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玫瑰果油通过上调高脂饮食喂养的C57BL/6J小鼠的PPAR-α和NRF2来预防氧化应激和炎症。

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.

作者信息

González-Mañán Daniel, D'Espessailles Amanda, Dossi Camila G, San Martín Marcela, Mancilla Rodrigo A, Tapia Gladys S

机构信息

Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile; and.

School of Biochemical Engineering, Faculty of Engineering, Pontifical Catholic University of Valparaiso, Valparaiso, Chile.

出版信息

J Nutr. 2017 Apr;147(4):579-588. doi: 10.3945/jn.116.243261. Epub 2017 Mar 15.

DOI:10.3945/jn.116.243261
PMID:28298541
Abstract

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. We studied the molecular mechanisms that underlie the role of RM in preventing high-fat diet (HFD)-induced oxidative stress and inflammation. 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 ⋅ d administered 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, and and mRNA expression in liver and visceral adipose tissue] were evaluated. 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) ( < 0.05). Visceral fat was 34% lower in the HFD + RM mice than in the HFD mice ( < 0.05). The blood glucose AUC was 29% lower and and expression levels were 47% and 59% lower, respectively, in the HFD + RM mice than in the HFD mice ( < 0.05). HFD + RM mice had 40% less hepatic steatosis ( < 0.05) and lower upregulation of PPAR-α (33%), ACOX1 (50%), NRF2 (39%), and HO-1 (68%) protein concentrations than did the HFD mice ( < 0.05). 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.

摘要

玫瑰果(RM)油的特点是含有高浓度的抗氧化剂和α-亚麻酸(ALA;18:3n-3)。我们之前在雄性C57BL/6J小鼠中证明,RM可减轻肝脂肪变性,这种情况与氧化应激和炎症密切相关。我们研究了RM在预防高脂饮食(HFD)诱导的氧化应激和炎症中所起作用的分子机制。将28日龄、体重12 - 14克的雄性C57BL/6J小鼠分为以下几组并喂养12周:对照饮食(CD;10%脂肪、20%蛋白质和70%碳水化合物);CD + RM(通过灌胃给予1.94毫克ALA·克体重·天);HFD(60%脂肪、20%蛋白质和20%碳水化合物);以及HFD + RM。评估了一般参数(体重、内脏脂肪和组织学);葡萄糖代谢[稳态模型评估和血糖曲线下面积(AUC)];氧化应激[肝细胞核因子(红细胞衍生2)样2(NRF2)和血红素加氧酶1(HO-1)浓度];以及炎症[肝过氧化物酶体增殖物激活受体α(PPAR-α)和酰基辅酶A氧化酶1(ACOX1)浓度、血液肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)浓度,以及肝和内脏脂肪组织中 和 的mRNA表达]。在HFD + RM小鼠中,最终体重(24.8±1.1克)比HFD小鼠(30.6±2.8克)低19%(<0.05)。HFD + RM小鼠的内脏脂肪比HFD小鼠低34%(<0.05)。HFD + RM小鼠的血糖AUC比HFD小鼠低29%, 和 的表达水平分别低47%和59%(<0.05)。HFD + RM小鼠的肝脂肪变性比HFD小鼠少40%(<0.05),PPAR-α(33%)、ACOX1(50%)、NRF2(39%)和HO-1(68%)蛋白浓度的上调也低于HFD小鼠(<0.05)。我们的研究结果表明,补充RM可通过下调炎性细胞因子的表达和分泌以及刺激肝脏抗氧化剂和脂肪酸氧化标志物,预防HFD喂养小鼠中观察到的肥胖表型。

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