Loss of Krüppel-like factor 3 (KLF3/BKLF) leads to upregulation of the insulin-sensitizing factor adipolin (FAM132A/CTRP12/C1qdc2)

Krüppel-like factor 3 (KLF3) is a transcriptional regulator that we have shown to be involved in the regulation of adipogenesis in vitro. Here, we report that KLF3-null mice are lean and protected from diet-induced obesity and glucose intolerance. On a chow diet, plasma levels of leptin are decrease...

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Main Authors: Bell-Anderson, Kim S., Funnell, Alister P., Williams, Helen, Mat Jusoh, Hanapi, Scully, Tiffany, Lim, Wooi, Burdach, Jon, Mak, Ka Sin, Knights, Alexander, Hoy, Andrew, Nicholas, Hannah R., Sainsbury, Amanda, Turner, Nigel, Pearson, Richard C., Crossley, Merlin
Format: Article
Language:English
Published: American Diabetes Association 2013
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Online Access:http://irep.iium.edu.my/49570/1/Diabetes-2013-Bell-Anderson-2728-37.pdf
http://irep.iium.edu.my/49570/
http://diabetes.diabetesjournals.org/content/62/8/2728.long
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spelling my.iium.irep.495702016-07-19T05:44:35Z http://irep.iium.edu.my/49570/ Loss of Krüppel-like factor 3 (KLF3/BKLF) leads to upregulation of the insulin-sensitizing factor adipolin (FAM132A/CTRP12/C1qdc2) Bell-Anderson, Kim S. Funnell, Alister P. Williams, Helen Mat Jusoh, Hanapi Scully, Tiffany Lim, Wooi Burdach, Jon Mak, Ka Sin Knights, Alexander Hoy, Andrew Nicholas, Hannah R. Sainsbury, Amanda Turner, Nigel Pearson, Richard C. Crossley, Merlin R Medicine (General) RB Pathology Krüppel-like factor 3 (KLF3) is a transcriptional regulator that we have shown to be involved in the regulation of adipogenesis in vitro. Here, we report that KLF3-null mice are lean and protected from diet-induced obesity and glucose intolerance. On a chow diet, plasma levels of leptin are decreased, and adiponectin is increased. Despite significant reductions in body weight and adiposity, wild-type and knockout animals show equivalent energy intake, expenditure, and excretion. To investigate the molecular events underlying these observations, we used microarray analysis to compare gene expression in Klf3(+/+) and Klf3(-/-) tissues. We found that mRNA expression of Fam132a, which encodes a newly identified insulin-sensitizing adipokine, adipolin, is significantly upregulated in the absence of KLF3. We confirmed that KLF3 binds the Fam132a promoter in vitro and in vivo and that this leads to repression of promoter activity. Further, plasma adipolin levels were significantly increased in Klf3(-/-) mice compared with wild-type littermates. Boosting levels of adipolin via targeting of KLF3 offers a novel potential therapeutic strategy for the treatment of insulin resistance. American Diabetes Association 2013-08 Article REM application/pdf en http://irep.iium.edu.my/49570/1/Diabetes-2013-Bell-Anderson-2728-37.pdf Bell-Anderson, Kim S. and Funnell, Alister P. and Williams, Helen and Mat Jusoh, Hanapi and Scully, Tiffany and Lim, Wooi and Burdach, Jon and Mak, Ka Sin and Knights, Alexander and Hoy, Andrew and Nicholas, Hannah R. and Sainsbury, Amanda and Turner, Nigel and Pearson, Richard C. and Crossley, Merlin (2013) Loss of Krüppel-like factor 3 (KLF3/BKLF) leads to upregulation of the insulin-sensitizing factor adipolin (FAM132A/CTRP12/C1qdc2). Diabetes, 62 (8). pp. 2728-2737. ISSN 1939-327X http://diabetes.diabetesjournals.org/content/62/8/2728.long 10.2337/db12-1745
institution Universiti Islam Antarabangsa Malaysia
building IIUM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider International Islamic University Malaysia
content_source IIUM Repository (IREP)
url_provider http://irep.iium.edu.my/
language English
topic R Medicine (General)
RB Pathology
spellingShingle R Medicine (General)
RB Pathology
Bell-Anderson, Kim S.
Funnell, Alister P.
Williams, Helen
Mat Jusoh, Hanapi
Scully, Tiffany
Lim, Wooi
Burdach, Jon
Mak, Ka Sin
Knights, Alexander
Hoy, Andrew
Nicholas, Hannah R.
Sainsbury, Amanda
Turner, Nigel
Pearson, Richard C.
Crossley, Merlin
Loss of Krüppel-like factor 3 (KLF3/BKLF) leads to upregulation of the insulin-sensitizing factor adipolin (FAM132A/CTRP12/C1qdc2)
description Krüppel-like factor 3 (KLF3) is a transcriptional regulator that we have shown to be involved in the regulation of adipogenesis in vitro. Here, we report that KLF3-null mice are lean and protected from diet-induced obesity and glucose intolerance. On a chow diet, plasma levels of leptin are decreased, and adiponectin is increased. Despite significant reductions in body weight and adiposity, wild-type and knockout animals show equivalent energy intake, expenditure, and excretion. To investigate the molecular events underlying these observations, we used microarray analysis to compare gene expression in Klf3(+/+) and Klf3(-/-) tissues. We found that mRNA expression of Fam132a, which encodes a newly identified insulin-sensitizing adipokine, adipolin, is significantly upregulated in the absence of KLF3. We confirmed that KLF3 binds the Fam132a promoter in vitro and in vivo and that this leads to repression of promoter activity. Further, plasma adipolin levels were significantly increased in Klf3(-/-) mice compared with wild-type littermates. Boosting levels of adipolin via targeting of KLF3 offers a novel potential therapeutic strategy for the treatment of insulin resistance.
format Article
author Bell-Anderson, Kim S.
Funnell, Alister P.
Williams, Helen
Mat Jusoh, Hanapi
Scully, Tiffany
Lim, Wooi
Burdach, Jon
Mak, Ka Sin
Knights, Alexander
Hoy, Andrew
Nicholas, Hannah R.
Sainsbury, Amanda
Turner, Nigel
Pearson, Richard C.
Crossley, Merlin
author_facet Bell-Anderson, Kim S.
Funnell, Alister P.
Williams, Helen
Mat Jusoh, Hanapi
Scully, Tiffany
Lim, Wooi
Burdach, Jon
Mak, Ka Sin
Knights, Alexander
Hoy, Andrew
Nicholas, Hannah R.
Sainsbury, Amanda
Turner, Nigel
Pearson, Richard C.
Crossley, Merlin
author_sort Bell-Anderson, Kim S.
title Loss of Krüppel-like factor 3 (KLF3/BKLF) leads to upregulation of the insulin-sensitizing factor adipolin (FAM132A/CTRP12/C1qdc2)
title_short Loss of Krüppel-like factor 3 (KLF3/BKLF) leads to upregulation of the insulin-sensitizing factor adipolin (FAM132A/CTRP12/C1qdc2)
title_full Loss of Krüppel-like factor 3 (KLF3/BKLF) leads to upregulation of the insulin-sensitizing factor adipolin (FAM132A/CTRP12/C1qdc2)
title_fullStr Loss of Krüppel-like factor 3 (KLF3/BKLF) leads to upregulation of the insulin-sensitizing factor adipolin (FAM132A/CTRP12/C1qdc2)
title_full_unstemmed Loss of Krüppel-like factor 3 (KLF3/BKLF) leads to upregulation of the insulin-sensitizing factor adipolin (FAM132A/CTRP12/C1qdc2)
title_sort loss of krüppel-like factor 3 (klf3/bklf) leads to upregulation of the insulin-sensitizing factor adipolin (fam132a/ctrp12/c1qdc2)
publisher American Diabetes Association
publishDate 2013
url http://irep.iium.edu.my/49570/1/Diabetes-2013-Bell-Anderson-2728-37.pdf
http://irep.iium.edu.my/49570/
http://diabetes.diabetesjournals.org/content/62/8/2728.long
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score 13.211869