Regulation of fatty acid metabolism by mTOR in adult murine hearts occurs independently of changes in PGC-1α

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 305, Issue 1, 2013, Pages

  Zhu, Yi ^a   Soto, Jamie ^a   Anderson, Brandon ^a   Riehle, Christian ^a   Zhang, Yi Cheng ^a   Wende, Adam R ^a   Jones, Deborah ^a   McClain, Donald A ^a   Abel, E Dale ^a  

^a UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

Author keywords

Cardiac substrate metabolism; Mechanistic target of rapamycin; Mitochondrial respiration; Peroxisome proliferator activated receptor coactivator 1

Indexed keywords

3 HYDROXYACYL COENZYME A DEHYDROGENASE; ACETYL COENZYME A ACYLTRANSFERASE; CARBONYL CYANIDE 4 (TRIFLUOROMETHOXY)PHENYLHYDRAZONE; CARNITINE PALMITOYLTRANSFERASE 2; CARNITINE PALMITOYLTRANSFERASE I; DOXYCYCLINE; ENOYL COENZYME A HYDRATASE; ENOYL COENZYME A HYDRATASE ALPHA; ENOYL COENZYME A HYDRATASE BETA; FATTY ACID BINDING PROTEIN; FATTY ACID BINDING PROTEIN 3; INSULIN; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; MEDIUM CHAIN ACYL COENZYME A DEHYDROGENASE; MESSENGER RNA; MITOCHONDRIAL DNA; PALMITIC ACID; PALMITOYLCARNITINE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1BETA; PYRUVIC ACID; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; AORTA PRESSURE; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; FATTY ACID METABOLISM; GENE EXPRESSION; GLUCOSE OXIDATION; GLUCOSE UTILIZATION; HEART; HEART CATHETERIZATION; HEART DISEASE; HEART FUNCTION; HEART MITOCHONDRION; HEART MUSCLE CELL; HEART MUSCLE METABOLISM; HEART OUTPUT; MITOCHONDRIAL RESPIRATION; MOUSE; NONHUMAN; OXIDATION; PRIORITY JOURNAL; RESPIRATORY CHAIN; SIGNAL TRANSDUCTION;

CARDIAC SUBSTRATE METABOLISM; MECHANISTIC TARGET OF RAPAMYCIN; MITOCHONDRIAL RESPIRATION; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-Γ COACTIVATOR-1Α;

ANIMALS; BLOOD PRESSURE; CARDIAC OUTPUT; DNA, MITOCHONDRIAL; FATTY ACIDS; HEART; METABOLOME; MICE; MITOCHONDRIA, HEART; MYOCARDIUM; OXIDATION-REDUCTION; TOR SERINE-THREONINE KINASES; TRANS-ACTIVATORS; TRANSCRIPTION, GENETIC;

EID: 84879574538     PISSN: 03636135     EISSN: 15221539     Source Type: Journal    
DOI: 10.1152/ajpheart.00877.2012     Document Type: Article

References (37)

1. Bentzinger CF, Romanino K, Cloëtta D, Lin S, Mascarenhas JB, Oliveri F, Xia J, Casanova E, Costa CF, Brink M, Zorzato F, Hall MN, Rüegg MA. Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy. Cell Metab 8: 411-424, 2008.
2. Boudina S, Sena S, O'Neill BT, Tathireddy P, Young ME, Abel ED. Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity. Circulation 112: 2686-2695, 2005.
3. Boudina S, Sena S, Theobald H, Sheng X, Wright JJ, Hu XX, Aziz S, Johnson JI, Bugger H, Zaha VG, Abel ED. Mitochondrial energetics in the heart in obesity-related diabetes: direct evidence for increased uncoupled respiration and activation of uncoupling proteins. Diabetes 56: 2457-2466, 2007.
4. Buchanan J, Mazumder PK, Hu P, Chakrabarti G, Roberts MW, Yun UJ, Cooksey RC, Litwin SE, Abel ED. Reduced cardiac efficiency and altered substrate metabolism precedes the onset of hyperglycemia and contractile dysfunction in two mouse models of insulin resistance and obesity. Endocrinology 146: 5341-5349, 2005.
5. Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P. mTOR controls mitochondrial oxidative function through a YY1-PGC-1α transcriptional complex. Nature 450: 736-740, 2007.
6. Cybulski N, Hall MN. TOR complex 2: a signaling pathway of its own. Trends Biochem Sci 34: 620-627, 2009.
7. Cybulski N, Polak P, Auwerx J, Ruegg MA, Hall MN. mTOR complex 2 in adipose tissue negatively controls whole-body growth. Proc Natl Acad Sci USA 106: 9902-9907, 2009.
8. Davila-Roman VG, Vedala G, Herrero P, de las Fuentes L, Rogers JG, Kelly DP, Gropler RJ. Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy. J Am Coll Cardiol 40: 271-277, 2002.
9. de las Fuentes L, Herrero P, Peterson LR, Kelly DP, Gropler RJ, Davila-Roman VG. Myocardial fatty acid metabolism: independent predictor of left ventricular mass in hypertensive heart disease. Hypertension 41: 83-87, 2003.
10. Distler AM, Kerner J, Hoppel CL. Post-translational modifications of rat liver mitochondrial outer membrane proteins identified by mass spectrometry. Biochim Biophys Acta 1774: 628-636, 2007.
11. Gangloff YG, Mueller M, Dann SG, Svoboda P, Sticker M, Spetz JF, Um SH, Brown EJ, Cereghini S, Thomas G, Kozma SC. Disruption of the mouse mTOR gene leads to early postimplantation lethality and prohibits embryonic stem cell development. Mol Cell Biol 24: 9508-9516, 2004.
12. Ganley IG, Lam du H, Wang J, Ding X, Chen S, Jiang X. ULK1, ATG13. FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem 284: 12297-12305, 2009.
13. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460: 392-395, 2009.
14. Hebert LF Jr, Daniels MC, Zhou J, Crook ED, Turner RL, Simmons ST, Neidigh JL, Zhu JS, Baron AD, McClain DA. Overexpression of glutamine:fructose-6-phosphate amidotransferase in transgenic mice leads to insulin resistance. J Clin Invest 98: 930-936, 1996.
15. Hue L, Taegtmeyer H. The Randle cycle revisited: a new head for an old hat. Am J Physiol Endocrinol Metab 297: E578-E591, 2009.
16. Jung CH, Jun CB, Ro SH, Kim YM, Otto NM, Cao J, Kundu M, Kim DH. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell 20: 1992-2003, 2009.
17. Koitabashi N, Bedja D, Zaiman AL, Pinto YM, Zhang M, Gabrielson KL, Takimoto E, Kass DA. Avoidance of transient cardiomyopathy in cardiomyocyte-targeted tamoxifen-induced MerCreMer gene deletion models. Circ Res 105: 12-15, 2009.
18. Laplante M, Sabatini DM. mTOR signaling at a glance. J Cell Sci 122: 3589-3594, 2009.
19. Mazumder PK, O'Neill BT, Roberts MW, Buchanan J, Yun UJ, Cooksey RC, Boudina S, Abel ED. Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts. Diabetes 53: 2366-2374, 2004.
20. Murakami M, Ichisaka T, Maeda M, Oshiro N, Hara K, Edenhofer F, Kiyama H, Yonezawa K, Yamanaka S. mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells. Mol Cell Biol 24: 6710-6718, 2004.
21. Randle PJ. Metabolic fuel selection: general integration at the wholebody level. Proc Nutr Soc 54: 317-327, 1995.
22. Riehle C, Wende AR, Zaha VG, Pires KM, Wayment B, Olsen C, Bugger H, Buchanan J, Wang X, Moreira AB, Doenst T, Medina-Gomez G, Litwin SE, Lelliott CJ, Vidal-Puig A, Abel ED. PGC-1β deficiency accelerates the transition to heart failure in pressure overload hypertrophy. Circ Res 109: 783-793, 2011.
23. Romanino K, Mazelin L, Albert V, Conjard-Duplany A, Lin S, Bentzinger CF, Handschin C, Puigserver P, Zorzato F, Schaeffer L, Gangloff YG, Ruegg MA. Myopathy caused by mammalian target of rapamycin complex 1 (mTORC1) inactivation is not reversed by restoring mitochondrial function. Proc Natl Acad Sci USA 108: 20808-20813, 2011.
24. Rosner M, Hengstschlager M. Cytoplasmic and nuclear distribution of the protein complexes mTORC1 and mTORC2: rapamycin triggers dephosphorylation and delocalization of the mTORC2 components rictor and sin1. Hum Mol Genet 17: 2934-2948, 2008.
25. Sack MN, Rader TA, Park S, Bastin J, McCune SA, Kelly DP. Fatty acid oxidation enzyme gene expression is downregulated in the failing heart. Circulation 94: 2837-2842, 1996.
26. Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar-Peled L, Sabatini DM. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320: 1496-1501, 2008.
27. Sengupta S, Peterson TR, Sabatini DM. Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell 40: 310-322, 2010.
28. Serviddio G, Giudetti AM, Bellanti F, Priore P, Rollo T, Tamborra R, Siculella L, Vendemiale G, Altomare E, Gnoni GV. Oxidation of hepatic carnitine palmitoyl transferase-I (CPT-I) impairs fatty acid β-oxidation in rats fed a methionine-choline deficient diet. PLos One 6: e24084, 2011.
29. Shende P, Plaisance I, Morandi C, Pellieux C, Berthonneche C, Zorzato F, Krishnan J, Lerch R, Hall MN, Ruegg MA, Pedrazzini T, Brink M. Cardiac raptor ablation impairs adaptive hypertrophy, alters metabolic gene expression, and causes heart failure in mice. Circulation 123: 1073-1082, 2011.
30. Sohal DS, Nghiem M, Crackower MA, Witt SA, Kimball TR, Tymitz KM, Penninger JM, Molkentin JD. Temporally regulated and tissuespecific gene manipulations in the adult and embryonic heart using a tamoxifen-inducible Cre protein. Circ Res 89: 20-25, 2001.
31. Song X, Kusakari Y, Xiao CY, Kinsella SD, Rosenberg MA, Scherrer-Crosbie M, Hara K, Rosenzweig A, Matsui T. mTOR attenuates the inflammatory response in cardiomyocytes and prevents cardiac dysfunction in pathological hypertrophy. Am J Physiol Cell Physiol 299: C1256-C1266, 2010.
32. Taegtmeyer H. Cardiac metabolism as a target for the treatment of heart failure. Circulation 110: 894-896, 2004.
33. Taegtmeyer H, Overturf ML. Effects of moderate hypertension on cardiac function and metabolism in the rabbit. Hypertension 11: 416-426, 1988.
34. Wende AR, Schaeffer PJ, Parker GJ, Zechner C, Han DH, Chen MM, Hancock CR, Lehman JJ, Huss JM, McClain DA, Holloszy JO, Kelly DP. A role for the transcriptional coactivator PGC-1α in muscle refueling. J Biol Chem 282: 36642-36651, 2007.
35. Zhang D, Contu R, Latronico MV, Zhang JL, Rizzi R, Catalucci D, Miyamoto S, Huang K, Ceci M, Gu Y, Dalton ND, Peterson KL, Guan KL, Brown JH, Chen J, Sonenberg N, Condorelli G. MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice. J Clin Invest 120: 2805-2816, 2010.
36. Zhu Y, Pereira RO, O'Neill BT, Riehle C, Ilkun O, Wende AR, Rawlings TA, Zhang YC, Zhang Q, Klip A, Shiojima I, Walsh K, Abel ED. Cardiac PI3K-Akt impairs insulin-stimulated glucose uptake independent of mTORC1 and GLUT4 translocation. Mol Endocrinol 27: 172-184, 2013.
37. Zhu Y, Pires KM, Whitehead KJ, Olsen CD, Wayment B, Zhang YC, Bugger H, Ilkun O, Litwin SE, Thomas G, Kozma SC, Abel ED. Mechanistic target of rapamycin (mtor) is essential for murine embryonic heart development and growth. PLoS One 8: e54221, 2013.