Transcriptome Analyses of Adipose Tissue Samples Identify EGFL6 as a Candidate Gene Involved in Obesity-Related Adipose Tissue Dysfunction in Children

• Published in: International journal of molecular sciences Vol. 23; no. 8; p. 4349
• Main Authors: Landgraf, Kathrin, Kühnapfel, Andreas, Schlanstein, Maria, Biemann, Ronald, Isermann, Berend, Kempf, Elena, Kirsten, Holger, Scholz, Markus, Körner, Antje
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.04.2022; MDPI
• Subjects: adipocyte; adipocyte hypertrophy; Adipocytes; Adipocytes - metabolism; Adiponectin; Adipose tissue; Adipose Tissue - metabolism; adipose tissue dysfunction; Age; Body fat; Body mass index; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Cell Adhesion Molecules - metabolism; Child; Children; Diabetes; Disease; Epidermal growth factor; Gene expression; Gene Expression Profiling; Genomes; Growth factors; Humans; Hypertrophy; Inflammation; Laboratories; Leptin; Leptin - genetics; Leptin - metabolism; Macrophages; Metabolic disorders; Metabolic pathways; Metabolic syndrome; Obesity; Obesity - metabolism; Overweight; Parameters; Pathogenesis; Software; Surgery; Transcriptomes; Weight control; United States > US; Germany; EGFL6; adipose tissue dysfunction; children; transcriptome; adipocyte; adipose tissue; metabolic disease; adipocyte hypertrophy; obesity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23084349

Obesity develops early in childhood and is accompanied by early signs of adipose tissue (AT) dysfunction and metabolic disease in children. In order to analyse the molecular processes during obesity-related AT accumulation in children, we investigated genome-wide expression profiles in AT samples, isolated adipocytes, and stromal vascular fraction (SVF) cells and assessed their relation to obesity as well as biological and functional AT parameters. We detected alterations in gene expression associated with obesity and related parameters, i.e., BMI SDS, adipocyte size, macrophage infiltration, adiponectin, and/or leptin. While differential gene expression in AT and adipocytes shared an enrichment in metabolic pathways and pathways related to extracellular structural organisation, SVF cells showed an overrepresentation in inflammatory pathways. In adipocytes, we found the strongest positive association for epidermal growth factor-like protein 6 ( ) with adipocyte hypertrophy. was also upregulated during in vitro adipocyte differentiation. In children, expression was positively correlated to parameters of AT dysfunction and metabolic disease such as macrophage infiltration into AT, hs-CRP, leptin levels, and HOMA-IR. In conclusion, we provide evidence for early alterations in AT gene expression related to AT dysfunction in children and identified as potentially being involved in processes underlying the pathogenesis of metabolic disease.