Acute Adaptation of Energy Expenditure Predicts Diet-Induced Weight Loss: Revisiting the Thrifty Phenotype.

Abstract

Energy expenditure decreases in response to weight loss. Although this phenomenon is likely driven, at least in part, by neuroendocrine adaptations to caloric imbalance, its underlying molecular mechanisms are not yet fully elucidated (1). Because adaptive thermogenesis intensifies and is sustained over time as weight loss increases (2,3), it is considered to mitigate weight loss. The variability of adaptive thermogenesis in response to weight changes has also been suggested to contribute to an individual’s relative susceptibility to obesity and associated complications, such as type 2 diabetes. Rooted in a gene-centered view of evolution and natural selection, this notion was coined the “thrifty gene” hypothesis (4). Its genetic basis having been largely refuted (5), this theory has now been supplanted by the “thrifty phenotype” hypothesis. The thrifty phenotype, originally applied to the susceptibility toward type 2 diabetes and later extended to obesity and its other complications, is thought to result from the complex interplay of environmental cues with the genome known as epigenetic mechanisms (6). In this issue of Diabetes , Reinhardt et al. (7) report on testing their hypothesis that individuals who display greater reduction in energy expenditure during fasting or weaker increases during overfeeding (i.e., a thrifty phenotype) are resistant to weight loss. After an initial weight-maintenance period, the authors submitted 12 obese volunteers …