Exercise improves systemic metabolism in a monocrotaline model of pulmonary hypertension

Exercise training in pulmonary arterial hypertension (PAH) has been gaining popularity with guidelines now recommending it as an important adjunct to medical therapy. Despite improvements in function and quality of life, an understanding of metabolic changes and their mechanisms remain unexplored. T...

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Main Authors: Ganesha Poojary, Sampara Vasishta, R. Huban Thomas, Kapaettu Satyamoorthy, Ramachandran Padmakumar, Manjunath B. Joshi, Abraham Samuel Babu
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-01-01
Series:Sports Medicine and Health Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666337624000295
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author Ganesha Poojary
Sampara Vasishta
R. Huban Thomas
Kapaettu Satyamoorthy
Ramachandran Padmakumar
Manjunath B. Joshi
Abraham Samuel Babu
author_facet Ganesha Poojary
Sampara Vasishta
R. Huban Thomas
Kapaettu Satyamoorthy
Ramachandran Padmakumar
Manjunath B. Joshi
Abraham Samuel Babu
author_sort Ganesha Poojary
collection DOAJ
description Exercise training in pulmonary arterial hypertension (PAH) has been gaining popularity with guidelines now recommending it as an important adjunct to medical therapy. Despite improvements in function and quality of life, an understanding of metabolic changes and their mechanisms remain unexplored. The objective of this study was therefore to understand the metabolic basis of exercise in a monocrotaline model of PAH.24 male Wistar rats (age: 8–12 weeks and mean body weight: [262.16 ​± ​24.49] gms) were assigned to one of the four groups (i.e., Control, PAH, Exercise and PAH ​+ ​Exercise). The exercise groups participated in treadmill running at 13.3 ​m/min, five days a week for five weeks. Demographic and clinical characteristics were monitored regularly. Following the intervention, LC-MS based metabolomics were performed on blood samples from all groups at the end of five weeks. Metabolite profiling, peak identification, alignment and isotope annotation were also performed. Statistical inference was carried out using dimensionality reducing techniques and analysis of variance.Partial-least-squares discrimination analysis and variable importance in the projection scores showed that the model was reliable, and not over lifting. The analysis demonstrated significant perturbations to lipid and amino acid metabolism, arginine and homocysteine pathways, sphingolipid (p ​< ​0.05), glycerophospholipid (p ​< ​0.05) and nucleotide metabolism in PAH. Exercise, however, was seen to restore arginine (p ​< ​0.05) and homocysteine(p ​< ​0.000 1) levels which were independent effects, irrespective of PAH.Dysregulated arginine and homocysteine pathways are seen in PAH. Exercise restores these dysregulated pathways and could potentially impact severity and outcome in PAH.
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spelling doaj-art-df1d1ec529eb4de7afadd9fc89a0ec792024-11-20T05:08:18ZengKeAi Communications Co., Ltd.Sports Medicine and Health Science2666-33762025-01-01713747Exercise improves systemic metabolism in a monocrotaline model of pulmonary hypertensionGanesha Poojary0Sampara Vasishta1R. Huban Thomas2Kapaettu Satyamoorthy3Ramachandran Padmakumar4Manjunath B. Joshi5Abraham Samuel Babu6Department of Physiotherapy, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, IndiaDepartment of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, IndiaDepartment of Anatomy, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, IndiaSDM College of Medical Sciences and Hospital, Shri Dharmasthala Manjunatheshwara (SDM) University, Manjushree Nagar, Sattur, Dharwad, Karnataka, 580009, IndiaDepartment of Cardiology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, IndiaDepartment of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, IndiaDepartment of Physiotherapy, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India; Corresponding author.Exercise training in pulmonary arterial hypertension (PAH) has been gaining popularity with guidelines now recommending it as an important adjunct to medical therapy. Despite improvements in function and quality of life, an understanding of metabolic changes and their mechanisms remain unexplored. The objective of this study was therefore to understand the metabolic basis of exercise in a monocrotaline model of PAH.24 male Wistar rats (age: 8–12 weeks and mean body weight: [262.16 ​± ​24.49] gms) were assigned to one of the four groups (i.e., Control, PAH, Exercise and PAH ​+ ​Exercise). The exercise groups participated in treadmill running at 13.3 ​m/min, five days a week for five weeks. Demographic and clinical characteristics were monitored regularly. Following the intervention, LC-MS based metabolomics were performed on blood samples from all groups at the end of five weeks. Metabolite profiling, peak identification, alignment and isotope annotation were also performed. Statistical inference was carried out using dimensionality reducing techniques and analysis of variance.Partial-least-squares discrimination analysis and variable importance in the projection scores showed that the model was reliable, and not over lifting. The analysis demonstrated significant perturbations to lipid and amino acid metabolism, arginine and homocysteine pathways, sphingolipid (p ​< ​0.05), glycerophospholipid (p ​< ​0.05) and nucleotide metabolism in PAH. Exercise, however, was seen to restore arginine (p ​< ​0.05) and homocysteine(p ​< ​0.000 1) levels which were independent effects, irrespective of PAH.Dysregulated arginine and homocysteine pathways are seen in PAH. Exercise restores these dysregulated pathways and could potentially impact severity and outcome in PAH.http://www.sciencedirect.com/science/article/pii/S2666337624000295Pulmonary arterial hypertensionMonocrotaline modelMetabolitesMetabolomicsEndothelial dysfunctionExercise
spellingShingle Ganesha Poojary
Sampara Vasishta
R. Huban Thomas
Kapaettu Satyamoorthy
Ramachandran Padmakumar
Manjunath B. Joshi
Abraham Samuel Babu
Exercise improves systemic metabolism in a monocrotaline model of pulmonary hypertension
Sports Medicine and Health Science
Pulmonary arterial hypertension
Monocrotaline model
Metabolites
Metabolomics
Endothelial dysfunction
Exercise
title Exercise improves systemic metabolism in a monocrotaline model of pulmonary hypertension
title_full Exercise improves systemic metabolism in a monocrotaline model of pulmonary hypertension
title_fullStr Exercise improves systemic metabolism in a monocrotaline model of pulmonary hypertension
title_full_unstemmed Exercise improves systemic metabolism in a monocrotaline model of pulmonary hypertension
title_short Exercise improves systemic metabolism in a monocrotaline model of pulmonary hypertension
title_sort exercise improves systemic metabolism in a monocrotaline model of pulmonary hypertension
topic Pulmonary arterial hypertension
Monocrotaline model
Metabolites
Metabolomics
Endothelial dysfunction
Exercise
url http://www.sciencedirect.com/science/article/pii/S2666337624000295
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