ArticlePloS one2014
Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed.
- Functions of FGF21 and its role in cardiac hypertrophy.Journal of advanced research · 2026Review
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Protective Effects of Regular Physical Activity: Differential Expression ofInternational journal of molecular sciences · 2025Article
- Hepato-cardiac interorgan communication controls cardiac hypertrophy via combined endocrine-autocrine FGF21 signaling.Cell reports. Medicine · 2025Article
- Exercise in Diabetic Cardiomyopathy: Its Protective Effects and Molecular Mechanism.International journal of molecular sciences · 2025Review
- Role of the serum levels of the inter-organs messenger fibroblast growth factor 21 (FGF21) in the diagnosis and prognosis of breast cancer patients.Cell communication and signaling : CCS · 2025Article
- UPRmt-regulated mitokines: novel strategies for myocardial injury repair.Frontiers in cell and developmental biology · 2025Review
- Research progress on the role of FGF21 in insulin resistance.Frontiers in endocrinology · 2025Review
- FGFR4 Is Required for Concentric Growth of Cardiac Myocytes during Physiologic Cardiac Hypertrophy.Journal of cardiovascular development and disease · 2024Article
- Effect of Fibroblast Growth Factor-21 Molecule on Coronary CollateralDevelopment.Combinatorial chemistry & high throughput screening · 2024Article
- The Role of the FGF19 Family in the Pathogenesis of Gestational Diabetes: A Narrative Review.International journal of molecular sciences · 2023Review
- Recent progress in understanding mitokines as diagnostic and therapeutic targets in hepatocellular carcinoma.World journal of clinical cases · 2023Review
- The association of circulating fibroblast growth factor 21 levels with incident heart failure: The Multi-Ethnic Study of Atherosclerosis.Metabolism: clinical and experimental · 2023Article
- FGF21/FGFR1-β-KL cascade in cardiomyocytes modulates angiogenesis and inflammation under metabolic stress.Heliyon · 2023Article
- Fibroblast growth factor 21 in heart failure.Heart failure reviews · 2023Review
- Supplementation with the Prebiotic High-Esterified Pectin Improves Blood Pressure and Cardiovascular Risk Biomarker Profile, Counteracting Metabolic Malprogramming.Journal of agricultural and food chemistry · 2022Article
- Fibroblast growth factor 21 is associated with widening QRS complex and prolonged corrected QT interval in patients with stable angina.BMC cardiovascular disorders · 2022Article
- FGF21-FGFR4 signaling in cardiac myocytes promotes concentric cardiac hypertrophy in mouse models of diabetes.Scientific reports · 2022Article
- The potential function and clinical application of FGF21 in metabolic diseases.Frontiers in pharmacology · 2022Review
- Multi-organ FGF21-FGFR1 signaling in metabolic health and disease.Frontiers in cardiovascular medicine · 2022Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsFibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect of FGF21 on cardio-protection in obese and lean hearts in response to ischemia. METHODS AND
resultsFGF21, FGF21-receptor 1 (FGFR1) and beta-Klotho (βKlotho) were expressed in rodent, human hearts and primary rat cardiomyocytes. Cardiac FGF21 was expressed and secreted (real time RT-PCR/western blot and ELISA) in an autocrine-paracrine manner, in response to obesity and hypoxia, involving FGFR1-βKlotho components. Cardiac-FGF21 expression and secretion were increased in response to global ischemia. In contrast βKlotho was reduced in obese hearts. In isolated adult rat cardiomyocytes, FGF21 activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt), ERK1/2(extracellular signal-regulated kinase) and AMPK (AMP-activated protein kinase) pathways. In Langendorff perfused rat [adult male wild-type wistar] hearts, FGF21 administration induced significant cardio-protection and restoration of function following global ischemia. Inhibition of PI3K/Akt, AMPK, ERK1/2 and ROR-α (retinoic-acid receptor alpha) pathway led to significant decrease of FGF21 induced cardio-protection and restoration of cardiac function in response to global ischemia. More importantly, this cardio-protective response induced by FGF21 was reduced in obesity, although the cardiac expression profiles and circulating FGF21 levels were increased.
conclusionIn an ex vivo Langendorff system, we show that FGF21 induced cardiac protection and restoration of cardiac function involving autocrine-paracrine pathways, with reduced effect in obesity. Collectively, our findings provide novel insights into FGF21-induced cardiac effects in obesity and ischemia.
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