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.

肥胖的饮食指南通常着重于三种食物（碳水化合物，脂肪和蛋白质）和热量限制。很少讨论摄入非热量营养素，例如盐。然而，最近有报道称高盐摄入量可预测肥胖和胰岛素抵抗的发展。这种作用的机制尚不清楚。在这里，我们显示出大量摄入的盐会激活肝脏和下丘脑中的醛糖还原酶-果糖激酶途径，导致内源性果糖的产生，并导致瘦素抵抗和食欲亢进，从而导致肥胖症，胰岛素抵抗和脂肪肝。还发现高盐饮食可以预测健康人群中糖尿病和非酒精性脂肪肝的发生。