RT Journal Article T1 Effects of a long-term lifestyle intervention on metabolically healthy women with obesity: Metabolite profiles according to weight loss response. A1 Palau-Rodriguez, Magali A1 Garcia-Aloy, Mar A1 Miñarro, Antonio A1 Bernal-Lopez, M Rosa A1 Brunius, Carl A1 Gómez-Huelgas, Ricardo A1 Landberg, Rikard A1 Tinahones, Francisco J A1 Andres-Lacueva, Cristina K1 LC-MS K1 Lifestyle intervention K1 Mediterranean diet K1 Metabolically healthy obese K1 Metabolomics K1 Obesity AB 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. 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% (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. 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. 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. PB Elsevier YR 2019 FD 2019-01-15 LK http://hdl.handle.net/10668/13694 UL http://hdl.handle.net/10668/13694 LA en NO Palau-Rodriguez M, Garcia-Aloy M, Miñarro A, Bernal-Lopez MR, Brunius C, Gómez-Huelgas R, et al. Effects of a long-term lifestyle intervention on metabolically healthy women with obesity: Metabolite profiles according to weight loss response. Clin Nutr. 2020 Jan;39(1):215-224 NO This work was supported by the Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL) [grant number FOODBALL-PCIN-2014-133], the award of the Generalitat de Catalunya’s Agency AGAUR [grant number 2017SGR1546] and the Instituto de Salud Carlos III de Madrid, Spain, PI12/01373, CIBERFES and CIBEROBN co-financed by the Fondo Europeo de Desarrollo Regional-FEDER. Additionally, this work was partly supported by a grant from the Associacio Catalana de Diabetis [Ajut de Recerca en Diabetis 2016, modalitat basica]. M.P.R was supported the APIF- INSA-UB fellowship (University of Barcelona), and M Rosa BernalLopez was supported by the “Miguel Servet Type I” programme (CP15/00028) from the ISCIII-Madrid (Spain), co-financed by the Fondo Europeo de Desarrollo Regional-FEDER. CA-L gratefully acknowledges the financial support by ICREA under the ICREA Academia programme. DS RISalud RD Apr 5, 2025