Effect of Gut Microbiota Modulation on Hepatic Lipid Metabolism

Abstract

Non‐alcoholic fatty liver disease is characterized by fat accumulation in the liver and commonly seen in patients with components of the metabolic syndrome. The mechanisms underlying its development are not completely defined, but there has been an increasing body of evidence linking gut microbiota to the development and progression of fat accumulation in the liver. Our objective was to investigate the effect of gut microbiota modulation on hepatic lipid metabolism.MethodsSix week old C57BL/6 male mice, fed with a control diet (CD, n=18) or high‐fat diet (HFD, n=30). At the age of 7 weeks, they were randomly assigned into 5 groups to receive (i) CD and vehicle, (ii) CD and antibiotics, (iii) HFD and vehicle, (iv) HFD and antibiotics, and (v) and HFD and antibiotics followed by fecal transplantation from CD‐ fed donors. Antibiotics (ciprofloxacin 0.2g l−1 and vancomycin 0.5 g l−1) were administered from the 10th to the 15th week, in drinking water. Fecal transplantation was carried out at the 13th week, following antibiotic withdrawal and maintenance of recipient mice on HFD. Weight was measured weekly and water intake twice a week. An oral glucose tolerance test (GTT) was performed at the 12th weeks. Mice were euthanized by decapitation and liver samples were stored for histological analysis and gene expression by real time quantitative polymerase chain reaction.ResultsHFD‐fed mice showed significantly increased weight gain when compared with CD‐fed mice. Antibiotic treatment did not change weight gain in CD‐fed mice but increased weight gain in HFD‐fed mice. Mice fed a CD and treated with antibiotics showed increased glucose tolerance when compared with control (CD, vehicle), and antibiotic treatment of HFD‐fed mice did not change glucose tolerance. CD‐fed mice treated with antibiotics exhibited increased expression of mRNA levels of PPAR‐α in liver and no change in lipogenesis‐related transcripts (Srepb1 and Acsl1), when compared with CD‐fed mice treated with vehicle. Mice fed a HFD and treated with antibiotics showed no change in PPARa, Srepb1 and Acsl1 levels when compared with control (HFD, vehicle), whereas HFD‐fed mice receiving fecal transplantation from CD‐fed mice showed a trend towards increased PPARa levels in the liver.ConclusionOur preliminary data may 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 extension and mechanisms underlying these effects.Support or Funding InformationThis study was supported by the Fundação de Amparo à Pesquisa do Distrito Federal (FAP‐DF).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.