TY - JOUR

T1 - Network analyses reveal negative link between changes in adipose tissue GDF15 and BMI during dietary induced weight loss

AU - Imbert, Alyssa

AU - Vialaneix, Nathalie

AU - Marquis, Julien

AU - Vion, Julie

AU - Charpagne, Aline

AU - Metairon, Sylviane

AU - Laurens, Claire

AU - Moro, Cedric

AU - Boulet, Nathalie

AU - Walter, Ondine

AU - Lefebvre, Grégory

AU - Hager, Jörg

AU - Langin, Dominique

AU - Saris, Wim H M

AU - Astrup, Arne

AU - Viguerie, Nathalie

AU - Valsesia, Armand

N1 - © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2022

Y1 - 2022

N2 - 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).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/d) 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 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.

AB - 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).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/d) 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 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.

KW - Faculty of Science

KW - Adipocyte

KW - Macrophage

KW - Weight loss

KW - Network analyses

KW - Low calorie diet

KW - Inflammation

U2 - 10.1210/clinem/dgab621

DO - 10.1210/clinem/dgab621

M3 - Journal article

C2 - 34415992

VL - 107

SP - e130-e142

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 1

ER -