Elevated systemic monocyte chemoattractrant protein-1 levels in hepatic steatosis without significant hepatic inflammation

Abstract

Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity and diabetes mellitus. It encompasses a clinico-pathologic spectrum of conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). The latter develops upon pro-inflammatory cell infiltration and is widely considered as the first relevant pathophysiological step in NAFLD-progression. The chemokine monocyte chemoattractant proteins (MCP-1) plays an important role in the progression of hepatic inflammation and fibrosis and increased hepatic expression has been described in NASH. The aim of the present study was to investigate MCP-1 expression simple hepatic steatosis. Methods and Results: A high-fat diet (HFD; 30% lard) was fed to male BALB/c mice for 20 weeks leading to a significant increase of body weight and fasting glucose serum levels. Further, HFD-fed mice revealed marked hepatic lipid accumulation in the absence of significant hepatic inflammation as evidenced by unaltered serum transaminases and hepatic TNF expression. However, HFD-fed mice had elevated hepatic MCP-1 expression and significantly higher MCP-1 serum levels compared to control mice fed standard chow. Moreover, we detected markedly increased MCP-1 expression in visceral adipose tissue of HFD-fed mice. In addition, we assessed MCP-1 in a cohort of patients with bland steatosis and observed significantly increased serum levels, which correlated with the body-mass index and serum glucose levels. Conclusion: Our data indicate both the liver and adipose tissue as cellular sources of elevated circulating MCP-1 levels already in the early phase of hepatic steatosis. Since MCP-1 derived from visceral adipose tissue reaches the liver via portal circulation at high concentrations it may significantly contribute to the progression of simple steatosis to NASH.