Network Analyses Reveal Negative Link Between Changes in Adipose Tissue GDF15 and BMI During Dietary-induced Weight Loss

Alyssa Imbert; Nathalie Vialaneix; Julien Marquis; Julie Vion; Aline Charpagne; Sylviane Metairon; Claire Laurens; Cedric Moro; Nathalie Boulet; Ondine Walter; Grégory Lefebvre; Jörg Hager; Dominique Langin; Wim H M Saris; Arne Astrup; Nathalie Viguerie; Armand Valsesia

doi:10.1210/clinem/dgab621

Network Analyses Reveal Negative Link Between Changes in Adipose Tissue GDF15 and BMI During Dietary-induced Weight Loss

J Clin Endocrinol Metab. 2022 Jan 1;107(1):e130-e142. doi: 10.1210/clinem/dgab621.

Authors

Alyssa Imbert^{1

2

3}, Nathalie Vialaneix³, Julien Marquis⁴, Julie Vion^{1

2}, Aline Charpagne⁵, Sylviane Metairon⁵, Claire Laurens^{1

2}, Cedric Moro^{1

2}, Nathalie Boulet^{1

6}, Ondine Walter⁵, Grégory Lefebvre⁵, Jörg Hager⁵, Dominique Langin^{1

2

7

8}, Wim H M Saris⁹, Arne Astrup¹⁰, Nathalie Viguerie^{1

2

7}, Armand Valsesia⁵

Affiliations

¹ Institut National de la Santé et de la Recherche Médicale (Inserm), UMR1297, Institute of Metabolic and Cardiovascular Diseases, Team Metabolic Disorders and Diabesity, 31400, Toulouse, France.
² Université de Toulouse, UMR1297, Institute of Metabolic and Cardiovascular Diseases, Paul Sabatier University, 31400, Toulouse, France.
³ INRAE, UR875 Mathématiques et Informatique Appliquées Toulouse, F-31326 Castanet-Tolosan, France.
⁴ Université de Lausanne, Genomic Technologies Facility, 1015, Lausanne, Switzerland.
⁵ Nestlé Institute of Health Sciences, Metabolic Health Department, 1015, Lausanne, Switzerland.
⁶ Institut National de la Santé et de la Recherche Médicale (Inserm), UMR1297, Institute of Metabolic and Cardiovascular Diseases, Team Adipose tissue, microbiota and cardiometabolic flexibility, 31400, Toulouse, France.
⁷ Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague and Paul Sabatier University, Toulouse, France.
⁸ Toulouse University Hospitals, Laboratory of Clinical Biochemistry, 31000, Toulouse, France.
⁹ Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
¹⁰ Department of Nutrition, Exercise and Sports, Faculty of Sciences, University of Copenhagen, Denmark.

PMID: 34415992
DOI: 10.1210/clinem/dgab621

Abstract

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 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.

Trial registration: ClinicalTrials.gov NCT00390637.

Keywords: Adipocyte; inflammation; low calorie diet; macrophage; network analyses; weight loss.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue / metabolism
Adipose Tissue / pathology*
Adult
Biomarkers / metabolism
Body Mass Index
Diet, Reducing*
Female
Follow-Up Studies
Gene Regulatory Networks*
Growth Differentiation Factor 15 / genetics
Growth Differentiation Factor 15 / metabolism*
Humans
Male
Obesity / metabolism
Obesity / pathology*
Prognosis
Transcriptome*
Weight Loss*

Substances

Biomarkers
GDF15 protein, human
Growth Differentiation Factor 15

Associated data

ClinicalTrials.gov/NCT00390637