The Metabolically Obese, Normal-Weight Phenotype in Young Rats Is Associated with Cognitive Impairment and Partially...

Area of Science:

• Neuroscience
• Metabolic Health
• Developmental Biology

Background:

• High-fat diets (HFDs) and obesity are associated with cognitive deficits.
• The impact of an early metabolically obese, normal-weight (MONW) phenotype on cognition is not well understood.

Purpose of the Study:

• To investigate if an early MONW phenotype induced by HFD in young rats leads to cognitive dysfunction.
• To evaluate the cognitive benefits of neonatal leptin intake in the context of early HFD exposure.

Main Methods:

• Wistar rats received leptin or vehicle during lactation, followed by HFD or control diet post-weaning.
• Working memory was assessed using a T-maze.
• Hippocampal and peripheral blood mononuclear cell (PBMC) gene expression was analyzed using real-time RT-qPCR.

Main Results:

• Young MONW-like rats exhibited hippocampal gene expression changes and reduced working memory.
• Leptin-treated animals showed similar gene expression changes but maintained working memory despite HFD, partly due to improved insulin sensitivity.
• PBMC Syn1 expression correlated with cognitive health, reflecting HFD effects and leptin's benefits.

Conclusions:

• Early-onset MONW phenotype is linked to cognitive dysfunction and transcriptomic changes in PBMCs.
• Neonatal leptin intake can partially mitigate cognitive impairment caused by early HFD consumption.
• PBMC Syn1 expression serves as a potential biomarker for early cognitive health assessment.