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Body Composition and Metabolic Caging Analysis in High Fat Fed Mice
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Altered Hippocampal Transcriptomic Profile Reveals Cognitive Impairment in Young Metabolically Obese, Normal-Weight

Carmen García-Ruano1,2,3, Andrea Costa1,2,3,4, Andreu Palou1,2,3

  • 1Nutrigenomics, Biomarkers and Risk Evaluation (NuBE) Group, University of the Balearic Islands (UIB), Palma, Mallorca, Spain.

Molecular Nutrition & Food Research
|September 13, 2025
PubMed
Summary

Early high-fat diet exposure impairs cognitive function and alters gene expression. Leptin supplementation during development may prevent these negative effects, offering potential therapeutic strategies for metabolic and cognitive health.

Keywords:
PBMCcognitionearly biomarkersobesity phenotypesperinatal programming

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Area of Science:

  • Neuroscience
  • Metabolic Health
  • Genomics

Background:

  • Early-life nutrition profoundly influences long-term cognitive and metabolic outcomes.
  • A high-fat diet (HFD) during development can lead to a metabolically obese, normal-weight (MONW) phenotype.
  • Understanding the molecular mechanisms linking early diet to health is crucial.

Purpose of the Study:

  • To investigate transcriptomic changes in the hippocampus and peripheral blood mononuclear cells (PBMCs) of rats exposed to an HFD early in life.
  • To assess the impact of leptin supplementation on these transcriptomic alterations and associated cognitive function.
  • To explore the potential of PBMCs as biomarkers for brain health.

Main Methods:

  • Rats were fed either a standard diet or an isocaloric HFD for 11 weeks post-weaning.
  • One HFD group received leptin supplementation during lactation (MONW-Lep).
  • Transcriptomic analysis of hippocampus and PBMCs was performed, alongside working memory assessment (T-maze test).

Main Results:

  • HFD-induced MONW rats showed disrupted hippocampal pathways related to obesity and cognitive decline.
  • Leptin supplementation (MONW-Lep) attenuated these hippocampal changes and preserved working memory.
  • PBMC transcriptomics revealed overlapping gene expression with the hippocampus, including Piwil1, which was upregulated in MONW but not MONW-Lep rats.

Conclusions:

  • Early HFD exposure negatively impacts cognitive function and molecular pathways in the brain.
  • Leptin supplementation during development offers a protective effect against HFD-induced metabolic and cognitive deficits.
  • PBMCs can serve as accessible biomarkers reflecting early brain changes and the efficacy of interventions.