G Lopaschuk

Summary

Affiliation: University of Alberta
Country: Canada

Publications

  1. ncbi Inhibition of carnitine palmitoyltransferase-1 activity alleviates insulin resistance in diet-induced obese mice
    Wendy Keung
    Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
    Diabetes 62:711-20. 2013
  2. ncbi Inhibition of malonyl-CoA decarboxylase reduces the inflammatory response associated with insulin resistance
    Victor Samokhvalov
    Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
    Am J Physiol Endocrinol Metab 303:E1459-68. 2012
  3. ncbi Pyridine nucleotide regulation of cardiac intermediary metabolism
    John R Ussher
    423 Heritage Medical Research Center, University of Alberta, Edmonton, Canada
    Circ Res 111:628-41. 2012
  4. ncbi Cardiac energy metabolism in obesity
    Gary D Lopaschuk
    Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada
    Circ Res 101:335-47. 2007
  5. ncbi Optimizing cardiac fatty acid and glucose metabolism as an approach to treating heart failure
    Gary D Lopaschuk
    Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada
    Semin Cardiothorac Vasc Anesth 10:228-30. 2006
  6. ncbi Malonyl-CoA decarboxylase inhibition as a novel approach to treat ischemic heart disease
    Gary D Lopaschuk
    Cardiovascular Research Group, 423 Heritage Medical Research Building, The University of Alberta, Edmonton, AL, T6G 2S2, Canada
    Cardiovasc Drugs Ther 20:433-9. 2006
  7. ncbi Beneficial effects of trimetazidine in ex vivo working ischemic hearts are due to a stimulation of glucose oxidation secondary to inhibition of long-chain 3-ketoacyl coenzyme a thiolase
    Gary D Lopaschuk
    Cardiovascular Research Group, Department of Pediatrics, University of Alberta, Edmonton, Canada
    Circ Res 93:e33-7. 2003
  8. ncbi Advantages and limitations of experimental techniques used to measure cardiac energy metabolism
    G D Lopaschuk
    Department of Pediatrics and Pharmacology, Faculty of Medicine, University of Alberta, Edmonton, Canada
    J Nucl Cardiol 4:316-28. 1997
  9. ncbi Targets for modulation of fatty acid oxidation in the heart
    Gary D Lopaschuk
    Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, 423 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada
    Curr Opin Investig Drugs 5:290-4. 2004
  10. ncbi AMP-activated protein kinase control of energy metabolism in the ischemic heart
    G D Lopaschuk
    Cardiovascular Research Group, Departments of Pediatrics and Pharmacology, Faculty of Medicine, University of Alberta, Edmonton, AB, Canada
    Int J Obes (Lond) 32:S29-35. 2008

Detail Information

Publications93

  1. ncbi Inhibition of carnitine palmitoyltransferase-1 activity alleviates insulin resistance in diet-induced obese mice
    Wendy Keung
    Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
    Diabetes 62:711-20. 2013
    ..This is associated with increased carbohydrate utilization and improved insulin signaling in the skeletal muscle, suggestive of an operating Randle Cycle in muscle...
  2. ncbi Inhibition of malonyl-CoA decarboxylase reduces the inflammatory response associated with insulin resistance
    Victor Samokhvalov
    Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
    Am J Physiol Endocrinol Metab 303:E1459-68. 2012
    ..Our results also demonstrate that pharmacological inhibition of MCD is a novel and promising approach to treat insulin resistance and its associated metabolic complications...
  3. ncbi Pyridine nucleotide regulation of cardiac intermediary metabolism
    John R Ussher
    423 Heritage Medical Research Center, University of Alberta, Edmonton, Canada
    Circ Res 111:628-41. 2012
    ....
  4. ncbi Cardiac energy metabolism in obesity
    Gary D Lopaschuk
    Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada
    Circ Res 101:335-47. 2007
    ..The clinical implications of obesity and energy metabolism on cardiac disease are also discussed...
  5. ncbi Optimizing cardiac fatty acid and glucose metabolism as an approach to treating heart failure
    Gary D Lopaschuk
    Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada
    Semin Cardiothorac Vasc Anesth 10:228-30. 2006
    ..In particular, there is now evidence that in the failing heart, shifting metabolism away from a preference for fatty acids toward more carbohydrate oxidation can improve contractile function and slow the progression of pump failure...
  6. ncbi Malonyl-CoA decarboxylase inhibition as a novel approach to treat ischemic heart disease
    Gary D Lopaschuk
    Cardiovascular Research Group, 423 Heritage Medical Research Building, The University of Alberta, Edmonton, AL, T6G 2S2, Canada
    Cardiovasc Drugs Ther 20:433-9. 2006
    ....
  7. ncbi Beneficial effects of trimetazidine in ex vivo working ischemic hearts are due to a stimulation of glucose oxidation secondary to inhibition of long-chain 3-ketoacyl coenzyme a thiolase
    Gary D Lopaschuk
    Cardiovascular Research Group, Department of Pediatrics, University of Alberta, Edmonton, Canada
    Circ Res 93:e33-7. 2003
    ..The full text of this article is available online at http://www.circresaha.org...
  8. ncbi Advantages and limitations of experimental techniques used to measure cardiac energy metabolism
    G D Lopaschuk
    Department of Pediatrics and Pharmacology, Faculty of Medicine, University of Alberta, Edmonton, Canada
    J Nucl Cardiol 4:316-28. 1997
    ..Each of these techniques has advantages and limitations...
  9. ncbi Targets for modulation of fatty acid oxidation in the heart
    Gary D Lopaschuk
    Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, 423 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada
    Curr Opin Investig Drugs 5:290-4. 2004
    ..This review describes these potential targets for modulation of energy metabolism in the heart...
  10. ncbi AMP-activated protein kinase control of energy metabolism in the ischemic heart
    G D Lopaschuk
    Cardiovascular Research Group, Departments of Pediatrics and Pharmacology, Faculty of Medicine, University of Alberta, Edmonton, AB, Canada
    Int J Obes (Lond) 32:S29-35. 2008
    ..As a result, AMPK activation has the potential to be either beneficial or harmful in the ischemic heart...
  11. ncbi Myocardial fatty acid metabolism in health and disease
    Gary D Lopaschuk
    Cardiovascular Research Group, Mazankowski Alberta Heart Institute, University of Alberta, Alberta T6G 2S2, Canada
    Physiol Rev 90:207-58. 2010
    ..The implications of inhibiting fatty acid beta-oxidation as a potential novel therapeutic approach for the treatment of various forms of heart disease are also discussed...
  12. ncbi Inhibition of de novo ceramide synthesis reverses diet-induced insulin resistance and enhances whole-body oxygen consumption
    John R Ussher
    Department of Pediatrics, University of Alberta, Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, Edmonton, Canada
    Diabetes 59:2453-64. 2010
    ..We determined the role of de novo ceramide synthesis in mediating muscle insulin resistance...
  13. ncbi Targeting intermediary metabolism in the hypothalamus as a mechanism to regulate appetite
    Gary D Lopaschuk
    423 Heritage Medical Research Center, University of Alberta, Edmonton, Canada T6G2S2
    Pharmacol Rev 62:237-64. 2010
    ....
  14. ncbi Energy metabolic phenotype of the cardiomyocyte during development, differentiation, and postnatal maturation
    Gary D Lopaschuk
    Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada
    J Cardiovasc Pharmacol 56:130-40. 2010
    ..In this article, we review the impact of alterations in energy substrate metabolism on cardiomyocyte proliferation, differentiation, and postnatal maturation...
  15. ncbi Novel O-palmitolylated beta-E1 subunit of pyruvate dehydrogenase is phosphorylated during ischemia/reperfusion injury
    Clifford Dl Folmes
    Cardiovascular Research Group and the Departments of Pharmacology and Pediatrics, The University of Alberta, Edmonton, Alberta, Canada
    Proteome Sci 8:38. 2010
    ..This metabolic phenotype is associated with contractile dysfunction during reperfusion. To determine the mechanism of this reliance on fatty acid oxidation as a source of ATP generation, a functional proteomics approach was utilized...
  16. ncbi Regulation of carbohydrate metabolism in ischemia and reperfusion
    G Lopaschuk
    University of Alberta, Edmonton, Canada
    Am Heart J 139:S115-9. 2000
    ..Controlled clinical trials will be useful in confirming the results from these experimental studies...
  17. ncbi Chronic central leptin decreases food intake and improves glucose tolerance in diet-induced obese mice independent of hypothalamic malonyl CoA levels and skeletal muscle insulin sensitivity
    Wendy Keung
    Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2
    Endocrinology 152:4127-37. 2011
    ..Although chronic ICV leptin treatment in HFD mice improves glucose tolerance, this occurs independent of changes in insulin sensitivity in the muscles of HFD mice...
  18. ncbi Fatty acids attenuate insulin regulation of 5'-AMP-activated protein kinase and insulin cardioprotection after ischemia
    Clifford D L Folmes
    Cardiovascular Research Group and Department of Pediatrics, The University of Alberta, Edmonton, Alberta, Canada
    Circ Res 99:61-8. 2006
    ..We demonstrate that the cardioprotective effect of insulin and its ability to inhibit AMPK activity are lost in the presence of high concentrations of fatty acids...
  19. ncbi Type 1 diabetic cardiomyopathy in the Akita (Ins2WT/C96Y) mouse model is characterized by lipotoxicity and diastolic dysfunction with preserved systolic function
    Ratnadeep Basu
    Department of Physiology, Rm 474, Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta T6G 2S2, Canada
    Am J Physiol Heart Circ Physiol 297:H2096-108. 2009
    ..We conclude that early type 1 diabetic cardiomyopathy is characterized by diastolic dysfunction associated with lipotoxic cardiomyopathy with preserved systolic function in the absence of interstitial fibrosis and hypertrophy...
  20. ncbi gAd-globular head domain of adiponectin increases fatty acid oxidation in newborn rabbit hearts
    Arzu Onay-Besikci
    Cardiovascular Research Group, University of Alberta, Edmonton, Alberta T6G 2S2, Canada
    J Biol Chem 279:44320-6. 2004
    ..These results suggest that a decrease in plasma insulin and increase in gAd are involved in the increase of cardiac fatty acid oxidation in the immediate newborn period...
  21. ncbi Suppression of 5'-AMP-activated protein kinase activity does not impair recovery of contractile function during reperfusion of ischemic hearts
    Clifford D L Folmes
    Cardiovascular Research Group and Department of Pediatrics and Pharmacology, University of Alberta, Edmonton, Alberta, Canada
    Am J Physiol Heart Circ Physiol 297:H313-21. 2009
    ..4% vs. 85.3 +/- 4.3%). These data demonstrate that the suppression of cardiac AMPK activity does not produce an energetically compromised phenotype and does not impair, but may in fact improve, the recovery of function after ischemia...
  22. ncbi Fatty acid translocase/CD36 deficiency does not energetically or functionally compromise hearts before or after ischemia
    Michael Kuang
    Cardiovascular Research Group, Department of Pediatrics, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada
    Circulation 109:1550-7. 2004
    ..In this report we assessed the contribution of FAT/CD36 to overall fatty acid oxidation rates in the intact heart and determined the effect of FAT/CD36 on energy metabolism during reperfusion of ischemic hearts...
  23. ncbi AMP-activated protein kinase (AMPK) control of fatty acid and glucose metabolism in the ischemic heart
    Nandakumar Sambandam
    Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
    Prog Lipid Res 42:238-56. 2003
    ..This review attempts to update some of the recent findings that delineate various pathways through which AMPK regulates glucose and fatty acid metabolism in the ischemic myocardium...
  24. ncbi Isoproterenol stimulates 5'-AMP-activated protein kinase and fatty acid oxidation in neonatal hearts
    Jagdip S Jaswal
    Department of Pediatrics, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
    Am J Physiol Heart Circ Physiol 299:H1135-45. 2010
    ....
  25. ncbi Malonyl CoA control of fatty acid oxidation in the ischemic heart
    Jason R B Dyck
    Cardiovascular Research Group, Departments of Pediatrics and Pharmacology, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada
    J Mol Cell Cardiol 34:1099-109. 2002
    ..This paper will discuss some of the molecular changes that occur in fatty acid oxidation in the ischemic heart and will include a discussion of the important role of malonyl CoA in this process...
  26. ncbi High levels of fatty acids increase contractile function of neonatal rabbit hearts during reperfusion following ischemia
    Masayoshi Ito
    Departments of Pediatrics and Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, 423 Heritage Medical Research Centre, Edmonton, AB, Canada
    Am J Physiol Heart Circ Physiol 298:H1426-37. 2010
    ..These data indicate that the neonatal heart has decreased energy reserve, and, in contrast to the mature heart, increasing availability of fatty acid substrate increases energy production and improves recovery of function after ischemia...
  27. ncbi AMPK alterations in cardiac physiology and pathology: enemy or ally?
    Jason R B Dyck
    Cardiovascular Research Group, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
    J Physiol 574:95-112. 2006
    ..Resolving this issue has important implications as to whether therapeutic approaches to protect the ischaemic heart should be developed which either activate or inhibit AMPK...
  28. ncbi Role of malonyl-CoA in heart disease and the hypothalamic control of obesity
    Clifford D L Folmes
    Cardiovascular Research Group, Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada
    Cardiovasc Res 73:278-87. 2007
    ..Targeting enzymes that control malonyl-CoA levels may be an important therapeutic approach to treating heart disease and obesity...
  29. ncbi Control of cardiac pyruvate dehydrogenase activity in peroxisome proliferator-activated receptor-alpha transgenic mice
    Teresa A Hopkins
    Departments of Pharmacology and Pediatrics, University of Alberta, Edmonton, Alberta, Canada T6G 2S2
    Am J Physiol Heart Circ Physiol 285:H270-6. 2003
    ....
  30. ncbi Potential mechanisms and consequences of cardiac triacylglycerol accumulation in insulin-resistant rats
    Laura L Atkinson
    Cardiovascular Research Group, Department of Pediatrics, Faculty of Medicine, The University of Alberta, Edmonton, Alberta, Canada T6G 2S2
    Am J Physiol Endocrinol Metab 284:E923-30. 2003
    ..Furthermore, the accumulation of cardiac TG is associated with a reduction in insulin-stimulated glucose metabolism...
  31. ncbi Insulin-stimulated cardiac glucose oxidation is increased in high-fat diet-induced obese mice lacking malonyl CoA decarboxylase
    John R Ussher
    Cardiovascular Research Group, University of Alberta, Edmonton, Canada
    Diabetes 58:1766-75. 2009
    ....
  32. ncbi A role for peroxisome proliferator-activated receptor alpha (PPARalpha ) in the control of cardiac malonyl-CoA levels: reduced fatty acid oxidation rates and increased glucose oxidation rates in the hearts of mice lacking PPARalpha are associated with hig
    Fiona M Campbell
    Department of Pharmacology, University of Alberta, Edmonton, Alberta T6G 2S2, Canada
    J Biol Chem 277:4098-103. 2002
    ..This study demonstrates that PPARalpha is an important regulator of fatty acid oxidation in the heart and that this regulation of fatty acid oxidation may in part occur due to the transcriptional control of malonyl-CoA decarboxylase...
  33. ncbi Chronic activation of PPARalpha is detrimental to cardiac recovery after ischemia
    Nandakumar Sambandam
    Department of Pediatrics and Pharmacology, Univ of Alberta, Edmonton, AB, Canada
    Am J Physiol Heart Circ Physiol 290:H87-95. 2006
    ..75 +/- 9%). This study demonstrates that chronic activation of PPARalpha is detrimental to the cardiac recovery during reperfusion after ischemia...
  34. ncbi Role of fatty acid uptake and fatty acid beta-oxidation in mediating insulin resistance in heart and skeletal muscle
    Liyan Zhang
    Cardiovascular Research Group, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
    Biochim Biophys Acta 1801:1-22. 2010
    ....
  35. ncbi Metabolic abnormalities in the diabetic heart
    Gary D Lopaschuk
    Cardiovascular Research Group, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada
    Heart Fail Rev 7:149-59. 2002
    ..This paper will review the evidence linking alterations in energy metabolism to alterations in contractile function in the diabetic...
  36. ncbi Matrix metalloproteinase-7 and ADAM-12 (a disintegrin and metalloproteinase-12) define a signaling axis in agonist-induced hypertension and cardiac hypertrophy
    Xiang Wang
    Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada
    Circulation 119:2480-9. 2009
    ..Here, we report that matrix metalloproteinase-7 (MMP-7) and a disintegrin and metalloproteinase-12 (ADAM-12) form a novel signaling axis in these processes...
  37. ncbi Fatty acid oxidation inhibitors in the management of chronic complications of atherosclerosis
    Clifford D L Folmes
    Cardiovascular Research Group, University of Alberta, Edmonton, Alberta T6G 2S2, Canada
    Curr Atheroscler Rep 7:63-70. 2005
    ..Alternatively, fatty acid oxidation can be directly inhibited using trimetazidine, ranolazine, or glucose oxidation directly activated using dichloroacetate, which significantly improves the efficiency of the heart...
  38. ncbi Myocardial ischemia differentially regulates LKB1 and an alternate 5'-AMP-activated protein kinase kinase
    Judith Y Altarejos
    Cardiovascular Research Group, University of Alberta, Edmonton T6G 2S2, Canada
    J Biol Chem 280:183-90. 2005
    ..Additionally, we show that changes in high energy phosphates are not essential for the activation of AMPK by ischemia. Our data emphasize the critical role AMPKK plays in mediating AMPK signaling during myocardial ischemia...
  39. ncbi High levels of fatty acids delay the recovery of intracellular pH and cardiac efficiency in post-ischemic hearts by inhibiting glucose oxidation
    Que Liu
    Cardiovascular Research Group, University of Alberta, Edmonton, Canada
    J Am Coll Cardiol 39:718-25. 2002
    ..Improving the coupling of glucose metabolism by stimulating glucose oxidation accelerates the recovery of pH(i) and improves both mechanical function and cardiac efficiency...
  40. ncbi Alterations in energy metabolism in cardiomyopathies
    Maysa Taha
    Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada
    Ann Med 39:594-607. 2007
    ....
  41. ncbi Relative importance of malonyl CoA and carnitine in maturation of fatty acid oxidation in newborn rabbit heart
    Arzu Onay-Besikci
    Department of Pharmacology, University of Alberta, Edmonton, Canada T6G 2S2
    Am J Physiol Heart Circ Physiol 284:H283-9. 2003
    ..Our data suggest that a decrease in malonyl CoA control of CPT-1 is primarily responsible for the increase in fatty acid oxidation seen in the newborn heart...
  42. ncbi Effects of chronic AICAR administration on the metabolic and contractile phenotypes of rat slow- and fast-twitch skeletal muscles
    Jeremy A Bamford
    Faculty of Physical Education and Recreation, University of Alberta, Edmonton, Canada
    Can J Physiol Pharmacol 81:1072-82. 2003
    ....
  43. ncbi MEDICA 16 inhibits hepatic acetyl-CoA carboxylase and reduces plasma triacylglycerol levels in insulin-resistant JCR: LA-cp rats
    Laura L Atkinson
    Cardiovascular Research Group, Faculty of Medicine, The University of Alberta, Edmonton, Canada
    Diabetes 51:1548-55. 2002
    ..However, increased liver ACC activity in the JCR:LA-cp rat appears to contribute to the development of lipid abnormalities, although this increase does not appear to occur secondary to a decrease in AMPK activity...
  44. ncbi Metabolic profiling of hearts exposed to sevoflurane and propofol reveals distinct regulation of fatty acid and glucose oxidation: CD36 and pyruvate dehydrogenase as key regulators in anesthetic-induced fuel shift
    Lianguo Wang
    Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Alberta, Canada
    Anesthesiology 113:541-51. 2010
    ..This study profiled the metabolites and metabolic changes in the myocardium exposed to sevoflurane, propofol, and Intralipid and investigated the underlying molecular mechanisms...
  45. ncbi Alpha-catalytic subunits of 5'AMP-activated protein kinase display fiber-specific expression and are upregulated by chronic low-frequency stimulation in rat muscle
    Charles T Putman
    Faculty of Physical Education and Recreation and The Centre for Neuroscience, Faculty of Medicine and Dentistry, University of Alberta, E 417 Van Vliet Centre, Edmonton, Alberta, Canada
    Am J Physiol Regul Integr Comp Physiol 293:R1325-34. 2007
    ..These findings indicate that fiber types differ with regard to their capacity for AMPK signaling and that this potential is increased by CLFS...
  46. ncbi Metabolic therapy for the treatment of ischemic heart disease: reality and expectations
    Wei Wang
    University of Alberta, 423 Heritage Medical Research Center, Edmonton, Alberta T6G 2S2, Canada
    Expert Rev Cardiovasc Ther 5:1123-34. 2007
    ....
  47. ncbi Tumor necrosis factor-alpha-converting enzyme is a key regulator of agonist-induced cardiac hypertrophy and fibrosis
    Xiang Wang
    Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada
    Hypertension 54:575-82. 2009
    ..Targeting TACE has potential therapeutic importance for modulating agonist-induced cardiac remodeling...
  48. ncbi The malonyl CoA axis as a potential target for treating ischaemic heart disease
    John R Ussher
    Cardiovascular Research Group, Department of Pediatrics, University of Alberta, Edmonton, Canada
    Cardiovasc Res 79:259-68. 2008
    ..Hence, the malonyl CoA axis represents an exciting new target for the treatment of ischaemic heart disease...
  49. ncbi Introduction to JMCC symposium on myocardial energy metabolism in health and disease
    Gary D Lopaschuk
    Cardiovascular Research Group, University of Alberta-Faculty of Med./Dentist, 423 Heritage Medical Research Centre, Edmonton, AB, T6G 2S2, Canada
    J Mol Cell Cardiol 34:1075-6. 2002
  50. ncbi Malonyl coenzyme a decarboxylase inhibition protects the ischemic heart by inhibiting fatty acid oxidation and stimulating glucose oxidation
    Jason R B Dyck
    Cardiovascular Research Group, Department of Pediatrics, Faculty of Medicine, 474 Heritage Medical Research Centre, The University of Alberta, Edmonton, Alberta, T6G 2S2 Canada
    Circ Res 94:e78-84. 2004
    ..This switch in energy substrate preference improves cardiac function during and after ischemia, suggesting that pharmacological inhibition of MCD may be a novel approach to treating ischemic heart disease...
  51. ncbi High rates of residual fatty acid oxidation during mild ischemia decrease cardiac work and efficiency
    Clifford D L Folmes
    Cardiovascular Research Group and Departments of Pharmacology and Pediatrics, University of Alberta, Edmonton, Alberta, Canada
    J Mol Cell Cardiol 47:142-8. 2009
    ..We demonstrate that fatty acid oxidation dominates as the main source of residual oxidative metabolism during mild ischemia, which is accompanied by suppressed cardiac function and efficiency in the presence of high fat...
  52. ncbi Myocardial hypertrophy and the maturation of fatty acid oxidation in the newborn human heart
    Michael A Yatscoff
    Department of Pediatrics, University of Alberta, Edmonton, Alberta T6G 2S2, Canada
    Pediatr Res 64:643-7. 2008
    ..This indicates that increased expression of MCD, and the decreased expression of ACC and AMPK are important regulators of the maturation of fatty acid oxidation in the newborn human heart...
  53. ncbi Pyruvate prevents cardiac dysfunction and AMP-activated protein kinase activation by hydrogen peroxide in isolated rat hearts
    Hernando Leon
    Cardiovascular Reserach Group, Department of Pediatrics, University of Alberta, Edmonton, Canada
    Can J Physiol Pharmacol 82:409-16. 2004
    ..1%) showed reduced impairment in cardiac mechanical function. Compound C but not its vehicle significantly inhibited myocardial AMPK activity. Thus, H2O2 induces cardiac dysfunction via both AMPK-dependent and independent mechanisms...
  54. ncbi Absence of malonyl coenzyme A decarboxylase in mice increases cardiac glucose oxidation and protects the heart from ischemic injury
    Jason R B Dyck
    Cardiovascular Research Group, Department of Pediatrics, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada, T6G 2S2
    Circulation 114:1721-8. 2006
    ..However, it is unknown whether chronic inhibition of MCD results in altered cardiac function, energy metabolism, or ischemic cardioprotection...
  55. ncbi Calorie restriction prevents hypertension and cardiac hypertrophy in the spontaneously hypertensive rat
    Vernon W Dolinsky
    458 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta T6G 2S2, Canada
    Hypertension 56:412-21. 2010
    ..As a result, CR may serve as an effective nonpharmacological treatment of hypertension, and targeting the adiponectin/AMPK/eNOS pathway may improve treatment of hypertension...
  56. ncbi Fatty acid oxidation and malonyl-CoA decarboxylase in the vascular remodeling of pulmonary hypertension
    Gopinath Sutendra
    Pulmonary Hypertension Program, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2B7
    Sci Transl Med 2:44ra58. 2010
    ....
  57. ncbi Anti-anginal effects of partial fatty acid oxidation inhibitors
    Anna Lam
    Cardiovascular Research Group, 423 Heritage Medical Research Building, The University of Alberta, Edmonton, Alberta, Canada
    Curr Opin Pharmacol 7:179-85. 2007
    ..The approach of optimizing energy substrate preference in the heart is a new and effective approach to treating angina pectoris...
  58. ncbi Leptin activates cardiac fatty acid oxidation independent of changes in the AMP-activated protein kinase-acetyl-CoA carboxylase-malonyl-CoA axis
    Laura L Atkinson
    Cardiovascular Research Group, Muttart Diabetes Research and Training Center, Department of Pediatrics, Faculty of Medicine, University of Alberta, Edmonton, Alberta T6G 2S2, Canada
    J Biol Chem 277:29424-30. 2002
    ..These data demonstrate for the first time that leptin activates fatty acid oxidation and decreases TG content in the heart. We also show that the effects of leptin in the heart are independent of changes in the AMPK-ACC-malonyl-CoA axis...
  59. ncbi H(2)O(2)-induced left ventricular dysfunction in isolated working rat hearts is independent of calcium accumulation
    Lianguo Wang
    Department of Pharmacology and Cardiovascular Research Group, University of Alberta, Edmonton, AB, Canada
    J Mol Cell Cardiol 45:787-95. 2008
    ..The ability of further increases in [Ca(2+)](i) to reverse H(2)O(2)-induced LV dysfunction suggests that Ca(2+) desensitization is the predominant mechanism of ROS-induced contractile dysfunction...
  60. ncbi Targeting malonyl CoA inhibition of mitochondrial fatty acid uptake as an approach to treat cardiac ischemia/reperfusion
    John R Ussher
    Department of Pediatrics, 423 Heritage Medical Research Center, University of Alberta, Edmonton, Canada
    Basic Res Cardiol 104:203-10. 2009
    ..Therefore, targeting malonyl CoA is a novel exciting approach for the treatment of cardiac ischemia/reperfusion...
  61. ncbi Dichloroacetate, a metabolic modulator, prevents and reverses chronic hypoxic pulmonary hypertension in rats: role of increased expression and activity of voltage-gated potassium channels
    Evangelos D Michelakis
    Department of Medicine, University of Alberta, Edmonton, Canada
    Circulation 105:244-50. 2002
    ..We hypothesized that dichloroacetate (DCA), a metabolic modulator that can shift redox balance toward an oxidized state and increase Kv current in myocardial cells, would reverse CH-PHT...
  62. ncbi A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth
    Sebastien Bonnet
    Pulmonary Hypertension Program and Vascular Biology Group, Department of Physiology, University of Alberta, Edmonton, AB T6G 2B7, Canada
    Cancer Cell 11:37-51. 2007
    ..Molecular inhibition of PDK2 by siRNA mimics DCA. The mitochondria-NFAT-Kv axis and PDK are important therapeutic targets in cancer; the orally available DCA is a promising selective anticancer agent...
  63. ncbi Role of the atypical protein kinase Czeta in regulation of 5'-AMP-activated protein kinase in cardiac and skeletal muscle
    John R Ussher
    Cardiovascular Research Group, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
    Am J Physiol Endocrinol Metab 297:E349-57. 2009
    ..We conclude that PKCzeta plays a very minor role in the regulation of AMPK in cardiac and skeletal muscle and may actually be a downstream target of AMPK in skeletal muscle...
  64. ncbi Early activation of matrix metalloproteinases underlies the exacerbated systolic and diastolic dysfunction in mice lacking TIMP3 following myocardial infarction
    Vijay Kandalam
    Department of Physiology, University of Alberta, Edmonton, Alberta
    Am J Physiol Heart Circ Physiol 299:H1012-23. 2010
    ..Hence, timing of treatments to improve cardiac response to MI may be critical in producing favorable outcome...
  65. ncbi AT(1) and AT(2) receptor expression and blockade after acute ischemia-reperfusion in isolated working rat hearts
    Yi Xu
    Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2R7
    Am J Physiol Heart Circ Physiol 282:H1206-15. 2002
    ..Other groups (except CHA) did not improve recovery. The results suggest that, in isolated working hearts, AT(2)R plays a significant role in ischemia-reperfusion and AT(2)R blockade induces increased AT(2)R protein and cardioprotection...
  66. ncbi Expression of an active LKB1 complex in cardiac myocytes results in decreased protein synthesis associated with phenylephrine-induced hypertrophy
    Anna A Noga
    Cardiovascular Research Group, Department of Pediatrics, Faculty of Medicine and Dentistry, Univ of Alberta, Edmonton, Alberta, Canada
    Am J Physiol Heart Circ Physiol 292:H1460-9. 2007
    ..Together, our data show that increased LKB1 activity in the cardiac myocyte can decrease hypertrophy-induced protein synthesis and suggest that LKB1 activation may be a method for the prevention of pathological cardiac hypertrophy...
  67. ncbi Malonyl-CoA decarboxylase (MCD) is differentially regulated in subcellular compartments by 5'AMP-activated protein kinase (AMPK). Studies using H9c2 cells overexpressing MCD and AMPK by adenoviral gene transfer technique
    Nandakumar Sambandam
    Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
    Eur J Biochem 271:2831-40. 2004
    ..7 kDa isoform of MCD protein in the mitochondria. This differential regulation of MCD expression and activity in the mitochondria by AMPK may potentially regulate malonyl-CoA levels at sites nearby CPT-I on the mitochondria...
  68. ncbi Malonyl-CoA mediates leptin hypothalamic control of feeding independent of inhibition of CPT-1a
    Su Gao
    Department of Pediatrics, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
    Am J Physiol Regul Integr Comp Physiol 301:R209-17. 2011
    ..Together, our results suggest that Arc intracellular mechanisms of malonyl-CoA's anorectic actions induced by leptin are independent of CPT-1a. The data suggest that target(s), rather than CPT-1a, mediates malonyl-CoA action on feeding...
  69. ncbi Reduced synthesis of NO causes marked alterations in myocardial substrate metabolism in conscious dogs
    Fabio A Recchia
    Department of Physiology, New York Medical College, Valhalla, New York 10595, USA
    Am J Physiol Endocrinol Metab 282:E197-206. 2002
    ..In conclusion, the acute inhibition of NO synthesis causes marked metabolic alterations that do not involve key rate-controlling enzymes of fatty acid oxidation nor glyceraldehyde-3-phosphate dehydrogenase...
  70. ncbi The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus
    Brian N Finck
    Center for Cardiovascular Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA
    J Clin Invest 109:121-30. 2002
    ....
  71. ncbi Metabolic modulation: a means to mend a broken heart
    Gary D Lopaschuk
    Circulation 105:140-2. 2002
  72. ncbi Accelerated rates of glycolysis in the hypertrophied heart: are they a methodological artifact?
    Hon Sing Leong
    McDonald Research Laboratories The iCAPTUR, University of British Columbia St Paul s Hospital, Vancouver, British Columbia, V6Z 1Y6
    Am J Physiol Endocrinol Metab 282:E1039-45. 2002
    ..Furthermore, the PPP does not appear to be increased in cardiac hypertrophy induced by abdominal aortic constriction...
  73. ncbi Impaired myocardial fatty acid oxidation and reduced protein expression of retinoid X receptor-alpha in pacing-induced heart failure
    Juan Carlos Osorio
    Department of Physiology, New York Medical College, Valhalla, NY 10595, USA
    Circulation 106:606-12. 2002
    ..CONCLUSIONS: Our results provide the first evidence for a link between the reduced expression of RXRalpha and the switch in metabolic phenotype in severe heart failure...
  74. ncbi Cardiac energy metabolism alterations in angiotensin II induced hypertrophy
    Gary D Lopaschuk
    J Mol Cell Cardiol 41:418-20. 2006
  75. ncbi Energy metabolism in the hypertrophied heart
    Nandakumar Sambandam
    Department of Pathology and Laboratory Medicine, University of British Columbia--St Paul's Hospital, Vancouver, Canada V6Z 1Y6
    Heart Fail Rev 7:161-73. 2002
    ..g., ranolazine, trimetazidine), also produce beneficial effects in ischemic and reperfused hypertrophied hearts...
  76. ncbi beta-Hydroxybutyrate inhibits myocardial fatty acid oxidation in vivo independent of changes in malonyl-CoA content
    William C Stanley
    Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106 4970, USA
    Am J Physiol Heart Circ Physiol 285:H1626-31. 2003
    ..In conclusion, fatty acid uptake and oxidation is blocked by an infusion of beta-hydroxybutyrate; this effect was not due to elevated myocardial malonyl-CoA content...
  77. ncbi Malonyl-CoA decarboxylase inhibition suppresses fatty acid oxidation and reduces lactate production during demand-induced ischemia
    William C Stanley
    Dept of Physiology and Biophysics, School of Medicine, Case Western Reserve Univ, 10900 Euclid Ave, Cleveland, OH 44106 4970, USA
    Am J Physiol Heart Circ Physiol 289:H2304-9. 2005
    ..Thus modulation of MCD activity is an effective means of regulating myocardial fatty acid oxidation under normal and ischemic conditions and reducing lactate production during demand-induced ischemia...
  78. ncbi Validation of 18F-fluoro-4-thia-palmitate as a PET probe for myocardial fatty acid oxidation: effects of hypoxia and composition of exogenous fatty acids
    Timothy R DeGrado
    Department of Radiology, School of Medicine, Indiana University, Indianapolis, 46077, USA
    J Nucl Med 47:173-81. 2006
    ....
  79. ncbi Synthesis and structure-activity relationship of small-molecule malonyl coenzyme A decarboxylase inhibitors
    Jie Fei Cheng
    Department of Chemistry, Chugai Pharma USA, LLC, 6225 Nancy Ridge Drive, San Diego, California 92121, USA
    J Med Chem 49:1517-25. 2006
    ....
  80. ncbi Heteroaryl substituted bis-trifluoromethyl carbinols as malonyl-CoA decarboxylase inhibitors
    Jie Fei Cheng
    Department of Chemistry and Discovery Biology, Chugai Pharma LLC, 6275 Nancy Ridge Dr, San Diego, CA 92121, USA
    Bioorg Med Chem Lett 16:3484-8. 2006
    ..Some thiazole-based derivatives showed potent in vitro MCD inhibitory activities and significantly increased glucose oxidation rates in isolated working rat hearts...
  81. ncbi Selective versus nonselective beta-adrenergic receptor blockade in chronic heart failure: differential effects on myocardial energy substrate utilization
    Abdul Al-Hesayen
    Division of Cardiology, Department of Medicine, Mount Sinai Hospital and University Health Network Hospitals, University of Toronto, 600 University Avenue, Suite 1609, Toronto, Ontario, Canada, M5G 1X5
    Eur J Heart Fail 7:618-23. 2005
    ..These differences are most probably related to the differential effects of these two agents on efferent cardiac sympathetic activity and may be relevant to the reported differential effects of these drugs on clinical outcomes...
  82. ncbi Discovery of potent and orally available malonyl-CoA decarboxylase inhibitors as cardioprotective agents
    Jie Fei Cheng
    Department of Chemistry, Chugai Pharma USA, LLC, 6275 Nancy Ridge Drive, San Diego, California 92121, USA
    J Med Chem 49:4055-8. 2006
    ..Compound 5 improved the cardiac efficiency and function in a rat heart global ischemia/reperfusion model, suggesting MCD inhibitors may be useful for the treatment of ischemic heart diseases...
  83. ncbi Interaction between altered insulin and lipid metabolism in CEACAM1-inactive transgenic mice
    Tong Dai
    Departments of Pharmacology and Therapeutics, Medical College of Ohio, Toledo, Ohio 43614, USA
    J Biol Chem 279:45155-61. 2004
    ..Taken together, these data suggest that chronic elevation in plasma FFAs levels contributes to the regulation of insulin metabolism and action in L-SACC1 mice...
  84. ncbi Alpha-lipoic acid increases cardiac glucose oxidation independent of AMP-activated protein kinase in isolated working rat hearts
    Arzu Onay Besikci
    Ankara University, Faculty of Pharmacy, Department of Pharmacology, Ankara, Turkey
    Basic Res Cardiol 102:436-44. 2007
    ..The beneficial effects of ALA treatment in diabetic patients may be at least in part related to its effect on glucose metabolism...
  85. ncbi Regulation of malonyl-CoA concentration and turnover in the normal heart
    Aneta E Reszko
    Department of Biochemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA
    J Biol Chem 279:34298-301. 2004
    ..Our data show that, in the absence of enzyme inhibitors, the rate of acetyl-CoA carboxylation is the main determinant of the malonyl-CoA concentration in the heart...
  86. ncbi Regulation of cardiac malonyl-CoA content and fatty acid oxidation during increased cardiac power
    Kristen L King
    Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106-4970, USA
    Am J Physiol Heart Circ Physiol 289:H1033-7. 2005
    ....
  87. ncbi Leptin activates hypothalamic acetyl-CoA carboxylase to inhibit food intake
    Su Gao
    Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 104:17358-63. 2007
    ..Together, these findings highlight site-specific impacts of hypothalamic ACC activation in leptin's anorectic signaling cascade...
  88. ncbi Metabolic response to an acute jump in cardiac workload: effects on malonyl-CoA, mechanical efficiency, and fatty acid oxidation
    Lufang Zhou
    Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA
    Am J Physiol Heart Circ Physiol 294:H954-60. 2008
    ....
  89. ncbi Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance
    Timothy R Koves
    Sarah W Stedman Nutrition and Metabolism Center, Department of Medicine, Duke University, Durham, NC 27710, USA
    Cell Metab 7:45-56. 2008
    ..These findings reveal a strong connection between skeletal muscle insulin resistance and lipid-induced mitochondrial stress...
  90. ncbi Signalling in cardiac metabolism
    Gary D Lopaschuk
    Cardiovasc Res 79:205-7. 2008
  91. ncbi Cyclic GMP signaling in cardiomyocytes modulates fatty acid trafficking and prevents triglyceride accumulation
    Ramzi J Khairallah
    Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada
    J Mol Cell Cardiol 45:230-9. 2008
    ....
  92. ncbi Myocardial substrate metabolism in the normal and failing heart
    William C Stanley
    Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, Ohio 44106 4970, USA
    Physiol Rev 85:1093-129. 2005
    ....
  93. ncbi Thioredoxin-interacting protein deficiency disrupts the fasting-feeding metabolic transition
    Sonal S Sheth
    Department of Human Genetics, Medicine, Molecular Biology Institute, University of California, Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    J Lipid Res 46:123-34. 2005
    ..These results indicate a role for Txnip in the metabolic response to feeding and the maintenance of the redox status...