Effects of U62631.5 on short-chain fatty acid receptor 41(GPR41) and the related intestinal bacterium Butyricicoccus pullicaecorum after fecal bacterial transplantation in nonalcoholic fatty liver disease

LncRNAs exhibit diverse biological functions and may be crucial in nonalcoholic fatty liver disease (NAFLD) development. Our focus is on the mechanism of lncRNA U62631.5, regulating GPR41 and Butyricicoccus pullicaecorum (B. pullicaecorum), an intestinal bacterium producing butyric acid. Ensembl analysis suggests an interaction between U62631.5 and GPR41. 1. Male C57BL/6 mice were randomly divided into control group, model group, transplantation control group, transplantation model group by using the fecal microbiota transplantation (FMT) technique in this study. The liver tissue and small intestine tissue in each group were observed by hematoxylin-eosin (HE) staining, and liver histopathology was quantitatively assessed using the NAFLD Activity Score (NAS). The expression of U62631.5 and GPR41 in peripheral blood, liver tissue, and small intestine tissues were detected by PCR. Fecal samples were used by16S rRNA sequencing. The contents of short chain fatty acids in intestinal were detected by gas chromatography, and the expression of B. pullicaecorum was detected by PCR. 2.Hepatic lipid accumulation was observed in HepG2 cells. GPR41 promoter function analysis was detected. After siRNA and overexpression of U62631.5, the U62631.5 and GPR41 were further detected by PCR. 1. Animal level: Compared with the model group, hepatic lipid accumulation and the injury of intestinal mucosal were improved, the expression of U62631.5 and GPR41 were increased, the content of butyric acid was increased, and B. pullicaecorum was increased in the transplantation model group. The results were contrary to the above results in the model group compared with the control group, the transplantation control group compared with the control group, and the transplantation model group compared with the transplantation control group. 2.Cell levels: It was found that the promoter activity of GPR41 gene was increased significantly by U62631.5. We interfered with U62631.5 by siRNA and found that GPR41 was almost undetectable by PCR. After overexpression of U62631.5, the expression of GPR41 was increased. U62631.5 may play a role by regulating adjacent gene GPR41 related intestinal bacteria in NAFLD, and B.pullicaecorum may be one of the intestinal bacteria in this process.