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Papers In Press, published online ahead of print May 16, 2005
J. Lipid Res., doi:10.1194/jlr.C500010-JLR200
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Experimental Medicine, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285
Corresponding Author: konrad_robert{at}lilly.com
Apolipoprotein A5 (ApoA5) first gained attention as a regulator of triglycerides through transgenic mouse studies. Furthermore, PPAR-alpha agonists such as fenofibrate increase ApoA5 mRNA expression. Our group recently developed the first assay to quantitate serum ApoA5 levels. Therefore, we sought to determine if administration of a PPAR-alpha agonist would increase circulating ApoA5. Cynomolgus monkeys were dosed for 14 days with 0.3 mg/kg/day of LY570977 L-lysine, a potent and selective PPAR-alpha agonist. Blood samples were drawn throughout the treatment period and following a 2-week washout. Administration of the PPAR-alpha agonist caused a 50% decrease in triglycerides that reversed at washout. Serum ApoA5 concentrations increased 2-fold, correlated inversely with triglycerides, and were reversible at washout. The ApoA5/Apolipoprotein C3 ratio increased more than 2-fold, with this increase also reversible at washout. These data demonstate for the first time that a PPAR-alpha agonist increases circulating ApoA5 protein levels and the Apolipoprotein A5/Apolipoprotein C3 ratio.
Revised on May 9, 2005
Accepted on May 9, 2005
Administration of a PPAR-
agonist increases serum apolipoprotein A5 levels and the apolipoprotein A5/apolipoprotein C3 ratio
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