Chronic intake of a high-cholesterol diet resulted in hepatic steatosis, focal nodular hyperplasia and fibrosis in non-obese mice.
We investigated the effects of a high-cholesterol (HC) diet administered long term (25 or 55 weeks) on metabolic disorders including hepatic damage in mice. The mice were fed the HC diet (15 % milk fat, 1.5 % cholesterol and 0.1 % cholic acid, w/w) for 25 or 55 weeks. Body and adipose tissue weights were similar to those of mice fed a control diet. Consumption of the HC diet long term resulted in hypercholesterolaemia, hepatic steatosis and gallstones. In addition, focal nodular hyperplasia (FNH) and mild fibrosis of the liver developed in all mice fed the HC diet for 55 weeks. Plasma levels of monocyte chemoattractant protein (MCP)-1 were elevated, and the level of hepatic platelet-derived growth factor (PDGF)-B protein was increased in mice fed the HC diet compared with those fed the control diet. Thus, it seems likely that the liver fibrosis and FNH caused by the long-term consumption of a HC diet may be partly due to an elevation of plasma MCP-1 and hepatic PDGF expression.
Sumiyoshi
Maho
M
Division of Functional Histology, Department of Functional Biomedicine, Graduate School of Medicine, Ehime University, Shitsukawa, Toon-City, Ehime 791-0295, Japan.
Sakanaka
Masahiro
M
Kimura
Yoshiyuki
Y
D000818:Animals; D000077214:Becaplermin; D001835:Body Weight / Q000187:drug effects; D018932:Chemokine CCL2 / Q000097:blood / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D005234:Fatty Liver / Q000139:chemically induced*; D042882:Gallstones / Q000139:chemically induced* / Q000378:metabolism; D005951:Glucose Tolerance Test; D008055:Lipids / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008103:Liver Cirrhosis / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000187:drug effects / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D012016:Reference Values
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D002791:Cholesterol, Dietary; D016207:Cytokines; D008055:Lipids; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D002784:Cholesterol