Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice
Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice
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DOI：
10.1073/pnas.1008872107
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发表时间：
2010-10-12
影响因子：
11.1
通讯作者：
Lundberg, Jon O.
中科院分区：
文献类型：
--
作者：
Carlstrom, Mattias;Larsen, Filip J.;Lundberg, Jon O.
代谢综合征是一组代谢源性危险因素，可增加心血管疾病和2型糖尿病的风险。代谢综合征的一个中心事件是内皮NO合酶（eNOS）产生的生物可利用的一氧化氮（NO）的量减少。最近，描述了哺乳动物中NO形成的替代途径，其中无机硝酸盐（假定为惰性NO氧化产物和不需要的膳食成分）连续还原为亚硝酸盐，然后还原为NO和其他生物活性氮氧化物。在这里，我们表明，在eNOS缺陷小鼠中发展的代谢综合征的几个特征可以通过饮食补充硝酸钠来逆转，其量与正常条件下来自eNOS的量相似。在人类中，这一剂量对应于丰富的蔬菜摄入量，这是主要的膳食硝酸盐来源。硝酸盐管理增加组织和血浆中的生物活性氮氧化物水平。此外，慢性硝酸盐治疗减少了内脏脂肪积累和甘油三酯的循环水平，并逆转了这些动物的糖尿病前期表型。在大鼠中，慢性硝酸盐治疗降低血压，这种效果也存在于NOS抑制期间。我们的研究结果表明，膳食硝酸盐燃料硝酸盐-亚硝酸盐-NO途径，可以部分补偿干扰内源性NO生成eNOS。这些发现可能对针对心血管疾病和2型糖尿病的新型基于营养的预防和治疗策略产生影响。
The metabolic syndrome is a clustering of risk factors of metabolic origin that increase the risk for cardiovascular disease and type 2 diabetes. A proposed central event in metabolic syndrome is a decrease in the amount of bioavailable nitric oxide (NO) from endothelial NO synthase (eNOS). Recently, an alternative pathway for NO formation in mammals was described where inorganic nitrate, a supposedly inert NO oxidation product and unwanted dietary constituent, is serially reduced to nitrite and then NO and other bioactive nitrogen oxides. Here we show that several features of metabolic syndrome that develop in eNOS-deficient mice can be reversed by dietary supplementation with sodium nitrate, in amounts similar to those derived from eNOS under normal conditions. In humans, this dose corresponds to a rich intake of vegetables, the dominant dietary nitrate source. Nitrate administration increased tissue and plasma levels of bioactive nitrogen oxides. Moreover, chronic nitrate treatment reduced visceral fat accumulation and circulating levels of triglycerides and reversed the prediabetic phenotype in these animals. In rats, chronic nitrate treatment reduced blood pressure and this effect was also present during NOS inhibition. Our results show that dietary nitrate fuels a nitrate-nitrite-NO pathway that can partly compensate for disturbances in endogenous NO generation from eNOS. These findings may have implications for novel nutrition-based preventive and therapeutic strategies against cardiovascular disease and type 2 diabetes.