Bar Alon, Karin Omer, Mayo Avi, Ben-Zvi Danny, Alon Uri
Department Molecular Cell Biology, Weizmann Institute, Rehovot, Israel.
Department of Mathematics, Imperial College London, London, SW7 2AZ, UK.
iScience. 2023 Jan 25;26(2):106047. doi: 10.1016/j.isci.2023.106047. eCollection 2023 Feb 17.
Interventions to reduce fat are important for human health. However, they can have opposing effects such as exercise that decreases fat but increases food intake, or coherent effects such as leptin resistance which raises both. Furthermore, some interventions show an overshoot in food intake, such as recovery from a diet, whereas others do not. To explain these properties we present a graphical framework called the operating point model, based on leptin control of feeding behavior. Steady-state fat and food intake is given by the intersection of two experimental curves - steady-state fat at a given food intake and food intake at a given fat level. Depending on which curve an intervention shifts, it has opposing or coherent effects with or without overshoot, in excellent agreement with rodent data. The model also explains the quadratic relation between leptin and fat in humans. These concepts may guide the understanding of fat regulation disorders.
减少脂肪的干预措施对人类健康很重要。然而，它们可能会产生相反的效果，比如运动虽能减少脂肪，但会增加食物摄入量；或者产生一致的效果，比如瘦素抵抗会同时增加脂肪和食物摄入量。此外，一些干预措施会出现食物摄入量的超调现象，比如节食恢复后，而其他一些则不会。为了解释这些特性，我们基于瘦素对进食行为的控制，提出了一个名为“工作点模型”的图形框架。稳态脂肪和食物摄入量由两条实验曲线的交点给出——给定食物摄入量下的稳态脂肪以及给定脂肪水平下的食物摄入量。根据干预措施使哪条曲线发生移动，它会产生有或无超调的相反或一致的效果，这与啮齿动物的数据高度吻合。该模型还解释了人类瘦素与脂肪之间的二次关系。这些概念可能有助于理解脂肪调节紊乱。
