DOI: 10.5061/dryad.7sqv9s4pb
title: Fat distribution in women associates with depot-specific transcriptomics signatures and chromatin structure

description: Preferential accumulation of fat in the upper body (apple shape) is
 associated with higher risk of developing metabolic syndrome relative to
 lower body fat (pear shape). We previously discovered that chromatin
 openness defined partially the transcriptome of pre-adipocytes isolated
 from abdominal and gluteofemoral fat. However, the molecular mechanisms
 underlying inter individual fat repartition variation are unknown.
 Adipocyte fraction was isolated from abdominal and gluteofemoral fat
 biopsies of premenopausal women (age and BMI-matched) segregated initially
 only by their waist to hip ratio. We evaluated transcriptomic and
 chromatin accessibility using RNA-seq and ATAC-seq along with key clinical
 parameters. Our data showed that higher lower body fat mass was associated
 with better lipid profile and free fatty acid turnover after glucose
 administration. Lipid and glucose metabolic pathways genes were expressed
 at higher levels in gluteofemoral adipocyte fraction in pears, while genes
 associated with inflammation were higher in both abdominal and
 gluteofemoral apple adipocyte fraction. Gluteofemoral adipocyte chromatin
 from pear-shaped women contained a significantly higher number of
 differentially open ATAC-seq peaks relative to chromatin from the
 apple-shaped gluteofemoral adipocytes. In contrast, abdominal adipocyte
 chromatin openness showed few differences between apple and pear-shaped
 women. We revealed a correlation between gene transcription and open
 chromatin at the proximity of the TSS of some of the differentially
 expressed genes.
description: <b>Figure
 S1:</b> <b>Depot-specific gene expression in
 adipocytes.</b><b> </b>(A and B) -<b>
 </b>Heat map representation of depot-specific gene expression
 determined by RNA-seq from the abdominal (ABD) and gluteofemoral (GF)
 depots in the 5 apple (left side, in red) and 5 pear-shaped women (right
 side, in blue). (C and D) - Venn diagrams depict number of genes
 up-regulated in each depot only in apples (red circle), only in pears
 (blue circle) or in both groups (intersection). <b>Figure S2:</b>
 <b>ATAC-seq peaks in ABD and GF depots for both groups of body shape
 women. </b>A-<b> </b>Read distribution plot of open
 chromatin regions in apple and pear adipocytes isolated from ABD and GF
 depot from each subject. Sub=Subject; Rep=Replicate. (B-C) Correlation
 plot of all the accessible chromatin regions defined by ATAC-seq from the
 10 participants (Apples and Pears) in Abdominal (B) and gluteofemoral (C)
 depot. D- Genomic distribution of the accessible chromatin regions in
 abdominal and GF depot. E- Graphic representation of the genomic
 distribution of the apple and pear-specific open chromatin regions
 observed in the GF depot (p value&lt;0.05). <b>Figure S3:</b>
 <b>Differential binding analysis identifies depot-specific chromatin
 accessibility in adipocytes isolated from apple and pear-shaped women.
 </b>A- Correlation plot of accessible chromatin regions defined by
 ATAC-seq from fat depots (Gluteofemoral-GF, Abdominal-ABD) in apple women
 (left side, in red) and pear women (right side, in blue). B- Volcano plot
 representation of abdominal and GF-specific open chromatin regions in
 adipocytes isolated from apples (left side, p≤0.05) and pear (right side,
 p≤0.1) women. Abdominal- (highlighted in darker red and darker blue) and
 GF-specific (highlighted in lighter red and lighter blue) open chromatin
 regions are represented. C- Promoter analysis of differentially expressed
 genes in ABD and GF. Boxplot representation of the average RPKM calculated
 from the 5 apple participants (left side) or from the 5 pear participants
 (right side) *p&lt;0.05, **p&lt;0.01, ***p&lt;0.001 paired
 t-test. <b>Figure S4:</b> Heat map representation of
 the individual gene expression data of the nuclear receptor ligand
 identified in abdominal (ABD) and gluteo-femoral (GF) adipocyte fraction
 isolated from apple- and pear-shaped subjects. In red are the nuclear
 receptor ligand the most expressed. <b>SUPPLEMENTAL
 TABLES</b> <b>Table S1. </b>Clinical characteristics of
 the 10 participants used for RNA-seq and ATAC-seq analysis.
 <b>Table S2.
 </b>Computational tools, docker images and Common Workflows
 Language used to process the RNA-Seq data. <b>Table S3.
 </b>List of genes differentially regulated between ABD and GF depot
 in apple- and pear-shaped women. <b>Table S4. </b>List of genes
 differentially regulated between apple and pear group in ABD and GF
 depots. <b>Table S5.</b> List of genes up-regulated
 in apple-shaped women in the GF depot and involved in inflammatory/immune
 pathways with the associated average TPM values (average from 5 apple and
 5 pear subjects). <b>Table S6. </b>List of ATAC-seq peaks
 body-shape specific in ABD and GF depots. <b>Table S7.
 </b>List of ATAC-seq peaks depot-specific in apple- and pear-shaped
 women.