Choline deficiency, lipotrope deficiency and the development of liver disease including liver cancer: a new perspective.
Thus, the pathologic consequences of feeding a CD diet are fatty liver, liver cell death, liver cell proliferation, and liver cell cancer. The fatty liver with CD is similar to that with other types of fatty liver in that the most attractive current hypothesis is based on some interference with the production and output of VLDL by the liver. The induction of cell death appears to be consistent with quite a different hypothesis, genesis and/or increase in liver free radicals leading to both acute necrosis and initiation of carcinogenesis. Especially noteworthy is the low incidence of liver cirrhosis, even after 2 years of exposure to the CD diet. The feeding of the CD diet reproducibly induces severe and persistent fatty liver coupled with extensive cell death, a combination that is frequently considered to be appropriate for the induction of "micronodular" (fatty) cirrhosis in humans. The findings with the LD diet, the high incidence of cirrhosis, with severe persistent fatty liver without significant cell death, together with the low incidence of cirrhosis with the CD diet, stand out as unpredictable and strange, according to current concepts of the pathogenesis of human cirrhosis. The CD model offers an unusual opportunity to explore in increasing detail the possible roles of free radicals in two important problems in pathology and medicine-acute cell injury and neoplasia. The challenges include mechanistic studies on how the free radicals are generated and how they relate to the biological consequences. The relatively slow sequential changes in the induction of cell injury and neoplasia makes the CD model one of the best for mechanistic studies relating to free radicals.
Ghoshal
A K
AK
Department of Pathology, University of Toronto, Ontario, Canada.
Farber
E
E
D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D002796:Choline Deficiency / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008082:Lipotropic Agents / Q000378:metabolism*; D008107:Liver Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D008113:Liver Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D008659:Metabolic Diseases / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D013577:Syndrome
D008082:Lipotropic Agents