Network analyses reveal negative link between changes in adipose tissue GDF15 and BMI during dietary induced weight loss.

Context 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 three steps of a two-phase dietary intervention (DI). Design 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/d) followed with a 6-month ad libitum randomized DI. Methods Transcriptome profiles obtained with QuantSeq sequencing were benchmarked against Illumina RNAseq. RT-qPCR was used to further confirm associations. Cell specificity was assessed using freshly isolated cells and THP-1 cell line. Results During LCD, five modules were found, of which three included at least one bio-clinical variable. Change in BMI connected with changes in mRNA level of genes with inflammatory response signature. In this module, change in BMI was negatively associated to 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.