TRANSCRIPTIONAL AND HISTOLOGICAL RESPONSE OF LIVER IN AN OBESE MICE MODEL DUE TO THE EFFECT OF A SYNBIOTIC SUPPLEMENTATION.

Abstract

Introduction. Obesity is a pathology characterized by excessive fat accumulation that alters the functioning of pathways such as bile acid production, predisposing the liver to ectopic lipid accumulation, a histological visible characteristic of non-alcoholic fatty liver disease (NAFLD). Clinical studies indicate that the consumption of probiotics and prebiotics modulates the intestinal microbiota, promoting weight loss and decreasing fat deposits influencing metabolic pathways. Hypothesis. The use of Lactobacillus acidophilus + inulin (synbiotic) as a supplement in a normocaloric diet, can modify the liver transcriptome reducing the negative effects of NAFLD Main methods. The model murine used was C57BLACK6, inducing obesity with a high-fat diet for 8 weeks followed by synbiotic supplements in a normocaloric diet for another 8 weeks. Pool screening analysis (5 samples) was completed using a synthesis of cDNA. The transcriptome was analyzed by DNA microarrays hybridizing on 22,000 mouse genes. Differentially expressed genes (DEGs) were analyzed under 3 hybridization processes with the aid of GenArise software using the z-score value. As a result of transcriptome analysis, fatty acid-binding genes (Cyp7a1 and Acox2) were selected to analyze the liver response, molecular and histologically. Results. The transcriptome analysis results indicate 1.26% overexpression and a 2.2% average repression in relation to the hybridized genome; DEGs allow us to identify genes associated with fatty acid metabolism. The synbiotic treatment increases the expression of Cyp7a1 and Acox2 significantly (p<0.05) in correlation with a decrease in the histological level of accumulated fat in the tissue. Conclusion. The synbiotic treatment could be an adjuvant to obesity and NAFLD as it can increase the production of bile acids coming from the classical pathway which promotes the absorption of ectopically accumulated lipids thus reducing the development of NAFLD at histological and molecular level. (IAGM thanks CONACYT for the postdoctoral grant.)