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慢性无机硝酸盐给药增加去卵巢大鼠性腺脂肪组织棕色化相关基因的表达。

Chronic Inorganic Nitrate Administration Increases the Expression of Genes Involved in the Browning of Gonadal Adipose Tissue in Ovariectomized Rats.

机构信息

Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Endocr Metab Immune Disord Drug Targets. 2024;24(7):820-831. doi: 10.2174/0118715303239481231030043730.

Abstract

BACKGROUND AND OBJECTIVE

Nitrate, as nitric oxide (NO) donor, has been suggested as a nutrition-based treatment for decreasing the risk of menopause-related obesity. This study aimed to specify the effects of chronic inorganic nitrate administration on uncoupling protein-1 (UCP-1), peroxisome proliferator-activated-receptor-947; (PPAR-947;) coactivator-1945; (PGC-1945;), and PPAR-947; expression in gonadal adipose tissue (GAT) of ovariectomized (OVX) rats.

METHODS

Female rats were assigned to 3 groups: Control, OVX, and OVX+nitrate (n=7/group), which consumed water containing inorganic nitrate (100 mg/L) for 9 months. At month 9, GAT was used for the measurement of NO metabolites (NOx), mRNA levels of NO synthases (endothelial (eNOS), inducible (iNOS), neuronal (nNOS)), and mRNA and protein levels of UCP-1, PGC-1945;, and PPAR-947;.

RESULTS

OVX rats had lower NOx concentration (45%) and eNOS (38%) and nNOS (30%) expression in GAT that was restored to normal values following nitrate administration. OVX rats had significantly lower mRNA and protein levels of UCP-1 (83% and 30%), PGC-1945; (65% and 39%), and PPAR-947; (66% and 34.5%) in GAT. Chronic inorganic nitrate administration in OVXrats increased mRNA and protein levels of UCP-1 (128% and 34%), PGC-1945; (115% and 43%), and PPAR-947; (236% and 38%), respectively.

CONCLUSION

In OVX rats, chronic nitrate administration increased gene and protein levels of UCP-1, PGC-1945;, and PPAR-947; in GAT, indicating the anti-obesity effects of nitrate are partially mediated by the white adipose tissue (WAT) browning. Moreover, the stimulatory effect of inorganic nitrate on the WAT browning in OVX rats was associated with blunting the OVXinduced NO deficiency in GAT.

摘要

背景与目的

硝酸盐作为一氧化氮(NO)供体,已被提议作为一种基于营养的治疗方法,以降低与绝经相关的肥胖风险。本研究旨在明确慢性无机硝酸盐给药对去偶蛋白-1(UCP-1)、过氧化物酶体增殖物激活受体-947;(PPAR-947;)共激活因子-1945;(PGC-1945;)和 PPAR-947;在卵巢切除(OVX)大鼠性腺脂肪组织(GAT)中的表达。

方法

将雌性大鼠分为 3 组:对照组、OVX 组和 OVX+硝酸盐组(n=7/组),它们在 9 个月内饮用含有无机硝酸盐(100mg/L)的水。在第 9 个月时,使用 GAT 测量 NO 代谢物(NOx)、NO 合酶(内皮(eNOS)、诱导型(iNOS)、神经元(nNOS))的 mRNA 水平以及 UCP-1、PGC-1945;和 PPAR-947;的 mRNA 和蛋白水平。

结果

OVX 大鼠的 GAT 中 NOx 浓度(45%)和 eNOS(38%)以及 nNOS(30%)表达降低,而硝酸盐给药后恢复正常。OVX 大鼠的 GAT 中 UCP-1(83%和 30%)、PGC-1945;(65%和 39%)和 PPAR-947;(66%和 34.5%)的 mRNA 和蛋白水平明显降低。慢性无机硝酸盐给药可增加 OVX 大鼠的 GAT 中 UCP-1(128%和 34%)、PGC-1945;(115%和 43%)和 PPAR-947;(236%和 38%)的 mRNA 和蛋白水平。

结论

在 OVX 大鼠中,慢性硝酸盐给药可增加 GAT 中 UCP-1、PGC-1945;和 PPAR-947;的基因和蛋白水平,表明硝酸盐的抗肥胖作用部分是通过白色脂肪组织(WAT)褐变介导的。此外,无机硝酸盐对 OVX 大鼠 WAT 褐变的刺激作用与 GAT 中 OVX 诱导的 NO 缺乏有关。

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