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

TL;DR

This study used adipose tissue transcriptome profiling during a dietary weight loss intervention to identify a negative link between GDF15 expression and BMI changes, highlighting GDF15's role in anti-inflammatory macrophages.

Contribution

It reveals a novel association between GDF15 expression in adipose tissue and weight loss, emphasizing its potential as a biomarker for anti-inflammatory responses during dieting.

Findings

GDF15 expression increases with calorie restriction-induced weight loss.

GDF15 is specifically expressed in anti-inflammatory macrophages and preadipocytes.

Change in BMI is negatively associated with GDF15 and related gene expression changes.

Abstract

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.