Academic Journal
Adropin protects against cardiac remodeling and metabolic dysfunction in a male mouse HFpEF model.
| Τίτλος: | Adropin protects against cardiac remodeling and metabolic dysfunction in a male mouse HFpEF model. |
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| Συγγραφείς: | Mushala BAS; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Division of Cardiology, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A., Stoner MW; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Division of Cardiology, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A., Sharifi-Sanjani M; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Division of Cardiology, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A., Manning JR; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Division of Cardiology, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A., Bugga P; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Division of Cardiology, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A., Bhattarai N; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Division of Cardiology, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A., McMahon B; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A., Vandevender A; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A., Mullet SJ; Health Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A., Kaufman BA; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Division of Cardiology, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A., Shiva SS; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Division of Classical Hematology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A., Zhang C; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A., Goetzman ES; Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A., Chan SY; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Division of Cardiology, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A., Gelhaus SL; Health Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A., Jurczak MJ; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A., Scott I; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.; Division of Cardiology, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A. |
| Πηγή: | Clinical science (London, England : 1979) [Clin Sci (Lond)] 2026 Jul 15; Vol. 140 (7), pp. 1399-1414. |
| Τύπος έκδοσης: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Portland Press on behalf of the Medical Research Society and the Biochemical Society Country of Publication: England NLM ID: 7905731 Publication Model: Print Cited Medium: Internet ISSN: 1470-8736 (Electronic) Linking ISSN: 01435221 NLM ISO Abbreviation: Clin Sci (Lond) Subsets: MEDLINE |
| Imprint Name(s): | Publication: London : Portland Press on behalf of the Medical Research Society and the Biochemical Society Original Publication: London, Medical Research Society. |
| Ιατρικοί όροι (MeSH): | Heart Failure*/physiopathology , Heart Failure*/metabolism , Heart Failure*/drug therapy , Ventricular Remodeling*/drug effects , Intercellular Signaling Peptides and Proteins*/pharmacology , Stroke Volume*/drug effects , Blood Proteins*/pharmacology, Acyl-CoA Dehydrogenase, Long-Chain/metabolism ; Myocardium/metabolism ; Hexosamines/metabolism ; Hexosamines/biosynthesis ; Carnitine/analogs & derivatives ; Carnitine/metabolism ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/metabolism ; Animals ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice |
| Περίληψη: | Cardiometabolic heart failure with preserved ejection fraction (HFpEF) is a heterogenous metabolic disease, which in the heart presents as left ventricle diastolic dysfunction, ventricular stiffness, and myocardial structural remodeling. Deleterious changes in cardiac metabolism are central to HFpEF pathophysiology, and proposed treatments for the disease have focused on repairing these defects. In the present study, we used a preclinical mouse model that recapitulates cardiometabolic HFpEF to elucidate the molecular mechanisms driving cardiac dysfunction and tested whether recombinant adropin (Adr.) (a liver- and brain-derived endogenous peptide hormone) could reverse observed defects. We show that long-term treatment with Adr. reversed multiple markers of HFpEF-related cardiac dysfunction (including fibrosis, diastolic dysfunction, and cardiomyocyte hypertrophy). Using untargeted metabolomics, we found that Adr. treatment reduced hexosamine biosynthesis pathway activity, leading to a reduction in the O-GlcNAcylation of the cardiac fatty acid oxidation enzyme long-chain acyl-CoA dehydrogenase (LCAD). Reducing LCAD O-GlcNAcylation increased LCAD activity in vitro and reduced the accumulation of long-chain acylcarnitines in HFpEF mouse hearts in vivo. Our results suggest that Adr. may restore cardiac metabolic function in HFpEF and that targeting this pathway may be a novel therapeutic avenue for this disease. (© 2026 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.) |
| Σχόλια: | Update of: bioRxiv. 2025 Nov 18:2025.05.03.652038. doi: 10.1101/2025.05.03.652038.. (PMID: 40654632) |
| Grant Information: | F31DK134089 HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); T32HL110849 HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); S10OD023402 HHS | NIH | NIH Office of the Director (OD); S10OD032141 HHS | NIH | NIH Office of the Director (OD); HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI); R01HL124021 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI); R01HL122596 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI); R01HL151228 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI); R01HL147861 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI); R0HL156874 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI); 23EIA1037834 American Heart Association (AHA) |
| Contributed Indexing: | Keywords: fatty acid oxidation; heart failure; mitochondria |
| Substance Nomenclature: | 0 (Enho protein, mouse) 0 (Intercellular Signaling Peptides and Proteins) EC 1.3.8.8 (Acyl-CoA Dehydrogenase, Long-Chain) 0 (Blood Proteins) 0 (Hexosamines) S7UI8SM58A (Carnitine) |
| Entry Date(s): | Date Created: 20260611 Date Completed: 20260622 Latest Revision: 20260709 |
| Update Code: | 20260711 |
| DOI: | 10.1042/CS20261501 |
| PMID: | 42275197 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1470-8736 |
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| DOI: | 10.1042/CS20261501 |