Histone demethylase KDM1A represses inflammatory gene expression in preadipocytes. (5th July 2013)

• Record Type: Journal Article
• Authors: Hanzu, Felicia A.; Musri, Melina M.; Sánchez‐Herrero, Alvaro; Claret, Marc; Esteban, Yaiza; Kaliman, Perla; Gomis, Ramon; Párrizas, Marcelina
• Is Part Of: Obesity. Volume 21:Number 12(2013:Dec.)
• Page Start: E616
• Page End: E625
• Publication Date: 2013-07-05
• Subjects: Obesity -- Periodicals; 616.398005
• DOI: 10.1002/oby.20479
• Languages: English
• ISSNs: 1930-7381

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="oby20479-sec-0001" sec-type="section"> <title>Objective</title> <p>Persistent inflammation and impaired adipogenesis are frequent features of obesity and underlie the development of its complications. However, the factors behind adipose tissue dysfunction are not completely understood. Previously it was shown that histone demethylase KDM1A is required for adipogenesis.</p> </sec> <sec id="oby20479-sec-0002" sec-type="section"> <title>Design and Methods</title> <p> <italic>Kdm1a</italic> expression was knocked down in 3T3‐L1 preadipocytes by siRNA transfection and whole‐genome expression profiling was performed by microarray hybridization. The role of NF‐κβ and C/EBPβ was analyzed by incubation with the inhibitor parthenolide and by cebpb knockdown, respectively.</p> </sec> <sec id="oby20479-sec-0003" sec-type="section"> <title>Results</title> <p>Knockdown of <italic>kdm1a</italic> or <italic>rcor2</italic> in 3T3‐L1 preadipocytes results in impaired differentiation and induction of inflammatory gene expression. Enhanced expression of <italic>il6</italic> in <italic>kdm1a</italic> knocked down preadipocytes is associated with increased recruitment of C/EBPβ and the NF‐κβ subunit RelA to the <italic>il6</italic> promoter. <italic>Cebpb</italic> knockdown attenuates the induction of <italic>il6</italic> expression in <italic>kdm1a</italic> knocked down cells, whereas simultaneous <italic>cebpb</italic> knockdown and NF‐κβ inhibition abrogates it. Dietary‐induced and genetic mouse models of obesity display decreased KDM1A in adipose tissue, and this correlates with increased expression of proinflammatory genes and C/EBPβ.</p> </sec> <sec id="oby20479-sec-0004" sec-type="section"> <title>Conclusion</title> <p>KDM1A represses the expression of inflammatory genes in preadipocytes. Dysregulated <italic>kdm1a</italic> expression in preadipocytes may thus participate in the development of obesity‐associated inflammation.</p> </sec> </abstract>