941
Views
6
CrossRef citations to date
0
Altmetric
Reviews

AMP-activated protein kinase in the heart: role in cardiac glucose and fatty acid metabolism

Pages 643-661 | Published online: 18 Jan 2017

  • Carling D, Zammit VA, Hardie DG: A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. FEBS Lett. 223, 217–222 (1987).
  • Woods A, Cheung PC, Smith FC et al.: Characterization of AMP-activated protein kinase b and g subunits. Assembly of the heterotrimeric complex in vitro. J. Biol. Chem. 271, 10282–10290 (1996).
  • Pang T, Xiong B, Li JY et al.: Conserved a-helix acts as autoinhibitory sequence in AMP-activated protein kinase a subunits. J. Biol. Chem. 282, 495–506 (2007).
  • Woods A, Vertommen D, Neumann D et al.: Identification of phosphorylation sites in AMP-activated protein kinase (AMPK) for upstream AMPK kinases and study of their roles by site-directed mutagenesis. J. Biol. Chem. 278, 28434–28442 (2003).
  • Key review that identifies new phosphorylation sites that could play a subtle role in the regulation of AMP-activated protein kinase (AMPK).
  • Mitchelhill KI, Michell BJ, House CM et al.: Posttranslational modifications of the 5´-AMP-activated protein kinase b1 subunit. J. Biol. Chem. 272, 24475–24479 (1997).
  • Wong KA, Lodish HF: A revised model for AMP-activated protein kinase structure: the a-subunit binds to both the b- and g-subunits although there is no direct binding between the b- and g-subunits. J. Biol. Chem. 281, 36434–36442 (2006).
  • Warden SM, Richardson C, O’Donnell J Jr et al.: Post-translational modifications of the b-1 subunit of AMP-activated protein kinase affect enzyme activity and cellular localization. Biochem. J. 354, 275–283 (2001).
  • Salt I, Celler JW, Hawley SA et al.: AMP-activated protein kinase: greater AMP dependence, and preferential nuclear localization, of complexes containing the a2 isoform. Biochem. J. 334(Pt 1), 177–187 (1998).
  • Kemp BE: Bateman domains and adenosine derivatives form a binding contract. J. Clin. Invest. 113, 182–184 (2004).
  • Witczak CA, Sharoff CG, Goodyear LJ: AMP-activated protein kinase in skeletal muscle: from structure and localization to its role as a master regulator of cellular metabolism. Cell. Mol. Life Sci. 65, 3737–3755 (2008).
  • Kodiha M, Rassi JG, Brown CM, Stochaj U: Localization of AMP kinase is regulated by stress, cell density, and signaling through the MEK-->ERK1/2 pathway. Am. J. Physiol. Cell Physiol. 293, C1427–C1436 (2007).
  • Scott JW, Hawley SA, Green KA et al.:
  • Kyriakis JM: At the crossroads: AMP-activated kinase and the LKB1 tumor suppressor link cell proliferation to metabolic regulation. J. Biol. 2, 26 (2003).
  • Baas AF, Boudeau J, Sapkota GP et al.: Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD. EMBO J. 22, 3062–3072 (2003).
  • Kim AS, Miller EJ, Young LH: AMPactivated protein kinase: a core signalling pathway in the heart. Acta Physiol. (Oxf.) 196, 37–53 (2009).
  • Sakamoto K, Zarrinpashneh E, Budas GR et al.: Deficiency of LKB1 in heart prevents ischemia-mediated activation of AMPKa2 but not AMPKa1. Am. J. Physiol. Endocrinol. Metab. 290, E780–E788 (2006).
  • Establishes LKB1 as a crucial upstream kinase regulating cardiac AMPK function.
  • Sanders MJ, Grondin PO, Hegarty BD, Snowden MA, Carling D: Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascade. Biochem. J. 403, 139–148 (2007).
  • Key study which identified that AMP sensitivity for Thr172 phosphorylation site was due to the ability of AMP to inhibit phosphatases and hence prevent AMPK dephosphorylation.
  • Hardie DG: Role of AMP-activated protein kinase in the metabolic syndrome and in heart disease. FEBS Lett. 582, 81–89 (2008).
  • Altarejos JY, Taniguchi M, Clanachan AS, Lopaschuk GD: Myocardial ischemia differentially regulates LKB1 and an alternate 5´-AMP-activated protein kinase kinase. J. Biol. Chem. 280, 183–190 (2005).
  • Xie Z, Dong Y, Scholz R, Neumann D, Zou MH: Phosphorylation of LKB1 at serine 428 by protein kinase C-z is required for metformin-enhanced activation of the AMP-activated protein kinase in endothelial cells. Circulation 117, 952–962 (2008).
  • Xie Z, Dong Y, Zhang M et al.: Activation of protein kinase C z by peroxynitrite regulates LKB1-dependent AMP-activated protein kinase in cultured endothelial cells. J. Biol. Chem. 281, 6366–6375 (2006).
  • Shaw RJ, Lamia KA, Vasquez D et al.: The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 310, 1642–1646 (2005).
  • Hawley SA, Selbert MA, Goldstein EG et al.: 5´-AMP activates the AMP-activated protein kinase cascade, and Ca2+/calmodulin activates the calmodulin-dependent protein kinase I cascade, via three independent mechanisms. J. Biol. Chem. 270, 27186–27191 (1995).
  • Hawley SA, Boudeau J, Reid JL et al.: Complexes between the LKB1 tumor suppressor, STRAD a/b and MO25 a/b are upstream kinases in the AMP-activated protein kinase cascade. J. Biol. 2, 28 (2003).
  • Nath N, McCartney RR, Schmidt MC: Yeast Pak1 kinase associates with and activates Snf1. Mol. Cell. Biol. 23, 3909–3917 (2003).
  • Sutherland CM, Hawley SA, McCartney RR et al.: Elm1p is one of three upstream kinases for the Saccharomyces cerevisiae SNF1 complex. Curr. Biol. 13, 1299–1305 (2003).
  • Jensen TE, Rose AJ, Jorgensen SB et al.: Possible CaMKK-dependent regulation of AMPK phosphorylation and glucose uptake at the onset of mild tetanic skeletal muscle contraction. Am. J. Physiol. Endocrinol. Metab. 292, E1308–E1317 (2007).
  • Kewalramani G, Puthanveetil P, Wang F et al.: AMP-activated protein kinase confers protection against TNF-a-induced cardiac cell death. Cardiovasc. Res. DOI: 10.1093/ cvr/cvp166 (2009) (Epub ahead of print).
  • Soderling TR: The Ca-calmodulin-dependent protein kinase cascade. Trends Biochem. Sci. 24, 232–236 (1999).
  • Anderson KA, Means RL, Huang QH et al.: Components of a calmodulin-dependent protein kinase cascade. Molecular cloning, functional characterization and cellular localization of Ca2+/calmodulin-dependent protein kinase kinase b. J. Biol. Chem. 273, 31880–31889 (1998).
  • Towler MC, Hardie DG: AMP-activated protein kinase in metabolic control and insulin signaling. Circ. Res. 100, 328–341 (2007).
  • Wu Y, Song P, Xu J, Zhang M, Zou MH: Activation of protein phosphatase 2A by palmitate inhibits AMP-activated protein kinase. J. Biol. Chem. 282, 9777–9788 (2007).
  • Momcilovic M, Hong SP, Carlson M: Mammalian TAK1 activates Snf1 protein kinase in yeast and phosphorylates AMP-activated protein kinase in vitro. J. Biol. Chem. 281, 25336–25343 (2006).
  • Identifies a new upstream kinase that could regulate AMPK function.
  • Kishimoto K, Matsumoto K, Ninomiya-Tsuji J: TAK1 mitogen-activated protein kinase kinase kinase is activated by autophosphorylation within its activation loop. J. Biol. Chem. 275, 7359–7364 (2000).
  • Xie M, Zhang D, Dyck JR et al.: A pivotal role for endogenous TGF-b-activated kinase-1 in the LKB1/AMP-activated protein kinase energy-sensor pathway. Proc. Natl Acad. Sci. USA 103, 17378–17383 (2006).
  • Wang MY, Unger RH: Role of PP2C in cardiac lipid accumulation in obese rodents and its prevention by troglitazone. Am. J. Physiol. Endocrinol. Metab. 288, E216–E221 (2005).
  • Davies SP, Helps NR, Cohen PT, Hardie DG: 5´-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C a and native bovine protein phosphatase-2AC. FEBS Lett. 377, 421–425 (1995).
  • Corton JM, Gillespie JG, Hawley SA, Hardie DG: 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? Eur. J. Biochem. 229, 558–565 (1995).
  • Kim MS, Kewalramani G, Puthanveetil P et al.: Acute diabetes moderates trafficking of cardiac lipoprotein lipase through p38
  • Vincent MF, Erion MD, Gruber HE, Van den Berghe G: Hypoglycaemic effect of AICAriboside in mice. Diabetologia 39, 1148–1155 (1996).
  • Owen MR, Doran E, Halestrap AP: Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem. J. 348(Pt 3), 607–614 (2000).
  • Davidson MB, Peters AL: An overview of metformin in the treatment of Type 2 diabetes mellitus. Am. J. Med. 102, 99–110 (1997).
  • Yang J, Holman GD: Long-term metformin treatment stimulates cardiomyocyte glucose transport through an AMP-activated protein kinase-dependent reduction in GLUT4 endocytosis. Endocrinology 147, 2728–2736 (2006).
  • Fujii N, Hirshman MF, Kane EM et al.: AMP-activated protein kinase a2 activity is not essential for contraction- and hyperosmolarity-induced glucose transport in skeletal muscle. J. Biol. Chem. 280, 39033–39041 (2005).
  • Korystov YN, Kublik LN, Kudryavtsev AA et al.: Opposite effects of low oligomycin concentrations on the apoptosis of normal and tumor cells. Dokl. Biol. Sci. 392, 475–477 (2003).
  • An D, Pulinilkunnil T, Qi D et al.: The metabolic ‘switch’ AMPK regulates cardiac heparin-releasable lipoprotein lipase. Am. J. Physiol. Endocrinol. Metab. 288, E246–E253 (2005).
  • Luiken JJ, Coort SL, Willems J et al.: Contraction-induced fatty acid translocase/ CD36 translocation in rat cardiac myocytes is mediated through AMP-activated protein kinase signaling. Diabetes 52, 1627–1634 (2003).
  • Goransson O, McBride A, Hawley SA et al.: Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase. J. Biol. Chem. 282, 32549–32560 (2007).
  • Viana AY, Sakoda H, Anai M et al.: Role of hepatic AMPK activation in glucose metabolism and dexamethasone-induced regulation of AMPK expression. Diabetes Res. Clin. Pract. 73, 135–142 (2006).
  • Qi D, An D, Kewalramani G et al.: Altered cardiac fatty acid composition and utilization following dexamethasone-induced insulin resistance. Am. J. Physiol. Endocrinol. Metab. 291, E420–E427 (2006).
  • Sun W, Lee TS, Zhu M et al.: Statins activate AMP-activated protein kinase in vitro and in vivo. Circulation 114, 2655–2662 (2006).
  • Zhou G, Myers R, Li Y et al.: Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167–1174 (2001).
  • Fryer LG, Parbu-Patel A, Carling D: Protein kinase inhibitors block the stimulation of the AMP-activated protein kinase by 5-amino-4-imidazolecarboxamide riboside. FEBS Lett. 531, 189–192 (2002).
  • Bain J, Plater L, Elliott M et al.: The selectivity of protein kinase inhibitors: a further update. Biochem. J. 408, 297–315 (2007).
  • Musi N, Hayashi T, Fujii N et al.: AMP-activated protein kinase activity and glucose uptake in rat skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 280, E677–E684 (2001).
  • Horman S, Vertommen D, Heath R et al.: Insulin antagonizes ischemia-induced Thr172 phosphorylation of AMP-activated protein kinase a-subunits in heart via hierarchical phosphorylation of Ser485/491. J. Biol. Chem. 281, 5335–5340 (2006).
  • Kovacic S, Soltys CL, Barr AJ et al.: Akt activity negatively regulates phosphorylation of AMP-activated protein kinase in the heart. J. Biol. Chem. 278, 39422–39427 (2003).
  • Reported that the ability of insulin to inhibit AMPK might be controlled via an Akt-mediated mechanism.
  • Bertrand L, Ginion A, Beauloye C et al.: AMPK activation restores the stimulation of glucose uptake in an in vitro model of insulin-resistant cardiomyocytes via the activation of protein kinase B. Am. J. Physiol. Heart Circ. Physiol. 291, H239–H250 (2006).
  • Folmes CD, Clanachan AS, Lopaschuk GD: Fatty acids attenuate insulin regulation of 5´-AMP-activated protein kinase and insulin cardioprotection after ischemia. Circ. Res. 99, 61–68 (2006).
  • Beauloye C, Marsin AS, Bertrand L et al.: The stimulation of heart glycolysis by increased workload does not require AMP-activated protein kinase but a wortmannin-sensitive mechanism. FEBS Lett. 531, 324–328 (2002).
  • Hall JL, Lopaschuk GD, Barr A et al.: Increased cardiac fatty acid uptake with dobutamine infusion in swine is accompanied by a decrease in malonyl CoA levels. Cardiovasc. Res. 32, 879–885 (1996).
  • Goodwin GW, Taegtmeyer H: Regulation of fatty acid oxidation of the heart by MCD and ACC during contractile stimulation. Am. J. Physiol. 277, E772–E777 (1999).
  • Kahn BB, Alquier T, Carling D, Hardie DG: AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 1, 15–25 (2005).
  • Yamauchi T, Kamon J, Minokoshi Y et al.: Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat. Med. 8, 1288–1295 (2002).
  • Jager S, Handschin C, St-Pierre J, Spiegelman BM: AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1a. Proc. Natl Acad. Sci. USA 104, 12017–12022 (2007).
  • Kewalramani G, An D, Kim MS et al.: AMPK control of myocardial fatty acid metabolism fluctuates with the intensity of insulin-deficient diabetes. J. Mol. Cell Cardiol. 42, 333–342 (2007).
  • Brownsey RW, Boone AN, Elliott JE, Kulpa JE, Lee WM: Regulation of acetyl-CoA carboxylase. Biochem. Soc. Trans. 34, 223–227 (2006).
  • Hardie DG: The AMP-activated protein kinase pathway – new players upstream and downstream. J. Cell. Sci. 117, 5479–5487 (2004).
  • Ruderman NB, Park H, Kaushik VK et al.: AMPK as a metabolic switch in rat muscle, liver and adipose tissue after exercise. Acta Physiol. Scand. 178, 435–442 (2003).
  • Russell RR 3rd, Bergeron R, Shulman GI, Young LH: Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR. Am. J. Physiol. 277, H643–H649 (1999).
  • Ojuka EO, Jones TE, Nolte LA et al.: Regulation of GLUT4 biogenesis in muscle: evidence for involvement of AMPK and Ca2+. Am. J. Physiol. Endocrinol. Metab. 282, E1008–E1013 (2002).
  • Daval M, Foufelle F, Ferre P: Functions of AMP-activated protein kinase in adipose tissue. J. Physiol. 574, 55–62 (2006).
  • Chen ZP, Mitchelhill KI, Michell BJ et al.: AMP-activated protein kinase phosphorylation of endothelial NO synthase. FEBS Lett. 443, 285–289 (1999).
  • Viollet B, Athea Y, Mounier R et al.: AMPK: Lessons from transgenic and knockout animals. Front Biosci. 14, 19–44 (2009).
  • Hong YH, Varanasi US, Yang W, Leff T: AMP-activated protein kinase regulates HNF4a transcriptional activity by inhibiting dimer formation and decreasing protein stability. J. Biol. Chem. 278, 27495–27501 (2003).
  • Bolster DR, Crozier SJ, Kimball SR, Jefferson LS: AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. J. Biol. Chem. 277, 23977–23980 (2002).
  • Lage R, Dieguez C, Vidal-Puig A, Lopez M: AMPK: a metabolic gauge regulating whole-body energy homeostasis. Trends Mol. Med. 14, 539–549 (2008).
  • Minokoshi Y, Kim YB, Peroni OD et al.: Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415, 339–343 (2002).
  • Dolinsky VW, Dyck JR: Role of AMP-activated protein kinase in healthy and diseased hearts. Am. J. Physiol. Heart Circ. Physiol. 291, H2557–H2569 (2006).
  • Puthanveetil P, Wang F, Kewalramani G et al.: Cardiac glycogen accumulation after dexamethasone is regulated by AMPK. Am. J. Physiol. Heart Circ. Physiol. 295, H1753–H1762 (2008).
  • Habets DD, Coumans WA, Voshol PJ et al.: AMPK-mediated increase in myocardial long-chain fatty acid uptake critically depends on sarcolemmal CD36. Biochem. Biophys. Res. Commun. 355, 204–210 (2007).
  • Blazquez C, Geelen MJ, Velasco G, Guzman M: The AMP-activated protein kinase prevents ceramide synthesis de novo and apoptosis in astrocytes. FEBS Lett. 489, 149–153 (2001).
  • Ido Y, Carling D, Ruderman N: Hyperglycemia-induced apoptosis in human umbilical vein endothelial cells: inhibition by the AMP-activated protein kinase activation. Diabetes 51, 159–167 (2002).
  • Hwang JT, Kwon DY, Park OJ, Kim MS: Resveratrol protects ROS-induced cell death by activating AMPK in H9c2 cardiac muscle cells. Genes Nutr. 2, 323–326 (2008).
  • An D, Kewalramani G, Chan JK et al.: Metformin influences cardiomyocyte cell death by pathways that are dependent and independent of caspase-3. Diabetologia 49, 2174–2184 (2006).
  • Demonstrated that metformin by activating AMPK confers protection against palmitate-induced cell death in adult rat ventricular cardiomyocytes.
  • Stanley WC, Recchia FA, Lopaschuk GD: Myocardial substrate metabolism in the normal and failing heart. Physiol. Rev. 85, 1093–1129 (2005).
  • Houten SM, Chegary M, Te Brinke H et al.: Pyruvate dehydrogenase kinase 4 expression is synergistically induced by AMP-activated protein kinase and fatty acids. Cell. Mol. Life Sci. 66, 1283–1294 (2009).
  • Holness MJ, Sugden MC: Regulation of pyruvate dehydrogenase complex activity by reversible phosphorylation. Biochem. Soc. Trans. 31, 1143–1151 (2003).
  • Pulinilkunnil T, Rodrigues B: Cardiac lipoprotein lipase: metabolic basis for diabetic heart disease. Cardiovasc. Res. 69, 329–340 (2006).
  • Barta E, Sideman S, Bassingthwaighte JB: Facilitated diffusion and membrane permeation of fatty acid in albumin solutions. Ann. Biomed. Eng. 28, 331–345 (2000).
  • Bonen A, Chabowski A, Luiken JJ, Glatz JF: Is membrane transport of FFA mediated by lipid, protein, or both? Mechanisms and regulation of protein-mediated cellular fatty acid uptake: molecular, biochemical, and physiological evidence. Physiology (Bethesda) 22, 15–29 (2007).
  • Glatz JF, van Nieuwenhoven FA, Luiken JJ, Schaap FG, van der Vusse GJ: Role of membrane-associated and cytoplasmic fatty acid-binding proteins in cellular fatty acid metabolism. Prostaglandins Leukot. Essent. Fatty Acids 57, 373–378 (1997).
  • Zammit VA, Fraser F, Orstorphine CG: Regulation of mitochondrial outer-membrane carnitine palmitoyltransferase (CPT I): role of membrane-topology. Adv. Enzyme Regul. 37, 295–317 (1997).
  • Ussher JR, Lopaschuk GD: The malonyl CoA axis as a potential target for treating ischaemic heart disease. Cardiovasc. Res. 79, 259–268 (2008).
  • Cuthbert KD, Dyck JR: Malonyl-CoA decarboxylase is a major regulator of myocardial fatty acid oxidation. Curr. Hypertens. Rep. 7, 407–411 (2005).
  • In addition to AMPK, this study identified the crucial role of malonyl-CoA decarboxylase (MCD) in regulating cardiac fatty acid oxidation.
  • Rodrigues B, Cam MC, McNeill JH: Myocardial substrate metabolism: implications for diabetic cardiomyopathy. J. Mol. Cell Cardiol. 27, 169–179 (1995).
  • Peterson LR, Herrero P, Schechtman KB et al.: Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation 109, 2191–2196 (2004).
  • Schwenk RW, Luiken JJ, Bonen A, Glatz JF: Regulation of sarcolemmal glucose and fatty acid transporters in cardiac disease. Cardiovasc. Res. 79, 249–258 (2008).
  • Avogaro A, Nosadini R, Doria A et al.: Myocardial metabolism in insulin-deficient diabetic humans without coronary artery disease. Am. J. Physiol. 258, E606–E618 (1990).
  • Nuutila P, Knuuti J, Ruotsalainen U et al.: Insulin resistance is localized to skeletal but not heart muscle in Type 1 diabetes. Am. J. Physiol. 264, E756–E762 (1993).
  • Luiken JJ, Arumugam Y, Bell RC et al.: Changes in fatty acid transport and transporters are related to the severity of insulin deficiency. Am. J. Physiol. Endocrinol. Metab. 283, E612–E621 (2002).
  • Gottlicher M, Widmark E, Li Q, Gustafsson JA: Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor. Proc. Natl Acad. Sci. USA 89, 4653–4657 (1992).
  • Sharma S, Adrogue JV, Golfman L et al.: Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. FASEB J. 18, 1692–1700 (2004).
  • Kraegen EW, Sowden JA, Halstead MB et al.: Glucose transporters and in vivo glucose uptake in skeletal and cardiac muscle: fasting, insulin stimulation and immunoisolation studies of GLUT1 and GLUT4. Biochem. J. 295(Pt 1), 287–293 (1993).
  • Yang J, Holman GD: Insulin and contraction stimulate exocytosis, but increased AMP-activated protein kinase activity resulting from oxidative metabolism stress slows endocytosis of GLUT4 in cardiomyocytes. J. Biol. Chem. 280, 4070–4078 (2005).
  • Arad M, Seidman CE, Seidman JG: AMP-activated protein kinase in the heart: role during health and disease. Circ. Res. 100, 474–488 (2007).
  • Russell RR 3rd, Li J, Coven DL et al.: AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury. J. Clin. Invest. 114, 495–503 (2004).
  • Coven DL, Hu X, Cong L et al.: Physiological role of AMP-activated protein kinase in the heart: graded activation during exercise. Am. J. Physiol. Endocrinol. Metab. 285, E629–E636 (2003).
  • Li J, Miller EJ, Ninomiya-Tsuji J, Russell RR 3rd, Young LH: AMP-activated protein kinase activates p38 mitogen-activated protein kinase by increasing recruitment of p38 MAPK to TAB1 in the ischemic heart. Circ. Res. 97, 872–879 (2005).
  • Pelletier A, Joly E, Prentki M, Coderre L: Adenosine 5´-monophosphate-activated protein kinase and p38 mitogen-activated protein kinase participate in the stimulation of glucose uptake by dinitrophenol in adult cardiomyocytes. Endocrinology 146, 2285–2294 (2005).
  • Lopaschuk GD: AMP-activated protein kinase control of energy metabolism in the ischemic heart. Int. J. Obes. (Lond.) 32(Suppl. 4), S29–S35 (2008).
  • Marsin AS, Bertrand L, Rider MH et al.: Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia. Curr. Biol. 10, 1247–1255 (2000).
  • Stremmel W: Fatty acid uptake by isolated rat heart myocytes represents a carrier-mediated transport process. J. Clin. Invest. 81, 844–852 (1988).
  • Koonen DP, Glatz JF, Bonen A, Luiken JJ: Long-chain fatty acid uptake and FAT/CD36 translocation in heart and skeletal muscle. Biochim. Biophys. Acta 1736, 163–180 (2005).
  • Chabowski A, Coort SL, Calles-Escandon J et al.: The subcellular compartmentation of fatty acid transporters is regulated differently by insulin and by AICAR. FEBS Lett. 579, 2428–2432 (2005).
  • Chabowski A, Momken I, Coort SL et al.: Prolonged AMPK activation increases the expression of fatty acid transporters in cardiac myocytes and perfused hearts. Mol. Cell. Biochem. 288, 201–212 (2006).
  • Habets DD, Coumans WA, El Hasnaoui M et al.: Crucial role for LKB1 to AMPKa2 axis in the regulation of CD36-mediated long-chain fatty acid uptake into cardiomyocytes. Biochim. Biophys. Acta 1791, 212–219 (2009).
  • Merkel M, Eckel RH, Goldberg IJ: Lipoprotein lipase: genetics, lipid uptake, and regulation. J. Lipid Res. 43, 1997–2006 (2002).
  • Detailed review summarizing the regulation of lipoprotein lipase (LPL) at multiple levels including clinical implications of human LPL gene variations, LPL actions in the nervous system, liver and heart, and LPL gene regulation.
  • Camps L, Reina M, Llobera M, Vilaro S, Olivecrona T: Lipoprotein lipase: cellular origin and functional distribution. Am. J. Physiol. 258, C673–C681 (1990).
  • Augustus AS, Buchanan J, Park TS et al.: Loss of lipoprotein lipase-derived fatty acids leads to increased cardiac glucose metabolism and heart dysfunction. J. Biol. Chem. 281, 8716–8723 (2006).
  • An D, Kewalramani G, Qi D et al.: b-agonist stimulation produces changes in cardiac AMPK and coronary lumen LPL only during increased workload. Am. J. Physiol. Endocrinol. Metab. 288, E1120–E1127 (2005).
  • Hardie DG: Regulation of fatty acid and cholesterol metabolism by the AMP-activated protein kinase. Biochim. Biophys. Acta 1123, 231–238 (1992).
  • Abu-Elheiga L, Brinkley WR, Zhong L et al.: The subcellular localization of acetyl-CoA carboxylase 2. Proc. Natl Acad. Sci. USA 97, 1444–1449 (2000).
  • Abu-Elheiga L, Matzuk MM, Abo-Hashema KA, Wakil SJ: Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science 291, 2613–2616 (2001).
  • Forman BM, Chen J, Evans RM: Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors a and d. Proc. Natl Acad. Sci. USA 94, 4312–4317 (1997).
  • Barger PM, Kelly DP: PPAR signaling in the control of cardiac energy metabolism. Trends Cardiovasc. Med. 10, 238–245 (2000).
  • Finck BN, Han X, Courtois M et al.: A critical role for PPARa-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: modulation by dietary fat content. Proc. Natl Acad. Sci. USA 100, 1226–1231 (2003).
  • Key study that linked dysregulation of the PPARa gene regulatory pathway to cardiac dysfunction in the diabetic and provided a rationale for serum lipid-lowering strategies in the treatment of diabetic cardiomyopathy.
  • Cheng L, Ding G, Qin Q et al.: Cardiomyocyte-restricted peroxisome proliferator-activated receptor-d deletion perturbs myocardial fatty acid oxidation and leads to cardiomyopathy. Nat. Med. 10, 1245–1250 (2004).
  • Vidal-Puig AJ, Considine RV, Jimenez-Linan M et al.: Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J. Clin. Invest. 99, 2416–2422 (1997).
  • Kukidome D, Nishikawa T, Sonoda K et al.: Activation of AMP-activated protein kinase reduces hyperglycemia-induced mitochondrial reactive oxygen species production and promotes mitochondrial biogenesis in human umbilical vein endothelial cells. Diabetes 55, 120–127 (2006).
  • Gaidhu MP, Fediuc S, Anthony NM et al.: Prolonged AICAR-induced AMP-kinase activation promotes energy dissipation in white adipocytes: novel mechanisms integrating HSL and ATGL. J. Lipid Res. 50, 704–715 (2009).
  • Hongo M, Ishizaka N, Furuta K et al.: Administration of angiotensin II, but not catecholamines, induces accumulation of lipids in the rat heart. Eur. J. Pharmacol. 604, 87–92 (2009).
  • Kudo N, Barr AJ, Barr RL, Desai S, Lopaschuk GD: High rates of fatty acid oxidation during reperfusion of ischemic hearts are associated with a decrease in malonyl-CoA levels due to an increase in 5´-AMP-activated protein kinase inhibition of acetyl-CoA carboxylase. J. Biol. Chem. 270, 17513–17520 (1995).
  • Sakamoto J, Barr RL, Kavanagh KM, Lopaschuk GD: Contribution of malonyl-CoA decarboxylase to the high fatty acid oxidation rates seen in the diabetic heart. Am. J. Physiol. Heart Circ. Physiol. 278, H1196–H1204 (2000).
  • Saha AK, Schwarsin AJ, Roduit R et al.: Activation of malonyl-CoA decarboxylase in rat skeletal muscle by contraction and the AMP-activated protein kinase activator 5-aminoimidazole-4-carboxamide-1-b -d-ribofuranoside. J. Biol. Chem. 275, 24279–24283 (2000).
  • Park H, Kaushik VK, Constant S et al.: Coordinate regulation of malonyl-CoA decarboxylase, sn-glycerol-3-phosphate acyltransferase, and acetyl-CoA carboxylase by AMP-activated protein kinase in rat tissues in response to exercise. J. Biol. Chem. 277, 32571–32577 (2002).
  • Sambandam N, Steinmetz M, Chu A et al.: 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. Eur. J. Biochem. 271, 2831–2840 (2004).
  • Igata M, Motoshima H, Tsuruzoe K et al.: Adenosine monophosphate-activated protein kinase suppresses vascular smooth muscle cell proliferation through the inhibition of cell cycle progression. Circ. Res. 97, 837–844 (2005).
  • Kefas BA, Cai Y, Ling Z et al.: AMP-activated protein kinase can induce apoptosis of insulin-producing MIN6 cells through stimulation of c-Jun-N-terminal kinase. J. Mol. Endocrinol. 30, 151–161 (2003).
  • Hickson-Bick DL, Buja LM, McMillin JB: Palmitate-mediated alterations in the fatty acid metabolism of rat neonatal cardiac myocytes. J. Mol. Cell Cardiol. 32, 511–519 (2000).
  • Shibata R, Sato K, Pimentel DR et al.: Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat. Med. 11, 1096–1103 (2005).
  • Terai K, Hiramoto Y, Masaki M et al.: AMP-activated protein kinase protects cardiomyocytes against hypoxic injury through attenuation of endoplasmic reticulum stress. Mol. Cell. Biol. 25, 9554–9575 (2005).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.