The metabolic cascade leading to eicosanoid precursors--desaturases, elongases, and phospholipases A2--is altered in Zucker fatty rats

Biochim Biophys Acta. 2011 Jun;1811(6):409-17. doi: 10.1016/j.bbalip.2010.12.004. Epub 2010 Dec 21.


Metabolic syndrome characterized by insulin resistance and obesity is accompanied by severe lipid metabolism perturbations and chronic low-grade inflammation. However, many unresolved questions remained regarding the regulation that underlie dyslipidemia, particularly the regulation of the metabolic cascade (synthesis and release) leading to eicosanoid precursors release. This study was undertaken to investigate the regulation of desaturases/elongases and phospholipases A(2) during the establishment of metabolic syndrome. Our results showed that delta-6 desaturase as well as elongase-6 expressions were upregulated in 3-month-old Zucker fatty rats as compared to lean littermates, independently of SREBP-1c activation. We also demonstrated for the first time an increase of liver group VII phospholipase A(2) gene expression in the obese animals together with a strong specific inhibition of type IVA and VIA phospholipases A(2). These results suggest that the regulation of unsaturated fatty acids biosynthesis and signalling cascade could contribute to the development of liver lipid dysregulation related to metabolic syndrome and may be considered as new potential targets in such pathological conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism*
  • Animals
  • Blotting, Western
  • Eicosanoids / metabolism*
  • Fatty Acid Desaturases / genetics
  • Fatty Acid Desaturases / metabolism*
  • Fatty Acid Elongases
  • Fatty Acids, Unsaturated / biosynthesis
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Group IV Phospholipases A2 / genetics
  • Group IV Phospholipases A2 / metabolism
  • Group VI Phospholipases A2 / genetics
  • Group VI Phospholipases A2 / metabolism
  • Insulin Resistance
  • Linoleoyl-CoA Desaturase / genetics
  • Linoleoyl-CoA Desaturase / metabolism
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Metabolic Syndrome / genetics
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / pathology
  • Obesity / genetics
  • Obesity / metabolism*
  • Obesity / pathology
  • Phospholipases A2 / genetics
  • Phospholipases A2 / metabolism*
  • Rats
  • Rats, Zucker
  • Reverse Transcriptase Polymerase Chain Reaction


  • Eicosanoids
  • Fatty Acids, Unsaturated
  • Fatty Acid Desaturases
  • Linoleoyl-CoA Desaturase
  • Acetyltransferases
  • Fatty Acid Elongases
  • Group IV Phospholipases A2
  • Group VI Phospholipases A2
  • Phospholipases A2
  • Pla2g4a protein, rat
  • Pla2g6 protein, rat
  • Pla2g7 protein, rat