title: Upregulated expression of brain enzymatic markers of arachidonic and docosahexaenoic acid metabolism in a rat model of the metabolic syndrome.
abstract: BACKGROUND
  In animal models, the metabolic syndrome elicits a cerebral response characterized by altered phospholipid and unesterified fatty acid concentrations and increases in pro-apoptotic inflammatory mediators that may cause synaptic loss and cognitive impairment. We hypothesized that these changes are associated with phospholipase (PLA2) enzymes that regulate arachidonic (AA, 20:4n-6) and docosahexaenoic (DHA, 22:6n-6) acid metabolism, major polyunsaturated fatty acids in brain. Male Wistar rats were fed a control or high-sucrose diet for 8 weeks. Brains were assayed for markers of AA metabolism (calcium-dependent cytosolic cPLA2 IVA and cyclooxygenases), DHA metabolism (calcium-independent iPLA2 VIA and lipoxygenases), brain-derived neurotrophic factor (BDNF), and synaptic integrity (drebrin and synaptophysin). Lipid concentrations were measured in brains subjected to high-energy microwave fixation.
  
  
  RESULTS
  The high-sucrose compared with control diet induced insulin resistance, and increased phosphorylated-cPLA2 protein, cPLA2 and iPLA2 activity and 12-lipoxygenase mRNA, but decreased BDNF mRNA and protein, and drebrin mRNA. The concentration of several n-6 fatty acids in ethanolamine glycerophospholipids and lysophosphatidylcholine was increased, as was unesterified AA concentration. Eicosanoid concentrations (prostaglandin E2, thromboxane B2 and leukotriene B4) did not change.
  
  
  CONCLUSIONS
  These findings show upregulated brain AA and DHA metabolism and reduced BDNF and drebrin, but no changes in eicosanoids, in an animal model of the metabolic syndrome. These changes might contribute to altered synaptic plasticity and cognitive impairment in rats and humans with the metabolic syndrome.
authors.affiliation: Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ameer Y
authors.initials: AY
authors.lastname: Taha
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Epolia
authors.initials: E
authors.lastname: Ramadan
authors.forename: Yewon
authors.initials: Y
authors.lastname: Cheon
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
authors.forename: Hyung-Wook
authors.initials: HW
authors.lastname: Kim
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D054467:Phospholipases A2 / Q000378:metabolism; D011868:Radioisotopes; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor; D005227:Fatty Acids; D007328:Insulin; D011868:Radioisotopes; D014280:Triglycerides; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D054467:Phospholipases A2; D020155:3-Hydroxybutyric Acid