ArticleNature communications2021
Xbp1s-FoxO1 axis governs lipid accumulation and contractile performance in heart failure with preserved ejection fraction.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
90 citing papers in PubMed, 141 citations in OpenAlex.
- Diastolic contributors in cardiomyocytes of a cardiometabolic HFpEF-like mouse model.The Journal of general physiology · 2026Article
- SSUH2 Promotes Odontogenic Differentiation of SCAPs via the FOXM1/PDK1-Mediated Regulation of Mitochondrial Function.International endodontic journal · 2026Article
- HFpEF and MASLD: converging mechanisms and clinical implications.Nature reviews. Cardiology · 2026Review
- Inflammation, metabolism, and aging in heart failure with preserved ejection fraction: Mechanisms and treatment perspectives.Journal of translational internal medicine · 2026Article
- A high-fat diet nutritional intervention reprograms cardiac metabolism and improves systolic function in a pig model of heart failure with reduced ejection fraction.Basic research in cardiology · 2026Article
- Organelle homeostasis disruption: A driving force in the progression of cardiomyopathy (Review).Experimental and therapeutic medicine · 2026Review
- Metabolic syndrome and a broken heart: trust your gut or risk your heart.American journal of physiology. Heart and circulatory physiology · 2026Review
- Lipotoxicity in Diabetic Cardiomyopathy: Molecular Basis and Emerging Therapeutic Targets.International journal of molecular sciences · 2026Review
- Cellular Interactions and Immunometabolic Mechanisms in Heart Failure With Preserved Ejection Fraction: From Molecular Mechanisms to Clinical Evidence.Circulation. Heart failure · 2026Review
- Sex-specific cardioprotective role of miR-30a-5p through estrogen-dependent mechanisms in a mouse model of heart failure.Cardiovascular diabetology · 2026Article
- Sec8: a novel positive regulator of RIG-I in anti-RNA viral defense.Cell death & disease · 2026Article
- CTRP9 ameliorates heart failure with preserved ejection fraction by regulating lipid metabolism.Journal of translational medicine · 2026Article
- The Regulatory Landscape of Ferroptosis and Iron Homeostasis: Pathophysiological Mechanisms and Therapeutic Horizons in Cardiovascular Disease.Drug design, development and therapy · 2026Review
- Circular RNA circDhx32 promotes cardiac inflammatory responses in mouse cardiac ischemia-reperfusion injury via binding to FOXO1 competed with AdipoR1.Acta pharmacologica Sinica · 2025Article
- AI662270/GRP94 axis couples the unfolded protein response to mitochondrial dynamics during acute myocardial infarction.JCI insight · 2025Article
- What Is Cardiometabolic HFpEF and How Can We Study it Preclinically?JACC. Basic to translational science · 2025Review
- Cardiac intermediary metabolism in heart failure: substrate use, signalling roles and therapeutic targets.Nature reviews. Cardiology · 2025Review
- Review
- Deletion of PTP1B in cardiomyocytes alters cardiac metabolic signaling to protect against cardiomyopathy induced by a high-fat diet.Science signaling · 2025Article
- The Hidden Price of Plenty: Oxidative Stress and Calorie-Induced Cardiometabolic Dysfunction.Life (Basel, Switzerland) · 2025Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 4 countries.
Funding
Abstract
Heart failure with preserved ejection fraction (HFpEF) is now the dominant form of heart failure and one for which no efficacious therapies exist. Obesity and lipid mishandling greatly contribute to HFpEF. However, molecular mechanism(s) governing metabolic alterations and perturbations in lipid homeostasis in HFpEF are largely unknown. Here, we report that cardiomyocyte steatosis in HFpEF is coupled with increases in the activity of the transcription factor FoxO1 (Forkhead box protein O1). FoxO1 depletion, as well as over-expression of the Xbp1s (spliced form of the X-box-binding protein 1) arm of the UPR (unfolded protein response) in cardiomyocytes each ameliorates the HFpEF phenotype in mice and reduces myocardial lipid accumulation. Mechanistically, forced expression of Xbp1s in cardiomyocytes triggers ubiquitination and proteasomal degradation of FoxO1 which occurs, in large part, through activation of the E3 ubiquitin ligase STUB1 (STIP1 homology and U-box-containing protein 1) a novel and direct transcriptional target of Xbp1s. Our findings uncover the Xbp1s-FoxO1 axis as a pivotal mechanism in the pathogenesis of cardiometabolic HFpEF and unveil previously unrecognized mechanisms whereby the UPR governs metabolic alterations in cardiomyocytes.
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