Effect of Dietary Fat on Ito Cell Activation by Chronic Ethanol Intake: A Long-Term Serial Morphometric Study on Alcohol-Fed and Control Rats

Authors

  • Hisao Takahashi,

    1. Department of Internal Medicine, National Kurihama Hospital, National Institute on Alcoholism of Japan, Kanagawa. Japan (H. T.); the Department of Pathology, Faculty of Health Science, University of Ottawa, Ottawa, ONT, Canada (K.W., L.J.); the Department of Laboratory Medicine, New England Deaconess Hospital, Harvard School of Medicine, Boston, Massachusetts (A.A.N.); the Department of Internal Medicine, VA Medical Center, University of Cincinnati, Ohio (C.S.M.); and the Department of Pathology, Harbor-UCLA Medical Center, Torr-ance, California (S. W.F).
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  • Kim Wong,

    1. Department of Internal Medicine, National Kurihama Hospital, National Institute on Alcoholism of Japan, Kanagawa. Japan (H. T.); the Department of Pathology, Faculty of Health Science, University of Ottawa, Ottawa, ONT, Canada (K.W., L.J.); the Department of Laboratory Medicine, New England Deaconess Hospital, Harvard School of Medicine, Boston, Massachusetts (A.A.N.); the Department of Internal Medicine, VA Medical Center, University of Cincinnati, Ohio (C.S.M.); and the Department of Pathology, Harbor-UCLA Medical Center, Torr-ance, California (S. W.F).
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  • Linda Jui,

    1. Department of Internal Medicine, National Kurihama Hospital, National Institute on Alcoholism of Japan, Kanagawa. Japan (H. T.); the Department of Pathology, Faculty of Health Science, University of Ottawa, Ottawa, ONT, Canada (K.W., L.J.); the Department of Laboratory Medicine, New England Deaconess Hospital, Harvard School of Medicine, Boston, Massachusetts (A.A.N.); the Department of Internal Medicine, VA Medical Center, University of Cincinnati, Ohio (C.S.M.); and the Department of Pathology, Harbor-UCLA Medical Center, Torr-ance, California (S. W.F).
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  • Amin A. Nanji,

    1. Department of Internal Medicine, National Kurihama Hospital, National Institute on Alcoholism of Japan, Kanagawa. Japan (H. T.); the Department of Pathology, Faculty of Health Science, University of Ottawa, Ottawa, ONT, Canada (K.W., L.J.); the Department of Laboratory Medicine, New England Deaconess Hospital, Harvard School of Medicine, Boston, Massachusetts (A.A.N.); the Department of Internal Medicine, VA Medical Center, University of Cincinnati, Ohio (C.S.M.); and the Department of Pathology, Harbor-UCLA Medical Center, Torr-ance, California (S. W.F).
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  • Charles S. Mendenhall,

    1. Department of Internal Medicine, National Kurihama Hospital, National Institute on Alcoholism of Japan, Kanagawa. Japan (H. T.); the Department of Pathology, Faculty of Health Science, University of Ottawa, Ottawa, ONT, Canada (K.W., L.J.); the Department of Laboratory Medicine, New England Deaconess Hospital, Harvard School of Medicine, Boston, Massachusetts (A.A.N.); the Department of Internal Medicine, VA Medical Center, University of Cincinnati, Ohio (C.S.M.); and the Department of Pathology, Harbor-UCLA Medical Center, Torr-ance, California (S. W.F).
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  • Samuel W. French

    Corresponding author
    1. Department of Internal Medicine, National Kurihama Hospital, National Institute on Alcoholism of Japan, Kanagawa. Japan (H. T.); the Department of Pathology, Faculty of Health Science, University of Ottawa, Ottawa, ONT, Canada (K.W., L.J.); the Department of Laboratory Medicine, New England Deaconess Hospital, Harvard School of Medicine, Boston, Massachusetts (A.A.N.); the Department of Internal Medicine, VA Medical Center, University of Cincinnati, Ohio (C.S.M.); and the Department of Pathology, Harbor-UCLA Medical Center, Torr-ance, California (S. W.F).
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Department of Pathology, Los Angeles County Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90509.

Abstract

We studied the effects of long-term ethanol ingestion and dietary fat on Ito cell activation morphometrically in rats. Sixteen pairs of Wistar male rats were divided into two groups, one fed tallow and the other fed corn oil as the source of dietary fat. Each group of rats were pair-fed a nutritional adequate liquid diet containing either corn oil (CF) or tallow (TF) as fat as well as protein and carbohydrate. Half of each group received ethanol, the rest were pair-fed isocaloric amounts of dextrore via an implanted gastric tube for up to 5 months. Morphometric analysis of the change in fat and rough endoplasmic reticulum (RER) of Ito cells was performed on electron micrographs obtained from monthly biopsies including baseline. Ito cell activation was assessed by a decrease in the ratio of fat/RER in Ito cells. The ratio of fat/RER in Ito cells of alcoholic rats fed the CF diet (CFA) gradually decreased. The ratio war found to be lower than in the pair-fed control rats (CFC) at 5 months of feeding. CFA 1.74 ± 0.57, vs. 7.46 ± 2.05, respectlvely, p < 0.05, mean ± se). Ito cell fat also significantly decreased at 5 months of feeding (p < 0.05). The fat/ RER ratio In CFA significantly decreased only subsequent to the development of fatty change, necrosis, and inflammation followed by fibrosis of the liver. In contrast, the TFA rats did not show a significant decrease in the fat/RER ratio in the Ito cells throughout the study, while TFC rats showed an increase in the fat/RER ratio. Minimal pathological changes were observed In the livers of CFC, TFA, and TFC rats. These results indicate that activation of Ito cells at a signifiant level occurred only late in the course of feeding alcohol after moderate to severe abnormalities in liver hlstology had developed, although activation may have begun at an earlier time of ethanol feeding. The results Indicate that dietary fatty acid composition may be an important factor in the pathogenesis of ethanol-induced Ito cII activation.

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