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Originally published In Press as doi:10.1194/jlr.C500010-JLR200 on May 16, 2005
Journal of Lipid Research, Vol. 46, 1591-1595, August 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology
Administration of a PPAR agonist increases serum apolipoprotein A-V levels and the apolipoprotein A-V/apolipoprotein C-III ratio
Albert E. Schultze,
William E. Alborn,
Ronald K. Newton and
Robert J. Konrad1
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285
Published, JLR Papers in Press, May 16, 2005. DOI 10.1194/jlr.C500010-JLR200
1 To whom correspondence should be addressed. e-mail: konrad_robert{at}lilly.com
ABSTRACT
Apolipoprotein A-V (apoA-V) first gained attention as a regulator of triglycerides through transgenic mouse studies. Furthermore, peroxisome proliferator-activated receptor  (PPAR) agonists such as fenofibrate increase apoA-V mRNA expression. Our group recently developed the first assay to quantitate serum apoA-V levels. Therefore, we sought to determine whether administration of a PPAR agonist would increase circulating apoA-V. Cynomolgus monkeys were dosed for 14 days with 0.3 mg/kg/day LY570977 L-lysine, a potent and selective PPAR agonist. Blood samples were drawn throughout the treatment period and after a 2 week washout. Administration of the PPAR agonist caused a 50% decrease in triglycerides that reversed at washout. Serum apoA-V concentrations increased 2-fold, correlated inversely with triglycerides, and were reversible at washout. The apoA-V/apoC-III ratio increased >2-fold, with this increase also reversible at washout.
These data demonstrate for the first time that a PPAR agonist increases circulating apoA-V protein levels and the apoA-V/apoC-III ratio.
Supplementary key words triglycerides • cholesterol • enzyme-linked immunosorbent assay • lipids • cynomolgus monkeys • peroxisome proliferator-activated receptor
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Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.
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