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Effects of type 5-phosphodiesterase inhibition on energy metabolism and mitochondrial biogenesis in human adipose tissue ex vivo

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Abstract

Objective: An excess of adipose tissue (AT) in obese individuals is linked to increased cardiovascular risk and mitochondria have been shown to be defective in the muscle and AT of patients with metabolic disorders such as obesity and Type 2 diabetes. Nitric oxide (NO) generated by endothelial NO synthase (eNOS) plays a role in mitochondrial biogenesis through cyclic-GMP (cGMP). AT harbors the whole molecular signaling pathway of NO, together with type 5-phosphodiesterase (PDE-5), the main cGMP catabolising enzyme. Aim: Our aim was to evaluate the effect of the modulation of NO pathway, through PDE-5 inhibition, on energy metabolism and mitochondria biogenesis in human omental AT. Methods and measurements: Cultured human omental AT was stimulated with PDE-5 inhibitor, vardenafil, at different concentration for 24 and 72 h. Analysis of the expression of both key-regulator genes of adipocyte metabolism and mitochondria- biogenesis markers was performed. Results: We found an increased gene expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), adiponectin, and proliferator- activated receptor gamma coactivator- 1 α (PGC- 1α) after a 24- h stimulation with vardenafil at the lowest concentration employed compared to controls (p<0.05). After 72 h of stimulation, a significant increase of mitochondrial DNA was found compared to control samples (p<0.05). Conclusion: Our data suggest that PDE-5 inhibition could have an impact on mitochondrial content of human AT suggesting a positive effect on energy metabolism and adding new elements in the comprehension of AT pathophysiology.

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Authors and Affiliations

  1. Department of Histology, Microbiology and Medical Biotechnologies, Section of Clinical Pathology and Centre for Human Reproduction Pathology, University of Padova, Via Gabelli 63, 35121, Padova, Italy

    L. De Toni, G. Strapazzon, L. Gianesello, N. Caretta & C. Foresta MD

  2. EURAC Institute of Mountain Emergency Medicine, Bozen/Bolzano, Italy

    G. Strapazzon

  3. Endocrine-Metabolic Laboratory, Internal Medicine 3, University of Padua, Padua, Italy

    C. Pilon

  4. Clinical Surgery II, Department of Oncological and Surgical Sciences, University Hospital of Padua, Padua, Italy

    A. Bruttocao

Authors
  1. L. De Toni
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  2. G. Strapazzon
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  3. L. Gianesello
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  4. N. Caretta
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  5. C. Pilon
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  6. A. Bruttocao
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  7. C. Foresta MD
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Correspondence to C. Foresta MD.

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De Toni, L., Strapazzon, G., Gianesello, L. et al. Effects of type 5-phosphodiesterase inhibition on energy metabolism and mitochondrial biogenesis in human adipose tissue ex vivo . J Endocrinol Invest 34, 738–741 (2011). https://doi.org/10.1007/BF03346724

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  • DOI: https://doi.org/10.1007/BF03346724

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