Curcumin adds spice to the debate: lipid metabolism in liver disease.
Activated hepatic stellate cells (HSCs), the major source of the collagens involved in fibrosis and non-alcoholic fatty liver disease (NAFLD), undergo a profound loss of lipid and vitamin A storage capacity, as a consequence of a decline in expression of 'adipogenic' transcription factors such as peroxisome proliferator-activated receptor-gamma (PPARgamma). By contrast, hepatocytes undergo a micro- and macro-vesicular steatosis, reflecting the accumulation of triacylglycerol, and associated with chronic inflammation and fibrosis. These paradoxical findings are extended in this issue: Kang and Chen demonstrate that while low-density lipoproteins (LDL) can activate HSCs, curcumin can inhibit this process by activation of PPARgamma, which not only represses gene expression of SREBP-2 and LDLR, but via induction of expression of SREBP-1c, restores the lipid storage capacity characteristic of quiescent HSCs, suggesting that curcumin may be of therapeutic usage in protecting against liver steatosis and fibrosis.
Graham
Annette
A
Vascular Biology Group, Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, UK. Ann.Graham@gcal.ac.uk
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008107:Liver Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000378:metabolism; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism
D008077:Lipoproteins, LDL; D047495:PPAR gamma; D051779:Sterol Regulatory Element Binding Proteins; D003474:Curcumin
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