Medium-chain fatty acids inhibit mitochondrial metabolism in astrocytes promoting astrocyte-neuron lactate and ketone body shuttle systems

FASEB Journal

Volumn 30, Issue 5, 2016, Pages 1913-1926

  Thevenet, Jonathan ^a   De Marchi, Umberto ^a   Domingo, Jaime Santo ^a   Christinat, Nicolas ^a   Bultot, Laurent ^a   Lefebvre, Gregory ^a   Sakamoto, Kei ^a   Descombes, Patrick ^a   Masoodi, Mojgan ^a   Wiederkehr, Andreas ^a  

^a NESTLÉ RESEARCH CENTER   (Switzerland)

Author keywords

Energy metabolism; IPSC; Medium chain triglycerides; NAD(P)H

Indexed keywords

ADENOSINE TRIPHOSPHATE; DECANOIC ACID; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; KETONE BODY; LACTIC ACID; MEDIUM CHAIN FATTY ACID; OCTANOIC ACID; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; FATTY ACID; MESSENGER RNA;

ARTICLE; ASTROCYTE; CELL METABOLISM; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; ELECTRIC POTENTIAL; ENERGY METABOLISM; GLYCOLYSIS; HUMAN; HUMAN CELL; INDUCED PLURIPOTENT STEM CELL; INTRACELLULAR SPACE; KETOGENESIS; MITOCHONDRIAL RESPIRATION; NERVE CELL; PRIORITY JOURNAL; RESPIRATORY CHAIN; SIGNAL TRANSDUCTION; SINGLE CELL ANALYSIS; BIOSYNTHESIS; CELL CULTURE; GENETICS; METABOLISM; MITOCHONDRION; OXIDATION REDUCTION REACTION; OXYGEN CONSUMPTION; PHYSIOLOGY; PLURIPOTENT STEM CELL;

ADENOSINE TRIPHOSPHATE; ASTROCYTES; CELLS, CULTURED; FATTY ACIDS; GLYCOLYSIS; HUMANS; KETONE BODIES; LACTIC ACID; MITOCHONDRIA; NEURONS; OXIDATION-REDUCTION; OXYGEN CONSUMPTION; PLURIPOTENT STEM CELLS; RNA, MESSENGER;

EID: 84966372836     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.201500182     Document Type: Article

References (41)

1. Bélanger, M., Allaman, I., and Magistretti, P. J. (2011) Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab. 14, 724-738
2. Bernardinelli, Y., Muller, D., and Nikonenko, I. (2014) Astrocytesynapse structural plasticity. Neural Plast. 2014, 232105
3. Pellerin, L., Bouzier-Sore, A. K., Aubert, A., Serres, S., Merle, M., Costalat, R., and Magistretti, P. J. (2007) Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55, 1251-1262
4. Pellerin, L., and Magistretti, P. J. (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc. Natl. Acad. Sci. USA 91, 10625-10629
5. Itoh, Y., Esaki, T., Shimoji, K., Cook, M., Law, M. J., Kaufman, E., and Sokoloff, L. (2003) Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization bybraininvivo. Proc. Natl. Acad. Sci. USA 100, 4879-4884
6. Herrero-Mendez, A., Almeida, A., Fernández, E., Maestre, C., Moncada, S., and Bolaños, J. P. (2009) The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/C-Cdh1. Nat. Cell Biol. 11, 747-752
7. Owen, O. E., Morgan, A. P., Kemp, H. G., Sullivan, J. M., Herrera, M. G., and Cahill, G. F., Jr. (1967) Brain metabolism during fasting. J. Clin. Invest. 46, 1589-1595
8. Ruderman, N.B., Ross, P.S., Berger, M., and Goodman, M.N. (1974) Regulation of glucose and ketone-body metabolism in brain of anaesthetized rats. Biochem. J. 138, 1-10
9. Hasselbalch, S. G., Knudsen, G. M., Jakobsen, J., Hageman, L. P., Holm, S., and Paulson, O. B. (1994) Brain metabolism during shortterm starvation in humans. J. Cereb. Blood Flow Metab. 14, 125-131
10. Guzmán, M., and Blázquez, C. (2001) Is there an astrocyte-neuron ketone body shuttle? Trends Endocrinol. Metab. 12, 169-173
11. Cahill, G. F., Jr., and Veech, R. L. (2003) Ketoacids? Good medicine? Trans. Am. Clin. Climatol. Assoc. 114, 149-161; discussion 162-143
12. Pan, J. W., Rothman, T. L., Behar, K. L., Stein, D. T., and Hetherington, H. P. (2000) Human brain beta-hydroxybutyrate and lactate increase in fasting-induced ketosis. J. Cereb. Blood Flow Metab. 20, 1502-1507
13. Auestad, N., Korsak, R. A., Morrow, J. W., and Edmond, J. (1991) Fatty acid oxidation and ketogenesis by astrocytes in primary culture. J. Neurochem. 56, 1376-1386
14. Bixel, M. G., and Hamprecht, B. (1995) Generation of ketone bodies from leucine by cultured astroglial cells. J. Neurochem. 65, 2450-2461
15. Ebert, D., Haller, R. G., and Walton, M. E. (2003) Energy contribution of octanoate to intact rat brain metabolism measured by 13C nuclear magnetic resonance spectroscopy. J. Neurosci. 23, 5928-5935
16. Neal, E. G., and Cross, J. H. (2010) Efficacy of dietary treatments for epilepsy. J. Hum. Nutr. Diet. 23, 113-119
17. Paoli, A., Rubini, A., Volek, J. S., and Grimaldi, K. A. (2013) Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur. J. Clin. Nutr. 67, 789-796
18. Fuehrlein, B. S., Rutenberg, M. S., Silver, J. N., Warren, M. W., Theriaque, D.W., Duncan, G.E., Stacpoole, P.W., and Brantly, M.L. (2004) Differential metabolic effects of saturated versus polyunsaturated fats in ketogenic diets. J. Clin. Endocrinol. Metab. 89, 1641-1645
19. Huttenlocher, P. R. (1976) Ketonemia and seizures: metabolic and anticonvulsant effects of two ketogenic diets in childhood epilepsy. Pediatr. Res. 10, 536-540
20. Neal, E. G., Chaffe, H., Schwartz, R. H., Lawson, M. S., Edwards, N., Fitzsimmons, G., Whitney, A., and Cross, J. H. (2009) A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy. Epilepsia 50, 1109-1117
21. Seaton, T. B., Welle, S. L., Warenko, M. K., and Campbell, R. G. (1986) Thermic effect of medium-chain and long-chain triglycerides in man. Am. J. Clin. Nutr. 44, 630-634
22. Dean, H. G., Bonser, J. C., and Gent, J. P. (1989) HPLC analysis of brain and plasma for octanoic and decanoic acids. Clin. Chem. 35, 1945-1948
23. Poburko, D., Santo-Domingo, J., and Demaurex, N. (2011) Dynamic regulation of the mitochondrial proton gradient during cytosolic calcium elevations. J. Biol. Chem. 286, 11672-11684
24. Imamura, H., Nhat, K. P., Togawa, H., Saito, K., Iino, R., Kato-Yamada, Y., Nagai, T., and Noji, H. (2009) Visualization of ATP levels inside single living cells with fluorescence resonance energy transfer-based genetically encoded indicators. Proc. Natl. Acad. Sci. USA 106, 15651-15656
25. Passonneau, J. V., Lowry, O. H., eds. (1993) Enzymatic Analysis: A Practical Guide, The Humana Press Inc., Louisville, KY doi:10.1007/ 978-1-60327-407-4
26. Hardie, D. G. (2015) AMPK: positive and negative regulation, and its role in whole-body energy homeostasis. Curr. Opin. Cell Biol. 33, 1-7
27. Ducommun, S., Deak, M., Sumpton, D., Ford, R. J., Núñez Galindo, A., Kussmann, M., Viollet, B., Steinberg, G. R., Foretz, M., Dayon, L., Morrice, N. A., and Sakamoto, K. (2015) Motif affinity and mass spectrometry proteomic approach for the discovery of cellular AMPK targets: identification of mitochondrial fission factor as a new AMPK substrate. Cell. Signal. 27, 978-988
28. Lai, Y. C., Kviklyte, S., Vertommen, D., Lantier, L., Foretz, M., Viollet, B., Hallén, S., and Rider, M. H. (2014) A small-molecule benzimidazole derivative that potently activates AMPK to increase glucose transport in skeletal muscle: comparison with effects of contraction and other AMPK activators. Biochem. J. 460, 363-375
29. Olson, J. E., Evers, J. A., and Holtzman, D. (1992) Astrocyte volume regulation and ATP and phosphocreatine concentrations after exposure to salicylate, ammonium, and fatty acids. Metab. Brain Dis. 7, 183-196
30. Danial, N. N., Hartman, A. L., Stafstrom, C. E., and Thio, L. L. (2013) How does the ketogenic diet work? Four potential mechanisms. J. Child Neurol. 28, 1027-1033
31. Gano, L. B., Patel, M., and Rho, J. M. (2014) Ketogenic diets, mitochondria, and neurological diseases. J. Lipid Res. 55, 2211-2228
32. Wiederkehr, A., Park, K. S., Dupont, O., Demaurex, N., Pozzan, T., Cline, G. W., and Wollheim, C. B. (2009) Matrix alkalinization: a novel mitochondrial signal for sustained pancreatic beta-cell activation. EMBO J. 28, 417-428
33. Azarias, G., Perreten, H., Lengacher, S., Poburko, D., Demaurex, N., Magistretti, P. J., and Chatton, J. Y. (2011) Glutamate transport decreases mitochondrial pH and modulates oxidative metabolism in astrocytes. J. Neurosci. 31, 3550-3559
34. Di Paola, M., and Lorusso, M. (2006) Interaction of free fatty acids with mitochondria: coupling, uncoupling and permeability transition. Biochim. Biophys. Acta 1757, 1330-1337
35. Berardi, M. J., and Chou, J. J. (2014) Fatty acid flippase activity of UCP2 is essential for its proton transport in mitochondria. Cell Metab. 20,541-552
36. Perreten Lambert, H., Zenger, M., Azarias, G., Chatton, J. Y., Magistretti, P. J., and Lengacher, S. (2014) Control of mitochondrial pH by uncoupling protein 4 in astrocytes promotes neuronal survival. J. Biol. Chem. 289, 31014-31028
37. Almeida, A., Almeida, J., Bolaños, J. P., and Moncada, S. (2001) Different responses of astrocytes and neurons to nitric oxide: the role of glycolytically generated ATP in astrocyte protection. Proc. Natl. Acad.Sci.USA98, 15294-15299
38. Stobart, J. L., and Anderson, C. M. (2013) Multifunctional role of astrocytes as gatekeepers of neuronal energy supply. Front. Cell. Neurosci. 7, 38
39. Sampol, D., Ostrofet, E., Jobin, M. L., Raffard, G., Sanchez, S., Bouchaud, V., Franconi, J. M., Bonvento, G., and Bouzier-Sore, A. K. (2013) Glucose and lactate metabolism in the awake and stimulated rat: a (13)C-NMR study. Front. Neuroenergetics 5, 5
40. Lutas, A., and Yellen, G. (2013) The ketogenic diet: metabolic influences on brain excitability and epilepsy. Trends Neurosci. 36, 32-40
41. Giménez-Cassina, A., Martínez-François, J. R., Fisher, J. K., Szlyk, B., Polak, K., Wiwczar, J., Tanner, G. R., Lutas, A., Yellen, G., and Danial, N. N. (2012) BAD-dependent regulation of fuel metabolism and K (ATP) channel activityconfers resistance toepileptic seizures. Neuron 74, 719-730