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烟酰胺核糖可降低热量限制下肥胖 Wistar 大鼠的心脏代谢风险因素并调节心脏氧化应激。

Nicotinamide riboside reduces cardiometabolic risk factors and modulates cardiac oxidative stress in obese Wistar rats under caloric restriction.

机构信息

Programa de Pós-Graduação em Ciências Biológicas (PPG): Farmacologia e Terapêutica - Instituto de Ciências Básicas da Saúde (ICBS) - Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Laboratório de Farmacologia da Dor e Neuromodulação: Investigações Pré-clínicas - Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.

Laboratório de Farmacologia da Dor e Neuromodulação: Investigações Pré-clínicas - Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Medicina: Ciências Médicas - Faculdade de Medicina - UFRGS, Porto Alegre, RS, Brazil.

出版信息

Life Sci. 2020 Dec 15;263:118596. doi: 10.1016/j.lfs.2020.118596. Epub 2020 Oct 17.

Abstract

AIMS

NAD-based therapeutic strategies are encouraged against obesity and heart disease. Our study, therefore, aimed to investigate the effects of nicotinamide riboside (NR), isolated or combined with caloric restriction (CR), both approaches well-known for stimulating NAD levels, on adiposity parameters, cardiometabolic factors and cardiac oxidative stress in rats submitted to cafeteria diet (CAF).

MAIN METHODS

After 42 days of CAF-induced obesity (hypercaloric and ultra-processed foods common to humans), we examined the effects of oral administration of NR (400 mg/kg for 28 days), combined or not with CR (-62% kcal, for 28 days), on anthropometric, metabolic, tissue, and cardiac oxidative stress parameters in obese male Wistar rats.

KEY FINDINGS

In obese rats, treatment with NR alone mitigated final body weight gain, reduced adiposity (visceral and subcutaneous), improved insulin resistance, and decreased TG/HDL ratio and heart size. In cardiac OS, treatment with NR increased the antioxidant capacity via glutathione peroxidase and catalase enzymes (in rats under CR) as well as reduced the pro-oxidant complex NADPH oxidase (in obese and lean rats). Hyperglycemia, hypertriglyceridemia and elevated levels of TBARS in the heart were state-dependent adverse effects, induced by treatment with NR.

SIGNIFICANCE

This is the first study to report effects of nicotinamide riboside on cardiac oxidative stress in an obesity model. Nicotinamide riboside, a natural dietary compound, presented antiobesity effects and cardiometabolic benefits, in addition to positively modulating oxidative stress in the heart, in a state-dependent manner.

摘要

目的

基于烟酰胺腺嘌呤二核苷酸(NAD)的治疗策略被提倡用于治疗肥胖和心脏病。因此,本研究旨在探讨烟酰胺核糖(NR),无论是单独使用还是与热量限制(CR)联合使用,对喂食 cafeteria 饮食(CAF)的肥胖大鼠的肥胖参数、心脏代谢因子和心脏氧化应激的影响。CAF 饮食可引起肥胖(高热量和超加工食品,与人类常见的饮食相似)。

方法

在肥胖大鼠(喂食 CAF 42 天)中,我们检测了 NR(400mg/kg,口服,28 天)单独或联合 CR(热量限制 62%,28 天)对肥胖雄性 Wistar 大鼠的体重、代谢、组织和心脏氧化应激参数的影响。

主要发现

在肥胖大鼠中,NR 单独治疗可减轻最终体重增加,减少脂肪堆积(内脏和皮下),改善胰岛素抵抗,降低甘油三酯/高密度脂蛋白比值和心脏大小。在心脏氧化应激方面,NR 治疗通过谷胱甘肽过氧化物酶和过氧化氢酶酶增加抗氧化能力(在 CR 大鼠中),并减少促氧化复合物 NADPH 氧化酶(在肥胖和瘦大鼠中)。NR 治疗导致血糖升高、甘油三酯升高和心脏 TBARS 水平升高,这是一种状态依赖性的不良反应。

意义

这是首次报道烟酰胺核糖对肥胖模型中心脏氧化应激影响的研究。烟酰胺核糖是一种天然的膳食化合物,具有抗肥胖作用和心脏代谢益处,此外,还以一种状态依赖性的方式积极调节心脏氧化应激。

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