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.

Department of Human Biology NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Medical Centre Maastricht The Netherlands

Department of Nutrition Exercise and Sports Faculty of Sciences University of Copenhagen Denmark

Franco Czech Laboratory for Clinical Research on Obesity 3rd Faculty of Medicine Prague and Paul Sabatier University Toulouse France

INRAE UR875 Mathématiques et Informatique Appliquées Toulouse F 31326 Castanet Tolosan France

Institut National de la Santé et de la Recherche Médicale UMR1297 Institute of Metabolic and Cardiovascular Diseases Team Adipose tissue microbiota and cardiometabolic flexibility 31400 Toulouse France

Institut National de la Santé et de la Recherche Médicale UMR1297 Institute of Metabolic and Cardiovascular Diseases Team Metabolic Disorders and Diabesity 31400 Toulouse France

Nestlé Institute of Health Sciences Metabolic Health Department 1015 Lausanne Switzerland

Toulouse University Hospitals Laboratory of Clinical Biochemistry 31000 Toulouse France

Université de Lausanne Genomic Technologies Facility 1015 Lausanne Switzerland

Université de Toulouse UMR1297 Institute of Metabolic and Cardiovascular Diseases Paul Sabatier University 31400 Toulouse France

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An integrated single cell and spatial transcriptomic map of human white adipose tissue

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ClinicalTrials.gov
NCT00390637