IRIG: Vitamin A and aP2 inhibitor in Nature and Nature medicine

Association of vitamin A (or its products) with glucose metabolism is indicated by the finding of RBP4 (retinol binding protein 4) in the regulation of insulin sensitivity. In 2005, RBP4 was reported as an insulin resistance protein secreted by adipocytes of GLUT4 knockout mice. The study suggests a possible role of vitamin A or its derivatives such as ratinoic acids in the regulation of insulin sensitivity. This possibility is confirmed in a new study in Nature Medicine, in which vitamin A product, Retinaldehyde, is shown to enhance insulin sensitivity in mice. An increase in Retinaldehyde led to resistance to dietary obesity and prevention of insulin resistance. The mechanism is about inhibition of adipocyte differentiation. In this report, retinaldehyde is claimed to bind to RBP4, but the biological consequence of the binding was not clearly discussed. See attached PDF file of the paper.   
 
      aP2 (fatty acid binding protein 4) was thought to be expressed in adipocytes only. Therefore, aP2 gene promoter has been used as a adipocyte-specific promoter in transgenic studies to control fat-specific gene expression. Although it is known now that aP2 is also expressed in macrophages, the aP2 promoter is still widely used for the fat-specific gene expression in the absence of substitute promoter. Knockout of aP2 gene was shown to prevent obesity and insulin resistance in transgenic mice. Then, does aP2 inhibitor work in the same way? This question is answered by a new study in Nature advanced online publication, in which an orally active small-molecule inhibitor of aP2 is shown to be an effective therapeutic agent against severe atherosclerosis and type 2 diabetes in mouse models. 
See attached PDF files.
 
Have a nice weekend.  
 
By Jianping at PBRC/LSU

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Jianping Ye, MD
Professor of Molecular Biology
Pennington Biomedical Research Center
Louisiana State University System
6400 Perkins Road
Baton Rouge, LA 70808
Phone: (225) 763-3163
Fax: (225) 763-2525
E-mail:
yej@pbrc.edu
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