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J. Lipid Res.
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A more recent version of this article appeared on August 1, 2008 Originally published In Press as doi:10.1194/jlr.M800046-JLR200 on April 25, 2008 Originally published In Press as doi:10.1194/jlr.M800046-JLR200 on April 19, 2008

Papers In Press, published online ahead of print April 28, 2008
J. Lipid Res., doi:10.1194/jlr.M800046-JLR200
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Submitted on January 28, 2008
Revised on March 27, 2008
Accepted on April 19, 2008

L-4F treatment reduces adiposity, increases adiponectin levels and improves insulin sensitivity in obese mice

Stephen J. Peterson, George Drummond, Dong Hyun Kim, Ming Li, Adam L. Kruger, Susumu Ikehara, and Nader G. Abraham

Department of Pharmacology, New York Medical College, Valhalla, NY 10595

Corresponding Author: nader_abraham{at}nymc.edu

We hypothesized that the apolipoprotein mimetic peptide, L-4F, which induced arterial anti-oxidative enzymes and was vasoprotective in a rat model of diabetes would ameliorate insulin resistance and diabetes in obese mice. L-4F (2 mg/kg/d) administered to ob/ob mice for 6 weeks limited weight gain without altering food intake, decreased abdominal fat content (p<0.005), and decreased plasma IL-1beta and IL-6 levels (p<0.05). L-4F treatment increased insulin sensitivity resulting in decreased glucose (p <0.001) and insulin levels (p<0.036). L-4F treatment also increased aortic and bone marrow heme oxygenase (HO) activity and decreased aortic and bone marrow superoxide production (p <0.001). L-4F treatment increased serum adiponectin levels (p<0.037) and decreased adipogenesis in mouse bone marrow (p<0.039) and in cultures of human bone marrow derived mesenchymal stem cells (p<0.022). L-4F treatment reduced adiposity, improved insulin sensitivity, improved glucose tolerance, increased plasma adiponectin levels and reduced IL-1beta & IL-6 levels in obese mice.


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