Pachikian Barbara D, Druart Céline, Catry Emilie, Bindels Laure B, Neyrinck Audrey M, Larondelle Yvan, Cani Patrice D, Delzenne Nathalie M
Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
Institut des Sciences de la Vie, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
PLoS One. 2018 Feb 1;13(2):e0192447. doi: 10.1371/journal.pone.0192447. eCollection 2018.
Conjugated 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.
In 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).
The 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.
共轭亚油酸是饮食中发现的亚油酸异构体,也可通过多不饱和脂肪酸的细菌代谢产生。我们的目的是评估肠道微生物群在体内由多不饱和脂肪酸产生的脂肪酸代谢产物对肝脏脂质代谢和脂肪变性调节的贡献。
在n-3多不饱和脂肪酸缺乏的小鼠中,我们观察到肝脏组织中反式-11,反式-13共轭亚油酸和顺式-9,顺式-11共轭亚油酸的积累,这与甘油三酯含量增加和脂肪生成基因的表达有关。我们使用体外模型评估这两种共轭亚油酸对肝脏脂质代谢的影响。在HepG2细胞中,我们观察到只有反式-11,反式-13共轭亚油酸重现了甘油三酯积累并增加了脂肪生成基因的表达,这一现象可能涉及核因子固醇调节元件结合蛋白1c(SREBP-1c)和碳水化合物反应元件结合蛋白(ChREBP)。
反式-11,反式-13共轭亚油酸可刺激肝脏脂肪生成,这支持了在非酒精性肝病治疗中应考虑肠道微生物群及相关代谢产物的结论。