Implication of trans-11,trans-13 conjugated linoleic acid in the development of hepatic steatosis

ScopeConjugated linoleic acids are linoleic acid isomers found in the diet that can also be produced through bacterial metabolism of polyunsaturated fatty acids. Our objective was to evaluate the contribution of fatty acid metabolites produced from polyunsaturated fatty acids by the gut microbiota in vivo to regulation of hepatic lipid metabolism and steatosis.Methods and resultsIn mice with depleted n-3 polyunsaturated fatty acids, we observed an accumulation of trans-11,trans-13 CLA and cis-9,cis-11 conjugated linoleic acids in the liver tissue that were associated with an increased triglyceride content and expression of lipogenic genes. We used an in vitro model to evaluate the impact of these two conjugated linoleic acids on hepatic lipid metabolism. In HepG2 cells, we observed that only trans-11,trans-13 conjugated linoleic acids recapitulated triglyceride accumulation and increased lipogenic gene expression, which is a phenomenon that may implicate the nuclear factors sterol regulatory element binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP).ConclusionThe trans-11,trans-13 conjugated linoleic acids can stimulate hepatic lipogenesis, which supports the conclusion that gut microbiota and related metabolites should be considered in the treatment of non-alcoholic liver disease.【研究范围】共轭亚油酸（Conjugated linoleic acids, CLA）是膳食中存在的亚油酸异构体，亦可通过多不饱和脂肪酸的细菌代谢途径生成。本研究旨在评估体内肠道菌群代谢多不饱和脂肪酸所产生的脂肪酸代谢物，对肝脏脂质代谢与脂肪变性的调控作用。 【方法与结果】在n-3多不饱和脂肪酸耗竭的小鼠模型中，我们观测到肝组织中反式-11,反式-13共轭亚油酸与顺式-9,顺式-11共轭亚油酸的蓄积，该现象与甘油三酯含量升高及脂肪生成基因表达上调显著相关。我们采用体外模型评估了这两种共轭亚油酸对肝脏脂质代谢的影响。在HepG2细胞中，仅反式-11,反式-13共轭亚油酸可重现甘油三酯蓄积及脂肪生成基因表达上调的表型，这一过程可能涉及核因子固醇调节元件结合蛋白1c（sterol regulatory element binding protein 1c, SREBP-1c）与碳水化合物反应元件结合蛋白（carbohydrate-responsive element-binding protein, ChREBP）。 【结论】反式-11,反式-13共轭亚油酸可促进肝脏脂肪生成，该结果支持在非酒精性肝病的治疗中，应将肠道菌群及其相关代谢物纳入考量范畴。