title: Antioxidant supplementation and obesity have independent effects on hepatic oxylipin profiles in insulin-resistant, obesity-prone rats.
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.
authors.affiliation: USDA-ARS Grand Forks Human Nutrition Research Center 2420 2(nd) Avenue North Grand Forks, ND 58203-9034, USA; Department of Chemistry, University of North Dakota, Grand Forks, ND 58201, USA. Electronic address: matthew.picklo@ars.usda.gov.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Picklo
authors.affiliation: USDA-ARS Western Human Nutrition Research Center, Davis, CA 95616, USA; West Coast Metabolomics Center, University of California Davis, Davis, CA 95616, USA; Department of Nutrition, University of California Davis, Davis, CA 95616, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Newman
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000008:administration & dosage; D001786:Blood Glucose / Q000378:metabolism; D019587:Dietary Supplements; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D054883:Oxylipins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000008:administration & dosage
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D007328:Insulin; D054883:Oxylipins; D014810:Vitamin E; D001205:Ascorbic Acid
keywords: Cytochrome P450; Epoxide hydrolase; Insulin resistance; Lipoxygenase; Obesity; Oxylipins; Vitamin C; α-Tocopherol