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

  1. Merlin Crossley2
  1. 1School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia
  2. 2School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia
  3. 3School of Medical Sciences, University of Sydney, Sydney, NSW 2006, Australia
  4. 4Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, Sydney, NSW 2006, Australia
  5. 5Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia
  1. *Corresponding author: Kim S. Bell-Anderson, E-mail address: kim.bellanderson{at}sydney.edu.au

Abstract

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, wildtype 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 to wild-type littermates. Boosting levels of adipolin via targeting of KLF3 offers a novel potential therapeutic strategy for the treatment of insulin resistance.

  • Received December 12, 2012.
  • Accepted April 17, 2013.

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  1. Diabetes
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