title: High fat diet induced diabetic cardiomyopathy.
abstract: In response to a chronic high plasma concentration of long-chain fatty acids (FAs), the heart is forced to increase the uptake of FA at the cost of glucose. This switch in metabolic substrate uptake is accompanied by an increased presence of the FA transporter CD36 at the cardiac plasma membrane and over time results in the development of cardiac insulin resistance and ultimately diabetic cardiomyopathy. FA can interact with peroxisome proliferator-activated receptors (PPARs), which induce upregulation of the expression of enzymes necessary for their disposal through mitochondrial β-oxidation, but also stimulate FA uptake. This then leads to a further increase in FA concentration in the cytoplasm of cardiomyocytes. These metabolic changes are supposed to play an important role in the development of cardiomyopathy. Although the onset of this pathology is an increased FA utilization by the heart, the subsequent lipid overload results in an increased production of reactive oxygen species (ROS) and accumulation of lipid intermediates such as diacylglycerols (DAG) and ceramide. These compounds have a profound impact on signaling pathways, in particular insulin signaling. Over time the metabolic changes will introduce structural changes that affect cardiac contractile characteristics. The present mini-review will focus on the lipid-induced changes that link metabolic perturbation, characteristic for type 2 diabetes, with cardiac remodeling and dysfunction.
authors.affiliation: Department of Molecular Genetics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. ellen.dirkx@gen.unimaas.nl
authors.forename: Ellen
authors.initials: E
authors.lastname: Dirkx
authors.forename: Robert W
authors.initials: RW
authors.lastname: Schwenk
authors.forename: Jan F C
authors.initials: JF
authors.lastname: Glatz
authors.forename: Joost J F P
authors.initials: JJ
authors.lastname: Luiken
authors.forename: Guillaume J J M
authors.initials: GJ
authors.lastname: van Eys
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D002518:Ceramides / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D058065:Diabetic Cardiomyopathies / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004041:Dietary Fats / Q000009:adverse effects*; D004075:Diglycerides / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D002518:Ceramides; D004041:Dietary Fats; D004075:Diglycerides; D005227:Fatty Acids; D047492:Peroxisome Proliferator-Activated Receptors; D017382:Reactive Oxygen Species