High-resolution genomic profiling and locus-specific FISH in subcutaneous and visceral adipose tissue of obese patients

Vivian-Pascal Brandt; Heidrun Holland; Matthias Blüher; Nora Klöting

doi:10.3389/fgene.2023.1323052

High-resolution genomic profiling and locus-specific FISH in subcutaneous and visceral adipose tissue of obese patients

Front Genet. 2024 Mar 7:14:1323052. doi: 10.3389/fgene.2023.1323052. eCollection 2023.

Authors

Vivian-Pascal Brandt¹, Heidrun Holland¹, Matthias Blüher^{2

3}, Nora Klöting^{2

3}

Affiliations

¹ Saxonian Incubator for Clinical Translation (SIKT), University of Leipzig, Leipzig, Germany.
² Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany.
³ Medical Department III-Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany.

Abstract

Obesity is known as a heterogeneous and multifactorial disease. The distribution of body fat is crucial for the development of metabolic complications. Comprehensive genetic analyses on different fat tissues are rare but necessary to provide more detailed information. Therefore, we performed genetic analyses of three patients with obesity using high resolution genome wide SNP array (blood, visceral fat tissue) and fluorescence in situ hybridization (FISH) analyses (visceral and subcutaneous fat tissue). Altogether, we identified 31 small Copy Number Variations (losses: 1p31.1, 1p22.2, 1q21.3, 2q34, 2q37.1, 3q28, 6p25.3, 7q31.33, 7q33, 8p23.3, 10q22.3, 11p15.4, 11p15.1, 11p14.2, 11p12, 13q12.3, 15q11.2-q13.1, 15q13.3, 20q13.2, 22q11.21; gains: 2q22.1-q22.2, 3p14.3, 4p16.3, 4q32.2, 6q27, 7p14.3, 7q34, 11p12, 12p11.21, 16p11.2-p11.1, 17q21.31) and 289 small copy-neutral Loss of Heterozygosity (cn-LOH). For the chromosomal region 15q11.2-q13.1, we detected a microdeletion (Prader-Willi-Syndrome) in one patient. Interestingly, we identified chromosomal SNP differences between EDTA-blood and visceral fat tissue (deletion and gain). Small losses of 7q31.33, 7q33, 11p14.2, 11p12, 13q12.3 as well as small gain of 7q34 were detected only in fat tissue and not in blood. Furthermore, FISH analyses on 7q31.33, 7q33 and 11p12 revealed differences between subcutaneous and visceral fat tissue. Generally, the deletions were detected more frequent in visceral fat tissue. Predominantly detected cn-LOH vs. CNV suggests a meaning of these cn-LOH for the pathogenesis of obesity. We conclude that the SNP array and FISH analyses used is applicable to generate more information for basic research on difficult cell subpopulations (e.g., visceral adipose tissue) and could opens up new diagnostic aspects in the field of obesity. Altogether, the significance of these mostly not yet described genetic aberrations in different fat tissues needs to confirmed in a larger series.

Keywords: SNP array; adiposity; locusspecific FISH; obesity; subcutaneous fat tissue; visceral fat tissue.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was supported by Deutsche Forschungsgemeinschaft (DFG, # 209933838; SFB1052/3 B01 to MB, B04 to NK) and by Saxon Ministry of Science and Fine Arts (SMWK, URL: http://www.smwk.sachsen.de/) to HH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.