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Antioxidant supplementation and obesity have independent effects on hepatic oxylipin profiles in insulin resistant, obese-prone rats

Matthew J. Picklo Sr., John W. Newman
Free Radical Biology and Medicine 2015 v.89 no. pp. 182-191
alpha-linolenic acid, antioxidants, arachidonic acid, ascorbic acid, cytochrome P-450, dietary supplements, enzyme activity, epoxides, insulin resistance, laboratory animals, linoleic acid, lipid metabolism, lipoxygenases, liver, obesity, oxylipins, phenotype, rats, vitamin E
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 per-oxidation. 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 hepaticoxylipins. Using obesity-prone Sprague–Dawley rats fed a high-fat, hyper caloric 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 F(2)-isoprostane (F(2)-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 (LXA(4)), 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.