Identification of distinct transcriptome signatures of human adipose tissue from fifteen depots.
Dorit JohnKerstin KrauseTobias WohlandClaudia GebhardtNicolas LinderMichael StumvollMatthias BlüherIngo BechmannPeter KovacsMartin GerickeAnke TönjesPublished in: European journal of human genetics : EJHG (2020)
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.
Keyphrases
- adipose tissue
- insulin resistance
- gene expression
- genome wide
- endothelial cells
- high fat diet
- oxidative stress
- extracellular matrix
- single cell
- rna seq
- poor prognosis
- healthcare
- induced pluripotent stem cells
- metabolic syndrome
- dna methylation
- high fat diet induced
- pluripotent stem cells
- fatty acid
- type diabetes
- polycystic ovary syndrome
- public health
- skeletal muscle
- emergency department
- binding protein
- physical activity
- cell death
- artificial intelligence
- machine learning
- big data
- single molecule
- mental health
- south africa
- long non coding rna
- climate change
- endoplasmic reticulum stress
- deep learning
- cell cycle arrest
- body mass index
- pi k akt
- kidney transplantation
- bioinformatics analysis