Sex Dimorphism in the Metabolome of Metabolic Syndrome in Morbidly Obese Individuals

Abstract

Adult morbid obesity is defined as abnormal or excessive fat accumulation, mostly resulting from a long-term unhealthy lifestyle. Between 10% and 30% of people with obesity exhibit low cardiometabolic risk. The metabolic syndrome has been suggested as an indicator of obesity-related metabolic dysregulation. Although the prevalence of obesity does not seem to be sex-related and metabolic syndrome occurs at all ages, in the last few years, sex-specific differences in the pathophysiology, diagnosis, and treatment of metabolic syndrome have received attention. The aim of this study was to determine the prevalence of metabolic syndrome and its components in different sex and age groups in people with metabolic unhealthy obesity and to compare them with people with metabolic healthy obesity. We analyzed the metabolome in 1350 well-phenotyped morbidly obese individuals and showed that there is a strong sex-dependent association of metabolic syndrome with circulating metabolites. Importantly, we demonstrated that metabolic dysregulation in women and men with severe obesity and metabolic syndrome is age-dependent. The metabolic profiles from our study showed age-dependent sex differences in the impact of MetS which are consistent with the cardiometabolic characterization. Although there is common ground for MetS in the metabolome of severe obesity, men older than 54 are affected in a more extensive and intensive manner. These findings strongly argue for more studies aimed at unraveling the mechanisms that underlie this sex-specific metabolic dysregulation in severe obesity. Moreover, these findings suggest that women and men might benefit from differential sex and age specific interventions to prevent the adverse cardiometabolic effects of severe obesity.