Submitted on November 3, 2008
Revised on November 28, 2008
Accepted on December 11, 2008
Adiponectin translation is increased by the PPAR
agonists pioglitazone and 
-3 fatty acids
Anannya Banga1, Resat Unal1, Preeti Tripathi1, Irine Pokrovskaya1, Randall J. Owens1, Philip A. Kern2, and Gouri Ranganathan3*
1 University of Arkansas for Medical Science
2 University of Arkansas Med Sciences, Little Rock, AR, 72205
3 University of Arkansas for Medical Sciences
* To whom correspondence should be addressed. E-mail: ranganathangouri{at}uams.edu.
Adiponectin, made exclusively by adipocytes is a 30 kDa secretory protein assembled post translationally into low molecular weight, middle molecular weight and high molecular weight homo oligomers. PPAR
ligands thiozolidinediones (TZD) which are widely used in the treatment of type II diabetes, increase adiponectin levels. PPAR also has several putative ligands which include fatty acid derivatives. Overnight treatment of rat adipocytes with pioglitazone, docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) triggered a 2-fold increase in the synthesis and secretion of HMW adiponectin and this increase was blocked by the addition of PPAR inhibitor GW9662. Inhibition of glycosylation using 2-2' dipyridyl decreased the synthesis of high molecular weight adiponectin by pioglitazone, EPA and DHA but there was increased secretion of trimeric adiponectin resulting from increased translation. Although pioglitazone, DHA and EPA increased adiponectin synthesis by over 60% there was no increase in total protein synthesis, and there was no corresponding change in adiponectin mRNA expression, indicating the up-regulation of translation. We examined the possibility of transacting factors in the cytoplasmic extracts from adipocytes treated with pioglitazone or DHA. In vitro translation of adiponectin mRNA was inhibited by S-100 fraction, of control adipocytes, and increased by S-100 extracts from adipocytes treated with pioglitazone or DHA. Consistent with this observation both pioglitazone and DHA treatments increased the association of adiponectin mRNA with the heavier polysome fractions. Together, these data suggest that pioglitazone and the fish oils DHA or EPA are PPAR agonists in adipocytes with regards to adiponectin expression, and the predominant mode of adiponectin stimulation is via an increase in translation.
