Combination of low-dose testosterone and vildagliptin confers cardioprotection in castrated obese rats

© 2019 Society for Endocrinology Published by Bioscientifica Ltd. Although a physiological dose of testosterone replacement therapy (p-TRT) has been shown to improve left ventricular (LV) function, some studies reported that it increased the risk of myocardial infarction in testosterone-deprived men...

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Main Authors: Apiwan Arinno, Nattayaporn Apaijai, Puntarik Kaewthep, Wasana Pratchayasakul, Thidarat Jaiwongkam, Sasiwan Kerdphoo, Siriporn C. Chattipakorn, Nipon Chattipakorn
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Published: 2019
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/65389
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spelling th-cmuir.6653943832-653892019-08-05T04:40:52Z Combination of low-dose testosterone and vildagliptin confers cardioprotection in castrated obese rats Apiwan Arinno Nattayaporn Apaijai Puntarik Kaewthep Wasana Pratchayasakul Thidarat Jaiwongkam Sasiwan Kerdphoo Siriporn C. Chattipakorn Nipon Chattipakorn Biochemistry, Genetics and Molecular Biology Medicine © 2019 Society for Endocrinology Published by Bioscientifica Ltd. Although a physiological dose of testosterone replacement therapy (p-TRT) has been shown to improve left ventricular (LV) function, some studies reported that it increased the risk of myocardial infarction in testosterone-deprived men. We previously reported that vildagliptin might be used as an alternative to p-TRT. In this study, we hypothesized that a combined low-dose TRT with vildagliptin exerts greater efficacy than single regimen in improving cardiometabolic function in obese, insulin-resistant rats with testosterone deprivation. Male rats were fed on a normal diet or high-fat diet for 12 weeks. Then, they were divided into two subgroups, sham operation and orchiectomy (normal diet rats with orchiectomy (NDO), high-fat diet rats with orchiectomy (HFO)) and fed their diets for another 12 weeks. At week 25, orchiectomized rats were subdivided into four groups: vehicle, p-TRT, vildagliptin and combined drugs. At week 29, cardiometabolic and biochemical parameters were determined. HFO rats had obese insulin resistance with a worse LV dysfunction, compared with sham. Vildagliptin and combined drugs effectively reduced insulin resistance. All treatments reduced blood pressure, cardiac autonomic imbalance, LV dysfunction, mitochondrial dysfunction, apoptosis and increased mitochondrial fusion in NDO and HFO rats. However, p-TRT and combined drugs, but not vildagliptin, reduced mitochondrial fission in NDO and HFO rats. We concluded that combined low-dose TRT with vildagliptin mitigated LV function at a similar level to the p-TRT alone and vildagliptin via improving mitochondrial fusion, reducing mitochondrial dysfunction and apoptosis in testosterone-deprived rats. Our findings suggest that low-dose TRT combined with vildagliptin may be an alternative for p-TRT in conditions of obese insulin resistance with testosterone deprivation. 2019-08-05T04:32:34Z 2019-08-05T04:32:34Z 2019-03-01 Journal 14796805 00220795 2-s2.0-85063658846 10.1530/JOE-18-0673 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85063658846&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/65389
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Biochemistry, Genetics and Molecular Biology
Medicine
spellingShingle Biochemistry, Genetics and Molecular Biology
Medicine
Apiwan Arinno
Nattayaporn Apaijai
Puntarik Kaewthep
Wasana Pratchayasakul
Thidarat Jaiwongkam
Sasiwan Kerdphoo
Siriporn C. Chattipakorn
Nipon Chattipakorn
Combination of low-dose testosterone and vildagliptin confers cardioprotection in castrated obese rats
description © 2019 Society for Endocrinology Published by Bioscientifica Ltd. Although a physiological dose of testosterone replacement therapy (p-TRT) has been shown to improve left ventricular (LV) function, some studies reported that it increased the risk of myocardial infarction in testosterone-deprived men. We previously reported that vildagliptin might be used as an alternative to p-TRT. In this study, we hypothesized that a combined low-dose TRT with vildagliptin exerts greater efficacy than single regimen in improving cardiometabolic function in obese, insulin-resistant rats with testosterone deprivation. Male rats were fed on a normal diet or high-fat diet for 12 weeks. Then, they were divided into two subgroups, sham operation and orchiectomy (normal diet rats with orchiectomy (NDO), high-fat diet rats with orchiectomy (HFO)) and fed their diets for another 12 weeks. At week 25, orchiectomized rats were subdivided into four groups: vehicle, p-TRT, vildagliptin and combined drugs. At week 29, cardiometabolic and biochemical parameters were determined. HFO rats had obese insulin resistance with a worse LV dysfunction, compared with sham. Vildagliptin and combined drugs effectively reduced insulin resistance. All treatments reduced blood pressure, cardiac autonomic imbalance, LV dysfunction, mitochondrial dysfunction, apoptosis and increased mitochondrial fusion in NDO and HFO rats. However, p-TRT and combined drugs, but not vildagliptin, reduced mitochondrial fission in NDO and HFO rats. We concluded that combined low-dose TRT with vildagliptin mitigated LV function at a similar level to the p-TRT alone and vildagliptin via improving mitochondrial fusion, reducing mitochondrial dysfunction and apoptosis in testosterone-deprived rats. Our findings suggest that low-dose TRT combined with vildagliptin may be an alternative for p-TRT in conditions of obese insulin resistance with testosterone deprivation.
format Journal
author Apiwan Arinno
Nattayaporn Apaijai
Puntarik Kaewthep
Wasana Pratchayasakul
Thidarat Jaiwongkam
Sasiwan Kerdphoo
Siriporn C. Chattipakorn
Nipon Chattipakorn
author_facet Apiwan Arinno
Nattayaporn Apaijai
Puntarik Kaewthep
Wasana Pratchayasakul
Thidarat Jaiwongkam
Sasiwan Kerdphoo
Siriporn C. Chattipakorn
Nipon Chattipakorn
author_sort Apiwan Arinno
title Combination of low-dose testosterone and vildagliptin confers cardioprotection in castrated obese rats
title_short Combination of low-dose testosterone and vildagliptin confers cardioprotection in castrated obese rats
title_full Combination of low-dose testosterone and vildagliptin confers cardioprotection in castrated obese rats
title_fullStr Combination of low-dose testosterone and vildagliptin confers cardioprotection in castrated obese rats
title_full_unstemmed Combination of low-dose testosterone and vildagliptin confers cardioprotection in castrated obese rats
title_sort combination of low-dose testosterone and vildagliptin confers cardioprotection in castrated obese rats
publishDate 2019
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85063658846&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/65389
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