Toward a More Complete (and Less Controversial) Understanding of Energy Expenditure and Its Role in Obesity Pathogenesis
- 1Department of Dental Public Health Sciences, School of Dentistry, University of Washington, Seattle, Washington;
- 2Division of Endocrinology, Metabolism and Nutrition, School of Medicine, University of Washington, Seattle, Washington;
- 3Diabetes and Obesity Center of Excellence, University of Washington, Seattle, Washington.
- Corresponding author: Karl J. Kaiyala, .
The global obesity epidemic has stimulated intense interest in the study of homeostatic mechanisms governing the balance between energy intake and energy expenditure over time, and recent progress in gene targeting and related technologies has pushed mouse models to the forefront of this effort. Although current methods for the measurement of energy expenditure (EE) in mice are sensitive, reproducible, and widely available, their potential to inform the study of obesity remains limited by controversy regarding how best to control for the powerful, independent impact on EE of variation in body size per se (1,2). In this article, we briefly review the recent work that has fueled this controversy and propose an approach to its resolution. We also highlight aspects of EE measurement relevant to obesity pathogenesis that merit additional study. Although we focus on studies in mice, the principles presented can be applied to most other animal models.
Dramatic increases in the prevalence of obesity and its burden of health and economic consequences heighten the need for new insights into mechanisms that govern energy balance. At a superficial level, the problem of obesity resolves to simple math: energy balance, defined as the difference between rates of EE and energy intake (EI), sums over time to determine body energy content stored as fat mass (FM). Hence, obesity can be seen as the consequence of a sustained increase of energy intake relative to energy expenditure. This simplistic thermodynamic explanation, however, belies a far more complex pathophysiology that is crucial for understanding why weight loss is so difficult to achieve and sustain in obese individuals. At the core of this complexity is a biological process termed energy homeostasis, through which energy intake and expenditure are matched over long time intervals to promote the stability of FM. This process is influenced by …