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Fat Distribution in Women Is Associated With Depot-Specific Transcriptomic Signatures and Chromatin Structure.

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Body shape influences metabolic health. Chromatin openness in fat cells, particularly in the lower body, may explain differences in metabolic syndrome risk between apple and pear body shapes.

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Area of Science:

  • Genomics and Epigenetics
  • Metabolic Health
  • Adipocyte Biology

Background:

  • Upper body fat (apple shape) increases metabolic syndrome risk compared to lower body fat (pear shape).
  • Previous work linked chromatin openness to preadipocyte gene expression.
  • Molecular drivers of body shape variation remain unclear.

Purpose of the Study:

  • Investigate molecular mechanisms behind body shape differences.
  • Determine the role of chromatin accessibility in adipocyte gene expression related to body fat distribution.
  • Explore links between body shape, adipocyte gene expression, and metabolic health.

Main Methods:

  • Isolated adipocytes from abdominal and gluteofemoral fat in premenopausal women stratified by waist-to-hip ratio.
  • Performed RNA sequencing and assay for transposase-accessible chromatin using sequencing (ATAC-seq).
  • Correlated transcriptomic and epigenomic data with clinical parameters.

Main Results:

  • Lower body fat correlated with improved lipid profiles and glucose metabolism.
  • Gluteofemoral adipocytes from pear shapes showed higher expression of metabolic genes and greater chromatin openness.
  • Apple shapes exhibited higher inflammatory gene expression in both fat depots; abdominal chromatin openness showed minimal differences.
  • Correlation found between gene transcription and open chromatin near transcription start sites.

Conclusions:

  • Chromatin openness in gluteofemoral adipocytes influences gene expression.
  • Epigenetic regulation via chromatin accessibility may contribute to metabolic syndrome predisposition linked to body shape.