Wnt5a Increases the Glycolytic Rate and the Activity of the Pentose Phosphate Pathway in Cortical Neurons.
In the last few years, several reports have proposed that Wnt signaling is a general metabolic regulator, suggesting a role for this pathway in the control of metabolic flux. Wnt signaling is critical for several neuronal functions, but little is known about the correlation between this pathway and energy metabolism. The brain has a high demand for glucose, which is mainly used for energy production. Neurons use energy for highly specific processes that require a high energy level, such as maintaining the electrical potential and synthesizing neurotransmitters. Moreover, an important metabolic impairment has been described in all neurodegenerative disorders. Despite the key role of glucose metabolism in the brain, little is known about the cellular pathways involved in regulating this process. We report here that Wnt5a induces an increase in glucose uptake and glycolytic rate and an increase in the activity of the pentose phosphate pathway; the effects of Wnt5a require the intracellular generation of nitric oxide. Our data suggest that Wnt signaling stimulates neuronal glucose metabolism, an effect that could be important for the reported neuroprotective role of Wnt signaling in neurodegenerative disorders.
CARE Biomedical Research Center, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Alameda 340, P.O. Box 114-D, Santiago, Chile; Facultad de Ciencias Naturales, Departamento de Química y Biología, Universidad de Atacama, Copayapu 485, Copiapó, Chile.
Pedro
P
Cisternas
CARE Biomedical Research Center, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Alameda 340, P.O. Box 114-D, Santiago, Chile.
Paulina
P
Salazar
CARE Biomedical Research Center, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Alameda 340, P.O. Box 114-D, Santiago, Chile.
Carmen
C
Silva-Álvarez
Centro de Estudios Científicos (CECs), Casilla 1469, Valdivia, Chile.
L Felipe
LF
Barros
CARE Biomedical Research Center, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Alameda 340, P.O. Box 114-D, Santiago, Chile; Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile.
Nibaldo C
0000-0003-3118-9726
NC
Inestrosa
IUBMB Life. 2010 Jan;62(1):14-8
19937972
J Nutr. 2004 Mar;134(3):489-92
14988435
Eur J Neurosci. 2011 Apr;33(8):1483-92
21395864
Front Cell Neurosci. 2013 Jun 25;7:97
23805073
J Neurosci. 1994 Dec;14(12):7521-8
7527844
J Biol Chem. 2006 Aug 11;281(32):22429-33
16793760
Front Cell Neurosci. 2015 May 05;9:166
25999816
Neuron. 2016 Apr 20;90(2):278-91
27068791
Biochem Biophys Res Commun. 2014 Feb 7;444(2):189-94
24440698
J Biol Chem. 2008 Feb 29;283(9):5918-27
18096705
Hum Mol Genet. 2011 Dec 1;20(23):4515-29
21873260
Biochem Cell Biol. 1998;76(1):107-13
9666312
Neurobiol Aging. 2005 Dec;26 Suppl 1:65-9
16266773
Andrologia. 1986 Nov-Dec;18(6):587-94
3813047
Biochim Biophys Acta. 2008 Jul-Aug;1777(7-8):789-93
18455501
J Neurochem. 2004 May;89(3):537-52
15086511
Prog Neurobiol. 2014 Oct;121:125-46
25084549
J Mol Cell Biol. 2014 Feb;6(1):64-74
24549157
EMBO Mol Med. 2011 Nov;3(11):667-81
21882344
Diabetes Metab Res Rev. 2013 Oct;29(7):551-6
23653377
J Neurosci Res. 2005 Jan 1-15;79(1-2):166-71
15573411
J Exp Biol. 2003 Jun;206(Pt 12):2049-57
12756287
J Cereb Blood Flow Metab. 2014 Mar;34(3):397-407
24326389
J Neurochem. 2009 May;109 Suppl 1:94-100
19393014
Aging Cell. 2014 Oct;13(5):935-45
25059425
Int J Obes (Lond). 2008 Sep;32 Suppl 4:S7-12
18719601
Neurodegener Dis. 2012;10 (1-4):23-6
22261402
Horm Metab Res. 2009 Feb;41(2):159-63
19214925
J Neurochem. 1981 Dec;37(6):1523-8
7334375
Nature. 2003 May 22;423(6938):448-52
12717451
Nat Cell Biol. 2009 Jun;11(6):747-52
19448625
Biochem J. 1990 Nov 15;272(1):127-32
2124803
Rinsho Shinkeigaku. 1990 Oct;30(10):1078-83
1703936
Cell Metab. 2012 Apr 4;15(4):492-504
22482731
J Neurochem. 2014 May;129(4):663-71
24460956
Prog Neurobiol. 2013 Sep;108:21-43
23850509
Cell Calcium. 2004 Sep-Oct;36(3-4):221-33
15261478
Cold Spring Harb Perspect Biol. 2012 Oct 01;4(10 ):null
22935904
Neuron. 2015 May 20;86(4):883-901
25996133
Biochem Soc Trans. 2007 Nov;35(Pt 5):1224-7
17956318
Nat Rev Cancer. 2013 Jan;13(1):11-26
23258168
Neurosci Lett. 2017 Jan 10;637:18-25
25725168
Eur J Neurosci. 2003 Apr;17(7):1482-8
12713651
Br J Cancer. 2013 Apr 30;108(8):1624-33
23531700
Br J Pharmacol. 1993 Sep;110(1):225-8
7693279
Mol Aspects Med. 2015 Dec;46:70-7
26344371
Nat Rev Neurosci. 2010 Feb;11(2):77-86
20010950
Ciba Found Symp. 1978 Mar;(56):171-97
97062
Nat Neurosci. 2007 Nov;10(11):1407-13
17952067
Curr Opin Clin Nutr Metab Care. 2008 Jul;11(4):385-92
18541996
J Cereb Blood Flow Metab. 2001 Oct;21(10):1133-45
11598490
J Biol Chem. 2009 Jun 5;284(23 ):15857-66
19332546
Exp Neurol. 2015 Feb;264:14-25
25450465
Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):21164-9
21084636
Eur J Biochem. 1994 Feb 1;219(3):713-25
8112322
Neural Plast. 2016;2016:4258171
26881110
Mol Cell Neurosci. 2015 Sep;68:314-22
26311509
J Cereb Blood Flow Metab. 2014 Jun;34(6):945-55
24569689
EMBO J. 2014 Jul 1;33(13):1454-73
24825347
Diabetes. 2010 Jul;59(7):1601-7
20393152
Front Cell Neurosci. 2015 Jun 15;9:227
26124704
Cell Commun Signal. 2014 Mar 28;12:23
24679124
J Biol Chem. 1977 Aug 10;252(15):5456-63
885863
Front Cell Neurosci. 2015 Oct 27;9:431
26578889
Science. 2003 Sep 5;301(5638):1391-4
12958364
EMBO J. 2014 Jul 1;33(13):1420-2
24843042
Arch Biochem Biophys. 1979 Dec;198(2):478-92
42355
Front Cell Neurosci. 2013 Oct 11;7:179
24130515
Antioxid Redox Signal. 2006 May-Jun;8(5-6):955-65
16771685
Biol Res. 2016 Feb 19;49:9
26895946
Mol Psychiatry. 2003 Feb;8(2):195-208
12610652
EMBO J. 2012 Jun 13;31(12):2670-84
22617420
J Physiol. 2015 Aug 15;593(16):3447-62
25809592
Trends Neurosci. 2013 Jul;36(7):396-404
23639382
Nat Neurosci. 2015 Apr;18(4):521-30
25730668