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Long-term pioglitazone treatment enhances lipolysis in rat adipose tissue

International Journal of Obesity volume 32, pages 1848–1853 (2008)Cite this article

Abstract

Objectives:

The insulin-sensitizing effects of thiazolidinediones are believed to depend at least in part on reductions in circulating levels of nonesterified fatty acids (NEFA). The mechanisms that mediate the reductions in NEFA are not fully understood and could involve reductions in adipose tissue lipolysis, increases in glyceroneogenesis and NEFA reesterification in triglycerides in adipose tissue and increases in NEFA metabolism by oxidative tissues.

Methods:

In a congenic strain of spontaneously hypertensive rats that fed a high-sucrose diet to promote features of the metabolic syndrome, we studied the effects of chronic pioglitazone treatment over 4 months on adipose tissue lipolysis and NEFA metabolism.

Results:

We observed significant increases in basal and adrenaline-stimulated NEFA and glycerol release, and near-total suppression of NEFA reesterification in epididymal adipose tissue isolated from rats chronically treated with pioglitazone. However, pioglitazone-treated rats also exhibited significant increases in mitochondrial DNA levels in adipose tissue (3.2-fold increase, P=0.001) and potentially greater sensitivity to the antilipolytic effects of insulin than untreated controls. In addition, chronic pioglitazone treatment was associated with increased palmitate oxidation in soleus muscle, reduced fasting levels of serum NEFA and triglycerides, as well as reduced serum levels of insulin and increased serum levels of adiponectin.

Conclusions:

Despite suppressing NEFA reesterification and increasing basal and adrenaline-stimulated lipolysis, chronic pioglitazone treatment may decrease circulating NEFA levels in part by increasing adipose tissue sensitivity to the antilipolytic effects of insulin and by enhancing NEFA oxidation in skeletal muscle.

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Acknowledgements

This work was supported by National Institutes of Health Grants HL35018, HL56028 and HL63709 (TWK) and by Grants 1M6837805002 and 1P05ME791 from the Ministry of Education of the Czech Republic, Grant IAA500110604 from the Czech Academy of Sciences, Grants NR9387 and NR9359 from the Ministry of Health of the Czech Republic and the European Commission within the Sixth Framework Programme through the Integrated Project EURATools (contract no. LSHG-CT-2005-019015) (MP). MP is an international research scholar of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic

    M Pravenec, V Zídek, P Mlejnek & M Šimáková

  2. Institute for Clinical and Experimental Medicine, Prague, Czech Republic

    L Kazdová & M Maxová

  3. Department of Laboratory Medicine, University of California, San Francisco, CA, USA

    T W Kurtz

Authors
  1. M Pravenec
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  2. L Kazdová
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  3. M Maxová
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  4. V Zídek
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  5. P Mlejnek
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  6. M Šimáková
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  7. T W Kurtz
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Correspondence to M Pravenec.

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Pravenec, M., Kazdová, L., Maxová, M. et al. Long-term pioglitazone treatment enhances lipolysis in rat adipose tissue. Int J Obes 32, 1848–1853 (2008). https://doi.org/10.1038/ijo.2008.192

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  • DOI: https://doi.org/10.1038/ijo.2008.192

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