Effect of Gut Microbiota Modulation on Hepatic Lipid Metabolism in C57Bl/6 and ob/ob Mice

Abstract

Non‐alcoholic fatty liver disease (NAFLD) describes a spectrum of related liver diseases, ranging from simple steatosis to non‐alcoholic steatohepatitis (NASH), liver fibrosis, and cirrhosis. In recent years, gut microbiota has been increasingly linked to a number of metabolic diseases, including NALFD. Our objective was to investigate the effect of gut microbiota modulation on hepatic lipid metabolism in C57Bl/6 and ob/ob mice.MethodsSix‐week old male C57BL/6 mice fed a control diet (CD, n = 18) or a high‐fat diet (HFD, n = 30) were used. At the age of 7 weeks, they were randomly assigned into 5 groups to receive CD and vehicle (CD+V), CD and antibiotics (CD+AB), HFD and vehicle (HFD+V), HFD and antibiotics (HFD+AB), and HFD and antibiotics followed by fecal transplantation from donors fed a CD (HFD+T). Antibiotics (ciprofloxacin 0.2 g l−1 and vancomycin 0.5 g l−1) were administered from the 10th to the 15th week in drinking water. Fecal transplantation was performed at week 13, following antibiotic withdrawal and maintenance of HFD in receptor mice.Male ob/ob mice at 17 weeks of age fed a CD were treated with vehicle (ob+V, n = 5) or antibiotics (ob+AB, n = 5) and euthanized at week 21.Liver gene expression was assessed by quantitative real‐time polymerase chain reaction. Gut microbiota from C57BL/6 mice from each group (n = 5) was analyzed after 5 weeks of antibiotic treatment, by 16S rRNA gene sequence analysis in DNA extracted from fecal samples.ResultsHFD‐fed mice showed significantly increased weight gain when compared to CD‐fed mice. Antibiotic treatment did not alter weight gain in CD‐fed mice, but increased weight gain in HFD‐mice. ACOX1 mRNA levels were significantly lower in the ob+V group than in the HFD+AB group. The expression of CPT1A mRNA levels was significantly lower in the HFD+AB and HFD+T groups compared to the CD + AB group and the HFD+T group had significantly lower expression when compared to the HFD+V group. The expression of TNF‐α mRNA levels decreased significantly in the HFD+T compared with the HFD+V and ob+V groups. Antibiotic treatment changed gut microbiota composition significantly. There was an increase in the representation of Firmicutes and Proteobacteria phyla in the CD+AB group compared to the CD+V group. On the other hand, mice in the HFD+AB showed decrease in Firmicutes and increase in Proteobacteria representation, when compared with the HFD group. Gut microbiota composition in the HFD+T group resembled that of the CD+V donor group.ConclusionOur data suggest that gut microbiota modulation with antibiotics may affect fatty acid metabolism in the liver by changing the balance between expression of lipogenesis and fatty acid oxidation‐related genes. Further studies are needed to clarify the functional impact of changes in gene expression and the mechanisms underlying these effects.Support or Funding InformationThis study was supported by the Fundação de Apoio à Pesquisa do Distrito Federal (FAP‐DF).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.