Matrix metalloproteinase-9 is increased in obese subjects and decreases in response to pioglitazone

Resat Unal, Aiwei Yao-Borengasser, Vijayalakshmi Varma, Neda Rasouli, Craig Labbate, Philip A. Kern, Gouri Ranganathan

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Context: The study investigated the regulation of matrix metalloproteinases (MMP)-9 in obesity-associated insulin resistance in humans. Objectives: The objectives of the investigation were to study MMP-9 regulation by insulin resistance and pioglitazone treatment in impaired glucose tolerant subjects using adipose tissue biopsies and study the mechanism of MMP-9 regulation by pioglitazone in adipocyte cultures. Research Design: 86 nondiabetic, weight-stable subjects between 21 and 66 yr of age were recruited in a university hospital research center setting. All subjects underwent a sc adipose tissue incisional biopsy from the lower abdominal wall and insulin sensitivity testing using a frequently sampled iv glucose tolerance test. Impaired glucose-tolerant subjects were randomized to receive metformin or pioglitazone for 10 wk. To study the mechanism of MMP-9 regulation in adipocytes, cells were treated with pioglitazone or protein kinase Cα antisense oligomers, and MMP-9 levels were examined. Results: There was a positive correlation between MMP-9 and body mass index (r = 0.40, P<0.01) and negative correlation between MMP-9 and insulin sensitivity (r = -0.46, P < 0.001). The improvement in insulin sensitivity from pioglitazone resulted in a 52 ± 0.2% reduction in MMP-9 mRNA. Fractionation of adipose tissue indicated that MMP-9 was mostly in the stromal vascular fraction. Pioglitazone also decreased MMP-9 in 3T3-F442A adipocytes and THP1 macrophages. Coculture of adipocytes with macrophages augmented MMP-9 expression in adipocytes and pioglitazone decreased MMP-9 in both adipocytes and macrophages. Conclusion: These data indicate that MMP-9 is elevated in insulin resistance and is reduced by pioglitazone.

Original languageEnglish
Pages (from-to)2993-3001
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Issue number6
StatePublished - Jun 2010

Bibliographical note

Funding Information:
This work was supported by merit review grants (to G.R. and N.R.) and research enhancement award program (REAP) funds to GR from the Veterans Administration , Grants DK39176 and DK080327 (to P.A.K.) from the National Institutes of Health , and Grant M01RR14288 from the General Clinical Research Center.

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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