Body-weight-specific and shared metabolomic responses to acute sleep loss in young adults.

introductionInsufficient sleep increases the risk of weight gain and metabolic dysfunction, while obesity is linked to disrupted sleep and metabolic impairment. Although both conditions are tightly interconnected, it remains unclear whether body weight status determines how acute sleep loss alters metabolite levels. We aimed to assess whether acute sleep loss elicits different metabolic responses in individuals with and without obesity, and whether these responses are modified by sex.

methodsIn a within-subject, randomized crossover study, 42 adults (mean age 24.9 years; 18 women, 24 men; 18 with obesity; 24 with normal weight) completed one night of total sleep deprivation (TSD) and one night of normal sleep (NS; 8 h). Morning fasted blood samples were analyzed using targeted metabolomics. Mixed-effects models were used to assess within-individual changes from NS to TSD, and to determine the magnitude and direction of these changes within each body weight group and sex.

resultsIn response to TSD compared with NS, tryptophan levels increased (+12%, FDR < 0.05) only in participants with obesity, while histidine, L-kynurenine, and creatinine levels decreased (4-21%, FDR < 0.05) only in normal-weight individuals. Notably, the kynurenine-to-tryptophan ratio decreased after TSD in both groups, and levels of circulating medium-chain acylcarnitines (+26-39%) increased within both weight groups - together indicating shared metabolic responses to acute sleep deprivation. Exploratory sensitivity analyses indicated that several of these responses were sex-specific. Polysomnography-based sleep architecture during NS, available in a subset of 36 participants, was largely comparable between body weight groups, suggesting that observed metabolic differences were not attributable to baseline differences in sleep structure.

conclusionsAcute sleep loss elicits both shared and body-weight-specific changes in circulating metabolites in young adults. These findings indicate that body-weight status shapes which metabolic pathways respond to a single night of sleep loss, and in what direction, but larger studies are required to confirm the body weight- and sex-specific findings. Given that acute sleep loss is a common metabolic stressor that increases cardiometabolic risk, these differences may contribute to mechanistic hypotheses about the heightened vulnerability to metabolic dysregulation in individuals with obesity who are frequently exposed to sleep loss.