Effect of β3-Adrenergic Receptor Gene Polymorphism on Aerobic Exercise-Induced Lipolytic Response

Introduction: Diet and exercise interventions reduce the risk of obesity; however, fat loss varies across individuals. During moderate-intensity aerobic exercise, norepinephrine stimulates adipose lipolysis via β3-adrenergic receptors (β3AR). The β3AR Trp64Arg polymorphism has been linked to reduced lipolytic responsiveness. This study examined whether Trp64Arg influences fat breakdown during aerobic exercise in young women. We hypothesized that Trp64Arg carriers (Trp/Arg) would show a blunted rise in circulating free fatty acids (FFA) and higher respiratory quotient (RQ; VCO₂/VO₂) during exercise than that of non-carriers (Trp/Trp). Methods: Thirty-seven healthy female university students (20–23 years) completed 40 min of cycling at 55 W after a standardized dinner and 12-h fast. Serum FFA, energy expenditure, and RQ were measured at rest and during exercise. Participants were genotyped and classified as wild-type (Trp/Trp; n = 29) or heterozygous (Trp/Arg; n = 8). Repeated-measures analyses tested group, time, and group × time effects; estimated marginal means were used for model-based summaries. Results: Serum FFA at 40 min increased compared to that of rest in both groups, but reached significance only in the wild-type group (2.04 ± 1.25 vs 0.90 ± 0.48 mEq/L, p = 0.009). During exercise, RQ differed according to genotype (main effect of group: p = 0.003; group × time: p = 0.065), with higher RQ in heterozygous participants (0.91 ± 0.02, 95% CI 0.88–0.94) than in the wild-type group (0.86 ± 0.01, 95% CI 0.84–0.88). Conclusions: In young women, carrying the Trp64Arg polymorphism of the β3AR gene potentially contributes to a blunted lipolytic response and relatively high reliance on carbohydrate metabolism during moderate-intensity aerobic exercise.