Effects of dietary polyunsaturated fat on ethanol induced ito cell
activation.
Tsukamoto, Hidekazu, Steve Cheng, and William S. Blaner.
Department of Medicine, University of Southern California and VA
Outpatient Clinic, Los Angeles, CA; Children's Hospital in Oakland
Research Institute, Oakland, CA; and Institute of Human Nutrition,
College of Physicians and Surgeons of Columbia University, New York,
New York
APStracts 2:0210G, 1995.
Ito cells, vitamin A-storing, perisinusoidal cells are believed to
undergo myofibroblastic transformation in liver fibrogenesis. Our
previous studies have shown that a diet high in polyunsaturated fat
was key for induction of experimental alcoholic liver fibrosis. To
investigate the cellular basis for this fibrogenic effect of high fat
diet, we analyzed the content of vitamin A and cellular retinol
binding protein (CRBP), the steady state mRNA levels of procollagen
[alpha]1(I) (COLL), transforming growth factor [beta]1 (TGF[beta]1),
interleukin-6 (IL-6), and smooth muscle [alpha]-actin ([alpha]-SM) in
freshly isolated Ito cells from rats given isocaloric amounts of
ethanol and low or high fat diet. After 10 wk, the Ito cell content
of retinyl palmitate was severely reduced in both high and low fat
diet-ethanol fed animals to 13-17% of those measured in respective
pair-fed controls. On the other hand, the content of CRBP was reduced
only in the high fat-ethanol rats but not in the low fat-ethanol
group. The cells from the high fat-ethanol but not low-fat-ethanol
rats, showed a 18-fold increase in procollagen [alpha]1(I) mRNA at 17
wk, which was accompanied by 2.8 and 2.3 fold enhancement of
TGF[beta]1 and [alpha]-SM transcripts. IL-6 mRNA was not detected in
the cells from any groups. These results demonstrate: 1)
myofibroblastic activation of Ito cells is evident in rats given high
fat diet and ethanol but not in the low fat-ethanol animals; 2)
vitamin A depletion of Ito cells is the early and general effect of
chronic ethanol intake but does not necessarily predict subsequent
myofibroblastic activation; 3) reduced CRBP level is more closely
associated with the subsequent cellular activation seen under the
high fat-ethanol regimen; and 4) IL-6 is not expressed in vivo by Ito
cells from either normal livers or livers with alcoholic liver
fibrosis.
Received 5 June 1995; accepted in final form 13 October 1995.
APS Manuscript Number G238-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95