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Fatty Acid Synthase: A Target for the Reversal of Liver Steatosis

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Abstract:

Liver steatosis, or fatty liver, is characterized by the excess accumulation of triglycerides and fatty acids within hepatocytes. This accumulation is marked by an imbalance between the import/synthesis and export/degradation of fat in the liver. Liver steatosis is typically a benign condition, but is associated with severe complications following major liver surgery, as well as the progression of the liver to fibrosis, cirrhosis, and hepatocellular carcinoma. The hallmark of treatment has traditionally been the use of behavioral modification leading to long-term phenotypic reversal. However, the rapid reversal of liver steatosis is essential, especially prior to surgeries including hepatic resection or transplantation. The liver is a primary lipogenic tissue, making the enzyme fatty acid synthase (FAS, EC 2.3.1.85) a logical target for the treatment of steatosis. For steatosis of alcoholic or nonalcoholic etiology, fat accumulation is linked to the de novo synthesis of fatty acids through FAS. Recent reports have shown success using FAS inhibitors to reduce the amount of liver steatosis, and to reduce ischemia/reperfusion injury in those livers. Thus, FAS emerges as a key target for the reversal of hepatic steatosis, both for the preconditioning of livers prior to surgery.





Keywords: EGCG; Fatty acid synthase liver; cerulenin; fatty liver disease; steatosis; transplantation

Document Type: Research Article

Publication date: October 1, 2008

More about this publication?
  • Current Enzyme Inhibition aims to publish all the latest and outstanding developments in enzyme inhibition studies with regards to the mechanisms of inhibitory processes of enzymes, recognition of active sites, and the discovery of agonists and antagonists, leading to the design and development of new drugs of significant therapeutic value. Each issue contains a series of timely, in-depth reviews written by leaders in the field, covering a range of enzymes that can be exploited for drug development. Current Enzyme Inhibition is an essential journal for every pharmaceutical and medicinal chemist who wishes to have up-to-date knowledge about each and every development in the study of enzyme inhibition.
ben/cei/2008/00000004/00000003/art00002
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