Date Published: February 1, 2018
Publisher: Public Library of Science
Author(s): Barbara D. Pachikian, Céline Druart, Emilie Catry, Laure B. Bindels, Audrey M. Neyrinck, Yvan Larondelle, Patrice D. Cani, Nathalie M. Delzenne, Hervé Guillou.
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.
Non-alcoholic fatty liver disease represents a major worldwide health problem with a prevalence of 20% in the general population that increases up to 70% in obese and type 2 diabetic subjects . The first stage of the disease involves the accumulation of triglycerides (TG) in the liver, which is relatively benign. However, approximately 15% of non-alcoholic fatty liver disease cases evolve into hepatic inflammation (steatohepatitis) and fibrosis, and these cases can further progress to cirrhosis and hepatocellular cancer .
Several recent studies have showed that the gut microbiota is an important factor that should be taken into account when studying non-alcoholic fatty liver disease [33, 34]. Specifically, the metabolites that it can produce appear to regulate hepatic fatty acid metabolism . In our study, we found a new bacterial CLA associated with increased lipogenesis and hepatic TG accumulation in a model of nutritional depletion in n-3 PUFA (DEF mice).
We discovered that trans-11,trans-13 CLA issued from gut microbial biohydrogenation had a stimulatory effect on lipogenesis that led to hepatic lipid accumulation by a mechanism involving the activation of nuclear factors that typically respond to insulin and carbohydrates. These results demonstrate the importance of some fatty acid metabolites produced by the gut microbiota in the regulation of gene expression in the livers of hosts as well as the potential role of the microbiota in non-alcoholic fatty liver disease.