Role of Adaptive Thermogenesis in Unsuccessful Weight-Loss Intervention

Angelo Tremblay; Geneviève Major; Éric Doucet; Paul Trayhurn; Arne Astrup


Future Lipidology. 2007;2(6):651-658. 

In This Article

Adaptive Thermogenesis: A Historical Perspective & a Definition

Neumann was probably the first investigator who reported evidence documenting the possible existence of an adaptive component of energy expenditure. His personal observations pertained to the ability to maintain a stable body weight at various levels of energy intake, suggesting that compensations in energy expenditure have the potential to prevent deviations in energy balance when energy intake is changing. The experiments of Neumann[1] were followed by those of Gulick[2] who also demonstrated body weight stability despite significant variations in the diet. From a technical standpoint, these experiments emphasized the ability to document the existence of adaptive thermogenesis based on the measurement of the energy intake of weight maintenance.

The early works of Neumann and Gulick were followed by numerous investigations in which a large variety of experimental approaches were used. In this regard, Table 1 presents the main methodological strategies that were tested in humans over recent decades with the preoccupation to document the existence of a thermogenic deficit in obesity-prone individuals. These approaches are, in general, well justified from a conceptual standpoint and they are still in use in many laboratories by relying on the most rigorous procedures of standardization. In many cases, the results provided by the studies referenced in Table 1 revealed some thermogenic deficit or related physiological vulnerability in individuals predisposed to obesity. In addition, it is relevant to note that these effects were more easily detectable in weight-reduced obese individuals compared with when obese subjects were tested under conditions of habitual body weight stability. Despite the fact that many of these studies demonstrate the existence of an adaptive component of energy expenditure, the quantitative importance of the documented differences or experimental effects has not reached a level that would have led clinicians to believe that adaptive thermogenesis might be a factor which may influence the success of a weight-loss intervention.

In our opinion, the publication of a series of studies by Leibel et al.[56] has provided significant progress in the characterization of the thermogenic profile of the obese. These studies described the changes in energy expenditure in obese and nonobese individuals submitted to a 10% body weight gain and to a 10 and 20% diet-induced body weight loss. Total and resting energy expenditures were measured by indirect calorimetry at the beginning of each experiment and at each weight plateau after at least 2 weeks of body weight stability. From a technical viewpoint, these authors innovated by calculating predicted values of energy expenditure from fat-free mass and fat mass by using initial measurements as indicators of free-living normal variations in this phenotype. They used their predicted scores for comparison with measured values of energy expenditure following body weight change. In this context, adaptive thermogenesis represented the difference between predicted and measured total or resting energy expenditure values. These variations were substantial since the mean deviation from predicted total daily energy expenditure was -244 and -301 kcal/day following a 10 and 20% body weight loss, respectively. To our knowledge, this was the first time that energy expenditure was analyzed as a clinical variable, specifically, a variable that is compared with reference standardized values with the potential outcome to make a clinical diagnosis.

In continuation of the Leibel et al. studies, some of us investigated the impact of adaptive thermogenesis in the context of a standard weight-loss program. Adaptive thermogenesis was then defined as the decrease in energy expenditure beyond what could be predicted from body weight or its components (fat-free mass and fat mass) under conditions of standardized physical activity in response to a decrease in energy intake. As expected, energy expenditure, be it in the resting[57] or the active[58] state, was significantly more decreased compared with what was predicted by morphological changes. In addition, we recently reported the maximal decrease in resting energy expenditure in this study, which was sufficient to completely compensate for the prescribed energy deficit, possibly going beyond any good compliance of some subjects.[59] In the same paper, we also documented the potential impact of some normally unsuspected environmental factors on adaptive thermogenesis. As discussed in the next section, body weight instability can be considered as a factor that can induce substantial variations in energy expenditure.


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