Nonalcoholic fatty liver disease: emerging mechanisms and consequences.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Turkish
Aaron R
AR
Department of Pediatrics, Columbia University, New York, New York, USA. at2025@columbia.edu
D000818:Animals; D051048:Diacylglycerol O-Acyltransferase / Q000378:metabolism*; D018450:Disease Progression; D005234:Fatty Liver / Q000201:enzymology* / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D051379:Mice; D014280:Triglycerides / Q000096:biosynthesis*
D014280:Triglycerides; D051048:Diacylglycerol O-Acyltransferase