期刊
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
卷 23, 期 -, 页码 S104-S107出版社
WILEY
DOI: 10.1111/j.1440-1746.2007.05294.x
关键词
hepatic stellate cell; lipogenesis; liver fibrosis; peroxisome proliferator-activated receptor gamma; sterol-regulatory element-binding protein-1c; Wnt
资金
- NIAAA NIH HHS [P50AA11999, R24AA12885] Funding Source: Medline
Alcoholic and non-alcoholic steatohepatitis (ASH and NASH) constitute two major types of chronic liver disease with worldwide prevalence and are histologically indistinguishable with shared pathogenetic mechanisms. More importantly, they have synergistic interactions for liver pathology. Comparative studies on ASH and NASH have been hampered by the use of different animal models with confounding variables, particularly those with extreme genetic, toxic, and malnutrition etiologies. The mouse intragastric model circumvents these problems and reproduces the natural course and etiological background of ASH and NASH. Further, our recent work reproduces a profound synergism between the two in the model. Intracellular accumulation of neural lipids is a hallmark biochemical feature of ASH and NASH. Although impaired lipid oxidation and export may contribute to this pathological change, enhanced lipogenic regulation is frequently encountered, as characterized by induction of lipogenic or adipogenic transcription factors (peroxisome proliferator-activated receptor [PPAR gamma], liver X receptor alpha [LXR alpha], sterol-regulatory element-binding protem-1c [SREBP-1c]). In contrast, we have recently defined transdifferentiation of heatic stellate cells (HSC), a pivotal event in liver fibrogenesis, as an 'antilipogenic' or 'anti-adipogenic' phenomenon. Thus, there is an apparent paradox between hepatocytes and HSC in steatoltepatitis in terms of the outcome of lipogenic regulation. Our recent work suggests that defective insulin signaling in activated HSC may be responsible for this paradox. Further, activated Writ signaling is implicated in 'anti-adipogenic' stellate cell transdifferentiation in liver fibrogenesis.
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