Translational potential of mouse models of human metabolic disease

Authors: FAROOQI, I - University Of Cambridge; XU, YONG - Children'S Nutrition Research Center (CNRC)

Submitted to: Cell
Publication Type: Review Article
Publication Acceptance Date: 7/5/2024
Publication Date: 7/24/2024
Citation: Farooqi, I., Xu, Y. 2024. Translational potential of mouse models of human metabolic disease. Cell. https://doi.org/10.1016/j.cell.2024.07.011.
DOI: https://doi.org/10.1016/j.cell.2024.07.011

Interpretive Summary: Obesity causes a lot of health problems and deaths worldwide. Over the last thirty years, research has greatly improved our understanding of how our bodies regulate energy, thanks to important discoveries in mouse models of metabolic diseases. However, not all findings from rodent studies apply to humans, which has slowed down drug development in this area. This review looks at how studies in both mice and humans have shaped our current understanding of energy regulation, discusses the challenges and limitations of these studies, and suggests that future research in humans will be crucial for discovering disease mechanisms and identifying new treatments.

Technical Abstract: Obesity causes significant morbidity and mortality globally. Research in the last three decades has delivered a step-change in our understanding of the fundamental mechanisms that regulate energy homeostasis, building on foundational discoveries in mouse models of metabolic disease. However, not all findings made in rodents have translated to humans, hampering drug discovery in this field. Here, we review how studies in mice and humans have informed our current framework for understanding energy homeostasis, discuss their challenges and limitations, and offer a perspective on how human studies may play an increas-ingly important role in the discovery of disease mechanisms and identification of therapeutic targets in the future.