m6A Regulators in Human Adipose Tissue - Depot-Specificity and Correlation With Obesity

• Published in: Frontiers in endocrinology (Lausanne) Vol. 12; p. 778875
• Main Authors: Rønningen, Torunn, Dahl, Mai Britt, Valderhaug, Tone Gretland, Cayir, Akin, Keller, Maria, Tönjes, Anke, Blüher, Matthias, Böttcher, Yvonne
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 07-12-2021
• Subjects: Adenosine - analogs & derivatives; Adenosine - metabolism; Adipose Tissue - metabolism; Adipose Tissue - pathology; Adult; Aged; AlkB Homolog 5, RNA Demethylase - genetics; AlkB Homolog 5, RNA Demethylase - metabolism; Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics; Alpha-Ketoglutarate-Dependent Dioxygenase FTO - metabolism; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cohort Studies; Endocrinology; Epigenesis, Genetic - physiology; epitranscriptome; fat distribution; Female; Germany; Humans; m6A methylation; Male; Middle Aged; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; obesity; Obesity - genetics; Obesity - metabolism; Obesity - pathology; Organ Specificity - genetics; Polymorphism, Single Nucleotide; RNA methylome; RNA Processing, Post-Transcriptional - genetics; RNA Splicing Factors - genetics; RNA Splicing Factors - metabolism; RNA, Messenger - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; transcription; Germany; m6A methylation; fat distribution; epitranscriptome; transcription; RNA methylome; obesity
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2021.778875

N
-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications on mRNA influencing mRNA metabolism. There is emerging evidence for its implication in metabolic disease. No comprehensive analyses on gene expression of m6A regulators in human adipose tissue, especially in paired adipose tissue depots, and its correlation with clinical variables were reported so far. We hypothesized that inter-depot specific gene expression of m6A regulators may differentially correlate with clinical variables related to obesity and fat distribution.
We extracted intra-individually paired gene expression data (omental visceral adipose tissue (OVAT)
=48; subcutaneous adipose tissue (SAT)
=56) of m6A regulators from an existing microarray dataset. We also measured gene expression in another sample set of paired OVAT and SAT (
=46) using RT-qPCR. Finally, we extracted existing gene expression data from peripheral mononuclear blood cells (PBMCs) and single nucleotide polymorphisms (SNPs) in
and
from genome wide data from the Sorbs population (
=1049). The data were analysed for differential gene expression between OVAT and SAT; and for association with obesity and clinical variables. We further tested for association of SNP markers with gene expression and clinical traits.
In adipose tissue we observed that several m6A regulators (
,
,
and
) correlate with obesity and clinical variables. Moreover, we found adipose tissue depot specific gene expression for
,
,
,
and
In PBMCs, we identified
and
correlated with obesity. Genetic markers in
associate with BMI whilst SNPs in
are associated with its gene expression.
Our data show that expression of m6A regulators correlates with obesity, is adipose tissue depot-specific and related to clinical traits. Genetic variation in m6A regulators adds an additional layer of variability to the functional consequences.