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Research ArticleCARDIOVASCULAR

Heme Oxygenase-Mediated Increases in Adiponectin Decrease Fat Content and Inflammatory Cytokines Tumor Necrosis Factor-α and Interleukin-6 in Zucker Rats and Reduce Adipogenesis in Human Mesenchymal Stem Cells

Dong Hyun Kim, Angela P. Burgess, Ming Li, Peter L. Tsenovoy, Francesco Addabbo, John A. McClung, Nitin Puri and Nader G. Abraham
Journal of Pharmacology and Experimental Therapeutics June 2008, 325 (3) 833-840; DOI: https://doi.org/10.1124/jpet.107.135285
Dong Hyun Kim
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Angela P. Burgess
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Ming Li
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Peter L. Tsenovoy
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Francesco Addabbo
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John A. McClung
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Nitin Puri
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Nader G. Abraham
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Abstract

Adiponectin, an abundant adipocyte-derived plasma protein that modulates vascular function in type 2 diabetes, has been shown to provide cytoprotection to both pancreatic and vascular systems in diabetes. Therefore, we examined whether up-regulation of heme oxygenase (HO)-1 ameliorates the levels of inflammatory cytokines and influences serum adiponectin in Zucker fat (ZF) rats. ZF rats displayed a decrease in both HO activity and HO-1 and HO-2 protein levels and an increase in tumor necrosis factor (TNF)-α and interleukin (IL)-6 compared with Zucker lean (ZL) rats. Treatment of ZF animals with 2 mg/kg cobalt protoporphyrin IX (CoPP) increased protein levels of HO-1 and HO activity, but HO-2 was unaffected. The increase in HO-1 was associated with a decrease in superoxide levels (p < 0.05) and an increase in plasma adiponectin (p < 0.005), compared with untreated ZF rats. CoPP treatment decreased visceral and s.c. fat content, and it reduced weight gain (p < 0.01). In addition, the inflammatory cytokines TNF-α and IL-6 were decreased (p < 0.04 and p < 0.008, respectively). Treatment of human bone marrow-derived adipocytes cultured with CoPP resulted in an increase in HO-1 and a decrease in superoxide levels. Up-regulation of HO-1 caused adipose remodeling, smaller adipocytes, and increased adiponectin secretion in the culture medium of human bone marrow-derived adipocytes. In summary, this study demonstrates that the antiobesity effect of HO-1 induction results in an increase in adiponectin secretion, in vivo and in vitro, a decrease in TNF-α and IL-6, and a reduction in weight gain. These findings highlight the pivotal role and symbiotic relationship of HO-1 and adiponectin in the modulation of the metabolic syndrome phenotype.

Footnotes

  • This work was supported by National Institutes of Health Grants DK068134, HL55601, and HL34300.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • doi:10.1124/jpet.107.135285.

  • ABBREVIATIONS: ROS, reactive oxygen species; TNF, tumor necrosis factor; IL, interleukin; HMW, high molecular weight; PPAR, peroxisome proliferator-activated receptor; HO, heme oxygenase; CoPP, cobalt protoporphyrin IX; SnMP, tin mesoporphyrin; ZL, Zucker lean; ZF, Zucker fat; FBS, fetal bovine serum; MSC, mesenchymal stem cell; Math, superoxide; FACS, fluorescence-activated cell sorting; DMEM, Dulbecco's modified Eagle's medium; h, human.

    • Received December 21, 2007.
    • Accepted March 10, 2008.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 384 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 384, Issue 2
1 Feb 2023
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Research ArticleCARDIOVASCULAR

Heme Oxygenase-Mediated Increases in Adiponectin Decrease Fat Content and Inflammatory Cytokines Tumor Necrosis Factor-α and Interleukin-6 in Zucker Rats and Reduce Adipogenesis in Human Mesenchymal Stem Cells

Dong Hyun Kim, Angela P. Burgess, Ming Li, Peter L. Tsenovoy, Francesco Addabbo, John A. McClung, Nitin Puri and Nader G. Abraham
Journal of Pharmacology and Experimental Therapeutics June 1, 2008, 325 (3) 833-840; DOI: https://doi.org/10.1124/jpet.107.135285

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Research ArticleCARDIOVASCULAR

Heme Oxygenase-Mediated Increases in Adiponectin Decrease Fat Content and Inflammatory Cytokines Tumor Necrosis Factor-α and Interleukin-6 in Zucker Rats and Reduce Adipogenesis in Human Mesenchymal Stem Cells

Dong Hyun Kim, Angela P. Burgess, Ming Li, Peter L. Tsenovoy, Francesco Addabbo, John A. McClung, Nitin Puri and Nader G. Abraham
Journal of Pharmacology and Experimental Therapeutics June 1, 2008, 325 (3) 833-840; DOI: https://doi.org/10.1124/jpet.107.135285
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