Hepatic monocyte chemoattractant protein-1 is upregulated by dietary cholesterol and contributes to liver steatosis

被引：52

作者：

Rull, Anna ^{[1
]}

Rodriguez, Fernando ^{[1
]}

Aragones, Gerard ^{[1
]}

Marsillach, Judit ^{[1
]}

Beltran, Raul ^{[1
]}

Alonso-Villaverde, Carlos ^{[1
]}

Camps, Jordi ^{[1
]}

Joven, Jorge ^{[1
]}

机构：

[1] Univ Rovira & Virgili, Hosp Univ St Joan Reus, Ctr Recerca Biomed, IISPV, E-43201 Reus, Spain

来源：

CYTOKINE | 2009年 / 48卷 / 03期

关键词：

Dietary cholesterol; LDLr-deficient mice; Liver steatosis; MCP-1; Obesity; ADIPOSE-TISSUE; DEFICIENT MICE; INSULIN-RESISTANCE; GENE-EXPRESSION; DISEASE; ATHEROSCLEROSIS; INFLAMMATION; OBESITY; PARAOXONASE-1; ACCUMULATION;

D O I：

10.1016/j.cyto.2009.08.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：273 / 279

页数：7

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