TY - JOUR

T1 - On the pathogenesis of obesity

T2 - causal models and missing pieces of the puzzle

AU - Magkos, Faidon

AU - Sørensen, Thorkild I A

AU - Raubenheimer, David

AU - Dhurandhar, Nikhil V

AU - Loos, Ruth J F

AU - Bosy-Westphal, Anja

AU - Clemmensen, Christoffer

AU - Hjorth, Mads F

AU - Allison, David B

AU - Taubes, Gary

AU - Ravussin, Eric

AU - Friedman, Mark I

AU - Hall, Kevin D

AU - Ludwig, David S

AU - Speakman, John R

AU - Astrup, Arne

N1 - © 2024. Springer Nature Limited.

PY - 2024

Y1 - 2024

N2 - Application of the physical laws of energy and mass conservation at the whole-body level is not necessarily informative about causal mechanisms of weight gain and the development of obesity. The energy balance model (EBM) and the carbohydrate-insulin model (CIM) are two plausible theories, among several others, attempting to explain why obesity develops within an overall common physiological framework of regulation of human energy metabolism. These models have been used to explain the pathogenesis of obesity in individuals as well as the dramatic increases in the prevalence of obesity worldwide over the past half century. Here, we summarize outcomes of a recent workshop in Copenhagen that brought together obesity experts from around the world to discuss causal models of obesity pathogenesis. These discussions helped to operationally define commonly used terms; delineate the structure of each model, particularly focussing on areas of overlap and divergence; challenge ideas about the importance of purported causal factors for weight gain; and brainstorm on the key scientific questions that need to be answered. We hope that more experimental research in nutrition and other related fields, and more testing of the models and their predictions will pave the way and provide more answers about the pathogenesis of obesity than those currently available.

AB - Application of the physical laws of energy and mass conservation at the whole-body level is not necessarily informative about causal mechanisms of weight gain and the development of obesity. The energy balance model (EBM) and the carbohydrate-insulin model (CIM) are two plausible theories, among several others, attempting to explain why obesity develops within an overall common physiological framework of regulation of human energy metabolism. These models have been used to explain the pathogenesis of obesity in individuals as well as the dramatic increases in the prevalence of obesity worldwide over the past half century. Here, we summarize outcomes of a recent workshop in Copenhagen that brought together obesity experts from around the world to discuss causal models of obesity pathogenesis. These discussions helped to operationally define commonly used terms; delineate the structure of each model, particularly focussing on areas of overlap and divergence; challenge ideas about the importance of purported causal factors for weight gain; and brainstorm on the key scientific questions that need to be answered. We hope that more experimental research in nutrition and other related fields, and more testing of the models and their predictions will pave the way and provide more answers about the pathogenesis of obesity than those currently available.

U2 - 10.1038/s42255-024-01106-8

DO - 10.1038/s42255-024-01106-8

M3 - Review

C2 - 39164418

JO - Nature Metabolism

JF - Nature Metabolism

SN - 2522-5812

ER -