Factors affecting weight loss variability in obesity

Current obesity treatment strategies include diet, exercise, bariatric surgery, and a limited but growing repertoire of medications. Individual weight loss in response to each of these strategies is highly variable. Here we review research into factors potentially contributing to inter-individual variability in response to treatments for obesity, with a focus on studies in humans. Well-recognized factors associated with weight loss capacity include diet adherence, physical activity, sex, age, and specific medications. However, following control for each of these, differences in weight loss appear to persist in response to behavioral, pharmacological and surgical interventions. Adaptation to energy deficit involves complex feedback mechanisms, and inter-individual differences likely to arise from a host of poorly defined genetic factors, as well as differential responses in neurohormonal mechanisms (including gastrointestinal peptides), metabolic efficiency and capacity of tissues, non-exercise activity thermogenesis, thermogenic response to food, and in gut microbiome. A better understanding of the factors involved in inter-individual variability in response to therapies will guide more personalized approaches to the treatment of obesity.