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

BMC Neuroscience

Hyung-Wook Kim¹  Stanley I Rapoport²  Yewon Cheon²  Epolia Ramadan²  Fei Gao²  Ameer Y Taha² 

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

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

Others  :  1140858
DOI  :  10.1186/1471-2202-13-131

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

【 摘 要 】

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.

【 授权许可】

   
2012 Taha et al.; licensee BioMed Central Ltd.

【 图 表 】

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