Induction of macrophage scavenger receptor MARCO in nonalcoholic steatohepatitis indicates possible involvement of endotoxin in its pathogenic process

• Published in: International journal of experimental pathology 2004-12, Vol.85 (6), p.335-343
• Main Authors: Yoshimatsu, Mika, Terasaki, Yasuhiro, Sakashita, Naomi, Kiyota, Emi, Sato, Hiroo, Van Der Laan, Luc J. W., Takeya, Motohiro
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - blood; Animals; Apolipoproteins E - metabolism; Biological and medical sciences; Cholesterol - blood; Dietary Fats - administration & dosage; Disorders of blood lipids. Hyperlipoproteinemia; endotoxin; Endotoxins - analysis; Endotoxins - metabolism; Fatty Liver - complications; Fatty Liver - metabolism; Fatty Liver - pathology; Female; Hepatitis - complications; Hepatitis - metabolism; Hepatitis - pathology; high-fat diet; hyperlipidaemia; Hyperlipidemias - complications; Hyperlipidemias - metabolism; Immunohistochemistry - methods; Investigative techniques, diagnostic techniques (general aspects); Liver - pathology; MARCO; Medical sciences; Metabolic diseases; Mice; Mice, Inbred C57BL; nonalcoholic steatohepatitis; Original; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Receptors, Immunologic - metabolism; Receptors, Scavenger; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - analysis
• ISSN: 0959-9673; 1365-2613
• DOI: 10.1111/j.0959-9673.2004.00401.x

Summary Nonalcoholic steatohepatitis (NASH) is one of the life‐threatening hepatic diseases; however, its pathogenesis is still unknown. To evaluate the causative role of hyperlipidaemia and high‐fat diet, we compared C57BL/6 mice with inherited hyperlipidaemic model mice (LDLR–/–mice and ApoE–/– mice) fed a normal or a high‐fat diet. LDLR–/– and ApoE–/– mice fed the normal diet showed significantly higher serum cholesterol level than that of C57BL/6 mice fed the high‐fat diet. These mice, however, have shown neither significant elevation of serum alanine transaminase (ALT) level nor histopathologic features of steatohepatitis. High‐fat diet groups of all three strains showed histopathological characteristics of steatohepatitis with elevated serum ALT levels and high expression of macrophage scavenger receptor MARCO mRNA in the liver. Semiquantitative endotoxin analysis showed an elevated serum endotoxin level in the portal vein but not in the vena cava in ApoE–/– mice fed the high‐fat diet. These results indicate that long‐term feeding of a high‐fat diet induces NASH, whereas hyperlipidaemia alone is not enough to induce NASH. Liver‐restricted induction of MARCO in mice with high‐fat diet and portal endotoxaemia in ApoE–/– mice fed the high‐fat diet suggest the possible involvement of endotoxin in the pathogenesis of NASH.