Review Phosphodiesterase 5 as target for adipose tissue disorders Giovani Colombo a,⇑ , Maria Daniela H. Périco Colombo b , Leonardo De Lucca Schiavon a , Armando José d’Acampora a a Federal University of Santa Catarina, Brazil b Hematology and Transfusion Medicine Center of Santa Catarina (HEMOSC), Brazil article info Article history: Received 5 May 2013 Revised 26 September 2013 Available online 28 October 2013 Keywords: Adipocyte Adipogenesis Nitric oxide Phosphodiesterase 5 Phosphodiesterase 5 inhibitor White adipose tissue abstract Introduction: Adipose tissue as an endocrine organ is responsible for the release of multiple cytokines, which have the most diverse metabolic functions. Therefore, it is extremely important to preserve its physiological health in order to avoid local and systemic disorders. Experiments available in literature show the importance of the nitric oxide (NO)/guanosine 3 0 5 0 cyclic monophosphate (cGMP)/protein kinase G (PKG) pathway in adipocyte biology. Phosphodiesterase 5 (PDE5) is an enzyme responsible for cGMP inactivation, and the use of its inhibitors can be an alternative in the search of a more balanced adipose tissue. Objective: This review aims to describe the PDE5 role and the possibility of using PDE5 inhibitors in adi- pocyte physiology derangements and their consequences. Design and methods: Studies published in the last 10 years that related PDE5 and its inhibitors to adipose tissue were raised in major databases. Results: PDE5 is present in adipocyte, and PDE5 inhibitors can promote adipogenesis, interfere with adi- pokines secretion, decrease inflammatory markers expression, and increase the thermogenic potential of white adipose tissue. Conclusions: PDE5 plays an important role in adipocyte physiology and the use of its inhibitors may prove a useful tool to combat adipose tissue disorders and its highest expression, metabolic syndrome. Ó 2013 Elsevier Inc. All rights reserved. Contents Introduction........................................................................................................... 186 Cyclic nucleotide phosphodiesterases ...................................................................................... 187 Phosphodiesterase 5 (PDE5) .............................................................................................. 187 Phosphodiesterase inhibitors ............................................................................................. 187 Adipose tissue, adipokines, and inflammation ............................................................................... 188 NO/cGMP/PKG pathway and the adipocyte physiology ........................................................................ 188 NO pathway, PDE5 inhibitors and adipose tissue ............................................................................. 189 Conclusion ............................................................................................................ 191 Conflicts of interest ..................................................................................................... 191 References ............................................................................................................ 191 Introduction While hunger was a constant presence during human evolution, nowadays 65% of the world’s population live in countries where overweight and obesity kill more people than underweight [1,2]. Over the last years adipose tissue rose from a simple energy deposit to an endocrine organ, producing hormones known as adipokines, and also cytokines related to the onset and perpetua- tion of inflammation [3–5]. On account of its role in metabolic control, adipose tissue expansion leads to alteration of its normal 1089-8603/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.niox.2013.10.006 ⇑ Corresponding author. Address: Federal University of Santa Catarina, Rua Pastor William Richard Schisler Filho, 900/711, Itacorubi, Florianópolis, Santa Catarina, CEP 88034100, Brazil. Fax: +55 48 32229357. E-mail addresses: gcolomboufsc@gmail.com (G. Colombo), mdanielahemosc@ gmail.com (Maria Daniela H. Périco Colombo), leo-jf@uol.com.br (L.D.L. Schiavon), dacampora@gmail.com (A.J. d’Acampora). Nitric Oxide 35 (2013) 186–192 Contents lists available at ScienceDirect Nitric Oxide journal homepage: www.elsevier.com/locate/yniox