biostudies-literatureWang YCNHLBI NIH HHS371-389https://www.ebi.ac.uk/biostudies/studies/S-EPMC10923103biostudies-literatureUnknown134(4)<h4>Background</h4>Heart failure with preserved ejection fraction (HFpEF) is a common but poorly understood form of heart failure, characterized by impaired diastolic function. It is highly heterogeneous with multiple comorbidities, including obesity and diabetes, making human studies difficult.<h4>Methods</h4>Metabolomic analyses in a mouse model of HFpEF showed that levels of indole-3-propionic acid (IPA), a metabolite produced by gut bacteria from tryptophan, were reduced in the plasma and heart tissue of HFpEF mice as compared with controls. We then examined the role of IPA in mouse models of HFpEF as well as 2 human HFpEF cohorts.<h4>Results</h4>The protective role and therapeutic effects of IPA were confirmed in mouse models of HFpEF using IPA dietary supplementation. IPA attenuated Circulation researchIndole-3-Propionic Acid Protects Against Heart Failure With Preserved Ejection Fraction.PMC10923103R01 HL133169R01 HL148577R01 HL167831R01 HL144651R01 HL148110P01 HL147823Li XSKoay YCWang YCRey FEHazen SLZhou ZO'Sullivan JFPan CMarques FKaye DMCao YZagouras ALusis AJWilcox JTang WAllayee HfalseIndole-3-Propionic Acid Protects Against Heart Failure With Preserved Ejection Fraction.<h4>Background</h4>Heart failure with preserved ejection fraction (HFpEF) is a common but poorly understood form of heart failure, characterized by impaired diastolic function. It is highly heterogeneous with multiple comorbidities, including obesity and diabetes, making human studies difficult.<h4>Methods</h4>Metabolomic analyses in a mouse model of HFpEF showed that levels of indole-3-propionic acid (IPA), a metabolite produced by gut bacteria from tryptophan, were reduced in the plasma and heart tissue of HFpEF mice as compared with controls. We then examined the role of IPA in mouse models of HFpEF as well as 2 human HFpEF cohorts.<h4>Results</h4>The protective role and therapeutic effects of IPA were confirmed in mouse models of HFpEF using IPA dietary supplementation. IPA attenuated 2024-01-01T00:00:00Z2024 Feb2026-06-01T20:08:28.333Z2025-04-07T07:50:15.236ZS-EPMC109231033826490910.1161/circresaha.123.32238110.1161/CIRCRESAHA.123.322381