Challenges in tackling energy expenditure as obesity therapy: From preclinical models to clinical application

Mona C. Löffler, Matthias J. Betz, Denis P. Blondin, Robert Augustin, ... Heike Neubauer

Maintenance of energy homeostasis and body weight requires a balance between energy intake, loss, and expenditure. An imbalance in this energy homeostasis leads to obesity. Attempts to treat obesity, may either focus on decreasing energy intake or increasing energy expenditure/loss; ideally combining several aspects. The major organs involved are shown in this illustration.


A chronic imbalance of energy intake and energy expenditure results in excess fat storage. The obesity often caused by this overweight is detrimental to the health of millions of people. Understanding both sides of the energy balance equation and their counter-regulatory mechanisms is critical to the development of effective therapies to treat this epidemic.

Scope of review

Behaviors surrounding ingestion have been reviewed extensively. This review focuses more specifically on energy expenditure regarding bodyweight control, with a particular emphasis on the organs and attractive metabolic processes known to reduce bodyweight. Moreover, previous and current attempts at anti-obesity strategies focusing on energy expenditure are highlighted. Precise measurements of energy expenditure, which consist of cellular, animal, and human models, as well as measurements of their translatability, are required to provide the most effective therapies.

Major conclusions

A precise understanding of the components surrounding energy expenditure, including tailored approaches based on genetic, biomarker, or physical characteristics, must be integrated into future anti-obesity treatments. Further comprehensive investigations are required to define suitable treatments, especially because the complex nature of the human perspective remains poorly understood.