title: Glutamate and GABA in Appetite Regulation.
abstract: Appetite is regulated by a coordinated interplay between gut, adipose tissue, and brain. A primary site for the regulation of appetite is the hypothalamus where interaction between orexigenic neurons, expressing Neuropeptide Y/Agouti-related protein, and anorexigenic neurons, expressing Pro-opiomelanocortin cocaine/Amphetamine-related transcript, controls energy homeostasis. Within the hypothalamus, several peripheral signals have been shown to modulate the activity of these neurons, including the orexigenic peptide ghrelin and the anorexigenic hormones insulin and leptin. In addition to the accumulated knowledge on neuropeptide signaling, presence and function of amino acid neurotransmitters in key hypothalamic neurons brought a new light into appetite regulation. Therefore, the principal aim of this review will be to describe the current knowledge of the role of amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation and the associated neuronal-astrocytic metabolic coupling mechanisms. Glutamate and GABA dominate synaptic transmission in the hypothalamus and administration of their receptors agonists into hypothalamic nuclei stimulates feeding. By using (13)C High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance spectroscopy based analysis, the Cerdán group has shown that increased neuronal firing in mice hypothalamus, as triggered by appetite during the feeding-fasting paradigm, may stimulate the use of lactate as neuronal fuel leading to increased astrocytic glucose consumption and glycolysis. Moreover, fasted mice showed increased hypothalamic [2-(13)C]GABA content, which may be explained by the existence of GABAergic neurons in key appetite regulation hypothalamic nuclei. Interestingly, increased [2-(13)C]GABA concentration in the hypothalamus of fasted animals appears to result mainly from reduction in GABA metabolizing pathways, rather than increased GABA synthesis by augmented activity of the glutamate-glutamine-GABA cycle.
authors: Intermediary Metabolism Group, Center for Neurosciences and Cell Biology of Coimbra , Coimbra , Portugal.
authors: Teresa C
authors: TC
authors: Delgado
keywords: GABA; NMR spectroscopy; appetite; glutamate; hypothalamus
references: Glia. 2007 Sep;55(12):1251-62
references: 17659524
references: FASEB J. 2005 Oct;19(12):1680-2
references: 16099943
references: J Cereb Blood Flow Metab. 2011 Jan;31(1):90-101
references: 20736955
references: Diabetes. 2001 Nov;50(11):2540-7
references: 11679432
references: Neuron. 2002 Oct 10;36(2):199-211
references: 12383777
references: Biochem J. 2010 May 27;428(3):305-24
references: 20504281
references: Clin Exp Pharmacol Physiol. 2000 May-Jun;27(5-6):422-7
references: 10831247
references: Neurochem Int. 2009 Jul-Aug;55(1-3):9-12
references: 19428801
references: J Comp Neurol. 2002 Jul 1;448(3):217-29
references: 12115705
references: J Clin Endocrinol Metab. 2001 Dec;86(12):5992
references: 11739476
references: Neuron. 2012 Feb 9;73(3):511-22
references: 22325203
references: Obes Rev. 2005 Nov;6(4):297-306
references: 16246215
references: Physiol Behav. 1990 Sep;48(3):417-21
references: 2176292
references: J Neurosci. 2004 Feb 18;24(7):1578-83
references: 14973227
references: J Neurophysiol. 2006 Mar;95(3):1639-44
references: 16221751
references: Curr Top Med Chem. 2006;6(10):929-34
references: 16787266
references: J Neurosci. 1996 Feb 1;16(3):877-85
references: 8558256
references: J Neurosci Res. 2007 Nov 15;85(15):3284-93
references: 17455302
references: Endocrinology. 2000 Sep;141(9):3518-21
references: 10965927
references: Endocrinology. 2004 Jun;145(6):2687-95
references: 15001546
references: Endocrinology. 1987 Oct;121(4):1562-70
references: 3653038
references: NeuroRx. 2006 Jul;3(3):358-72
references: 16815219
references: Br J Pharmacol. 1990 Nov;101(3):559-62
references: 1963798
references: Endocrinology. 2007 Feb;148(2):647-59
references: 17095588
references: Cell. 2009 Jun 26;137(7):1225-34
references: 19563755
references: Pharmacol Biochem Behav. 1992 Nov;43(3):881-6
references: 1448482
references: Prog Neurobiol. 1990;35(4):245-96
references: 1980745
references: J Neuroendocrinol. 2011 Apr;23(4):371-80
references: 21251093
references: J Biol Chem. 1990 Aug 5;265(22):12916-26
references: 1973931
references: Pharmacol Biochem Behav. 2003 Dec;76(3-4):417-23
references: 14643840
references: J Clin Invest. 2012 Nov;122(11):3900-13
references: 23064363
references: Mol Cell Biochem. 2011 Jul;353(1-2):47-57
references: 21384157
references: Nat Neurosci. 2008 Sep;11(9):998-1000
references: 19160495
references: J Clin Invest. 1996 Sep 1;98(5):1101-6
references: 8787671
references: Nat Neurosci. 2011 Mar;14(3):351-5
references: 21209617
references: Eur J Pharmacol. 2011 Jun 11;660(1):21-7
references: 21211531
references: J Neurochem. 2000 Sep;75(3):889-907
references: 10936169
references: Nat Neurosci. 2005 Oct;8(10):1356-63
references: 16172601
references: J Cereb Blood Flow Metab. 2012 Jul;32(7):1152-66
references: 22027938
references: J Cereb Blood Flow Metab. 2011 Dec;31(12):2257-66
references: 21971349
references: Cell. 2011 Sep 16;146(6):992-1003
references: 21925320
references: Neuroimage. 2013 Jan 1;64:448-57
references: 23000787
references: Brain Res. 1988 Dec 6;474(2):231-45
references: 2463058
references: Physiol Behav. 1981 Dec;27(6):1031-40
references: 7335803
references: Science. 2004 Jun 18;304(5678):1815-9
references: 15118123
references: Cell. 1997 Jan 10;88(1):131-41
references: 9019399
references: Nat Med. 2004 May;10(5):524-9
references: 15077108
references: Endocrinology. 2011 May;152(5):1809-18
references: 21343257
references: J Physiol. 2009 Jan 15;587(1):19-25
references: 19064614
references: J Neurosci Res. 1998 May 1;52(3):307-21
references: 9590439
references: J Comp Neurol. 2012 Dec 1;520(17):3863-76
references: 22522889
references: Nutrition. 2010 May;26(5):459-73
references: 20022465
references: Brain Res. 1985 Mar 11;329(1-2):364-7
references: 3884090
references: Nature. 2000 Apr 6;404(6778):661-71
references: 10766253
references: J Neuroendocrinol. 2001 Jun;13(6):505-16
references: 11412337
references: Eur J Endocrinol. 2005 Sep;153(3):R1-5
references: 16131594
references: Neurochem Int. 2002 Aug-Sep;41(2-3):143-54
references: 12020614
references: Brain Res. 1993 Jun 4;613(1):88-95
references: 7688643
references: Neural Plast. 2012;2012:805830
references: 22530158
references: Annu Rev Physiol. 2003;65:401-27
references: 12524459
references: Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10625-9
references: 7938003
references: Eur J Neurosci. 2003 Sep;18(5):1265-78
references: 12956725
references: J Biol Chem. 2002 Mar 8;277(10):7799-807
references: 11744718
references: Nat Med. 1999 Sep;5(9):1066-70
references: 10470087
references: Regul Pept. 2008 Feb 7;146(1-3):140-6
references: 17916389
references: J Neurochem. 1993 Sep;61(3):1179-82
references: 8103082
references: Nutr Metab (Lond). 2007 Sep 01;4:18
references: 17764572
references: Neurosci Biobehav Rev. 1990 Fall;14(3):323-38
references: 2234610
references: Brain Res. 1997 May 9;756(1-2):283-6
references: 9187344
references: Nat Neurosci. 2005 Oct;8(10):1289-91
references: 16158063
references: Neurochem Int. 2004 Jul-Aug;45(2-3):297-303
references: 15145545
references: Physiol Behav. 1977 Apr;18(4):647-58
references: 896975
references: Endocrinology. 1993 Oct;133(4):1753-8
references: 8404618
references: Physiol Behav. 2007 Sep 10;92(1-2):263-71
references: 17586536
references: Eur J Neurosci. 2005 Apr;21(8):2111-9
references: 15869507
references: Cell. 2007 Apr 20;129(2):251-62
references: 17448988
references: J Clin Invest. 2011 Apr;121(4):1424-8
references: 21364278
references: Neuron. 2003 Dec 18;40(6):1059-61
references: 14687541
references: Neurochem Int. 2004 Sep;45(4):511-9
references: 15186917
references: Handb Exp Pharmacol. 2012;(209):185-207
references: 22249815
references: Endocrinology. 1993 Jul;133(1):29-32
references: 8100519
references: Front Neuroenergetics. 2013 Jun 13;5:6
references: 23781199
references: Metab Brain Dis. 2007 Dec;22(3-4):199-218
references: 17882538
references: Peptides. 1986 Nov-Dec;7(6):1189-92
references: 3470711
references: Nat Rev Neurosci. 2005 Mar;6(3):215-29
references: 15738957
references: Nature. 2001 May 24;411(6836):480-4
references: 11373681
references: Neuroreport. 2010 Jul 14;21(10):704-8
references: 20505551
references: Magn Reson Med. 2009 Aug;62(2):279-83
references: 19526502
references: Nature. 1997 Oct 23;389(6653):870-6
references: 9349821