  Adipose tissue (AT) transcriptome studies provide holistic pictures of
adaptation to weight and related bioclinical settings changes. Objective To
implement AT gene expression profiling and investigate the link between changes
in bioclinical parameters and AT gene expression during 3 steps of a 2-phase
dietary intervention (DI). Methods AT transcriptome profiling was obtained from
sequencing 1051 samples, corresponding to 556 distinct individuals enrolled in
a weight loss intervention (8-week low-calorie diet (LCD) at 800 kcal/day)
followed with a 6-month ad libitum randomized DI. Transcriptome profiles
obtained with QuantSeq sequencing were benchmarked against Illumina RNAseq.
Reverse transcription quantitative polymerase chain reaction was used to
further confirm associations. Cell specificity was assessed using freshly
isolated cells and THP-1 cell line. Results During LCD, 5 modules were found,
of which 3 included at least 1 bioclinical variable. Change in body mass index
(BMI) connected with changes in mRNA level of genes with inflammatory response
signature. In this module, change in BMI was negatively associated with changes
in expression of genes encoding secreted protein (GDF15, CCL3, and SPP1).
Through all phases of the DI, change in GDF15 was connected to changes in SPP1,
CCL3, LIPA and CD68. Further characterization showed that these genes were
specific to macrophages (with LIPA, CD68 and GDF15 expressed in
anti-inflammatory macrophages) and GDF15 also expressed in preadipocytes.
Conclusion Network analyses identified a novel AT feature with GDF15
upregulated with calorie restriction induced weight loss, concomitantly to
macrophage markers. In AT, GDF15 was expressed in preadipocytes and macrophages
where it was a hallmark of anti-inflammatory cells.
