Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Liver-specific loss of long chain acyl-CoA synthetase-1 decreases triacylglycerol synthesis and beta-oxidation and alters phospholipid fatty acid composition.

http://www.ncbi.nlm.nih.gov/pubmed/19648649

In mammals, a family of five acyl-CoA synthetases (ACSLs), each the product of a separate gene, activates long chain fatty acids to form acyl-CoAs. Because the ACSL isoforms have overlapping preferences for fatty acid chain length and saturation and are expressed in many of the same tissues, the individual function of each isoform has remained uncertain. Thus, we constructed a mouse model with a liver-specific knock-out of ACSL1, a major ACSL isoform in liver. Eliminating ACSL1 in liver resulted in a 50% decrease in total hepatic ACSL activity and a 25-35% decrease in long chain acyl-CoA content. Although the content of triacylglycerol was unchanged in Acsl1(L)(-/-) liver after mice were fed either low or high fat diets, in isolated primary hepatocytes the absence of ACSL1 diminished the incorporation of [(14)C]oleate into triacylglycerol. Further, small but consistent increases were observed in the percentage of 16:0 in phosphatidylcholine and phosphatidylethanolamine and of 18:1 in phosphatidylethanolamine and lysophosphatidylcholine, whereas concomitant decreases were seen in 18:0 in phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and lysophosphatidylcholine. In addition, decreases in long chain acylcarnitine content and diminished production of acid-soluble metabolites from [(14)C]oleate suggested that hepatic ACSL1 is important for mitochondrial beta-oxidation of long chain fatty acids. Because the Acsl1(L)(-/-) mice were not protected from developing either high fat diet-induced hepatic steatosis or insulin resistance, our study suggests that lowering the content of hepatic acyl-CoA without a concomitant decrease in triacylglycerol and other lipid intermediates is insufficient to protect against hepatic insulin resistance.

Pubmed ID: 19648649 RIS Download

Mesh terms: Animals | Cells, Cultured | Coenzyme A Ligases | Diet | Fasting | Fatty Acids | Gene Targeting | Glucose Tolerance Test | Hepatocytes | Isoenzymes | Liver | Male | Mice | Mice, Knockout | Oxidation-Reduction | Phospholipids | Triglycerides

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NIDDK NIH HHS, Id: DK40936
  • Agency: NIDDK NIH HHS, Id: DK59935
  • Agency: NHLBI NIH HHS, Id: HL069768
  • Agency: NIDDK NIH HHS, Id: P30 DK034987
  • Agency: NIDDK NIH HHS, Id: P30 DK056350
  • Agency: NIDDK NIH HHS, Id: P30 DK34987
  • Agency: NIDDK NIH HHS, Id: R01 DK040936
  • Agency: NIDDK NIH HHS, Id: R01 DK059935
  • Agency: NIDDK NIH HHS, Id: U24 DK059635
  • Agency: NIDDK NIH HHS, Id: U24 DK59635
  • Agency: Howard Hughes Medical Institute, Id:

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.