Upregulated expression of brain enzymatic markers of arachidonic and docosahexaenoic acid metabolism in a rat model of the metabolic syndrome

BMC Neuroscience

Research Article

Fei Gao¹  Ameer Y Taha¹  Epolia Ramadan¹  Stanley I Rapoport¹  Yewon Cheon¹  Hyung-Wook Kim² 

[1] Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, 20892, Bethesda, MD, USA;Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, 20892, Bethesda, MD, USA;Department of Environmental and Occupational Health Science, University of Washington, Box 357234, 1705 Pacific St, 98195, Seattle, WA, USA;

关键词: Arachidonic acid;    Docosahexaenoic acid;    BDNF;    Brain;    Polyunsaturated fatty acids (PUFA);    Metabolic syndrome;    Drebrin;    Sucrose;    Insulin resistance;   

DOI  :  10.1186/1471-2202-13-131

 received in 2012-07-17, accepted in 2012-10-05,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundIn 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.ResultsThe 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.ConclusionThese 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.

【 授权许可】

Unknown   
© Taha et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.