Cited by 25Adipose Tissue and MetabolismPhosphodiesterase function and regulationPeroxisome Proliferator-Activated Receptors

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

De Toni, L., Strapazzon, G., Gianesello, L., Caretta, N., Pilon, C., Bruttocao, A., Foresta, C.·2011·Journal of Endocrinological Investigation

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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  • Type 5-phosphodiesterase inhibitors such as sildenafil have been shown to increase mitochondrial biogenesis in human adipose tissue ex vivo.

    “While there are no reports of regulation of obesity in humans by type 5-phosphodiesterase inhibitors such as sildenafil, they have been shown to increase mitochondrial biogenesis in human adipose tissue ex vivo [285], suggesting at least the potential to promote energy expenditure.”

    From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [285]

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  1. Engeli S, Janke J, Gorzelniak K, et al. Regulation of the nitric oxide system in human adipose tissue. J Lipid Res 2004, 45: 1640-8.

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Authors
De Toni, L., Strapazzon, G., Gianesello, L., Caretta, N., Pilon, C., Bruttocao, A., & Foresta, C.
Affiliations
  • Eurac Research (IT)
  • University of Padua (IT)
  • Azienda Ospedale - Università Padova (IT)
Corresponding author
Foresta, C.
Venue
Journal of Endocrinological Investigation
Published
2011-11
Volume
34
Issue
10
Pages
738-741
ISSN
  • 0391-4097 (ISSN-L)
  • 1720-8386
OpenAlex
W2107686544
Cited by
25
References
24
Citations by year
2023: 1 · 2020: 1 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 6 · 2013: 4 · 2012: 2
FWCI
2.61
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Endocrinological Investigation (publishedVersion)
  • PubMed (publishedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords
vardenafil, adipose tissue, mitochondrial biogenesis, energy metabolism, nitric oxide signaling, endothelial nitric oxide synthase, cyclic GMP, PPARγ, adiponectin, PGC-1α, mitochondrial DNA, omental adipose tissue, obesity, type 2 diabetes
MeSH terms
Vardenafil Dihydrochloride, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Aged, DNA, Mitochondrial, Energy Metabolism, Heat-Shock Proteins, Humans, Imidazoles, Male, Middle Aged, Mitochondria, Nitric Oxide, Nitroso Compounds, Piperazines, Sulfones, Transcription Factors, Triazines, Up-Regulation, Nitric Oxide Donors, PPAR gamma, Intra-Abdominal Fat, Adiponectin, Phosphodiesterase 5 Inhibitors

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