Identification of distinct transcriptome signatures of human adipose tissue from fifteen depots

Dorit Schleinitz,Ingo Bechmann,Martin Gericke,Michael Stumvoll,Matthias Blüher,Tobias Wohland,Anke Tönjes,Claudia Gebhardt,Peter Kovacs,Kerstin Krause,Nicolas Linder

doi:10.1038/s41431-020-0681-1

Abstract

The functional and metabolic characteristics of specific adipose tissue (AT) depots seem to be determined by intrinsic mechanisms. We performed a comprehensive transcriptome profiling of human AT from distinct fat depots to unravel their unique features potentially explaining molecular mechanisms underlying AT distribution and their contribution to health and disease. Post-mortem AT samples of five body donors from 15 anatomical locations were collected. Global mRNA expression was measured by Illumina® Human HT-12 v4 Expression BeadChips. Data were validated using qPCR and Western Blot in a subset of ATs from seven additional body donors. Buccal and heel AT clearly separated from the “classical” subcutaneous AT depots, and perirenal and epicardial AT were distinct from visceral depots. Gene-set enrichment analyses pointed to an inflammatory environment and insulin resistance particularly in the carotid sheath AT depot. Moreover, the epicardial fat transcriptome was enriched for genes involved in extracellular matrix remodeling, inflammation, immune signaling, coagulation, thrombosis, beigeing, and apoptosis. Interestingly, a striking downregulation of the expression of leptin receptor was found in AT from heel compared with all other AT depots. The distinct gene expression patterns are likely to define fat depot specific AT functions in metabolism, energy storage, immunity, body insulation or as cushions. Improved knowledge of the gene expression profiles of various fat depots may strongly benefit studies aimed at better understanding of the genetics and the pathophysiology of obesity and adverse body fat composition.

Highlights

These authors contributed : Martin Gericke, Anke Tönjes
For example in subjects with lipodystrophy type Dunnigan, the heel fat pad is the only location not affected by the extreme loss of subcutaneous adipose tissue (ScAT) which is observed at the limbs suggesting different pathways of lipid accumulation
AT sections of all 15 studied fat depots revealed a high degree of perilipin expressing adipocytes indicating high tissue viability (Fig. 2, Supplemental Fig. 1)

Summary

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For example in subjects with lipodystrophy type Dunnigan, the heel fat pad is the only location not affected by the extreme loss of subcutaneous adipose tissue (ScAT) which is observed at the limbs suggesting different pathways of lipid accumulation (personal observation, Fig. 1). Lineage tracing studies raise evidence that white adipocytes may derive from different precursors such as mesenchymal progenitors (lateral plate mesoderm) and neural crest stem cells (ectoderm, suggested to be a source of ScAT) [9,10,11,12,13]. This is supported by transcriptional profiling studies that revealed. For validation of microarrays RNA was extracted from seven further body donors (subcutaneous depots (periumbilical region, upper leg, and upper arm) as well as from heel fat pad; Table 1)

Methods

Results

Discussion

Study limitations

Conclusion

Compliance with ethical standards