Abstract
BackgroundQishen granules (QSG) has been applied to treat heart failure (HF) for decades. Our previous transcriptomics study has suggested that Qishen granules (QSG) could regulate the pathways of cardiac energy metabolism in HF, but the specific regulatory mechanism has not yet been clarified. This study was to investigate the potential mechanism of QSG in regulating myocardial fatty acid (FA) and glucose metabolism in a rat model of HF.MethodsThe model of HF was induced by left anterior descending coronary artery ligation. Cardiac structure and function were assessed by cine magnetic resonance imaging (MRI) and echocardiography. Level of glucose metabolism was non-invasively evaluated by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT). Blood lipid levels were determined by enzymatic analysis. The mitochondrial ultrastructure was observed with a transmission electron microscope. The critical proteins related to FA metabolism, glucose metabolism and mitochondrial function were measured by western blotting. The ANOVA followed by a Fisher’s LSD test was used for within-group comparisons.ResultsQSG ameliorated cardiac functions and attenuated myocardial remodeling in HF model. The levels of serum TC, TG and LDL-C were significantly reduced by QSG. The proteins mediating FA uptake, transportation into mitochondria and β-oxidation (FAT/CD36, CPT1A, ACADL, ACADM, ACAA2 and SCP2) as well as the upstreaming transcriptional regulators of FA metabolism (PPARα, RXRα, RXRβ and RXRγ) were up-regulated by QSG. As to glucose metabolism, QSG inhibited glycolytic activity by decreasing LDHA, while stimulated glucose oxidation by decreasing PDK4. Furthermore, QSG could facilitate tricarboxylic acid cycle, promote the transportation of ATP from mitochondria to cytoplasm and restore the mitochondrial function by increasing SUCLA2, CKMT2 and PGC-1α and decreasing UCP2 simultaneously.ConclusionQSG improved myocardial energy metabolism through increasing FA metabolism,inhibiting uncoupling of glycolysis from glucose oxidation.
Highlights
Qishen granules (QSG) has been applied to treat heart failure (HF) for decades
FA metabolism is mainly mediated by fatty acid translocase/cluster of differentiation 36 (FAT/CD36)—carnitine palmitoyltransferase 1 (CPT1)—fatty acid oxidation (FAO) pathway which is transcriptionally regulated by nuclear factor peroxisome proliferator activated receptor alpha (PPARα)—retinoid x receptors (RXRs) axis [12]
left ventricular end-diastolic anterior wall thickness (LVEDAWT) and left ventricular end-systolic anterior wall thickness (LVESAWT) were decreased whereas Left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), Left ventricular end-diastolic volume (LVEDV) and Left ventricular end-systolic volume (LVESV) were increased in the model group as compared to the sham group (P < 0.01, Fig. 1)
Summary
Our previous transcriptomics study has suggested that Qishen granules (QSG) could regulate the pathways of cardiac energy metabolism in HF, but the specific regulatory mechanism has not yet been clarified. This study was to investigate the potential mechanism of QSG in regulating myocardial fatty acid (FA) and glucose metabolism in a rat model of HF. The enhanced activity of glycolysis uncoupled from glucose oxidation will lead to energy deficiency and lactate accumulation which can eventually deteriorate the HF [10, 11]. It’s considered to be effective therapeutic strategies for HF to promote FA metabolism by facilitating β-oxidation or activating PPARα and enhance glucose oxidation through PDK inhibitor [9]
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