biostudies-literatureGarcia-Ruano CERDF A way of making EuropeMCIN/AEI/ 10.13039/501100011033/Spanish Governmente70262https://www.ebi.ac.uk/biostudies/studies/S-EPMC12643189biostudies-literatureUnknown69(22)Early-life metabolic environment significantly impacts long-term cognitive and metabolic health. This study investigates transcriptomic alterations in the hippocampus and peripheral blood mononuclear cells (PBMC) of young rats exposed to an isocaloric high-fat diet (HFD), resulting in the metabolically obese, normal-weight (MONW) phenotype. Rats were pair-fed either a standard (NW group) or HFD (MONW group) for 11 weeks after weaning. Another group (MONW-Lep) received leptin supplementation during lactation and subsequently HFD. Transcriptomic analysis of the hippocampus showed disruption of pathways linked to obesity and cognitive decline in the MONW group, which were attenuated by leptin intake. This was consistent with the results of working memory (T-maze test), impaired in MONW versusMolecular nutrition & food researchAltered Hippocampal Transcriptomic Profile Reveals Cognitive Impairment in Young Metabolically Obese, Normal-Weight Rats, Prevented by Perinatal Leptin Intake.PMC12643189FPU20/06127Garcia-Ruano CCosta APalou AOliver PfalseAltered Hippocampal Transcriptomic Profile Reveals Cognitive Impairment in Young Metabolically Obese, Normal-Weight Rats, Prevented by Perinatal Leptin Intake.Early-life metabolic environment significantly impacts long-term cognitive and metabolic health. This study investigates transcriptomic alterations in the hippocampus and peripheral blood mononuclear cells (PBMC) of young rats exposed to an isocaloric high-fat diet (HFD), resulting in the metabolically obese, normal-weight (MONW) phenotype. Rats were pair-fed either a standard (NW group) or HFD (MONW group) for 11 weeks after weaning. Another group (MONW-Lep) received leptin supplementation during lactation and subsequently HFD. Transcriptomic analysis of the hippocampus showed disruption of pathways linked to obesity and cognitive decline in the MONW group, which were attenuated by leptin intake. This was consistent with the results of working memory (T-maze test), impaired in MONW versus2025-01-01T00:00:00Z2025 Nov2026-06-06T14:34:09.237Z2026-05-31T03:10:15.253ZS-EPMC126431894094438410.1002/mnfr.70262