2311-PUB: Metformin Improves Hepatic Inflammation in Diet-Induced Obese Mice through Downregulating CYP7B1

Abstract

Metformin is an antidiabetic drug widely used to treat type 2 diabetes. Although it has been found for a very long time, its mechanism remains to be discovered. Recently, metformin has been reported to be effective in other disease, such as obesity and tumor. However, whether metformin is beneficial in nonalcoholic fatty liver disease remains controversial. CYP7B1, a cholesterol hydroxylase, has been reported to be upregulated in the inflammatory diseases. We investigated whether CYP7B1 plays an important role in the effect of metformin on the hepatic inflammation in diet-induced obese mice. In this study, eight-week-old C57BL/6 mice were subjected to a chow diet or a high fat diet (HFD) for 12 weeks. After the diet intervention, mice on an HFD were randomly divided into HFD group and HFD+Metformin group (HFDM group) for 4 weeks. The results showed that the body weight, fasting blood glucose, body fat mass, glucose metabolism and insulin sensitivity were remarkably improved by metformin. The histological results including H&E staining and oil red O staining showed that metformin significantly ameliorated fatty liver induced by HFD. And the quantification of liver triglyceride also proved that. The histological results also revealed that adipocytes of epididymal adipose tissue and subcutaneous adipose tissue were smaller after metformin treatment. Meanwhile, metformin also ameliorated the whitening of brown adipose tissue according to the H&E staining. Compared to HFD group, the mRNA levels of CYP7B1 and pro-inflammatory markers (TNFα, IL-1, F4/80 and MCP1) in liver were downregulated in HFDM group. How CYP7B1 functions in the beneficial effect of metformin on improving hepatic inflammation is going to be further studied. Disclosure W. Guo: None. W. Wang: None. X. Zheng: None. F. Xu: None.