The impact of P‐selectin deficiency on obesity‐associated non‐alcoholic fatty liver disease (1116.8)

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the worldwide, and occurs in patients who do not abuse alcohol. Metabolic syndrome is a major risk in the progression of NAFLD, steatosis and NASH (nonalcoholic steatohepatitis). In addition, obesity induced chronic low‐grade inflammation also play a crucial role in NAFLD formation. P‐selectin, an adhesion molecule, regulates leukocyte aggregation to vascular endothelium cell, induces the initial inflammatory response. In the study, we aimed to investigate the impact of P‐selectin deficiency on high fat diet (45% caloric from fat, HFD) induced NAFLD. C57BL6 wild‐type mice and P‐selectin KO mice were randomly divided into four groups, and fed with normal chow diet or HFD : wild‐type fed with chow diet (C) or high‐fat diet (H), P‐selectin KO mice fed with chow‐diet (PC) or high fat diet (PH). After 8 weeks HFD feeding, significantly increase body weight in wild‐type mice. The mice also exhibited higher liver weight, hyperglycemia, hyperinsulinemia and hyperlipidemia. Compared with the chow diet fed animal, the high fat diet impaired glucose tolerance and insulin sensitivity, enhanced glucose‐stimulated insulin secretion. High fat diet also induced plasma aspartate aminotransferase (AST) and alanine aminotranferease (ALT) elevation with imply hepatocyte damage. HFD promoted NF‐κB related inflammatory signaling in liver. However, P‐selectin KO mice reversed high‐fat diet induced AST, ALT elevation and NF‐κB inflammatory pathway in liver.P‐selectin KO mice also exhibited lower body weight, improved glucose intolerance and insulin resistance. Our studies indicate that P‐selectin is a crucial metabolic inducer. Deletion of P‐selectin correct high fat diet induced metabolic disturbance, liver injury and slow down the progression of NAFLD.