Effects of type 5-phosphodiesterase inhibition on energy metabolism and mitochondrial biogenesis in human adipose tissue ex vivo
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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Cites
Mitochondrial formation of reactive oxygen species
Turrens, J. F. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.049478 · Cited by 5,084 · see citing works
Fat and Beyond: The Diverse Biology of PPARγ
Tontonoz, P., & Spiegelman, B. M. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.77.061307.091829 · Cited by 2,085 · see citing works
Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide
Nisoli, E., Clementi, E., Paolucci, C., Cozzi, V., Tonello, C., Sciorati, C., Bracale, R., Valerio, A., Francolini, M., Moncada, S., et al. (2003) · Science · doi:10.1126/science.1079368 · Cited by 1,243 · see citing works
The role of mitochondria in the pathogenesis of type 2 diabetes
Patti, M.-E., & Corvera, S. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0027 · Cited by 551 · see citing works
Cyclic GMP Phosphodiesterases and Regulation of Smooth Muscle Function
Rybalkin, S. D., Chen, Y., Bornfeldt, K., & Beavo, J. A. (2003) · Circulation Research · doi:10.1161/01.res.0000087541.15600.2b · Cited by 511 · see citing works
Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals
Nisoli, E., Falcone, S., Tonello, C., Cozzi, V., Palomba, L., Fiorani, M., Pisconti, A., Brunelli, S., Cardile, A., Francolini, M., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405432101 · Cited by 495 · see citing works
Mitochondria are impaired in the adipocytes of type 2 diabetic mice.
Choo, H.-J., Kim, J.-H., Kwon, O.-B., Lee, C. S., Mun, J. Y., Han, S. S., Yoon, Y.-S., Yoon, G., Choi, K.-M., & Ko, Y.-G. (2006) · Diabetologia · doi:10.1007/s00125-006-0170-2 · Cited by 365 · see citing works
Protective vascular and myocardial effects of adiponectin
Goldstein, B. J., Scalia, R. G., & Ma, X. L. (2008) · Nature Clinical Practice Cardiovascular Medicine · doi:10.1038/ncpcardio1398 · Cited by 288 · see citing works
Miyashita, K., Itoh, H., Tsujimoto, H., Tamura, N., Fukunaga, Y., Sone, M., Yamahara, K., Taura, D., Inuzuka, M., Sonoyama, T., et al. (2009) · Diabetes · doi:10.2337/db09-0393 · Cited by 288 · see citing works
The metabolic consequences of childhood obesity
Weiss, R., & Caprio, S. (2005) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2005.04.009 · Cited by 278 · see citing works
Essential role of mitochondrial function in adiponectin synthesis in adipocytes
Koh, E. H., Park, J.-Y., Park, H.-S., Jeon, M. J., Ryu, J. W., Kim, M., Kim, S. Y., Kim, M.-S., Kim, S.-W., Park, I. S., et al. (2007) · Diabetes · doi:10.2337/db07-0510 · Cited by 275 · see citing works
Selemidis, S., Dusting, G. J., Peshavariya, H., Kemp‐Harper, B. K., & Drummond, G. R. (2007) · Cardiovascular Research · doi:10.1016/j.cardiores.2007.03.030 · Cited by 221 · see citing works
Tedesco, L., Valerio, A., Cervino, C., Cardile, A., Pagano, C., Vettor, R., Pasquali, R., Carruba, M. O., Marsicano, G., Lutz, B., et al. (2008) · Diabetes · doi:10.2337/db07-1623 · Cited by 145 · see citing works
Regulation of the nitric oxide system in human adipose tissue
Engeli, S., Janke, J., Gorzelniak, K., Böhnke, J., Ghose, N., Lindschau, C., Luft, F. C., & Sharma, A. M. (2004) · Journal of Lipid Research · doi:10.1194/jlr.m300322-jlr200 · Cited by 123 · see citing works
Inhibition of mitochondrial fission favours mutant over wild-type mitochondrial DNA
Malena, A., Loro, E., Di Re, M., Holt, I. J., & Vergani, L. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp281 · Cited by 107 · see citing works
Enoksson, S., Degerman, E., Toft, E., Large, V., & Arner, P. (1998) · Diabetologia · doi:10.1007/s001250050947 · Cited by 88 · see citing works
Muzaffar, S., Shukla, N., Angelini, G. D., & Jeremy, J. Y. (2004) · Circulation · doi:10.1161/01.cir.0000139851.50067.e4 · Cited by 75 · see citing works
Cell cycle-dependent mitochondrial biogenesis and dynamics in mammalian cells
Lee, S.-M., Kim, S., Sun, X., Lee, J. H., & Cho, H. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.03.091 · Cited by 71 · see citing works
Sildenafil promotes adipogenesis through a PKG pathway
Zhang, X., Ji, J., Yan, G., Wu, J., Sun, X., Shen, J., Jiang, H., & Wang, H. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.05.064 · Cited by 63 · see citing works
eNOS plays a major role in adiponectin synthesis in adipocytes
Koh, E. H., Kim, M. K., Ranjan, K. C., Kim, H. S., Park, H., Oh, K. S., Park, I.-S., Lee, W. J., Kim, M., Park, J., et al. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00008.2010 · Cited by 51 · see citing works
Moro, C., Klimčáková, E., Lafontan, M., Berlan, M., & Galitzky, J. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707485 · Cited by 49 · see citing works
Foresta, C., Caretta, N., Corona, G., Fabbri, A., Francavilla, S., Jannini, E. A., Maggi, M., Bettocchi, C., & Lenzi, A. (2008) · International Journal of Andrology · doi:10.1111/j.1365-2605.2008.00932.x · Cited by 49 · see citing works
Self-citationJahnke, V. E., Sabido, O., & Freyssenet, D. G. (2009) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00377.2008 · Cited by 45 · see citing works
Zoraghi, R., Francis, S. H., & Corbin, J. D. (2007) · Biochemistry · doi:10.1021/bi7010702 · Cited by 36 · see citing works
Flagged first, then by citations
Research works printed but not linked: 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.
Cited by
Sorted by citations
Cardiac Metabolism and its Interactions With Contraction, Growth, and Survival of Cardiomyocytes
Kolwicz, S. C., Purohit, S., & Tian, R. (2013) · Circulation Research · doi:10.1161/circresaha.113.302095 · Cited by 810 · see citing works
Mitochondria as a Therapeutic Target in Heart Failure
Bayeva, M., Gheorghiade, M., & Ardehali, H. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.08.1021 · Cited by 336 · see citing works
Regulation of obesity and insulin resistance by nitric oxide
Sansbury, B. E., & Hill, B. G. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.05.016 · Cited by 274 · see citing works
Mitochondrial Biogenesis as a Pharmacological Target: A New Approach to Acute and Chronic Diseases
Whitaker, R. M., Corum, D. G., Beeson, C., & Schnellmann, R. G. (2015) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103155 · Cited by 200 · see citing works
Whitaker, R. M., Wills, L. P., Stallons, L. J., & Schnellmann, R. G. (2013) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.208017 · Cited by 92 · see citing works
Obesity and Erectile Dysfunction: From Bench to Clinical Implication
Moon, K. H., Park, S., & Kim, Y.-W. (2018) · The World Journal of Men s Health · doi:10.5534/wjmh.180026 · Cited by 92 · see citing works
Bruckbauer, A., & Zemel, M. B. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089166 · Cited by 82 · see citing works
Cameron, R. B., Beeson, C. C., & Schnellmann, R. G. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00669 · Cited by 74 · see citing works
Chrysant, S. G. (2013) · Current Hypertension Reports · doi:10.1007/s11906-013-0377-9 · Cited by 61 · see citing works
Sildenafil induces browning of subcutaneous white adipose tissue in overweight adults
Li, S., Li, Y., Xiang, L., Dong, J., Liu, M., & Xiang, G. (2017) · Metabolism · doi:10.1016/j.metabol.2017.09.008 · Cited by 55 · see citing works
Ceddia, R. P., & Collins, S. (2020) · Clinical Science · doi:10.1042/cs20190579 · Cited by 51 · see citing works
Jagtap, U. A., & Paul, A. T. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103717 · Cited by 43 · see citing works
Haas, B., Schlinkert, P., Mayer, P. E., & Eckstein, N. (2012) · Diabetology & Metabolic Syndrome · doi:10.1186/1758-5996-4-43 · Cited by 42 · see citing works
Ciprofloxacin-Induced Antibacterial Activity Is Attenuated by Phosphodiesterase Inhibitors
Masadeh, M. M., Alzoubi, K. H., Khabour, O. F., & Al-Azzam, S. I. (2014) · Current Therapeutic Research · doi:10.1016/j.curtheres.2014.11.001 · Cited by 41 · see citing works
Hoffmann, L. S., Larson, C. J., & Pfeifer, A. (2015) · Handbook of experimental pharmacology · doi:10.1007/164_2015_3 · Cited by 28 · see citing works
Antiobesogenic Role of Endothelial Nitric Oxide Synthase
Sansbury, B. E., & Hill, B. G. (2014) · Vitamins and hormones · doi:10.1016/b978-0-12-800254-4.00013-1 · Cited by 25 · see citing works
Non-Sexual Implications of Phosphodiesterase Type 5 Inhibitors
Mostafa, T. (2016) · Sexual Medicine Reviews · doi:10.1016/j.sxmr.2016.02.004 · Cited by 18 · see citing works
Phosphodiesterase 5 as target for adipose tissue disorders
Colombo, G., Colombo, M. D. H. P., Schiavon, L. D. L., & d'Acâmpora, A. J. (2013) · Nitric Oxide · doi:10.1016/j.niox.2013.10.006 · Cited by 13 · see citing works
PDE5 inhibitor protects the mitochondrial function of hypoxic myocardial cells
Jia, H., Guo, Z., & Yao, Y. (2018) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2018.6951 · Cited by 13 · see citing works
Obesity and Erectile Dysfunction: From Bench to Clinical Implication
Moon, K. H., Park, S., & Kim, Y.-W. (2018) · The World Journal of Men s Health · doi:10.5534/wjmh.wjmh.180026 · Cited by 12 · see citing works
Rescue of Heart Failure by Mitochondrial Recovery
Marquez, J. C., Lee, S. R., Kim, N., & Han, J. (2006) · International Neurourology Journal · doi:10.5213/inj.1632570.285 · Cited by 12 · see citing works
Di Luigi, L., Botrè, F., Sabatini, S., Sansone, M., Mazzarino, M., Guidetti, L., Baldari, C., Lenzi, A., Caporossi, D., Romanelli, F., et al. (2014) · Endocrine · doi:10.1007/s12020-014-0185-2 · Cited by 11 · see citing works
Pharmacological Activation of Mitochondrial Biogenesis for the Treatment of Various Pathologies
Gibbs, W. S., Scholpa, N. E., Beeson, C. C., & Schnellmann, R. G. (2018) · Wiley eBooks · doi:10.1002/9781119329725.ch39 · Cited by 4 · see citing works
The anti-obesogenic effects of nitric oxide.
Sansbury, B. E. (2014) · doi:10.18297/etd/1262
A hipertóniától a szívelégtelenségig
Magyar, K., Deres, L., Gál, R., Riba, Á., Habon, T., Tóth, K., & Halmosi, R. (2017) · Cardiologia Hungarica · doi:10.26430/chungarica.2017.47.2.139
- 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
- Licence
- www.springer.com/tdm (tdm)
- 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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