Pioglitazone increases secretion of high-molecular-weight adiponectin from adipocytes.
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 micromM) 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.
Bodles
Angela M
AM
The Central Arkansas Veterans Healthcare System, and Department of Medicine, Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Banga
Anannya
A
Rasouli
Neda
N
Ono
Fumiyo
F
Kern
Philip A
PA
Owens
Randall J
RJ
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D052242:Adiponectin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000818:Animals; D001706:Biopsy; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007223:Infant; D007536:Isomerism; D051379:Mice; D008970:Molecular Weight; D000077205:Pioglitazone; D012333:RNA, Messenger; D050151:Subcutaneous Fat / Q000166:cytology; D045162:Thiazolidinediones / Q000494:pharmacology*
C499918:ADIPOQ protein, human; D052242:Adiponectin; C499919:Adipoq protein, mouse; D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077205:Pioglitazone