title: Rosa Mosqueta Oil Prevents Oxidative Stress and Inflammation through the Upregulation of PPAR-α and NRF2 in C57BL/6J Mice Fed a High-Fat Diet.
abstract: Background:Rosa mosqueta (RM) oil is characterized by high concentrations of antioxidants and α-linolenic acid (ALA; 18:3n-3). We have previously demonstrated in male C57BL/6J mice that RM decreases hepatic steatosis, a condition strongly associated with oxidative stress and inflammation.Objective:We studied the molecular mechanisms that underlie the role of RM in preventing high-fat diet (HFD)-induced oxidative stress and inflammation.Methods:Male C57BL/6J mice aged 28 d and weighing 12-14 g were divided into the following groups and fed for 12 wk: control diet (CD; 10% fat, 20% protein, and 70% carbohydrates); CD + RM (1.94 mg ALA ⋅ g body weight-1⋅ d-1administered by oral gavage); HFD (60% fat, 20% protein, and 20% carbohydrates); and HFD + RM. General parameters (body weight, visceral fat, and histology); glucose metabolism [homeostasis model assessment and blood glucose area under the curve (AUC)]; oxidative stress [hepatic nuclear factor (erythroid-derived 2)-like-2 (NRF2) and heme oxygenase 1 (HO-1) concentrations]; and inflammation [hepatic peroxisome proliferator-activated receptor α (PPAR-α) and acyl-coenzyme A oxidase 1 (ACOX1) concentrations, blood tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) concentrations, andTnfaandIl1bmRNA expression in liver and visceral adipose tissue] were evaluated.Results:In the HFD + RM mice, the final body weight (24.8 ± 1.1 g) was 19% lower than in the HFD mice (30.6 ± 2.8 g) (P< 0.05). Visceral fat was 34% lower in the HFD + RM mice than in the HFD mice (P< 0.05). The blood glucose AUC was 29% lower andTnfaandIl1bexpression levels were 47% and 59% lower, respectively, in the HFD + RM mice than in the HFD mice (P< 0.05). HFD + RM mice had 40% less hepatic steatosis (P< 0.05) and lower upregulation of PPAR-α (33%), ACOX1 (50%), NRF2 (39%), and HO-1 (68%) protein concentrations than did the HFD mice (P< 0.05).Conclusions:Our findings suggest that RM supplementation prevents the obese phenotype observed in HFD-fed mice by downregulating inflammatory cytokine expression and secretion and stimulating hepatic antioxidant and fatty acid oxidation markers.
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile; and.
authors.forename: Daniel
authors.identifier: 0000-0002-7631-6963
authors.initials: D
authors.lastname: González-Mañán
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile; and.
authors.forename: Amanda
authors.initials: A
authors.lastname: D'Espessailles
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile; and.
authors.forename: Camila G
authors.initials: CG
authors.lastname: Dossi
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile; and.
authors.forename: Marcela
authors.initials: M
authors.lastname: San Martín
authors.affiliation: School of Biochemical Engineering, Faculty of Engineering, Pontifical Catholic University of Valparaiso, Valparaiso, Chile.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Mancilla
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile; and gtapia@med.uchile.cl.
authors.forename: Gladys S
authors.initials: GS
authors.lastname: Tapia
mesh_terms: D000818:Animals; D001786:Blood Glucose; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy*; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D010938:Plant Oils / Q000737:chemistry / Q000494:pharmacology*; D027826:Rosa / Q000737:chemistry*; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D047493:PPAR alpha; D010938:Plant Oils; D051547:Heme Oxygenase-1
keywords: NRF2; PPAR-α; inflammation; oxidative stress; rosa mosqueta