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血管紧张素转换酶抑制剂依那普利和/或运动训练通过调节肾素-血管紧张素系统改善肥胖小鼠的内脏脂肪堆积。

Renin-angiotensin system modulation through enalapril and/or exercise training improves visceral adiposity in obese mice.

机构信息

Laboratory of Exercise Sciences, Biomedical Institute, Fluminense Federal University, Niteroi, RJ, Brazil; Research Center on Morphology and Metabolism, Biomedical Institute, Fluminense Federal University, Niteroi, RJ, Brazil.

Research Center on Morphology and Metabolism, Biomedical Institute, Fluminense Federal University, Niteroi, RJ, Brazil.

出版信息

Life Sci. 2022 Feb 15;291:120269. doi: 10.1016/j.lfs.2021.120269. Epub 2021 Dec 30.

DOI:10.1016/j.lfs.2021.120269
PMID:34974075
Abstract

INTRODUCTION

Obesity-related metabolic diseases occur as a result of disruptions in white adipose tissue (WAT) plasticity, especially through visceral fat accumulation and adipocyte hypertrophy. This study aimed to evaluate the impact of renin-angiotensin system (RAS) and bradykinin receptors modulation by enalapril treatment and/or exercise training on WAT morphology and related deleterious outcomes.

METHODS

Male C57BL/6 mice were fed either a standard chow or a high-fat (HF) diet for 16 weeks. At the 8th week, HF-fed animals were divided into sedentary (HF), enalapril treatment (HF-E), exercise training (HF-T), and enalapril treatment plus exercise training (HF-ET) groups. Following the experimental protocol, body mass gain, adiposity index, insulin resistance, visceral WAT morphometry, renin-angiotensin system, and bradykinin receptors were evaluated.

RESULTS

The HF group displayed increased adiposity, larger visceral fat mass, and adipocyte hypertrophy, which was accompanied by insulin resistance, overactivation of Ang II/AT1R arm, and favoring of B1R in bradykinin receptors profile. All interventions ameliorated visceral adiposity and related outcomes by favoring the Ang 1-7/MasR arm and the B2R expression in B1R/B2R ratio. However, combined therapy additively reduced Ang II/Ang 1-7 ratio.

CONCLUSION

Our results suggest that Ang 1-7/MasR arm and B2R activation might be relevant targets in the treatment of visceral obesity.

摘要

简介

肥胖相关的代谢疾病是由于白色脂肪组织(WAT)的可塑性受到破坏而发生的,尤其是通过内脏脂肪堆积和脂肪细胞肥大。本研究旨在评估血管紧张素转化酶抑制剂(ACEI)依那普利治疗和/或运动训练对 WAT 形态及其相关有害后果的影响,这种影响是通过调节肾素-血管紧张素系统(RAS)和缓激肽受体实现的。

方法

雄性 C57BL/6 小鼠分别用标准饲料或高脂肪(HF)饮食喂养 16 周。在第 8 周时,HF 喂养的动物被分为安静组(HF)、依那普利治疗组(HF-E)、运动训练组(HF-T)和依那普利治疗加运动训练组(HF-ET)。根据实验方案,评估了体重增加、肥胖指数、胰岛素抵抗、内脏 WAT 形态学、肾素-血管紧张素系统和缓激肽受体。

结果

HF 组表现出脂肪量增加、内脏脂肪质量更大和脂肪细胞肥大,同时伴有胰岛素抵抗、Ang II/AT1R 臂过度激活和缓激肽受体中 B1R 优势。所有干预措施均通过有利于 Ang 1-7/MasR 臂和 B1R/B2R 比值中 B2R 的表达,改善了内脏肥胖及其相关结局。然而,联合治疗可附加性地降低 Ang II/Ang 1-7 比值。

结论

我们的结果表明,Ang 1-7/MasR 臂和 B2R 的激活可能是内脏肥胖治疗的相关靶点。

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