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-1
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-1& IL-6 levels in obese mice.
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