Dobrzyn P, Pyrkowska A, Duda MK, Bednarski T, Maczewski M, Langfort J, Dobrzyn A. Expression of lipogenic genes is upregulated in the heart with exercise training-induced but not pressure overload-induced left ventricular hypertrophy. Am J Physiol Endocrinol Metab 304: E1348 -E1358, 2013. First published April 30, 2013 doi:10.1152/ajpendo.00603.2012.-Cardiac hypertrophy is accompanied by molecular remodeling that affects different cellular pathways, including fatty acid (FA) utilization. In the present study, we show that cardiac lipid metabolism is differentially regulated in response to physiological (endurance training) and pathological [abdominal aortic banding (AAB)] hypertrophic stimuli. Physiological hypertrophy was accompanied by an increased expression of lipogenic genes and the activation of sterol regulatory element-binding protein-1c and Akt signaling. Additionally, FA oxidation pathways regulated by AMPactivated protein kinase (AMPK) and peroxisome proliferator activated receptor-␣ (PPAR␣) were induced in trained hearts. Cardiac lipid content was not changed by physiological stimulation, underlining balanced lipid utilization in the trained heart. Moreover, pathological hypertrophy induced the AMPK-regulated oxidative pathway, whereas PPAR␣ and expression of its downstream targets, i.e., acylCoA oxidase and carnitine palmitoyltransferase I, were not affected by AAB. In contrast, pathological hypertrophy leads to cardiac triglyceride (TG) and diacylglycerol (DAG) accumulation, although the expression of lipogenic genes and the levels of FA transport proteins (CD36 and FATP) were not changed or reduced compared with the sham group. A possible explanation for this phenomenon is a decrease in lipolysis, as evidenced by the increased content of adipose triglyceride lipase inhibitor G0S2, the increased phosphorylation of hormone-sensitive lipase at Ser 565 , and the decreased protein levels of DAG lipase that attenuate TG and DAG contents. The increased TG and DAG accumulation observed in AAB-induced hypertrophy might have lipotoxic effects, thereby predisposing to cardiomyopathy and heart failure in the future. lipogenesis; endurance training; sterol regulatory element-binding protein-1; adipose triglyceride lipase; hormone-sensitive lipase CARDIAC HYPERTROPHY IS ASSOCIATED with extensive remodeling, which in due course will affect cardiac function and ultimately contribute to the transition from compensatory hypertrophy to cardiac failure (70). Molecular remodeling in the heart caused by hypertrophy differs between physiological and pathological stimuli. The physiological cardiac hypertrophy caused by endurance training shows enhancement of cardiac function at rest and during exercise and is not a risk factor for heart failure (19, 29). The adaptations include increases in cardiac mass and dimension, maximum oxygen consumption, and coronary blood flow (35). Additionally, exercise results in a balanced growth of cardiomyocytes with a normal myofibril to mitochondrial ratio (52, 71). Conversely, the hype...
Ventricular arrhythmias are an important cause of mortality in the acute myocardial infarction (MI). To elucidate the effect of the omega-3 polyunsaturated fatty acids (PUFAs) on ventricular arrhythmias in acute nonreperfused MI, rats were fed with normal or eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA)-enriched diet for 3 weeks. Subsequently the rats were subjected to either MI induction or sham operation. ECG was recorded for 6 h after the operation and episodes of ventricular tachycardia/fibrillation (VT/VF) were identified. Six hours after MI epicardial monophasic action potentials (MAPs) were recorded, cardiomyocyte Ca(2+) handling was assessed and expression of proteins involved in Ca(2+) turnover was studied separately in non-infarcted left ventricle wall and infarct borderzone. EPA and DHA had no effect on occurrence of post-MI ventricular arrhythmias or mortality. Nevertheless, DHA but not EPA prevented Ca(2+) overload in LV cardiomiocytes and improved rate of Ca(2+) transient decay, protecting PMCA and SERCA function. Moreover, both EPA and DHA prevented MI-induced hyperphosphorylation of ryanodine receptors (RyRs) as well as dispersion of action potential duration (APD) in the left ventricular wall. In conclusion, EPA and DHA have no antiarrhythmic effect in the non-reperfused myocardial infarction in the rat, although these omega-3 PUFAs and DHA in particular exhibit several potential antiarrhythmic effects at the subcellular and tissue level, that is, prevent MI-induced abnormalities in Ca(2+) handling and APD dispersion. In this context further studies are needed to see if these potential antiarrhythmic effects could be utilized in the clinical setting. J. Cell. Biochem. 117: 2570-2582, 2016. © 2016 Wiley Periodicals, Inc.
Molecular remodeling in the heart caused by hypertrophy differs between physiological and pathological stimuli. The main goal of this study was to determine how cardiac hypertrophy that is induced by pressure overload or endurance training influences lipid metabolism in the myocardium. The expression of lipogenic genes was upregulated in exercise‐induced hypertrophy and was accompanied by the activation of fatty acid (FA) oxidation pathways regulated by AMPK and RRARα. Intracellular diacylglyceride (DAG), triglyceride (TG) and free FA were not changed in trained compared with untrained hearts. In contrast, in the heart with abdominal aortic banding (AAB)‐induced hypertrophy, we found an increased accumulation of TG and DAG, although the expression of lipogenic genes and the level of FA transport proteins were not augmented. Cardiac steatosis in AAB‐induced hypertrophy was associated with decreased lipolysis, as evidenced by increased hormone‐sensitive lipase phosphorylation at Ser565 and decreased DAG lipase‐α and ‐β protein levels. Obtained results show that cardiac lipid metabolism is differentially regulated in response to physiological and pathological hypertrophic stimuli and suggest that activation of lipogenesis might be involved in the regulatory mechanisms of heart adaptation to stress. Support: NCN UMO‐2011/01/D/NZ3/04777, NCBR LIDER/19/2/L‐2/10/NCBiR/2011.
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