title: Interplay between exercise and dietary fat modulates myelinogenesis in the central nervous system.
abstract: Here we show that the interplay between exercise training and dietary fat regulates myelinogenesis in the adult central nervous system. Mice consuming high fat with coordinate voluntary running wheel exercise for 7weeks showed increases in the abundance of the major myelin membrane proteins, proteolipid (PLP) and myelin basic protein (MBP), in the lumbosacral spinal cord. Expression of MBP and PLP RNA, as well that for Myrf1, a transcription factor driving oligodendrocyte differentiation were also differentially increased under each condition. Furthermore, expression of IGF-1 and its receptor IGF-1R, known to promote myelinogenesis, were also increased in the spinal cord in response to high dietary fat or exercise training. Parallel increases in AKT signaling, a pro-myelination signaling intermediate activated by IGF-1, were also observed in the spinal cord of mice consuming high fat alone or in combination with exercise. Despite the pro-myelinogenic effects of high dietary fat in the context of exercise, high fat consumption in the setting of a sedentary lifestyle reduced OPCs and mature oligodendroglia. Whereas 7weeks of exercise training alone did not alter OPC or oligodendrocyte numbers, it did reverse reductions seen with high fat. Evidence is presented suggesting that the interplay between exercise and high dietary fat increase SIRT1, PGC-1α and antioxidant enzymes which may permit oligodendroglia to take advantage of diet and exercise-related increases in mitochondrial activity to yield increases in myelination despite higher levels of reactive oxygen species.
authors.affiliation: Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA; Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Hyesook
authors.initials: H
authors.lastname: Yoon
authors.affiliation: Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kleven
authors.affiliation: Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Paulsen
authors.affiliation: Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Laurel
authors.initials: L
authors.lastname: Kleppe
authors.affiliation: Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA; Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Integrative Biology and Physiology, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ying
authors.affiliation: Department of Integrative Biology and Physiology, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomez-Pinilla
authors.affiliation: Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA; Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: Scarisbrick.Isobel@mayo.edu.
authors.forename: Isobel A
authors.initials: IA
authors.lastname: Scarisbrick
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051379:Mice; D004676:Myelin Basic Protein / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism; D010805:Physical Conditioning, Animal; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D004676:Myelin Basic Protein; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
keywords: Dietary fat; Exercise; Myelin; Oligodendrocyte; Spinal cord; Western diet
references.citation: J Lipid Res. 2012 Feb;53(2):273-81
references.pmid: 22114039
references.citation: J Neurochem. 2013 Oct;127(2):283-98
references.pmid: 23647384
references.citation: Toxicol Appl Pharmacol. 2006 Oct 15;216(2):309-18
references.pmid: 16843508
references.citation: Ageing Res Rev. 2004 Nov;3(4):445-64
references.pmid: 15541711
references.citation: PLoS Biol. 2013;11(6):e1001577
references.pmid: 23762018
references.citation: Cell. 2009 Jul 10;138(1):172-85
references.pmid: 19596243
references.citation: Nat Med. 2011 Jul;17(7):816-21
references.pmid: 21725297
references.citation: Nat Rev Neurosci. 2010 Apr;11(4):275-83
references.pmid: 20216548
references.citation: J Neurosci. 2012 Feb 1;32(5):1817-25
references.pmid: 22302821
references.citation: Cell. 2006 Oct 20;127(2):397-408
references.pmid: 17055439
references.citation: J Neurochem. 2009 Jun;109(5):1440-51
references.pmid: 19453943
references.citation: Nature. 2000 Apr 6;404(6778):661-71
references.pmid: 10766253
references.citation: Science. 2004 Mar 26;303(5666):2011-5
references.pmid: 14976264
references.citation: Science. 2014 Oct 17;346(6207):318-22
references.pmid: 25324381
references.citation: Development. 2014 Feb;141(3):548-55
references.pmid: 24449836
references.citation: Neuroscience. 2006 Jul 7;140(3):823-33
references.pmid: 16650607
references.citation: J Neuroinflammation. 2012;9:173
references.pmid: 22799524
references.citation: J Neurosci. 2009 May 27;29(21):6860-70
references.pmid: 19474313
references.citation: J Neurochem. 1973 Oct;21(4):749-57
references.pmid: 4271082
references.citation: J Comp Neurol. 1977 Mar 15;172(2):247-63
references.pmid: 838881
references.citation: Neuron. 1997 Jul;19(1):205-18
references.pmid: 9247276
references.citation: Glia. 2007 Mar;55(4):400-11
references.pmid: 17186502
references.citation: Arch Phys Med Rehabil. 2012 Sep;93(9):1487-97
references.pmid: 22920448
references.citation: Curr Opin Clin Nutr Metab Care. 2013 Nov;16(6):726-33
references.pmid: 24071781
references.citation: Nat Neurosci. 2009 Nov;12(11):1370-1
references.pmid: 19820707
references.citation: J Lipid Res. 2011 Mar;52(3):419-34
references.pmid: 21062955
references.citation: Obes Rev. 2015 Apr;16(4):273-81
references.pmid: 25676886
references.citation: PLoS Biol. 2013;11(8):e1001625
references.pmid: 23966833
references.citation: Brain Res. 1995 Nov 6;698(1-2):86-94
references.pmid: 8581507
references.citation: J Neurosci. 2000 Oct 15;20(20):7622-30
references.pmid: 11027222
references.citation: J Biol Chem. 2011 Jan 28;286(4):2559-66
references.pmid: 20971845
references.citation: J Neurosci. 2011 Jun 29;31(26):9544-53
references.pmid: 21715619
references.citation: Ann Neurol. 2010 Nov;68(5):703-16
references.pmid: 20853437
references.citation: Glia. 2013 Sep;61(9):1456-70
references.pmid: 23832758
references.citation: Proc Natl Acad Sci U S A. 1987 Aug;84(16):5665-9
references.pmid: 2441390
references.citation: Neurogenetics. 2005 Feb;6(1):1-16
references.pmid: 15627202
references.citation: J Neurosci. 2014 Mar 26;34(13):4453-65
references.pmid: 24671992
references.citation: J Cereb Blood Flow Metab. 2003 Jun;23(6):739-47
references.pmid: 12796722
references.citation: Development. 2001 Jul;128(14):2723-33
references.pmid: 11526078
references.citation: Brain Pathol. 1998 Oct;8(4):771-93
references.pmid: 9804383
references.citation: Brain Res. 1988 May 31;450(1-2):1-8
references.pmid: 3401704
references.citation: Glia. 2004 Feb;45(3):269-77
references.pmid: 14730700
references.citation: Science. 2011 Sep 16;333(6049):1647-51
references.pmid: 21817014
references.citation: Nat Rev Neurosci. 2009 Jan;10(1):9-22
references.pmid: 19096367
references.citation: Neuropeptides. 2002 Apr-Jun;36(2-3):209-20
references.pmid: 12359511
references.citation: Brain Res. 1987 Oct 27;424(2):320-32
references.pmid: 3676831
references.citation: Nat Cell Biol. 2013 Jun;15(6):614-24
references.pmid: 23644469
references.citation: J Neurosci Res. 1988 Oct-Dec;21(2-4):199-209
references.pmid: 3216421
references.citation: Free Radic Biol Med. 2013 Sep;62:37-46
references.pmid: 23602910
references.citation: Aging (Albany NY). 2012 Jul;4(7):456-61
references.pmid: 22820707
references.citation: Brain Res. 1998 Nov 23;812(1-2):38-49
references.pmid: 9813233
references.citation: PLoS Biol. 2005 Apr;3(4):e101
references.pmid: 15760270
references.citation: Brain Res. 2015 Oct 14;1623:135-49
references.pmid: 25960351
references.citation: Prog Lipid Res. 2003 Jul;42(4):318-43
references.pmid: 12689622
references.citation: J Neurosci. 2008 Jul 9;28(28):7174-83
references.pmid: 18614687
references.citation: J Neurosci. 2009 May 13;29(19):6367-78
references.pmid: 19439614
references.citation: Glia. 2015 May;63(5):846-59
references.pmid: 25628003
references.citation: Brain Res. 2005 Nov 23;1063(1):15-26
references.pmid: 16259966
references.citation: Cold Spring Harb Perspect Biol. 2015 Jul;7(7):a020594
references.pmid: 25986556
references.citation: Adv Physiol Educ. 2006 Dec;30(4):145-51
references.pmid: 17108241
references.citation: J Neurosci. 2013 Jan 2;33(1):175-86
references.pmid: 23283332
references.citation: J Neurosci. 1999 Sep 15;19(18):7913-24
references.pmid: 10479693
references.citation: Neuropharmacology. 2016 Nov;110(Pt B):654-659
references.pmid: 25963414
references.citation: Hum Brain Mapp. 2011 Jan;32(1):10-21
references.pmid: 20235096
references.citation: Glia. 2010 Mar;58(4):458-68
references.pmid: 19780200
references.citation: Neurotherapeutics. 2011 Apr;8(2):262-73
references.pmid: 21404073
references.citation: Nat Neurosci. 2005 Sep;8(9):1148-50
references.pmid: 16116456
references.citation: Glia. 2011 Nov;59(11):1754-69
references.pmid: 21858874
references.citation: Brain. 2008 Jul;131(Pt 7):1749-58
references.pmid: 18515322
references.citation: J Neuroophthalmol. 2010 Dec;30(4):328-39
references.pmid: 21107122
references.citation: Neuroscientist. 2011 Feb;17(1):79-93
references.pmid: 21343408
references.citation: Eur J Neurosci. 2013 Sep;38(5):2672-83
references.pmid: 23763823
references.citation: Neurotherapeutics. 2010 Jan;7(1):51-61
references.pmid: 20129497
references.citation: Diabetes. 2012 Aug;61(8):2074-83
references.pmid: 22586586
references.citation: J Neurosci. 2012 Jun 27;32(26):8855-64
references.pmid: 22745486
references.citation: Nature. 2012 May 24;485(7399):517-21
references.pmid: 22622581
references.citation: Eur J Neurosci. 2002 Sep;16(6):1107-16
references.pmid: 12383240
references.citation: Nat Neurosci. 2013 May;16(5):571-9
references.pmid: 23542689
references.citation: Biol Psychiatry. 2004 Jul 15;56(2):80-5
references.pmid: 15231439
references.citation: Neuron. 1993 Apr;10(4):729-40
references.pmid: 8386530
references.citation: Glia. 2012 Mar;60(3):476-86
references.pmid: 22144101
references.citation: J Neurosci. 2010 Jun 30;30(26):8953-64
references.pmid: 20592216
references.citation: Front Cell Neurosci. 2015 Mar 09;9:64
references.pmid: 25805970
references.citation: Glia. 2014 Nov;62(11):1749-61
references.pmid: 25130164
references.citation: J Neurosci. 2011 Jan 19;31(3):843-50
references.pmid: 21248107
references.citation: J Neurotrauma. 2010 Jul;27(7):1311-20
references.pmid: 20392143
references.citation: Glia. 2006 Jul;54(1):1-10
references.pmid: 16652341
references.citation: J Neurosci. 2013 Nov 20;33(47):18402-8
references.pmid: 24259565
references.citation: Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3602-9
references.pmid: 17652729
references.citation: J Neurosci. 2010 Sep 15;30(37):12310-22
references.pmid: 20844127
references.citation: J Neurosci. 2012 Sep 5;32(36):12528-42
references.pmid: 22956843