Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8268437 | Free Radical Biology and Medicine | 2015 | 10 Pages |
Abstract
Obesity-induced changes in lipid metabolism are mechanistically associated with the development of insulin resistance and prediabetes. Recent studies have focused on the extent to which obesity-induced insulin resistance is mediated through oxylipins, derived from enzymatic and nonenzymatic lipid peroxidation. Vitamin E and vitamin C are widely used antioxidant supplements, but conflicting data exist as to whether supplementation with vitamins E and C reduces insulin resistance. The purpose of this work is (1) to test the hypothesis that supplementation with vitamin E and vitamin C prevents the development of insulin resistance and (2) to determine the extent to which antioxidant supplementation modifies obesity-induced changes in hepatic oxylipins. Using obesity-prone Sprague-Dawley rats fed a high-fat, hypercaloric diet, we found that vitamin E and C supplementation did not block the development of insulin resistance, despite increased plasma levels of these antioxidants and decreased hepatic F2-isoprostane (F2-IsoP) concentrations. The obese phenotype was associated with increased hepatic concentrations of cytochrome P450 (CYP450)-dependent linoleic acid and α-linolenic acid-derived epoxides. Antioxidant supplementation, but not obesity, decreased levels of the lipoxygenase (LOX)-dependent, arachidonic acid-derived products lipoxin A4 (LXA4), 8,15-dihydroxtetraenoate (8,15-DiHETE), and 5,15-DiHETE. Our data demonstrate that antioxidant supplementation and obesity impact hepatic LOX- and CYP450-dependent oxylipin metabolism.
Keywords
HEPEALAHOMA-IRMUFAOGTTF2-isoprostanesDiHETEOxylipinsF2-IsoPHETrEhydroxyeicosatrienoic acidDTPAHpODEDiHETrEHDoHETriHOMEHOTEKODEdihydroxydocosapentaenoic acidEpETEEpODEBHTEPACyPCOX2,6-di-tert-butyl-4-methylphenolAUCHODEROSsEHα-TocopherolOral glucose tolerance testcyclooxygenasehomeostasis model assessment of insulin resistanceα-linolenic acidArachidonic acidepoxyeicosatrienoic acidepoxydocosapentaenoic acidepoxyeicosatetraenoic acidEicosapentaenoic aciddocosahexaenoic aciddihydroxyeicosatrienoic aciddihydroxyeicosatetraenoic aciddihydroxyoctadecadienoic acidLinoleic acidhydroperoxyoctadecadienoic acidhydroxyeicosatetraenoic acidhydroxyeicosapentaenoic acidhydroxydocosahexaenoic acidhydroxyoctadecatrienoic acidhydroxyoctadecadienoic acidPolyunsaturated fatty acidPUFAmonounsaturated fatty acidsEpETrEEpOMELOXAuto-oxidationARADHADiethylenetriaminepentaacetic acidDiHOMEDiHODECytochrome P450lipoxygenaseObesityInsulin resistancearea under the curveHETEEpoxide hydrolaseSoluble epoxide hydrolasevitamin CReactive oxygen species
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Authors
Matthew J. Picklo Sr., John W. Newman,