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Related Experiment Video

Updated: Jul 19, 2025

Identification and Dissection of Diverse Mouse Adipose Depots
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Adipose tissue coregulates cognitive function.

Núria Oliveras-Cañellas1,2,3,4, Anna Castells-Nobau1,2,3,4, Lisset de la Vega-Correa1,2,3,4

  • 1Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, Spain.

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|August 11, 2023
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Summary

Obesity links to cognitive decline through an adipose tissue (AT)-brain axis. Gene expression in AT correlates with cognitive performance, offering new diagnostic and therapeutic avenues.

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Area of Science:

  • Neuroscience
  • Metabolomics
  • Genetics

Background:

  • Obesity is a growing concern linked to cognitive decline.
  • Emerging research suggests a connection between adipose tissue (AT) and brain function, termed the AT-brain axis.

Purpose of the Study:

  • To investigate the relationship between adipose tissue gene expression and cognitive performance.
  • To identify specific genes and metabolic pathways involved in the AT-brain axis and their impact on cognition.

Main Methods:

  • RNA sequencing of adipose tissue from three cohorts to identify genes associated with cognitive domains.
  • Analysis of plasma metabolome and gene expression in a large human cohort (816 participants).
  • Functional validation using gene misexpression in *Drosophila* models to assess effects on memory and learning.

Main Results:

  • 188 genes in AT were significantly associated with cognitive performance, primarily involved in synaptic function, lipid and vitamin metabolism, and immune signaling.
  • Circulating gene expression levels in plasma mirrored these associations in a large human cohort.
  • Down-regulation of *SLC18A2* and up-regulation of *RIMS1* in *Drosophila* fat body modulated cognitive abilities, with *SLC18A2* down-regulation improving cognition in mice.

Conclusions:

  • Establishes a novel link between the adipose tissue transcriptome and human brain function.
  • Identifies specific genes and pathways in AT as potential diagnostic and therapeutic targets for cognitive decline associated with obesity.