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Effects of sildenafil treatment on thermogenesis and glucose homeostasis in diet-induced obese mice

Stimulation of thermogenic pathways appears to be a promising approach to find new ways of tackling metabolic diseases like obesity and diabetes mellitus type 2. Thermogenic, weight reducing and insulin sensitizing effects of phosphodiesterase 5 (PDE 5) inhibitors have recently been postulated, sugg...

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Autores principales: Johann, Kornelia, Reis, Marlen Colleen, Harder, Lisbeth, Herrmann, Beate, Gachkar, Sogol, Mittag, Jens, Oelkrug, Rebecca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856821/
https://www.ncbi.nlm.nih.gov/pubmed/29549244
http://dx.doi.org/10.1038/s41387-018-0026-0
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author Johann, Kornelia
Reis, Marlen Colleen
Harder, Lisbeth
Herrmann, Beate
Gachkar, Sogol
Mittag, Jens
Oelkrug, Rebecca
author_facet Johann, Kornelia
Reis, Marlen Colleen
Harder, Lisbeth
Herrmann, Beate
Gachkar, Sogol
Mittag, Jens
Oelkrug, Rebecca
author_sort Johann, Kornelia
collection PubMed
description Stimulation of thermogenic pathways appears to be a promising approach to find new ways of tackling metabolic diseases like obesity and diabetes mellitus type 2. Thermogenic, weight reducing and insulin sensitizing effects of phosphodiesterase 5 (PDE 5) inhibitors have recently been postulated, suggesting that modulators of endogenous cGMP signaling have the therapeutic potential to treat metabolic disorders. However, most studies have been performed in vitro or in animals that were not glucose intolerant. We, thus, aimed to test the metabolic effects of the PDE 5 inhibitor sildenafil by treating diet-induced obese (DIO) mice orally for 8 days. Surprisingly, our results revealed no changes in body temperature, brown adipose tissue (BAT) thermogenesis and gene expression in BAT and inguinal white adipose tissue (iWAT), thus excluding a thermogenic or 'browning' effect of sildenafil in preexisting obesity. In contrast, sildenafil-treated DIO mice displayed changes in liver metabolism and glucose homeostasis resulting in impaired glucose tolerance (P < 0.05), demonstrating for the first time an unfavorable metabolic effect of increased hepatic cGMP signaling in obesity. As sildenafil is commonly prescribed to treat pulmonary arterial hypertension and erectile dysfunction in diabetic and/or obese patients, follow up studies are urgently required to re-evaluate the drug safety.
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spelling pubmed-58568212018-03-20 Effects of sildenafil treatment on thermogenesis and glucose homeostasis in diet-induced obese mice Johann, Kornelia Reis, Marlen Colleen Harder, Lisbeth Herrmann, Beate Gachkar, Sogol Mittag, Jens Oelkrug, Rebecca Nutr Diabetes Brief Communication Stimulation of thermogenic pathways appears to be a promising approach to find new ways of tackling metabolic diseases like obesity and diabetes mellitus type 2. Thermogenic, weight reducing and insulin sensitizing effects of phosphodiesterase 5 (PDE 5) inhibitors have recently been postulated, suggesting that modulators of endogenous cGMP signaling have the therapeutic potential to treat metabolic disorders. However, most studies have been performed in vitro or in animals that were not glucose intolerant. We, thus, aimed to test the metabolic effects of the PDE 5 inhibitor sildenafil by treating diet-induced obese (DIO) mice orally for 8 days. Surprisingly, our results revealed no changes in body temperature, brown adipose tissue (BAT) thermogenesis and gene expression in BAT and inguinal white adipose tissue (iWAT), thus excluding a thermogenic or 'browning' effect of sildenafil in preexisting obesity. In contrast, sildenafil-treated DIO mice displayed changes in liver metabolism and glucose homeostasis resulting in impaired glucose tolerance (P < 0.05), demonstrating for the first time an unfavorable metabolic effect of increased hepatic cGMP signaling in obesity. As sildenafil is commonly prescribed to treat pulmonary arterial hypertension and erectile dysfunction in diabetic and/or obese patients, follow up studies are urgently required to re-evaluate the drug safety. Nature Publishing Group UK 2018-03-13 /pmc/articles/PMC5856821/ /pubmed/29549244 http://dx.doi.org/10.1038/s41387-018-0026-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Brief Communication
Johann, Kornelia
Reis, Marlen Colleen
Harder, Lisbeth
Herrmann, Beate
Gachkar, Sogol
Mittag, Jens
Oelkrug, Rebecca
Effects of sildenafil treatment on thermogenesis and glucose homeostasis in diet-induced obese mice
title Effects of sildenafil treatment on thermogenesis and glucose homeostasis in diet-induced obese mice
title_full Effects of sildenafil treatment on thermogenesis and glucose homeostasis in diet-induced obese mice
title_fullStr Effects of sildenafil treatment on thermogenesis and glucose homeostasis in diet-induced obese mice
title_full_unstemmed Effects of sildenafil treatment on thermogenesis and glucose homeostasis in diet-induced obese mice
title_short Effects of sildenafil treatment on thermogenesis and glucose homeostasis in diet-induced obese mice
title_sort effects of sildenafil treatment on thermogenesis and glucose homeostasis in diet-induced obese mice
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856821/
https://www.ncbi.nlm.nih.gov/pubmed/29549244
http://dx.doi.org/10.1038/s41387-018-0026-0
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