pyrimidine metabolites. In summary, puerarin regulates the disturbances of amino acid and lipid metabolism pathways, and plays a protective role against NAFLD induced by high-fructose and high-fat diets, laying an experimental foundation for dietary regulation of fat metabolism and even fatty liver.

国家自然科学基金项目（32060539）