PMID- 23110484 OWN - NLM STAT- MEDLINE DCOM- 20130308 LR - 20211021 IS - 1471-2202 (Electronic) IS - 1471-2202 (Linking) VI - 13 DP - 2012 Oct 30 TI - Upregulated expression of brain enzymatic markers of arachidonic and docosahexaenoic acid metabolism in a rat model of the metabolic syndrome. PG - 131 LID - 10.1186/1471-2202-13-131 [doi] AB - 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. CONCLUSION: 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. FAU - Taha, Ameer Y AU - Taha AY AD - Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Gao, Fei AU - Gao F FAU - Ramadan, Epolia AU - Ramadan E FAU - Cheon, Yewon AU - Cheon Y FAU - Rapoport, Stanley I AU - Rapoport SI FAU - Kim, Hyung-Wook AU - Kim HW LA - eng GR - Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural DEP - 20121030 PL - England TA - BMC Neurosci JT - BMC neuroscience JID - 100966986 RN - 0 (Blood Glucose) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Fatty Acids) RN - 0 (Insulin) RN - 0 (Radioisotopes) RN - 0 (Triglycerides) RN - 25167-62-8 (Docosahexaenoic Acids) RN - 27YG812J1I (Arachidonic Acid) RN - EC 3.1.1.4 (Phospholipases A2) RN - TZP1275679 (3-Hydroxybutyric Acid) SB - IM MH - 3-Hydroxybutyric Acid/metabolism MH - Animals MH - Arachidonic Acid/*metabolism MH - Blood Glucose/metabolism MH - Brain/*metabolism MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Cytoplasm/metabolism MH - Dietary Supplements MH - Disease Models, Animal MH - Docosahexaenoic Acids/*metabolism MH - Fatty Acids/metabolism MH - Glucose Tolerance Test MH - Insulin/blood MH - Male MH - Metabolic Diseases/blood/metabolism/*pathology MH - Phospholipases A2/metabolism MH - Radioisotopes MH - Rats MH - Rats, Wistar MH - Triglycerides/blood MH - Up-Regulation/*physiology PMC - PMC3531256 EDAT- 2012/11/01 06:00 MHDA- 2013/03/09 06:00 PMCR- 2012/10/30 CRDT- 2012/11/01 06:00 PHST- 2012/07/17 00:00 [received] PHST- 2012/10/05 00:00 [accepted] PHST- 2012/11/01 06:00 [entrez] PHST- 2012/11/01 06:00 [pubmed] PHST- 2013/03/09 06:00 [medline] PHST- 2012/10/30 00:00 [pmc-release] AID - 1471-2202-13-131 [pii] AID - 10.1186/1471-2202-13-131 [doi] PST - epublish SO - BMC Neurosci. 2012 Oct 30;13:131. doi: 10.1186/1471-2202-13-131.