title: The metabolic cascade leading to eicosanoid precursors--desaturases, elongases, and phospholipases A2--is altered in Zucker fatty rats.
abstract: 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.
authors.affiliation: INSERM UMR 866/Université de Bourgogne, Lipides Nutrition Cancer, Faculté des Sciences Gabriel, 6 Bd Gabriel, 21000 Dijon, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Fèvre
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bellenger
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Pierre
authors.forename: Mélaine
authors.initials: M
authors.lastname: Minville
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bellenger
authors.forename: Joseph
authors.initials: J
authors.lastname: Gresti
authors.forename: Mickaël
authors.initials: M
authors.lastname: Rialland
authors.forename: Michel
authors.initials: M
authors.lastname: Narce
authors.forename: Christian
authors.initials: C
authors.lastname: Tessier
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D015777:Eicosanoids / Q000378:metabolism*; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D000081031:Fatty Acid Elongases; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D054513:Group IV Phospholipases A2 / Q000235:genetics / Q000378:metabolism; D054522:Group VI Phospholipases A2 / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D050602:Linoleoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054467:Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015777:Eicosanoids; D005231:Fatty Acids, Unsaturated; D044943:Fatty Acid Desaturases; D050602:Linoleoyl-CoA Desaturase; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; D054513:Group IV Phospholipases A2; D054522:Group VI Phospholipases A2; D054467:Phospholipases A2; C516391:Pla2g4a protein, rat; C535117:Pla2g6 protein, rat; C559656:Pla2g7 protein, rat