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

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 inmore » 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.« less
Authors:
; ;  [1] ; ;  [2] ;  [3] ;  [4] ; ;  [1] ;  [1]
  1. Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden)
  2. Department of Genomics of Common Disease, School of Public Health, Imperial College London (United Kingdom)
  3. Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (United States)
  4. Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry (United Kingdom)
Publication Date:
OSTI Identifier:
22416389
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 446; Journal Issue: 4; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADIPOSE TISSUE; ARTERIOSCLEROSIS; BUILDUP; CARBOXYLIC ACIDS; CELL PROLIFERATION; CHEMICAL VAPOR DEPOSITION; CHROMOSOMES; FATS; GENES; HUMAN POPULATIONS; INDICATORS; LIVER; METABOLIC DISEASES; NEOPLASMS; RNA