TRC150094 attenuates progression of nontraditional cardiovascular risk factors associated with obesity and type 2 diabetes in obese ZSF1 rats

Shitalkumar P Zambad1, Siralee Munshi2, Amita Dubey3, Ram Gupta1, Rosa Anna Busiello4, Antonia Lanni5, Fernando Goglia6, Ramesh C Gupta7, Vijay Chauthaiwale8, Chaitanya Dutt91Pharmacology, 2Cellular and Molecular Biology, 3Pre-clinical and Safety Evaluation, Torrent Research Centre, Torrent Pharmace...

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Autores principales:	Shitalkumar P Zambad, Siralee Munshi, Amita Dubey, et al
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/e84565ddb2e642eea6cb0aa11386a7cd
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spelling	oai:doaj.org-article:e84565ddb2e642eea6cb0aa11386a7cd2021-12-02T06:05:58ZTRC150094 attenuates progression of nontraditional cardiovascular risk factors associated with obesity and type 2 diabetes in obese ZSF1 rats1178-7007https://doaj.org/article/e84565ddb2e642eea6cb0aa11386a7cd2011-01-01T00:00:00Zhttp://www.dovepress.com/trc150094-attenuates-progression-of-nontraditional-cardiovascular-risk-a6002https://doaj.org/toc/1178-7007Shitalkumar P Zambad1, Siralee Munshi2, Amita Dubey3, Ram Gupta1, Rosa Anna Busiello4, Antonia Lanni5, Fernando Goglia6, Ramesh C Gupta7, Vijay Chauthaiwale8, Chaitanya Dutt91Pharmacology, 2Cellular and Molecular Biology, 3Pre-clinical and Safety Evaluation, Torrent Research Centre, Torrent Pharmaceuticals Ltd, Gujarat, India; 4Dipartimento di Biologia, Universita degli Studi di Napoli Federico II, Naples, Italy; 5Dipartimento di Scienze della Vita, Seconda Universita di Napoli, Caserta, Italy; 6Dipartimento di Scienze Biologiche ed Ambientali, Universita del Sannio, Benevento, Italy; 7Medicinal Chemistry, 8Discovery Research, 9Clinical Research, Torrent Research Centre, Torrent Pharmaceuticals Ltd, Gujarat, IndiaAbstract: Chronic overnutrition and consequential visceral obesity is associated with a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus. Moreover, individuals who have a triad of hypertension, dysglycemia, and elevated triglycerides along with reduced high-density lipoprotein cholesterol have a greater residual cardiovascular risk even after factoring for the traditional risk factors such as age, smoking, diabetes, and elevated low-density lipoprotein cholesterol. In our previous study we demonstrated that TRC150094, when administered to rats receiving a high-fat diet, stimulated mitochondrial fatty acid oxidation (FAO) and reduced visceral adiposity, opening an interesting perspective for a possible clinical application. In the present study, oral administration of TRC150094 to obese Zucker spontaneously hypertensive fatty rats (obese ZSF1) improved glucose tolerance and glycemic profile as well as attenuated a rise in blood pressure. Obese ZSF1 rats treated with TRC150094 also showed reduced hepatic steatosis, reduced progression of nephropathy, and improved skeletal muscle function. At the cellular level, TRC150094 induced a significant increase in mitochondrial respiration as well as an increased FAO in liver and skeletal muscle, ultimately resulting in reduced hepatic as well as total body fat accumulation, as evaluated by magnetic resonance spectroscopy and magnetic resonance imaging, respectively. If reproduced in humans, these results could confirm that TRC150094 may represent an attractive therapeutic agent to counteract multiple residual cardiovascular risk components.Keywords: CV risk factors, energy expenditure, fatty acid oxidation, obesity, TRC150094, type 2 diabetes Shitalkumar P ZambadSiralee MunshiAmita Dubeyet alDove Medical PressarticleSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol 2011, Iss default, Pp 5-16 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Specialties of internal medicine RC581-951
spellingShingle	Specialties of internal medicine RC581-951 Shitalkumar P Zambad Siralee Munshi Amita Dubey et al TRC150094 attenuates progression of nontraditional cardiovascular risk factors associated with obesity and type 2 diabetes in obese ZSF1 rats
description	Shitalkumar P Zambad1, Siralee Munshi2, Amita Dubey3, Ram Gupta1, Rosa Anna Busiello4, Antonia Lanni5, Fernando Goglia6, Ramesh C Gupta7, Vijay Chauthaiwale8, Chaitanya Dutt91Pharmacology, 2Cellular and Molecular Biology, 3Pre-clinical and Safety Evaluation, Torrent Research Centre, Torrent Pharmaceuticals Ltd, Gujarat, India; 4Dipartimento di Biologia, Universita degli Studi di Napoli Federico II, Naples, Italy; 5Dipartimento di Scienze della Vita, Seconda Universita di Napoli, Caserta, Italy; 6Dipartimento di Scienze Biologiche ed Ambientali, Universita del Sannio, Benevento, Italy; 7Medicinal Chemistry, 8Discovery Research, 9Clinical Research, Torrent Research Centre, Torrent Pharmaceuticals Ltd, Gujarat, IndiaAbstract: Chronic overnutrition and consequential visceral obesity is associated with a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus. Moreover, individuals who have a triad of hypertension, dysglycemia, and elevated triglycerides along with reduced high-density lipoprotein cholesterol have a greater residual cardiovascular risk even after factoring for the traditional risk factors such as age, smoking, diabetes, and elevated low-density lipoprotein cholesterol. In our previous study we demonstrated that TRC150094, when administered to rats receiving a high-fat diet, stimulated mitochondrial fatty acid oxidation (FAO) and reduced visceral adiposity, opening an interesting perspective for a possible clinical application. In the present study, oral administration of TRC150094 to obese Zucker spontaneously hypertensive fatty rats (obese ZSF1) improved glucose tolerance and glycemic profile as well as attenuated a rise in blood pressure. Obese ZSF1 rats treated with TRC150094 also showed reduced hepatic steatosis, reduced progression of nephropathy, and improved skeletal muscle function. At the cellular level, TRC150094 induced a significant increase in mitochondrial respiration as well as an increased FAO in liver and skeletal muscle, ultimately resulting in reduced hepatic as well as total body fat accumulation, as evaluated by magnetic resonance spectroscopy and magnetic resonance imaging, respectively. If reproduced in humans, these results could confirm that TRC150094 may represent an attractive therapeutic agent to counteract multiple residual cardiovascular risk components.Keywords: CV risk factors, energy expenditure, fatty acid oxidation, obesity, TRC150094, type 2 diabetes
format	article
author	Shitalkumar P Zambad Siralee Munshi Amita Dubey et al
author_facet	Shitalkumar P Zambad Siralee Munshi Amita Dubey et al
author_sort	Shitalkumar P Zambad
title	TRC150094 attenuates progression of nontraditional cardiovascular risk factors associated with obesity and type 2 diabetes in obese ZSF1 rats
title_short	TRC150094 attenuates progression of nontraditional cardiovascular risk factors associated with obesity and type 2 diabetes in obese ZSF1 rats
title_full	TRC150094 attenuates progression of nontraditional cardiovascular risk factors associated with obesity and type 2 diabetes in obese ZSF1 rats
title_fullStr	TRC150094 attenuates progression of nontraditional cardiovascular risk factors associated with obesity and type 2 diabetes in obese ZSF1 rats
title_full_unstemmed	TRC150094 attenuates progression of nontraditional cardiovascular risk factors associated with obesity and type 2 diabetes in obese ZSF1 rats
title_sort	trc150094 attenuates progression of nontraditional cardiovascular risk factors associated with obesity and type 2 diabetes in obese zsf1 rats
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/e84565ddb2e642eea6cb0aa11386a7cd
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TRC150094 attenuates progression of nontraditional cardiovascular risk factors associated with obesity and type 2 diabetes in obese ZSF1 rats

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