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Abdurrachim 2014 Biochim Biophys Acta
Coupling states LEAK  + , OXPHOS  + , ET  +
Diseases Obesity  +
Has abstract Obesity is often associated with abnormali
Obesity is often associated with abnormalities in cardiac morphology and function. This study tested the hypothesis that obesity-related cardiomyopathy is caused by impaired cardiac energetics. In a mouse model of high-fat diet (HFD)-induced obesity, we applied ''in vivo'' cardiac 31P magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) to investigate cardiac energy status and function, respectively. The measurements were complemented by ex vivo determination of oxygen consumption in isolated cardiac mitochondria, the expression of proteins involved in energy metabolism, and markers of oxidative stress and calcium homeostasis. We also assessed whether HFD induced myocardial lipid accumulation using ''in vivo'' 1H MRS, and if this was associated with apoptosis and fibrosis. Twenty weeks of HFD feeding resulted in early stage cardiomyopathy, as indicated by diastolic dysfunction and increased left ventricular mass, without any effects on systolic function. ''In vivo'' cardiac phosphocreatine-to-ATP ratio and ex vivo oxygen consumption in isolated cardiac mitochondria were not reduced after HFD feeding, suggesting that the diastolic dysfunction was not caused by impaired cardiac energetics. HFD feeding promoted mitochondrial adaptations for increased utilization of fatty acids, which was however not sufficient to prevent the accumulation of myocardial lipids and lipid intermediates. Myocardial lipid accumulation was associated with oxidative stress and fibrosis, but not apoptosis. Furthermore, HFD feeding strongly reduced the phosphorylation of phospholamban, a prominent regulator of cardiac calcium homeostasis and contractility. In conclusion, HFD-induced early stage cardiomyopathy in mice is associated with lipotoxicity-associated oxidative stress, fibrosis, and disturbed calcium homeostasis, rather than impaired cardiac energetics.
, rather than impaired cardiac energetics.  +
Has info [ PMID: 25086219]  +
Has publicationkeywords Calcium homeostasis  + , Cardiac energetics  + , Cardiomyopathy  + , Diet-induced obesity  + , Lipotoxicity  +
Has title Abdurrachim D, Ciapaite J, Wessels B, Nabb
Abdurrachim D, Ciapaite J, Wessels B, Nabben M, Luiken JJ, Nicolay K, Prompers JJ (2014) Cardiac diastolic dysfunction in high-fat diet fed mice is associated with lipotoxicity without impairment of cardiac energetics ''in vivo''. Biochim Biophys Acta 1842:1525-37.
vivo''. Biochim Biophys Acta 1842:1525-37.  +
Instrument and method Oxygraph-2k  +
Mammal and model Mouse  +
MiP area Respiration  + , Exercise physiology;nutrition;life style  +
Pathways F  + , N  +
Preparation Isolated mitochondria  +
Tissue and cell Heart  +
Was published by MiPNetLab NL Eindhoven Nicolay K + , NL Groningen Reijngoud RJ + , NL Maastricht Schrauwen P +
Was published in journal Biochim Biophys Acta +
Was published in year 2014  +
Was written by Abdurrachim D + , Ciapaite J + , Wessels B + , Nabben M + , Luiken JJ + , Nicolay K + , Prompers JJ +
Categories Publications
Modification date
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12:27:23, 27 March 2018  +
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