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Published on: May 19, 2023
Transcriptome Analyses of Adipose Tissue Samples Identify EGFL6 as a Candidate Gene Involved in Obesity-Related
Kathrin Landgraf1, Andreas Kühnapfel2, Maria Schlanstein1
1Center for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, Leipzig University, 04103 Leipzig, Germany.
Insights
Childhood obesity shows early adipose tissue dysfunction. Gene expression changes, particularly involving EGFL6, are linked to metabolic disease development in children.
Area of Science:
- Molecular biology
- Pediatric endocrinology
- Metabolic disease research
Background:
- Childhood obesity is linked to early adipose tissue (AT) dysfunction and metabolic disease.
- Understanding molecular changes in pediatric AT is crucial for early intervention.
Purpose of the Study:
- To investigate genome-wide gene expression profiles in pediatric adipose tissue (AT) during obesity.
- To identify molecular pathways and specific genes associated with AT dysfunction and metabolic disease in children.
Main Methods:
- Analysis of genome-wide expression profiles in AT samples, isolated adipocytes, and stromal vascular fraction (SVF) cells from children.
- Assessment of gene expression in relation to obesity parameters (BMI SDS, adipocyte size, macrophage infiltration, adiponectin, leptin).
- In vitro studies of epidermal growth factor-like protein 6 (EGFL6) during adipocyte differentiation and correlation analysis in children.
Main Results:
- Obesity in children is associated with altered gene expression in AT, adipocytes, and SVF cells.
- Metabolic and extracellular structural pathways were enriched in AT and adipocytes, while SVF cells showed enrichment in inflammatory pathways.
- EGFL6 expression in adipocytes positively correlated with adipocyte hypertrophy, AT dysfunction markers (macrophage infiltration, hs-CRP, leptin), and insulin resistance (HOMA-IR).
Conclusions:
- Early alterations in gene expression within adipose tissue are associated with AT dysfunction in children.
- EGFL6 is identified as a potential key player in the pathogenesis of childhood obesity-related metabolic disease.
Abstract:
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 (EGFL6) with adipocyte hypertrophy. EGFL6 was also upregulated during in vitro adipocyte differentiation. In children, EGFL6 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 EGFL6 as potentially being involved in processes underlying the pathogenesis of metabolic disease.
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