MicroRNA-451 Exacerbates Lipotoxicity in Cardiac Myocytes and High-Fat Diet-Induced Cardiac Hypertrophy in Mice Through Suppression of the LKB1/AMPK Pathway
- 16 January 2015
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 116 (2), 279-288
- https://doi.org/10.1161/circresaha.116.304707
Abstract
Rationale:In some patients with type 2 diabetes mellitus (DM) without hypertension, cardiac hypertrophy and attenuated cardiac function are observed, and this insult is termed diabetic cardiomyopathy. To date, microRNA (miRNAs or miR) functions in diabetic cardiomyopathy remain to be elucidated. Objective:To clarify the functions of miRNAs involved in diabetic cardiomyopathy caused by type 2 DM. Methods and Results:C57BL/6 mice were fed a high-fat diet (HFD) for 20 weeks, which induced obesity and type 2 DM. miRNA microarray analyses and real-time polymerase chain reaction revealed that miR-451 levels were significantly increased in the type 2 DM mouse hearts. Because excess supply of saturated fatty acids is a cause of diabetic cardiomyopathy, we stimulated neonatal rat cardiac myocytes with palmitic acid and confirmed that miR-451 expression was increased in a dose- and time-dependent manner. Loss of miR-451 function ameliorated palmitate-induced lipotoxicity in neonatal rat cardiac myocytes. Calcium-bi...Keywords
This publication has 40 references indexed in Scilit:
- A Glucagon-Like Peptide-1 Analog Reverses the Molecular Pathology and Cardiac Dysfunction of a Mouse Model of ObesityCirculation, 2013
- AMP-activated protein kinase—an energy sensor that regulates all aspects of cell functionGenes & Development, 2011
- MicroRNAs Involved in the Mitogen-Activated Protein Kinase Cascades Pathway During Glucose-Induced Cardiomyocyte HypertrophyThe American Journal of Pathology, 2011
- Intravenous Gene Therapy With PIM-1 Via a Cardiotropic Viral Vector Halts the Progression of Diabetic Cardiomyopathy Through Promotion of Prosurvival SignalingCirculation Research, 2011
- Lipotoxicity in the heartBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2009
- Nutrient Stress Activates Inflammation and Reduces Glucose Metabolism by Suppressing AMP-Activated Protein Kinase in the HeartDiabetes, 2009
- Cardiac cell death in early diabetes and its modulation by dietary fatty acidsBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2006
- Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heartThe FASEB Journal, 2004
- MO25 / interact with STRAD / enhancing their ability to bind, activate and localize LKB1 in the cytoplasmThe EMBO Journal, 2003
- Myocardial triglycerides and systolic function in humans: In vivo evaluation by localized proton spectroscopy and cardiac imagingMagnetic Resonance in Medicine, 2003