State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, PRC; University of Chinese Academy of Sciences, Shijingshan District, Beijing 100049, PRC; Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen AB24 2TZ, Scotland, UK.
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, PRC; University of Chinese Academy of Sciences, Shijingshan District, Beijing 100049, PRC.
Cell Metab. 2021 May 4;33(5):888-904.e6. doi: 10.1016/j.cmet.2021.01.017. Epub 2021 Mar 4.
The protein leverage hypothesis predicts that low dietary protein should increase energy intake and cause adiposity. We designed 10 diets varying from 1% to 20% protein combined with either 60% or 20% fat. Contrasting the expectation, very low protein did not cause increased food intake. Although these mice had activated hunger signaling, they ate less food, resulting in decreased body weight and improved glucose tolerance but not increased frailty, even under 60% fat. Moreover, they did not show hyperphagia when returned to a 20% protein diet, which could be mimicked by treatment with rapamycin. Intracerebroventricular injection of AAV-S6K1 significantly blunted the decrease in both food intake and body weight in mice fed 1% protein, an effect not observed with inhibition of eIF2a, TRPML1, and Fgf21 signaling. Hence, the 1% protein diet induced decreased food intake and body weight via a mechanism partially dependent on hypothalamic mTOR signaling.
蛋白质杠杆假说预测，低蛋白饮食应该会增加能量摄入并导致肥胖。我们设计了 10 种饮食，蛋白质含量从 1%到 20%不等，同时结合 60%或 20%的脂肪。出乎意料的是，极低蛋白饮食并没有导致食物摄入量增加。尽管这些小鼠的饥饿信号已被激活，但它们吃得更少，导致体重减轻和葡萄糖耐量改善，但不会增加脆弱性，即使在 60%的脂肪饮食下也是如此。此外，当它们回到 20%蛋白质饮食时，它们并没有表现出暴食，而雷帕霉素的治疗可以模拟这种情况。脑室内注射 AAV-S6K1 可显著减弱 1%蛋白质饮食喂养的小鼠的食物摄入量和体重下降，而抑制 eIF2a、TRPML1 和 Fgf21 信号则没有观察到这种效果。因此，1%蛋白质饮食通过部分依赖于下丘脑 mTOR 信号的机制诱导食物摄入量和体重下降。
