Rules for body fat interventions based on an operating point mechanism

Alon Bar; Omer Karin; Avi Mayo; Danny Ben-Zvi; Uri Alon

doi:10.1016/j.isci.2023.106047

Rules for body fat interventions based on an operating point mechanism

iScience. 2023 Jan 25;26(2):106047. doi: 10.1016/j.isci.2023.106047. eCollection 2023 Feb 17.

Authors

Alon Bar¹, Omer Karin^{1

2}, Avi Mayo¹, Danny Ben-Zvi³, Uri Alon¹

Affiliations

¹ Department Molecular Cell Biology, Weizmann Institute, Rehovot, Israel.
² Department of Mathematics, Imperial College London, London, SW7 2AZ, UK.
³ Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.

Abstract

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 ad libitum 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.

Keywords: Biological sciences; Endocrinology; Human metabolism; Mathematical biosciences; Physiology.