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Am J Physiol Endocrinol Metab 291: E1100-E1105, 2006. First published June 27, 2006; doi:10.1152/ajpendo.00187.2006
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Pioglitazone increases secretion of high-molecular-weight adiponectin from adipocytes

Angela M. Bodles,* Anannya Banga,* Neda Rasouli, Fumiyo Ono, Philip A. Kern, and Randall J. Owens

The Central Arkansas Veterans Healthcare System, and Department of Medicine, Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, Arkansas

Submitted 19 April 2006 ; accepted in final form 23 June 2006

Adiponectin is an adipocyte-derived serum protein that plays important roles in energy homeostasis, obesity, and insulin sensitivity. Using sucrose gradients and Western blotting of nondenaturing gels, we examined the adiponectin isoforms secreted from human adipose tissue, human and mouse adipocytes, and cell lines in response to pioglitazone added in vitro. The predominant form secreted from adipose tissue in vitro was the high-molecular-weight (HMW) isoform, with small amounts of low-molecular-weight (LMW) forms present. The addition of pioglitazone (1–3 µM) in vitro increased the secretion of the HMW isoform, with no significant effect on the other isoforms. Human adipose tissue was also examined for changes in adiponectin mRNA levels upon pioglitazone treatment. No difference was detected, suggesting that the effect of pioglitazone is not at the transcriptional level but, rather, at a posttranscriptional phase of the secretory pathway. Additional experiments were conducted to determine whether adiponectin expression was mechanistically similar in other adipose cells. Examination of primary human adipocytes revealed an increase in intracellular HMW isoform with a decline in LMW forms following pioglitazone treatment, with a corresponding increase in the secreted HMW form. Similar results were observed with primary mouse adipocytes, 3T3-F422A cells, and SGBS human adipocyte cells, although differences in the distribution of HMW and LMW isoforms were apparent between cell types. Although there are differences in isoforms between species, in all cases pioglitazone served to increase the secretion of the HMW form of adiponectin.


Address for reprint requests and other correspondence: R. J. Owens, Central Arkansas Veterans Healthcare System, 4300 West 7th St., Little Rock, AR 72205 (e-mail: OwensRandallJ{at}uams.edu)




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