Abstract
It is difficult to imagine that an individual living with obesity may gain body weight in response to a diet and physical activity program aiming at a negative energy balance. However, this type of case is a matter of usual occurrence in obesity clinics and has been traditionally explained by a lack of adherence to guidelines. While a link between adherence to a weight loss intervention and its outcome has been demonstrated, there is growing evidence showing that unsuccessful response to weight-reducing programs may happen in some individuals despite adequate adherence, be it imposed experimentally or spontaneously expressed in a free-living context. As described in this paper, the response to a weight loss program may range from a weight gain to a greater than expected weight loss. Based on our research findings and available literature, an unsuccessful body-weight response is seen in 5% to 20% of individuals and is attributable to behavioral and metabolic changes affecting appetite control and thermogenesis. Experimental evidence also shows that the response to a negative-energy balance is genetically determined. Globally, these observations emphasize the importance of future research in precision medicine to develop treatment approaches that progressively become more individualized.