CDKN2B expression and subcutaneous adipose tissue expandability: Possible influence of the 9p21 atherosclerosis locus

https://doi.org/10.1016/j.bbrc.2014.03.075Get rights and content
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Highlights

  • The tumor suppressor gene CDKN2B is highly expressed in human adipose tissue.

  • Risk alleles at the 9p21 locus modify CDKN2B expression in a BMI-dependent fashion.

  • There is an inverse relationship between expression of CDKN2B and adipogenic genes.

  • CDKN2B expression influences to postprandial triacylglycerol clearance.

  • CDKN2B expression in adipose tissue is linked to markers of hepatic steatosis.

Abstract

Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biological mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis.

Abbreviations

CVD
cardiovascular disease
SAT
subcutaneous adipose tissue
VAT
visceral adipose tissue
CDKN2A/B
cyclin-dependent kinase inhibitor 2A/B
ANRIL
antisense noncoding RNA in the INK4 locus
MTAP
methylthioadenosine phosphorylase
BMI
body mass index
TAG
triacylglycerol

Keywords

CDKN2B
Adipose tissue
Chromosome 9p21

Cited by (0)

1

P.-A.S. and B.W. are equal first authors.