High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism
High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism
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DOI：
10.1073/pnas.1713837115
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发表时间：
2018-03-20
影响因子：
11.1
通讯作者：
Johnson, Richard J.
中科院分区：
文献类型：
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作者：
Lanaspa, Miguel A.;Kuwabara, Masanari;Johnson, Richard J.
针对肥胖的饮食指南通常侧重于三类食物（碳水化合物、脂肪和蛋白质）和热量限制。摄入无热量营养素，如盐，很少被讨论。然而，最近有报道称高盐摄入可以预测肥胖和胰岛素抵抗的发展。这种效应的机制尚不清楚。本研究表明，高盐摄入激活了肝脏和下丘脑中的醛糖还原酶-果糖激酶途径，导致内源性果糖产生，同时产生瘦素抵抗和贪食，从而导致肥胖、胰岛素抵抗和脂肪肝。研究还发现，在健康人群中，高盐饮食可以预测糖尿病和非酒精性脂肪肝的发展。这些研究提供了对肥胖和糖尿病发病机制的见解，并提出了减少盐摄入量作为降低肥胖和代谢综合征发生风险的额外干预方法的潜力。
Dietary guidelines for obesity typically focus on three food groups (carbohydrates, fat, and protein) and caloric restriction. Intake of noncaloric nutrients, such as salt, are rarely discussed. However, recently high salt intake has been reported to predict the development of obesity and insulin resistance. The mechanism for this effect is unknown. Here we show that high intake of salt activates the aldose reductase-fructokinase pathway in the liver and hypothalamus, leading to endogenous fructose production with the development of leptin resistance and hyperphagia that cause obesity, insulin resistance, and fatty liver. A high-salt diet was also found to predict the development of diabetes and nonalcoholic fatty liver disease in a healthy population. These studies provide insights into the pathogenesis of obesity and diabetes and raise the potential for reduction in salt intake as an additional interventional approach for reducing the risk for developing obesity and metabolic syndrome.