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Research Article

Determining the Bioenergetic Capacity for Fatty Acid Oxidation in the Mammalian Nervous System

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Article: e00037-20 | Received 28 Jan 2020, Accepted 16 Feb 2020, Published online: 03 Mar 2023

REFERENCES

  • Owen OE, Morgan AP, Kemp HG, Sullivan JM, Herrera MG, Cahill GF, Jr. 1967. Brain metabolism during fasting. J Clin Invest 46:1589–1595. https://doi.org/10.1172/JCI105650.
  • Ahmed AT, Mahmoudian Dehkordi S, Bhattacharyya S, Arnold M, Liu D, Neavin D, Moseley MA, Thompson JW, John Williams LS, Louie G, Skime MK, Wang L, Riva-Posse P, McDonald W, Bobo WV, Craighead WE, Krishnan R, Weinshilboum RM, Dunlop BW, Millington DS, Rush AJ, Frye MA, Kaddurah-Daouk R. 2019. Acylcarnitine metabolomic profiles inform clincally-defined major depressive phenotypes. bioRxiv https://doi.org/10.1101/632448.
  • Barone R, MIMIC-Autism Group, Alaimo S, Messina M, Pulvirenti A, Bastin J, Ferro A, Frye RE, Rizzo R. 2018. A subset of patients with autism spectrum disorders show a distinctive metabolic profile by dried blood spot analyses. Front Psychiatry 9:636. https://doi.org/10.3389/fpsyt.2018.00636.
  • Clark-Taylor T, Clark-Taylor BE. 2004. Is autism a disorder of fatty acid metabolism? Possible dysfunction of mitochondrial beta-oxidation by long chain acyl-CoA dehydrogenase. Med Hypotheses 62:970–975. https://doi.org/10.1016/j.mehy.2004.01.011.
  • Ferguson JN, Young LJ, Insel TR. 2002. The neuroendocrine basis of social recognition. Front Neuroendocrinol 23:200–224. https://doi.org/10.1006/frne.2002.0229.
  • Rossignol DA, Frye RE. 2012. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry 17:290–314. https://doi.org/10.1038/mp.2010.136.
  • Xie Z, Jones A, Deeney JT, Hur SK, Bankaitis VA. 2016. Inborn errors of long-chain fatty acid beta-oxidation link neural stem cell self-renewal to autism. Cell Rep 14:991–999. https://doi.org/10.1016/j.celrep.2016.01.004.
  • Tyni T, Palotie A, Viinikka L, Valanne L, Salo MK, von Döbeln U, Jackson S, Wanders R, Venizelos N, Pihko H. 1997. Long-chain 3 hydroxyacyl-coenzyme A dehydrogenase deficiency with the G158C mutation clinical presentation of thirteen patients. J Pediatr 130:67–76. https://doi.org/10.1016/S0022-3476(97)70312-3.
  • Tyni T, Pihko H. 1999. Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Acta Paediatr 88:237–245. https://doi.org/10.1080/08035259950169954.
  • Merritt JL, II, Norris M, Kanungo S. 2018. Fatty acid oxidation disorders. Ann Transl Med 6:473. https://doi.org/10.21037/atm.2018.10.57.
  • Cahill GF, Jr. 2006. Fuel metabolism in starvation. Annu Rev Nutr 26:1–22. https://doi.org/10.1146/annurev.nutr.26.061505.111258.
  • Lopatina O, Yoshihara T, Nishimura T, Zhong J, Akther S, Fakhrul AA, Liang M, Higashida C, Sumi K, Furuhara K, Inahata Y, Huang JJ, Koizumi K, Yokoyama S, Tsuji T, Petugina Y, Sumarokov A, Salmina AB, Hashida K, Kitao Y, Hori O, Asano M, Kitamura Y, Kozaka T, Shiba K, Zhong F, Xie MJ, Sato M, Ishihara K, Higashida H. 2014. Anxiety- and depression-like behavior in mice lacking the CD157/BST1 gene, a risk factor for Parkinson’s disease. Front Behav Neurosci 8:133. https://doi.org/10.3389/fnbeh.2014.00133.
  • Camargo N, Brouwers JF, Loos M, Gutmann DH, Smit AB, Verheijen MH. 2012. High-fat diet ameliorates neurological deficits caused by defective astrocyte lipid metabolism. FASEB J 26:4302–4315. https://doi.org/10.1096/fj.12-205807.
  • Polyzos AA, Lee DY, Datta R, Hauser M, Budworth H, Holt A, Mihalik S, Goldschmidt P, Frankel K, Trego K, Bennett MJ, Vockley J, Xu K, Gratton E, McMurray CT. 2019. Metabolic reprogramming in astrocytes distinguishes region-specific neuronal susceptibility in Huntington mice. Cell Metab 29:1258–1273 e11. https://doi.org/10.1016/j.cmet.2019.03.004.
  • Mitchell RW, Hatch GM. 2011. Fatty acid transport into the brain: of fatty acid fables and lipid tails. Prostaglandins Leukot Essent Fatty Acids 85:293–302. https://doi.org/10.1016/j.plefa.2011.04.007.
  • Watkins PA, Hamilton JA, Leaf A, Spector AA, Moore SA, Anderson RE, Moser HW, Noetzel MJ, Katz R. 2001. Brain uptake and utilization of fatty acids: applications to peroxisomal biogenesis diseases. J Mol Neurosci 16:87–92. https://doi.org/10.1385/JMN:16:2-3:87.
  • Jernberg JN, Bowman CE, Wolfgang MJ, Scafidi S. 2017. Developmental regulation and localization of carnitine palmitoyltransferases (CPTs) in rat brain. J Neurochem 142:407–419. https://doi.org/10.1111/jnc.14072.
  • Clarke LE, Liddelow SA, Chakraborty C, Munch AE, Heiman M, Barres BA. 2018. Normal aging induces A1-like astrocyte reactivity. Proc Natl Acad Sci U S A 115:E1896–E1905. https://doi.org/10.1073/pnas.1800165115.
  • Fecher C, Trovo L, Muller SA, Snaidero N, Wettmarshausen J, Heink S, Ortiz O, Wagner I, Kuhn R, Hartmann J, Karl RM, Konnerth A, Korn T, Wurst W, Merkler D, Lichtenthaler SF, Perocchi F, Misgeld T. 2019. Cell-type-specific profiling of brain mitochondria reveals functional and molecular diversity. Nat Neurosci 22:1731–1742. https://doi.org/10.1038/s41593-019-0479-z.
  • Le Foll C, Levin BE. 2016. Fatty acid-induced astrocyte ketone production and the control of food intake. Am J Physiol Regul Integr Comp Physiol 310:R1186–R1192. https://doi.org/10.1152/ajpregu.00113.2016.
  • Auestad N, Korsak RA, Morrow JW, Edmond J. 1991. Fatty acid oxidation and ketogenesis by astrocytes in primary culture. J Neurochem 56:1376–1386. https://doi.org/10.1111/j.1471-4159.1991.tb11435.x.
  • Edmond J, Robbins RA, Bergstrom JD, Cole RA, de Vellis J. 1987. Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes, and oligodendrocytes from developing brain in primary culture. J Neurosci Res 18:551–561. https://doi.org/10.1002/jnr.490180407.
  • Vignais PM, Gallagher CH, Zabin I. 1958. Activation and oxidation of long chain fatty acids by rat brain. J Neurochem 2:283–287. https://doi.org/10.1111/j.1471-4159.1958.tb12375.x.
  • Kawamura N, Kishimoto Y. 1981. Characterization of water-soluble products of palmitic acid beta-oxidation by a rat brain preparation. J Neurochem 36:1786–1791. https://doi.org/10.1111/j.1471-4159.1981.tb00432.x.
  • Gnaedinger JM, Miller JC, Latker CH, Rapoport SI. 1988. Cerebral metabolism of plasma [14C]palmitate in awake, adult rat: subcellular localization. Neurochem Res 13:21–29. https://doi.org/10.1007/bf00971850.
  • Yang SY, He X, Schulz H. 1987. Fatty acid oxidation in rat brain is limited by the low activity of 3-ketoacyl-coenzyme A thiolase. J Biol Chem 262:13027–13032.
  • Wegener G. 1983. Brains burning fat: different forms of energy metabolism in the CNS of insects. Naturwissenschaften 70:43–45. https://doi.org/10.1007/bf00365961.
  • Cermenati G, Audano M, Giatti S, Carozzi V, Porretta-Serapiglia C, Pettinato E, Ferri C, D'Antonio M, De Fabiani E, Crestani M, Scurati S, Saez E, Azcoitia I, Cavaletti G, Garcia-Segura L-M, Melcangi RC, Caruso D, Mitro N. 2015. Lack of sterol regulatory element binding factor-1c imposes glial fatty acid utilization leading to peripheral neuropathy. Cell Metab 21:571–583. https://doi.org/10.1016/j.cmet.2015.02.016.
  • Ellis JM, Wong GW, Wolfgang MJ. 2013. Acyl coenzyme A thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity. Mol Cell Biol 33:1869–1882. https://doi.org/10.1128/MCB.01548-12.
  • Escartin C, Pierre K, Colin A, Brouillet E, Delzescaux T, Guillermier M, Dhenain M, Deglon N, Hantraye P, Pellerin L, Bonvento G. 2007. Activation of astrocytes by CNTF induces metabolic plasticity and increases resistance to metabolic insults. J Neurosci 27:7094–7104. https://doi.org/10.1523/JNEUROSCI.0174-07.2007.
  • Schonfeld P, Reiser G. 2017. Brain energy metabolism spurns fatty acids as fuel due to their inherent mitotoxicity and potential capacity to unleash neurodegeneration. Neurochem Int 109:68–77. https://doi.org/10.1016/j.neuint.2017.03.018.
  • Ioannou MS, Jackson J, Sheu SH, Chang CL, Weigel AV, Liu H, Pasolli HA, Xu CS, Pang S, Matthies D, Hess HF, Lippincott-Schwartz J, Liu Z. 2019. Neuron-astrocyte metabolic coupling protects against activity-induced fatty acid toxicity. Cell 177:1522–1535 e14. https://doi.org/10.1016/j.cell.2019.04.001.
  • Guest J, Garg M, Bilgin A, Grant R. 2013. Relationship between central and peripheral fatty acids in humans. Lipids Health Dis 12:79. https://doi.org/10.1186/1476-511X-12-79.
  • Ouellet M, Emond V, Chen CT, Julien C, Bourasset F, Oddo S, LaFerla F, Bazinet RP, Calon F. 2009. Diffusion of docosahexaenoic and eicosapentaenoic acids through the blood-brain barrier: an in situ cerebral perfusion study. Neurochem Int 55:476–482. https://doi.org/10.1016/j.neuint.2009.04.018.
  • Spector R. 1988. Fatty-acid transport through the blood-brain barrier. J Neurochem 50:639–643. https://doi.org/10.1111/j.1471-4159.1988.tb02958.x.
  • Lee J, Ellis JM, Wolfgang MJ. 2015. Adipose fatty acid oxidation is required for thermogenesis and potentiates oxidative stress-induced inflammation. Cell Rep 10:266–279. https://doi.org/10.1016/j.celrep.2014.12.023.
  • Reamy AA, Wolfgang MJ. 2011. Carnitine palmitoyltransferase-1c gain-of-function in the brain results in postnatal microencephaly. J Neurochem 118:388–398. https://doi.org/10.1111/j.1471-4159.2011.07312.x.
  • Stoll EA, Makin R, Sweet IR, Trevelyan AJ, Miwa S, Horner PJ, Turnbull DM. 2015. Neural stem cells in the adult subventricular zone oxidize fatty acids to produce energy and support neurogenic activity. Stem Cells 33:2306–2319. https://doi.org/10.1002/stem.2042.
  • Schulz JG, Laranjeira A, Van Huffel L, Gartner A, Vilain S, Bastianen J, Van Veldhoven PP, Dotti CG. 2015. Glial beta-oxidation regulates Drosophila energy metabolism. Sci Rep 5:7805. https://doi.org/10.1038/srep07805.
  • Liu L, Zhang K, Sandoval H, Yamamoto S, Jaiswal M, Sanz E, Li Z, Hui J, Graham BH, Quintana A, Bellen HJ. 2015. Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration. Cell 160:177–190. https://doi.org/10.1016/j.cell.2014.12.019.
  • Lam TK, Pocai A, Gutierrez-Juarez R, Obici S, Bryan J, Aguilar-Bryan L, Schwartz GJ, Rossetti L. 2005. Hypothalamic sensing of circulating fatty acids is required for glucose homeostasis. Nat Med 11:320–327. https://doi.org/10.1038/nm1201.
  • Lam TK, Schwartz GJ, Rossetti L. 2005. Hypothalamic sensing of fatty acids. Nat Neurosci 8:579–584. https://doi.org/10.1038/nn1456.
  • Obici S, Feng Z, Arduini A, Conti R, Rossetti L. 2003. Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production. Nat Med 9:756–761. https://doi.org/10.1038/nm873.
  • Giusti SA, Vercelli CA, Vogl AM, Kolarz AW, Pino NS, Deussing JM, Refojo D. 2014. Behavioral phenotyping of nestin-Cre mice: implications for genetic mouse models of psychiatric disorders. J Psychiatr Res 55:87–95. https://doi.org/10.1016/j.jpsychires.2014.04.002.
  • Savonenko AV, Xu GM, Price DL, Borchelt DR, Markowska AL. 2003. Normal cognitive behavior in two distinct congenic lines of transgenic mice hyperexpressing mutant APPSWE. Neurobiol Dis 12:194–211. https://doi.org/10.1016/S0969-9961(02)00012-8.
  • Seibenhener ML, Wooten MC. 2015. Use of the open field maze to measure locomotor and anxiety-like behavior in mice. J Vis Exp 96:e52434. https://doi.org/10.3791/52434.
  • Kalueff AV, Stewart AM, Song C, Berridge KC, Graybiel AM, Fentress JC. 2016. Neurobiology of rodent self-grooming and its value for translational neuroscience. Nat Rev Neurosci 17:45–59. https://doi.org/10.1038/nrn.2015.8.
  • Savonenko A, Munoz P, Melnikova T, Wang Q, Liang X, Breyer RM, Montine TJ, Kirkwood A, Andreasson K. 2009. Impaired cognition, sensorimotor gating, and hippocampal long-term depression in mice lacking the prostaglandin E2 EP2 receptor. Exp Neurol 217:63–73. https://doi.org/10.1016/j.expneurol.2009.01.016.
  • Lee J, Choi J, Scafidi S, Wolfgang MJ. 2016. Hepatic fatty acid oxidation restrains systemic catabolism during starvation. Cell Rep 16:201–212. https://doi.org/10.1016/j.celrep.2016.05.062.
  • Lee J, Choi J, Selen Alpergin ES, Zhao L, Hartung T, Scafidi S, Riddle RC, Wolfgang MJ. 2017. Loss of hepatic mitochondrial long-chain fatty acid oxidation confers resistance to diet-induced obesity and glucose intolerance. Cell Rep 20:655–667. https://doi.org/10.1016/j.celrep.2017.06.080.
  • Chakravarthy MV, Zhu Y, Lopez M, Yin L, Wozniak DF, Coleman T, Hu Z, Wolfgang M, Vidal-Puig A, Lane MD, Semenkovich CF. 2007. Brain fatty acid synthase activates PPARalpha to maintain energy homeostasis. J Clin Invest 117:2539–2552. https://doi.org/10.1172/JCI31183.
  • Guzman M, Blazquez C. 2004. Ketone body synthesis in the brain: possible neuroprotective effects. Prostaglandins Leukot Essent Fatty Acids 70:287–292. https://doi.org/10.1016/j.plefa.2003.05.001.
  • Jones LL, McDonald DA, Borum PR. 2010. Acylcarnitines: role in brain. Prog Lipid Res 49:61–75. https://doi.org/10.1016/j.plipres.2009.08.004.
  • Wu R, Wu Z, Wang X, Yang P, Yu D, Zhao C, Xu G, Kang L. 2012. Metabolomic analysis reveals that carnitines are key regulatory metabolites in phase transition of the locusts. Proc Natl Acad Sci U S A 109:3259–3263. https://doi.org/10.1073/pnas.1119155109.
  • Szczepankowska D, Nałecz KA. 2003. Palmitoylcarnitine modulates palmitoylation of proteins: implication for differentiation of neural cells. Neurochem Res 28:645–651. https://doi.org/10.1023/a:1022802229921.
  • Leonardi R, Rock CO, Jackowski S, Zhang YM. 2007. Activation of human mitochondrial pantothenate kinase 2 by palmitoylcarnitine. Proc Natl Acad Sci U S A 104:1494–1499. https://doi.org/10.1073/pnas.0607621104.
  • McKenna MC, Scafidi S, Robertson CL. 2015. Metabolic alterations in developing brain after injury: knowns and unknowns. Neurochem Res 40:2527–2543. https://doi.org/10.1007/s11064-015-1600-7.
  • Brenna JT, Diau GY. 2007. The influence of dietary docosahexaenoic acid and arachidonic acid on central nervous system polyunsaturated fatty acid composition. Prostaglandins Leukot Essent Fatty Acids 77:247–250. https://doi.org/10.1016/j.plefa.2007.10.016.
  • Brenna JT, Carlson SE. 2014. Docosahexaenoic acid and human brain development: evidence that a dietary supply is needed for optimal development. J Hum Evol 77:99–106. https://doi.org/10.1016/j.jhevol.2014.02.017.
  • Le Foll C, Dunn-Meynell AA, Miziorko HM, Levin BE. 2014. Regulation of hypothalamic neuronal sensing and food intake by ketone bodies and fatty acids. Diabetes 63:1259–1269. https://doi.org/10.2337/db13-1090.
  • Fernandez RF, Kim SQ, Zhao Y, Foguth RM, Weera MM, Counihan JL, Nomura DK, Chester JA, Cannon JR, Ellis JM. 2018. Acyl-CoA synthetase 6 enriches the neuroprotective omega–3 fatty acid DHA in the brain. Proc Natl Acad Sci U S A 115:12525–12530. https://doi.org/10.1073/pnas.1807958115.
  • Wolfgang MJ, Lane MD. 2011. Hypothalamic malonyl-CoA and CPT1c in the treatment of obesity. FEBS J 278:552–558. https://doi.org/10.1111/j.1742-4658.2010.07978.x.
  • Price NT, van der Leij FR, Jackson VN, Corstorphine CG, Thomson R, Sorensen A, Zammit VA. 2002. A novel brain-expressed protein related to carnitine palmitoyltransferase I. Genomics 80:433–442. https://doi.org/10.1006/geno.2002.6845.
  • Wolfgang MJ, Kurama T, Dai Y, Suwa A, Asaumi M, Matsumoto S, Cha SH, Shimokawa T, Lane MD. 2006. The brain-specific carnitine palmitoyltransferase-1c regulates energy homeostasis. Proc Natl Acad Sci U S A 103:7282–7287. https://doi.org/10.1073/pnas.0602205103.
  • Wolfgang MJ, Cha SH, Millington DS, Cline G, Shulman GI, Suwa A, Asaumi M, Kurama T, Shimokawa T, Lane MD. 2008. Brain-specific carnitine palmitoyl-transferase-1c: role in CNS fatty acid metabolism, food intake, and body weight. J Neurochem 105:1550–1559. https://doi.org/10.1111/j.1471-4159.2008.05255.x.
  • Lee J, Wolfgang MJ. 2012. Metabolomic profiling reveals a role for CPT1c in neuronal oxidative metabolism. BMC Biochem 13:23. https://doi.org/10.1186/1471-2091-13-23.
  • Wolfgang MJ, Lane MD. 2006. The role of hypothalamic malonyl-CoA in energy homeostasis. J Biol Chem 281:37265–37269. https://doi.org/10.1074/jbc.R600016200.
  • He W, Lam TK, Obici S, Rossetti L. 2006. Molecular disruption of hypothalamic nutrient sensing induces obesity. Nat Neurosci 9:227–233. https://doi.org/10.1038/nn1626.
  • Bowman CE, Zhao L, Hartung T, Wolfgang MJ. 2016. Requirement for the mitochondrial pyruvate carrier in mammalian development revealed by a hypomorphic allelic series. Mol Cell Biol 36:2089–2104. https://doi.org/10.1128/MCB.00166-16.
  • Eckel-Mahan KL, Patel VR, Mohney RP, Vignola KS, Baldi P, Sassone-Corsi P. 2012. Coordination of the transcriptome and metabolome by the circadian clock. Proc Natl Acad Sci U S A 109:5541–5546. https://doi.org/10.1073/pnas.1118726109.
  • Lee J, Choi J, Wong GW, Wolfgang MJ. 2016. Neurometabolic roles of ApoE and Ldl-R in mouse brain. J Bioenerg Biomembr 48:13–21. https://doi.org/10.1007/s10863-015-9636-6.
  • Brooks SP, Dunnett SB. 2009. Tests to assess motor phenotype in mice: a user’s guide. Nat Rev Neurosci 10:519–529. https://doi.org/10.1038/nrn2652.
  • Park MJ, Aja S, Li Q, Degano AL, Penati J, Zhuo J, Roe CR, Ronnett GV. 2014. Anaplerotic triheptanoin diet enhances mitochondrial substrate use to remodel the metabolome and improve lifespan, motor function, and sociability in MeCP2-null mice. PLoS One 9:e109527. https://doi.org/10.1371/journal.pone.0109527.
  • Gilli F, Royce DB, Pachner AR. 2016. Measuring progressive neurological disability in a mouse model of multiple sclerosis. J Vis Exp 117:54616. https://doi.org/10.3791/54616.
  • Yang J, Li Q, Wang Z, Qi C, Han X, Lan X, Wan J, Wang W, Zhao X, Hou Z, Gao C, Carhuapoma JR, Mori S, Zhang J, Wang J. 2017. Multimodality MRI assessment of grey and white matter injury and blood-brain barrier disruption after intracerebral haemorrhage in mice. Sci Rep 7:40358. https://doi.org/10.1038/srep40358.
  • Zhao X, Wu T, Chang CF, Wu H, Han X, Li Q, Gao Y, Li Q, Hou Z, Maruyama T, Zhang J, Wang J. 2015. Toxic role of prostaglandin E2 receptor EP1 after intracerebral hemorrhage in mice. Brain Behav Immun 46:293–310. https://doi.org/10.1016/j.bbi.2015.02.011.
  • Zhang J, van Zijl PC, Mori S. 2002. Three-dimensional diffusion tensor magnetic resonance microimaging of adult mouse brain and hippocampus. Neuroimage 15:892–901. https://doi.org/10.1006/nimg.2001.1012.

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