Intermittent Fasting Enhances Right Ventricular Function in Preclinical Pulmonary Arterial Hypertension

Background Intermittent fasting (IF) confers pleiotropic cardiovascular benefits including restructuring of the gut microbiome and augmentation of cellular metabolism. Pulmonary arterial hypertension (PAH) is a rare and lethal disease characterized by right ventricular (RV) mitochondrial dysfunction...

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Autores principales:	Sasha Z. Prisco, Megan Eklund, Daphne M. Moutsoglou, Anthony R. Prisco, Alexander Khoruts, E. Kenneth Weir, Thenappan Thenappan, Kurt W. Prins
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	gut microbiome intermittent fasting Lactobacillus lipotoxicity metabolism metabolomics Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/1099f9ffe3d84bde81da1673147ccca1
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spelling	oai:doaj.org-article:1099f9ffe3d84bde81da1673147ccca12021-11-16T10:22:43ZIntermittent Fasting Enhances Right Ventricular Function in Preclinical Pulmonary Arterial Hypertension10.1161/JAHA.121.0227222047-9980https://doaj.org/article/1099f9ffe3d84bde81da1673147ccca12021-11-01T00:00:00Zhttps://www.ahajournals.org/doi/10.1161/JAHA.121.022722https://doaj.org/toc/2047-9980Background Intermittent fasting (IF) confers pleiotropic cardiovascular benefits including restructuring of the gut microbiome and augmentation of cellular metabolism. Pulmonary arterial hypertension (PAH) is a rare and lethal disease characterized by right ventricular (RV) mitochondrial dysfunction and resultant lipotoxicity and microbiome dysbiosis. However, the effects of IF on RV function in PAH are unexplored. Therefore, we investigated how IF altered gut microbiota composition, RV function, and survival in the monocrotaline model of PAH. Methods and Results Male Sprague Dawley rats were randomly allocated into 3 groups: control, monocrotaline‐ad libitum feeding, and monocrotaline‐IF (every other day feeding). Echocardiography and invasive hemodynamics showed IF improved RV systolic and diastolic function despite no significant change in PAH severity. IF prevented premature mortality (30% mortality rate in monocrotaline‐ad libitum versus 0% in monocrotaline‐IF rats, P=0.04). IF decreased RV cardiomyocyte hypertrophy and reduced RV fibrosis. IF prevented RV lipid accrual on Oil Red O staining and ceramide accumulation as determined by metabolomics. IF mitigated the reduction in jejunum villi length and goblet cell abundance when compared with monocrotaline‐ad libitum. The 16S ribosomal RNA gene sequencing demonstrated IF changed the gut microbiome. In particular, there was increased abundance of Lactobacillus in monocrotaline‐IF rats. Metabolomics profiling revealed IF decreased RV levels of microbiome metabolites including bile acids, aromatic amino acid metabolites, and gamma‐glutamylated amino acids. Conclusions IF directly enhanced RV function and restructured the gut microbiome. These results suggest IF may be a non‐pharmacological approach to combat RV dysfunction, a currently untreatable and lethal consequence of PAH.Sasha Z. PriscoMegan EklundDaphne M. MoutsoglouAnthony R. PriscoAlexander KhorutsE. Kenneth WeirThenappan ThenappanKurt W. PrinsWileyarticlegut microbiomeintermittent fastingLactobacilluslipotoxicitymetabolismmetabolomicsDiseases of the circulatory (Cardiovascular) systemRC666-701ENJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 10, Iss 22 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	gut microbiome intermittent fasting Lactobacillus lipotoxicity metabolism metabolomics Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	gut microbiome intermittent fasting Lactobacillus lipotoxicity metabolism metabolomics Diseases of the circulatory (Cardiovascular) system RC666-701 Sasha Z. Prisco Megan Eklund Daphne M. Moutsoglou Anthony R. Prisco Alexander Khoruts E. Kenneth Weir Thenappan Thenappan Kurt W. Prins Intermittent Fasting Enhances Right Ventricular Function in Preclinical Pulmonary Arterial Hypertension
description	Background Intermittent fasting (IF) confers pleiotropic cardiovascular benefits including restructuring of the gut microbiome and augmentation of cellular metabolism. Pulmonary arterial hypertension (PAH) is a rare and lethal disease characterized by right ventricular (RV) mitochondrial dysfunction and resultant lipotoxicity and microbiome dysbiosis. However, the effects of IF on RV function in PAH are unexplored. Therefore, we investigated how IF altered gut microbiota composition, RV function, and survival in the monocrotaline model of PAH. Methods and Results Male Sprague Dawley rats were randomly allocated into 3 groups: control, monocrotaline‐ad libitum feeding, and monocrotaline‐IF (every other day feeding). Echocardiography and invasive hemodynamics showed IF improved RV systolic and diastolic function despite no significant change in PAH severity. IF prevented premature mortality (30% mortality rate in monocrotaline‐ad libitum versus 0% in monocrotaline‐IF rats, P=0.04). IF decreased RV cardiomyocyte hypertrophy and reduced RV fibrosis. IF prevented RV lipid accrual on Oil Red O staining and ceramide accumulation as determined by metabolomics. IF mitigated the reduction in jejunum villi length and goblet cell abundance when compared with monocrotaline‐ad libitum. The 16S ribosomal RNA gene sequencing demonstrated IF changed the gut microbiome. In particular, there was increased abundance of Lactobacillus in monocrotaline‐IF rats. Metabolomics profiling revealed IF decreased RV levels of microbiome metabolites including bile acids, aromatic amino acid metabolites, and gamma‐glutamylated amino acids. Conclusions IF directly enhanced RV function and restructured the gut microbiome. These results suggest IF may be a non‐pharmacological approach to combat RV dysfunction, a currently untreatable and lethal consequence of PAH.
format	article
author	Sasha Z. Prisco Megan Eklund Daphne M. Moutsoglou Anthony R. Prisco Alexander Khoruts E. Kenneth Weir Thenappan Thenappan Kurt W. Prins
author_facet	Sasha Z. Prisco Megan Eklund Daphne M. Moutsoglou Anthony R. Prisco Alexander Khoruts E. Kenneth Weir Thenappan Thenappan Kurt W. Prins
author_sort	Sasha Z. Prisco
title	Intermittent Fasting Enhances Right Ventricular Function in Preclinical Pulmonary Arterial Hypertension
title_short	Intermittent Fasting Enhances Right Ventricular Function in Preclinical Pulmonary Arterial Hypertension
title_full	Intermittent Fasting Enhances Right Ventricular Function in Preclinical Pulmonary Arterial Hypertension
title_fullStr	Intermittent Fasting Enhances Right Ventricular Function in Preclinical Pulmonary Arterial Hypertension
title_full_unstemmed	Intermittent Fasting Enhances Right Ventricular Function in Preclinical Pulmonary Arterial Hypertension
title_sort	intermittent fasting enhances right ventricular function in preclinical pulmonary arterial hypertension
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/1099f9ffe3d84bde81da1673147ccca1
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Intermittent Fasting Enhances Right Ventricular Function in Preclinical Pulmonary Arterial Hypertension

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