title: Elevated systemic monocyte chemoattractrant protein-1 in hepatic steatosis without significant hepatic inflammation.
abstract: Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity and the metabolic syndrome. 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 protein 1 (MCP-1) plays an important role in the progression of hepatic inflammation and fibrosis, and both increased hepatic expression and circulating serum levels have been described in NASH. Here, we aimed to investigate MCP-1 expression in simple hepatic steatosis. Upon feeding a high-fat diet mice developed hepatic steatosis in the absence of significant hepatic inflammation, but elevated hepatic MCP-1 expression compared to control mice fed a standard chow. Interestingly, high-fat diet fed mice had significantly higher MCP-1 serum levels, and MCP-1 mRNA expression was significantly increased in visceral adipose tissue. Furthermore, MCP-1 serum levels were also elevated in patients with ultrasound-diagnosed NAFLD and correlated with the body-mass index and fasting glucose. In 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.
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Georgi
authors.initials: G
authors.lastname: Kirovski
authors.forename: Christoph
authors.initials: C
authors.lastname: Dorn
authors.forename: Hanna
authors.initials: H
authors.lastname: Huber
authors.forename: Lukas
authors.initials: L
authors.lastname: Moleda
authors.forename: Catrin
authors.initials: C
authors.lastname: Niessen
authors.forename: Hella
authors.initials: H
authors.lastname: Wobser
authors.forename: Doris
authors.initials: D
authors.lastname: Schacherer
authors.forename: Christa
authors.initials: C
authors.lastname: Buechler
authors.forename: Reiner
authors.initials: R
authors.lastname: Wiest
authors.forename: Claus
authors.initials: C
authors.lastname: Hellerbrand
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015992:Body Mass Index; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000097:blood; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications / Q000503:physiopathology
chemical_list: D018932:Chemokine CCL2