Research Topics
Genomes and Genes
| Daniel P KellySummaryAffiliation: Washington University School of Medicine Country: USA Publications
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Publications
PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosisTeresa C Leone
Center for Cardiovascular Research, Washington University School of Medicine, St Louis, Missouri, USA
PLoS Biol 3:e101. 2005..Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha(-/-) mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life...
Transcriptional regulatory circuits controlling mitochondrial biogenesis and functionDaniel P Kelly
Center for Cardiovascula Research, Departments of Medicine, Molecular Biology and Pharmacology, and Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63119, USA
Genes Dev 18:357-68. 2004- A potential link between muscle peroxisome proliferator- activated receptor-alpha signaling and obesity-related diabetesBrian N Finck
Center for Cardiovascular Research, Washington University School of Medicine, St Louis, Missouri 63110, USA
Cell Metab 1:133-44. 2005..These results identify PPARalpha-driven alterations in muscle fatty acid oxidation and energetics as a potential link between obesity and the development of glucose intolerance and insulin resistance... - Impaired contractile function and calcium handling in hearts of cardiac-specific calcineurin b1-deficient micePaul J Schaeffer
Departments of Medicine, Washington University School of Medicine, Center for Cardiovascular Research, St Louis, Missouri, USA
Am J Physiol Heart Circ Physiol 297:H1263-73. 2009..These results define a novel mouse model of cardiac-specific Cn deficiency and demonstrate novel links between Cn signaling, postnatal growth of the heart, pathological ventricular remodeling, and excitation-contraction coupling... - Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) regulatory cascade in cardiac physiology and diseaseBrian N Finck
Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO 63110, USA
Circulation 115:2540-8. 2007 - The transcriptional coactivator PGC-1alpha is essential for maximal and efficient cardiac mitochondrial fatty acid oxidation and lipid homeostasisJohn J Lehman
Center for Cardiovascular Research, Washington Univ School of Medicine, St Louis, MO 63110, USA
Am J Physiol Heart Circ Physiol 295:H185-96. 2008..Overall, these results demonstrate that PGC-1alpha is essential for the maintenance of maximal, efficient cardiac mitochondrial fatty acid oxidation, ATP synthesis, and myocardial lipid homeostasis... - Estrogen-related receptor alpha directs peroxisome proliferator-activated receptor alpha signaling in the transcriptional control of energy metabolism in cardiac and skeletal muscleJanice M Huss
Center for Cardiovascular Research, Washington University School of Medicine, St Louis, MO 63110, USA
Mol Cell Biol 24:9079-91. 2004..We conclude that ERRalpha serves as a critical nodal point in the regulatory circuitry downstream of PGC-1alpha to direct the transcription of genes involved in mitochondrial energy-producing pathways in cardiac and skeletal muscle... - The nuclear receptor ERRalpha is required for the bioenergetic and functional adaptation to cardiac pressure overloadJanice M Huss
Center for Cardiovascular Research, Washington University School of Medicine, St Louis, MO 63110, USA
Cell Metab 6:25-37. 2007..These results demonstrate that the nuclear receptor ERRalpha is required for the adaptive bioenergetic response to hemodynamic stressors known to cause heart failure... - CD36 deficiency rescues lipotoxic cardiomyopathyJohn Yang
Center for Cardiovascular Research, Washington University School of Medicine, St Louis, MO 63110, USA
Circ Res 100:1208-17. 2007.... - PGC-1alpha coactivates PDK4 gene expression via the orphan nuclear receptor ERRalpha: a mechanism for transcriptional control of muscle glucose metabolismAdam R Wende
Center for Cardiovascular Research, Washington University School of Medicine, St Louis, MO 63110, USA
Mol Cell Biol 25:10684-94. 2005.... - Preferential oxidation of triacylglyceride-derived fatty acids in heart is augmented by the nuclear receptor PPARalphaNatasha H Banke
Program in Integrative Cardiac Metabolism, Center for Cardiovascular Research, University of Illinois at Chicago College of Medicine, Chicago, IL 60612, USA
Circ Res 107:233-41. 2010..However, the contribution of endogenous triacylglyceride (TAG) turnover to LCFA oxidation and the overall dependence of mitochondrial oxidation on endogenous lipid is largely unstudied... - PPARalpha-mediated remodeling of repolarizing voltage-gated K+ (Kv) channels in a mouse model of metabolic cardiomyopathyCeline Marionneau
Department of Molecular Biology and Pharmacology, Washington University Medical School, St Louis, MO 63110, USA
J Mol Cell Cardiol 44:1002-15. 2008..The molecular mechanisms underlying I(to,f) and I(ss) remodeling in MHC-PPARalpha ventricular myocytes, therefore, are distinct... - Dexamethasone induction of hypertension and diabetes is PPAR-alpha dependent in LDL receptor-null miceCarlos Bernal-Mizrachi
Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110 USA
Nat Med 9:1069-75. 2003..These results identify hepatic activation of PPAR-alpha as a mechanism underlying glucocorticoid-induced insulin resistance... - Lipin 1 is an inducible amplifier of the hepatic PGC-1alpha/PPARalpha regulatory pathwayBrian N Finck
Center for Cardiovascular Research and Washington University School of Medicine, St Louis, Missouri 63110, USA
Cell Metab 4:199-210. 2006..These results identify lipin 1 as a selective physiological amplifier of the PGC-1alpha/PPARalpha-mediated control of hepatic lipid metabolism... - Rescue of cardiomyopathy in peroxisome proliferator-activated receptor-alpha transgenic mice by deletion of lipoprotein lipase identifies sources of cardiac lipids and peroxisome proliferator-activated receptor-alpha activatorsJennifer G Duncan
Center for Cardiovascular Research, Washington University School of Medicine, St Louis, MO, USA
Circulation 121:426-35. 2010.... - Transcriptional coactivators PGC-1alpha and PGC-lbeta control overlapping programs required for perinatal maturation of the heartLing Lai
Center for Cardiovascular Research, Washington University School of Medicine, St Louis, Missouri 63110, USA
Genes Dev 22:1948-61. 2008..We conclude that PGC-1alpha and PGC-1beta share roles that collectively are necessary for the postnatal metabolic and functional maturation of heart and BAT... - A critical role for PPARalpha-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: modulation by dietary fat contentBrian N Finck
Department of Medicine, Center for Cardiovascular Research, Washington University School of Medicine, St Louis, MO 63110, USA
Proc Natl Acad Sci U S A 100:1226-31. 2003..These results link dysregulation of the PPARalpha gene regulatory pathway to cardiac dysfunction in the diabetic and provide a rationale for serum lipid-lowering strategies in the treatment of diabetic cardiomyopathy... - Nuclear receptors PPARbeta/delta and PPARalpha direct distinct metabolic regulatory programs in the mouse heartEileen M Burkart
Center for Cardiovascular Research, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Clin Invest 117:3930-9. 2007.... - Cardiac-specific induction of the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha promotes mitochondrial biogenesis and reversible cardiomyopathy in a developmental stage-dependent mannerLaurie K Russell
Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
Circ Res 94:525-33. 2004.... - Total skeletal muscle PGC-1 deficiency uncouples mitochondrial derangements from fiber type determination and insulin sensitivityChristoph Zechner
Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
Cell Metab 12:633-42. 2010..Taken together, we conclude that PGC-1 coactivators are necessary for the oxidative and mitochondrial programs of skeletal muscle but are dispensable for fundamental fiber type determination and insulin sensitivity... - Nuclear receptor signaling and cardiac energeticsJanice M Huss
Center for Cardiovascular Research and Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Circ Res 95:568-78. 2004..The dynamic regulation of the cardiac PPAR/PGC-1 complex in accordance with physiological and pathophysiological states will be described... - Insulin-resistant heart exhibits a mitochondrial biogenic response driven by the peroxisome proliferator-activated receptor-alpha/PGC-1alpha gene regulatory pathwayJennifer G Duncan
Center for Cardiovascular Research, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, USA
Circulation 115:909-17. 2007..We hypothesized that regulatory events involved in the control of mitochondrial function are activated in the prediabetic, insulin-resistant stage... - A role for the transcriptional coactivator PGC-1alpha in muscle refuelingAdam R Wende
Center for Cardiovascular Research, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Biol Chem 282:36642-51. 2007..These findings identify PGC-1alpha as a critical regulator of skeletal muscle fuel stores... - Chronic inhibition of pyruvate dehydrogenase in heart triggers an adaptive metabolic responseKari T Chambers
Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Biol Chem 286:11155-62. 2011.... - A PPARα promoter variant impairs ERR-dependent transactivation and decreases mortality after acute coronary ischemia in patients with diabetesSharon Cresci
Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, United States of America
PLoS ONE 5:e12584. 2010.... - G-protein signaling participates in the development of diabetic cardiomyopathyIan S Harris
Center for Cardiovascular Research, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA
Diabetes 53:3082-90. 2004..These results establish that Gq-mediated signaling plays a critical role in the pathogenesis of diabetic cardiomyopathy... - Mouse models of mitochondrial dysfunction and heart failureLaurie K Russell
Center for Cardiovascular Research, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8086, Saint Louis, MO 63110, USA
J Mol Cell Cardiol 38:81-91. 2005.... - Mitochondrial energy metabolism in heart failure: a question of balanceJanice M Huss
Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, Missouri 63110, USA
J Clin Invest 115:547-55. 2005..This review focuses on the molecular regulatory events and downstream effector pathways involved in mitochondrial energy metabolic derangements known to occur during the development of heart failure... - Toll-like receptor-mediated inflammatory signaling reprograms cardiac energy metabolism by repressing peroxisome proliferator-activated receptor γ coactivator-1 signalingJoel Schilling
Center for Cardiovascular Research, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA
Circ Heart Fail 4:474-82. 2011..Peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) α and β serve as critical physiological regulators of energy metabolic gene expression in heart... 
The PPAR trio: regulators of myocardial energy metabolism in health and diseaseJose A Madrazo
Center for Cardiovascular Research, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Mol Cell Cardiol 44:968-75. 2008....- Peroxisome proliferator-activated receptor alpha (PPARalpha) signaling in the gene regulatory control of energy metabolism in the normal and diseased heartBrian N Finck
Department of Medicine, Center for Cardiovascular Research, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA
J Mol Cell Cardiol 34:1249-57. 2002..This review summarizes the regulation of cardiac substrate utilization pathways via the PPARalpha complex in the normal and diseased heart... - Myocardial fatty acid metabolism: independent predictor of left ventricular mass in hypertensive heart diseaseLisa De Las Fuentes
Cardiovascular Imaging and Clinical Research Core Laboratory, Washington University School of Medicine, St Louis, MO 63110, USA
Hypertension 41:83-7. 2003..The extent to which reduced myocardial fatty acid metabolism affects cardiovascular morbidity and mortality and whether pharmacologic modulation results in improved outcomes remains to be determined... - Calcineurin and calcium/calmodulin-dependent protein kinase activate distinct metabolic gene regulatory programs in cardiac musclePaul J Schaeffer
Center for Cardiovascular Research and Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Biol Chem 279:39593-603. 2004..These data support a role for calcium-triggered signaling pathways in the regulation of cardiac energetics and identify pathway-specific control of metabolic targets... - PGC-1 coactivators: inducible regulators of energy metabolism in health and diseaseBrian N Finck
Center for Cardiovascular Research, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Clin Invest 116:615-22. 2006..This Review focuses on the biologic and physiologic functions of the PGC-1 coactivators, with particular emphasis on striated muscle, liver, and other organ systems relevant to common diseases such as diabetes and heart failure... - PPARalpha suppresses insulin secretion and induces UCP2 in insulinoma cellsKaren Tordjman
Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
J Lipid Res 43:936-43. 2002..Clofibric acid-induced suppression of glucose-simulated insulin secretion was prevented by the CPT-I inhibitor etomoxir. These data suggest that PPARalpha-stimulated fatty acid oxidation can impair beta cell function... - Gene regulatory mechanisms governing energy metabolism during cardiac hypertrophic growthJohn J Lehman
Center for Cardiovascular Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA
Heart Fail Rev 7:175-85. 2002.... - Ubiquitin proteasome-dependent degradation of the transcriptional coactivator PGC-1{alpha} via the N-terminal pathwayJulie Trausch-Azar
Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Biol Chem 285:40192-200. 2010..In contrast, the cellular localization of NT-PCG-1α results in a longer-half-life and possible distinct temporal and potentially biological actions... - The PGC-1 cascade as a therapeutic target for heart failureJoel Schilling
Center for Cardiovascular Research, Washington University School of Medicine, St Louis, MO, USA
J Mol Cell Cardiol 51:578-83. 2011..Potential strategies to modulate this target pathway are reviewed. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure.".. - Fatty acid synthase modulates homeostatic responses to myocardial stressBabak Razani
Division of Endocrinology, Metabolism, and Lipid Research, Washington University, St Louis, Missouri 63110, USA
J Biol Chem 286:30949-61. 2011..These data implicate a novel relationship between FAS and calcium signaling in the heart and suggest that FAS induction in stressed myocardium represents a compensatory response to protect cardiomyocytes from pathological calcium flux... - Retinoid X receptor alpha represses GATA-4-mediated transcription via a retinoid-dependent interaction with the cardiac-enriched repressor FOG-2Martha L Clabby
Center for Cardiovascular Research, Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Biol Chem 278:5760-7. 2003..These data reveal a novel mechanism by which retinoids regulate cardiogenic gene expression through direct interaction with GATA-4 and its co-repressor, FOG-2... - Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) coactivates the cardiac-enriched nuclear receptors estrogen-related receptor-alpha and -gamma. Identification of novel leucine-rich interaction motif within PGC-1alphaJanice M Huss
Department of Medicine, Center for Cardiovascular Research, Washington University School of Medicine, 660 S Euclid Avenue, St Louis, MO 63110, USA
J Biol Chem 277:40265-74. 2002.... - Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1Keith Baar
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA
FASEB J 16:1879-86. 2002..These findings suggest that increases in PGC-1, NRF-1, and NRF-2 represent key regulatory components of the stimulation of mitochondrial biogenesis by exercise and that PGC-1 mediates the coordinated increases in GLUT4 and mitochondria... - Cost of transport is increased after cold exposure in Monodelphis domestica: training for inefficiencyPaul J Schaeffer
Department of Biological Sciences, Physiology and Functional Morphology Group, Northern Arizona University, Flagstaff, AZ 86011, USA
J Exp Biol 208:3159-67. 2005..However, linked to the dramatic shift in muscle properties is an equally dramatic increase in whole animal muscle energetics during locomotion, suggesting an uncoupled state, or 'training for inefficiency'... - Interaction between PPARA genotype and beta-blocker treatment influences clinical outcomes following acute coronary syndromesSharon Cresci
Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8086, Saint Louis, MO 63110 1093, USA
Pharmacogenomics 9:1403-17. 2008.... - Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathyVictor G Davila-Roman
Cardiovascular Imaging and Clinical Research Core Laboratory, Cardiovascular Division, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
J Am Coll Cardiol 40:271-7. 2002..The purpose of this study was to determine whether patients with idiopathic dilated cardiomyopathy (IDCM) exhibit alterations in myocardial fatty acid and glucose metabolism... - Transcriptional activation of energy metabolic switches in the developing and hypertrophied heartJohn J Lehman
Center for Cardiovascular Research, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
Clin Exp Pharmacol Physiol 29:339-45. 2002..Future studies aim at defining whether this transcriptional 'switch' and its effects on myocardial metabolism are adaptive or maladaptive in the hypertrophied heart... - The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitusBrian 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.... - Chronic activation of PPARalpha is detrimental to cardiac recovery after ischemiaNandakumar 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... - Role of adiponectin in the protective action of dietary saturated fat against alcoholic fatty liver in miceMin You
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
Hepatology 42:568-77. 2005.... - PPARs of the heart: three is a crowdDaniel P Kelly
Circ Res 92:482-4. 2003 - Decreased contractile and metabolic reserve in peroxisome proliferator-activated receptor-alpha-null hearts can be rescued by increasing glucose transport and utilizationIvan Luptak
NMR Laboratory for Physiological Chemistry, Division of Cardiovascular Medicine, Brigham and Women s Hospital, Boston, MA, USA
Circulation 112:2339-46. 2005..Here, we sought to elucidate the functional significance of this shift in substrate preference... - Liver fatty acid binding protein is required for high rates of hepatic fatty acid oxidation but not for the action of PPARalpha in fasting miceErdal Erol
Department of Pathobiology, College of Veterinary Medicine, Texas A and M University, Raymond Stotzer Pkwy, College Station, Texas 77843 4467, USA
FASEB J 18:347-9. 2004..Thus, the mechanisms whereby L-FABP affects fatty acid oxidation may vary with physiological condition... - Signalling in cardiac metabolismGary D Lopaschuk
Cardiovasc Res 79:205-7. 2008 - Cardiac-specific overexpression of peroxisome proliferator-activated receptor-alpha causes insulin resistance in heart and liverSo Young Park
Yale University School of Medicine, Department of Internal Medicine, Section of Endocrinology and Metabolism, The Anlyan Center, S269C, P O Box 208020, 300 Cedar St, New Haven, CT 06520 8020, USA
Diabetes 54:2514-24. 2005..Additionally, age-associated hepatic insulin resistance develops in MHC-PPARalpha mice that may be due to altered cardiac metabolism, functions, and/or inflammatory cytokines... - Genome-wide orchestration of cardiac functions by the orphan nuclear receptors ERRalpha and gammaCatherine R Dufour
Molecular Oncology Group, McGill University Health Centre, Montreal, Quebec H3A 1A1, Canada
Cell Metab 5:345-56. 2007..Our study thus reveals that the ERRs orchestrate a comprehensive cardiac transcriptional program and further suggests that modulation of ERR activities could be used to manage cardiomyopathies... - 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 higFiona 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... - Hypoxic reprogrammingDaniel P Kelly
Nat Genet 40:132-4. 2008 - Developmental adaptation of the mouse cardiovascular system to elastin haploinsufficiencyGilles Faury
Laboratoire de Développement et Vieillissement de l Endothélium, Commisarriat à l Energie Atomique Institut National de la Santé et de la Recherche Médicale Equipq Mixte 0219, Universite Joseph Fourier, Grenoble, France
J Clin Invest 112:1419-28. 2003..The association of hypertension with elastin haploinsufficiency in humans and mice strongly suggests that elastin and other proteins of the elastic fiber should be considered as causal genes for essential hypertension... - Peroxisome proliferator-activated receptor alpha as a genetic determinant of cardiac hypertrophic growth: culprit or innocent bystander?Daniel P Kelly
Circulation 105:1025-7. 2002
Research Grants
- Interdisciplinary Studies of the Diabetic Heart (RMI)Daniel Kelly; Fiscal Year: 2006..It is envisioned that principles established by the fundamental paradigm shift developed through our efforts will be applicable to other complex disease states in the future. ..