{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:28:02Z","timestamp":1790782082691,"version":"4.1.0"},"reference-count":15,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,11,16]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Male Sprague Dawley rats were randomly allocated into 3 groups: control, monocrotaline\u2010ad libitum feeding, and monocrotaline\u2010IF (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\u2010ad libitum versus 0% in monocrotaline\u2010IF rats,\n                      <jats:italic>P<\/jats:italic>\n                      =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\u2010ad libitum. The 16S ribosomal RNA gene sequencing demonstrated IF changed the gut microbiome. In particular, there was increased abundance of\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      in monocrotaline\u2010IF rats. Metabolomics profiling revealed IF decreased RV levels of microbiome metabolites including bile acids, aromatic amino acid metabolites, and gamma\u2010glutamylated amino acids.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">IF directly enhanced RV function and restructured the gut microbiome. These results suggest IF may be a non\u2010pharmacological approach to combat RV dysfunction, a currently untreatable and lethal consequence of PAH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.121.022722","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T05:37:48Z","timestamp":1636349868000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":47,"title":["Intermittent Fasting Enhances Right Ventricular Function in Preclinical Pulmonary Arterial Hypertension"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9059-0635","authenticated-orcid":false,"given":"Sasha Z.","family":"Prisco","sequence":"first","affiliation":[{"name":"Cardiovascular Division Department of Medicine University of Minnesota Minneapolis MN"},{"name":"Lillehei Heart Institute University of Minnesota Minneapolis MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8126-1963","authenticated-orcid":false,"given":"Megan","family":"Eklund","sequence":"additional","affiliation":[{"name":"Cardiovascular Division Department of Medicine University of Minnesota Minneapolis MN"},{"name":"Lillehei Heart Institute University of Minnesota Minneapolis MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4071-3756","authenticated-orcid":false,"given":"Daphne M.","family":"Moutsoglou","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition Department of Medicine Center for Immunology BioTechnology Institute University of Minnesota Minneapolis MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2209-1831","authenticated-orcid":false,"given":"Anthony R.","family":"Prisco","sequence":"additional","affiliation":[{"name":"Cardiovascular Division Department of Medicine University of Minnesota Minneapolis MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3205-3188","authenticated-orcid":false,"given":"Alexander","family":"Khoruts","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition Department of Medicine Center for Immunology BioTechnology Institute University of Minnesota Minneapolis MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Kenneth","family":"Weir","sequence":"additional","affiliation":[{"name":"Cardiovascular Division Department of Medicine University of Minnesota Minneapolis MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6210-0467","authenticated-orcid":false,"given":"Thenappan","family":"Thenappan","sequence":"additional","affiliation":[{"name":"Cardiovascular Division Department of Medicine University of Minnesota Minneapolis MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0364-6742","authenticated-orcid":false,"given":"Kurt W.","family":"Prins","sequence":"additional","affiliation":[{"name":"Cardiovascular Division Department of Medicine University of Minnesota Minneapolis MN"},{"name":"Lillehei Heart Institute University of Minnesota Minneapolis MN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-071816-064634"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12930"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01887-2018"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.14294"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.006195"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-84152-6"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/metabo9030057"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2020.07.011"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28890"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14676-4"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00508-015-0755-1"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.05.006"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00243.2009"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.113.000978"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1905136"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.121.022722","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T07:19:13Z","timestamp":1715584753000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.121.022722"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,16]]},"references-count":15,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2021,11,16]]}},"alternative-id":["10.1161\/JAHA.121.022722"],"URL":"https:\/\/doi.org\/10.1161\/jaha.121.022722","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,16]]},"assertion":[{"value":"2021-06-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e022722"}}