title: Remodeling of glucose metabolism precedes pressure overload-induced left ventricular hypertrophy: review of a hypothesis.
abstract: When subjected to pressure overload, the ventricular myocardium shifts from fatty acids to glucose as its main source for energy provision and frequently increases its mass. Here, we review the evidence in support of the concept that metabolic remodeling, measured as an increased myocardial glucose uptake using dynamic positron emission tomography (PET) with the glucose analogue 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG), precedes the onset of left ventricular hypertrophy (LVH) and heart failure. Consistent with this, early intervention with propranolol, which attenuates glucose uptake, prevents the maladaptive metabolic response and preserves cardiac function in vivo. We also review ex vivo studies suggesting a link between dysregulated myocardial glucose metabolism, intracellular accumulation of glucose 6-phosphate (G6P) and contractile dysfunction of the heart. G6P levels correlate with activation of mTOR (mechanistic target of rapamycin) and endoplasmic reticulum stress. This sequence of events could be prevented by pretreatment with rapamycin (mTOR inhibition) or metformin (enzyme 5'-AMP-activated protein kinase activation). In conclusion, we propose that metabolic imaging with FDG PET may provide a novel approach to guide the treatment of patients with hypertension-induced LVH.
authors: Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, Va., USA.
authors: Bijoy K
authors: BK
authors: Kundu
authors: Min
authors: M
authors: Zhong
authors: Shiraj
authors: S
authors: Sen
authors: Giovanni
authors: G
authors: Davogustto
authors: Susanna R
authors: SR
authors: Keller
authors: Heinrich
authors: H
authors: Taegtmeyer
mesh_terms: D019325:3-O-Methylglucose / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000378:metabolism*; D006333:Heart Failure / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000150:complications; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology* / Q000628:therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008687:Metformin / Q000627:therapeutic use; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D049268:Positron-Emission Tomography; D051381:Rats; D020123:Sirolimus / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D016277:Ventricular Function, Left
chemical_list: D005227:Fatty Acids; D007004:Hypoglycemic Agents; D019325:3-O-Methylglucose; D019298:Glucose-6-Phosphate; C039921:2-deoxy-2-fluoro-3-O-methylglucose; D008687:Metformin; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus