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Hepatic triglyceride synthesis and nonalcoholic fatty liver disease.

Publication ,  Journal Article
Choi, SS; Diehl, AM
Published in: Curr Opin Lipidol
June 2008

PURPOSE OF REVIEW: Nonalcoholic fatty liver disease is a spectrum of diseases ranging from simple steatosis to cirrhosis. The hallmark of nonalcoholic fatty liver disease is hepatocyte accumulation of triglycerides. We will review the role of triglyceride synthesis in nonalcoholic fatty liver disease progression and summarize recent findings about triglyceride synthesis inhibition and prevention of progressive disease. RECENT FINDINGS: Attempts to inhibit triglyceride synthesis in animal models have resulted in improvement in hepatic steatosis. Studies in animal models of nonalcoholic fatty liver disease demonstrate that inhibition of acyl-coenzyme A:diacylglycerol acyltransferase, the enzyme that catalyzes the final step in triglyceride synthesis, results in improvement in hepatic steatosis and insulin sensitivity. We recently confirmed that hepatic specific inhibition of acyl-coenzyme A:diacylglycerol acyltransferase with antisense oligonucleotides improves hepatic steatosis in obese, diabetic mice but, unexpectedly, exacerbated injury and fibrosis in that model of progressive nonalcoholic fatty liver disease. When hepatocyte triglyceride synthesis was inhibited, free fatty acids accumulated in the liver, leading to induction of fatty acid oxidizing systems that increased hepatic oxidative stress and liver damage. These findings suggest that the ability to synthesize triglycerides may, in fact, be protective in obesity. SUMMARY: Nonalcoholic fatty liver disease is strongly associated with obesity and peripheral insulin resistance. Peripheral insulin resistance increases lipolysis in adipose depots, promoting increased free fatty acid delivery to the liver. In states of energy excess, such as obesity, the latter normally triggers hepatic triglyceride synthesis. When hepatic triglyceride synthesis is unable to accommodate increased hepatocyte free fatty acid accumulation, however, lipotoxicity results. Thus, rather than being hepatotoxic, liver triglyceride accumulation is actually hepato-protective in obese, insulin-resistant individuals.

Duke Scholars

Published In

Curr Opin Lipidol

DOI

ISSN

0957-9672

Publication Date

June 2008

Volume

19

Issue

3

Start / End Page

295 / 300

Location

England

Related Subject Headings

  • Triglycerides
  • Liver
  • Insulin Resistance
  • Humans
  • Fatty Liver
  • Disease Progression
  • Diacylglycerol O-Acyltransferase
  • Cardiovascular System & Hematology
  • Animals
  • 3205 Medical biochemistry and metabolomics
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Choi, S. S., & Diehl, A. M. (2008). Hepatic triglyceride synthesis and nonalcoholic fatty liver disease. Curr Opin Lipidol, 19(3), 295–300. https://doi.org/10.1097/MOL.0b013e3282ff5e55
Choi, Steve S., and Anna Mae Diehl. “Hepatic triglyceride synthesis and nonalcoholic fatty liver disease.Curr Opin Lipidol 19, no. 3 (June 2008): 295–300. https://doi.org/10.1097/MOL.0b013e3282ff5e55.
Choi SS, Diehl AM. Hepatic triglyceride synthesis and nonalcoholic fatty liver disease. Curr Opin Lipidol. 2008 Jun;19(3):295–300.
Choi, Steve S., and Anna Mae Diehl. “Hepatic triglyceride synthesis and nonalcoholic fatty liver disease.Curr Opin Lipidol, vol. 19, no. 3, June 2008, pp. 295–300. Pubmed, doi:10.1097/MOL.0b013e3282ff5e55.
Choi SS, Diehl AM. Hepatic triglyceride synthesis and nonalcoholic fatty liver disease. Curr Opin Lipidol. 2008 Jun;19(3):295–300.

Published In

Curr Opin Lipidol

DOI

ISSN

0957-9672

Publication Date

June 2008

Volume

19

Issue

3

Start / End Page

295 / 300

Location

England

Related Subject Headings

  • Triglycerides
  • Liver
  • Insulin Resistance
  • Humans
  • Fatty Liver
  • Disease Progression
  • Diacylglycerol O-Acyltransferase
  • Cardiovascular System & Hematology
  • Animals
  • 3205 Medical biochemistry and metabolomics