Effects of a long-term lifestyle intervention on metabolically healthy women with obesity: Metabolite profiles according to weight loss response.

BACKGROUND & AIMS: The benefits of weight loss in subjects with metabolically healthy obesity (MHO) are still a matter of controversy. We aimed to identify metabolic fingerprints and their associated pathways that discriminate women with MHO with high or low weight loss response after a lifestyle intervention, based on a hypocaloric Mediterranean diet (MedDiet) and physical activity.

METHODS: A UPLC-Q-Exactive-MS/MS metabolomics workflow was applied to plasma samples from 27 women with MHO before and after 12 months of a hypocaloric weight loss intervention with a MedDiet and increased physical activity. The subjects were stratified into two age-matched groups according to weight loss: <10% (low weight loss group, LWL) and >10% (high weight loss group, HWL). Random forest analysis was performed to identify metabolites discriminating between the LWL and the HWL as well as within-status effects. Modulated pathways and associations between metabolites and anthropometric and biochemical variables were also investigated.

RESULTS: Thirteen metabolites discriminated between the LWL and the HWL, including 1,5-anhydroglucitol, carotenediol, 3-(4-hydroxyphenyl)lactic acid, N-acetylaspartate and several lipid species (steroids, a plasmalogen, sphingomyelins, a bile acid and long-chain acylcarnitines). 1,5-anhydroglucitol, 3-(4-hydroxyphenyl)lactic acid and sphingomyelins were positively associated with weight variables whereas N-acetylaspartate and the plasmalogen correlated negatively with them. Changes in very long-chain acylcarnitines and hydroxyphenyllactic levels were observed in the HWL and positively correlated with fasting glucose, and changes in levels of the plasmalogen negatively correlated with insulin resistance. Additionally, the cholesterol profile was positively associated with changes in acid hydroxyphenyllactic, sphingolipids and 1,5-AG.

CONCLUSIONS: Higher weight loss after a hypocaloric MedDiet and increased physical activity for 12 months is associated with changes in the plasma metabolome in women with MHO. These findings are associated with changes in biochemical variables and may suggest an improvement of the cardiometabolic risk profile in those patients that lose greater weight. Further studies are needed to investigate whether the response of those subjects with MHO to this intervention differs from those with unhealthy obesity.