Hepatic monocyte chemoattractant protein-1 is upregulated by dietary cholesterol and contributes to liver steatosis.
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| Abstract |
To assess the role of monocyte chemoattractant protein-1 (MCP-1/CCL2) in the development of fatty liver, we have used LDLr(-/-) mice as an animal model of high-fat, high-cholesterol diet-induced liver steatosis. The rapid dietary induction of hepatic mRNA MCP-1 expression was paralleled by a concomitant increase in plasma MCP-1 that was strongly associated with the degree of liver steatosis. Hepatocytes showed an intense immunoreactivity for MCP-1 that was mainly located surrounding the hepatic lipid droplets. The intake of cholesterol also increased the concentration of MCP-1 in liver homogenates. This was accompanied by a differential expression of members of the PPAR family. Additionally, complete MCP-1 deficiency prevents the development of liver steatosis in LDLr(-/-) mice and partial deficiency is accompanied by a certain protective effect. Our data also suggest that MCP-1 may be important in the regulation of hepatic insulin resistance and may represent a link between inflammation and metabolic diseases. We conclude that dietary cholesterol upregulation of hepatic MCP-1 may help to understand the role of circulating MCP-1 in conditions where liver derangements are clinically important and in the association of liver steatosis with the metabolic syndrome.
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| Authors | Anna Rull, Fernando Rodríguez, Gerard Aragonès, Judit Marsillach, Raúl Beltrán, Carlos Alonso-Villaverde, Jordi Camps, Jorge Joven |
| Journal | Cytokine (Cytokine) Vol. 48 Issue 3 Pg. 273-9 (Dec 2009) ISSN: 1096-0023 [Electronic] England |
| PMID | 19748796 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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