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

Svensson, Per-Arne,1969Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine (author)

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. (C) 2014 The Authors. Published by Elsevier Inc.

NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
NATURVETENSKAP Biologi Biofysik hsv//swe
NATURAL SCIENCES Biological Sciences Biophysics hsv//eng
CDKN2B
Adipose tissue
Chromosome 9p21
CORONARY-ARTERY-DISEASE
CHROMOSOME 9P21
CARDIOVASCULAR-DISEASE
GENOMEWIDE ASSOCIATION
MYOCARDIAL-INFARCTION
CELL-PROLIFERATION
DIABETES-MELLITUS
HEART-DISEASE
RISK
OBESITY

Wahlstrand, Björn,1970Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine(Swepub:gu)xwahlb (author)
Olsson, Maja,1975Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xolmaj (author)
Froguel, P. (author)
Falchi, M. (author)
Bergman, R. N. (author)
McTernan, P. G. (author)
Hedner, Thomas,1949Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine(Swepub:gu)xhedto (author)
Carlsson, Lena M S,1957Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine(Swepub:gu)xcarle (author)
Jacobson, Peter,1962Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine(Swepub:gu)xjacop (author)
Göteborgs universitetInstitutionen för medicin (creator_code:org_t)

In:Biochemical and Biophysical Research Communications: Elsevier BV446:4, s. 1126-11310006-291X

By the author/editor: Svensson, Per-Ar ...; Wahlstrand, Björ ...; Olsson, Maja, 19 ...; Froguel, P.; Falchi, M.; Bergman, R. N.; show more...; McTernan, P. G.; Hedner, Thomas, ...; Carlsson, Lena M ...; Jacobson, Peter, ...; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biophysics

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