Nonalcoholic fatty liver disease: emerging mechanisms and consequences.

Abstract

PURPOSE OF REVIEW:

One of the critical complications of obesity and diabetes is nonalcoholic fatty liver disease, a disorder of triacylglycerol accumulation in the liver that has potential to develop into end stage liver failure. In this review, the recent progress in understanding the role of hepatic triacylglycerol synthesis in the development of nonalcoholic fatty liver disease is discussed.

RECENT FINDINGS:

It has become apparent that the development of hepatic steatosis is a complex, multifactorial process. Although the molecular pathways underlying its development have been described, there are no established therapies for nonalcoholic fatty liver disease. Recently, however, DGAT1 and DGAT2, the enzymes responsible for the final step in triacylglycerol synthesis, have been characterized as playing a vital role in hepatic triacylglycerol metabolism. Cellular and murine models in which diacylglycerol acyltransferase expression is altered suggest that these enzymes may play a role in the development hepatic steatosis, are feasible targets in the treatment of nonalcoholic fatty liver disease, but also function as lipotoxic buffers.

SUMMARY:

Hepatic steatosis remains the watershed event in the progression of nonalcoholic fatty liver disease. The diacylglycerol acyltransferases are emerging as important mediators of hepatic triacylglycerol accumulation. Therefore, these enzymes are attractive targets in the development of therapies to prevent liver triacylglycerol accumulation and the consequences of nonalcoholic fatty liver disease.

• Authors: Aaron R Turkish
• Journal: Current opinion in clinical nutrition and metabolic care (Curr Opin Clin Nutr Metab Care) Vol. 11 Issue 2 Pg. 128-33 (Mar 2008) ISSN: 1363-1950 [Print] England
• PMID: 18301087 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Triglycerides
• Diacylglycerol O-Acyltransferase

Topics

• Animals
• Diacylglycerol O-Acyltransferase (metabolism)
• Disease Progression
• Fatty Liver (enzymology, metabolism, pathology, prevention & control)
• Humans
• Mice
• Triglycerides (biosynthesis)