The Journal of biological chemistry, 2006-03, Vol.281 (13), p.8716-8723
2006
Details
- Autor(en) / Beteiligte
- Titel
- Loss of Lipoprotein Lipase-derived Fatty Acids Leads to Increased Cardiac Glucose Metabolism and Heart Dysfunction
- Ist Teil von
- The Journal of biological chemistry, 2006-03, Vol.281 (13), p.8716-8723
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2006
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Long-chain fatty acids (FAs) are the predominant energy substrate utilized by the adult heart. The heart can utilize unesterified FA bound to albumin or FA obtained from lipolysis of lipoprotein-bound triglyceride (TG). We used heart-specific lipoprotein lipase knock-out mice (hLpL0) to test whether these two sources of FA are interchangeable and necessary for optimal heart function. Hearts unable to obtain FA from lipoprotein TG were able to compensate by increasing glucose uptake, glycolysis, and glucose oxidation. HLpL0 hearts had decreased expression of pyruvate dehydrogenase kinase 4 and increased cardiomyocyte expression of glucose transporter 4. Conversely, FA oxidation rates were reduced in isolated perfused hLpL0 hearts. Following abdominal aortic constriction expression levels of genes regulating FA and glucose metabolism were acutely up-regulated in control and hLpL0 mice, yet all hLpL0 mice died within 48 h of abdominal aortic constriction. Older hLpL0 mice developed cardiac dysfunction characterized by decreased fractional shortening and interstitial and perivascular fibrosis. HLpL0 hearts had increased expression of several genes associated with transforming growth factor-β signaling. Thus, long term reduction of lipoprotein FA uptake is associated with impaired cardiac function despite a compensatory increase in glucose utilization.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0021-9258eISSN: 1083-351XDOI: 10.1074/jbc.M509890200Titel-ID: cdi_proquest_miscellaneous_67794530
- Format
- –
- Schlagworte
- Adenosine Triphosphate - analysis, Animals, Blood Glucose - analysis, Carbon Radioisotopes, Cardiomyopathies - etiology, Cardiomyopathies - metabolism, Cholesterol - blood, Cholesterol - metabolism, Echocardiography, Fasting, Fatty Acids - metabolism, Female, Gene Expression, Glucose - metabolism, Glucose Transporter Type 4 - genetics, Glucose Transporter Type 4 - metabolism, Glycolysis, Kinetics, Lipoprotein Lipase - analysis, Lipoprotein Lipase - deficiency, Lipoprotein Lipase - genetics, Lipoprotein Lipase - physiology, Lipoproteins, VLDL - metabolism, Male, Mice, Mice, Knockout, Myocardium - enzymology, Myocardium - pathology, Myocytes, Cardiac - metabolism, Oxidation-Reduction, Phosphocreatine - analogs & derivatives, Phosphocreatine - analysis, Protein Kinases - genetics, Protein Kinases - metabolism, Triglycerides - blood