Circulating Triglycerides Gate Dopamine-Associated Behaviors through DRD2-Expressing Neurons.
dopamine
dopamine receptor D2
fMRI
food-reward
lipoprotein lipase
nucleus accumbens
striatum
triglycerides
ventral tegmental area
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
07 04 2020
07 04 2020
Historique:
received:
23
04
2019
revised:
16
12
2019
accepted:
13
02
2020
pubmed:
7
3
2020
medline:
4
9
2021
entrez:
7
3
2020
Statut:
ppublish
Résumé
Energy-dense food alters dopaminergic (DA) transmission in the mesocorticolimbic (MCL) system and can promote reward dysfunctions, compulsive feeding, and weight gain. Yet the mechanisms by which nutrients influence the MCL circuitry remain elusive. Here, we show that nutritional triglycerides (TGs), a conserved post-prandial metabolic signature among mammals, can be metabolized within the MCL system and modulate DA-associated behaviors by gating the activity of dopamine receptor subtype 2 (DRD2)-expressing neurons through a mechanism that involves the action of the lipoprotein lipase (LPL). Further, we show that in humans, post-prandial TG excursions modulate brain responses to food cues in individuals carrying a genetic risk for reduced DRD2 signaling. Collectively, these findings unveil a novel mechanism by which dietary TGs directly alter signaling in the reward circuit to regulate behavior, thereby providing a new mechanistic basis by which energy-rich diets may lead to (mal)adaptations in DA signaling that underlie reward deficit and compulsive behavior.
Identifiants
pubmed: 32142669
pii: S1550-4131(20)30069-3
doi: 10.1016/j.cmet.2020.02.010
pmc: PMC7250662
mid: NIHMS1582414
pii:
doi:
Substances chimiques
DRD2 protein, human
0
DRD2 protein, mouse
0
Receptors, Dopamine D2
0
Triglycerides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
773-790.e11Subventions
Organisme : BLRD VA
ID : I01 BX003759
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA036612
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK063491
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
Références
J Neurosci. 2016 Jun 1;36(22):5988-6001
pubmed: 27251620
Endocrinology. 2008 May;149(5):2628-36
pubmed: 18276751
Neuroimage. 2008 Oct 1;42(4):1537-43
pubmed: 18598772
J Lipid Res. 1990 Jul;31(7):1307-13
pubmed: 2401861
J Clin Endocrinol Metab. 2009 May;94(5):1781-8
pubmed: 19223522
Psychopharmacology (Berl). 1991;103(2):271-6
pubmed: 1674160
Neurobiol Dis. 2004 Mar;15(2):312-25
pubmed: 15006701
Cell. 2015 Jul 30;162(3):635-47
pubmed: 26232229
Science. 1990 Dec 7;250(4986):1429-32
pubmed: 2147780
Proc Natl Acad Sci U S A. 1984 Dec;81(23):7604-7
pubmed: 6594703
Neurochem Res. 2003 Jan;28(1):73-82
pubmed: 12587665
ACS Chem Neurosci. 2016 Jul 20;7(7):941-51
pubmed: 27124386
Am J Physiol Regul Integr Comp Physiol. 2012 Sep 1;303(5):R459-76
pubmed: 22718809
Behav Neurosci. 2007 Oct;121(5):877-86
pubmed: 17907820
Eur J Neurosci. 2015 Dec;42(12):3095-104
pubmed: 26527415
Neuropsychopharmacology. 2016 Feb;41(3):811-21
pubmed: 26171719
Chem Senses. 2009 Nov;34(9):739-51
pubmed: 19833660
Nat Neurosci. 2009 Apr;12(4):393-5
pubmed: 19270687
Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18488-93
pubmed: 22025698
Nature. 2007 Jan 11;445(7124):168-76
pubmed: 17151600
Neurosci Biobehav Rev. 2016 Apr;63:223-38
pubmed: 26850211
Cell. 2018 Aug 9;174(4):999-1014.e22
pubmed: 30096314
Cell. 2008 Nov 14;135(4):749-62
pubmed: 19013282
Physiol Behav. 2004 Aug;82(1):109-14
pubmed: 15234598
Mol Psychiatry. 1999 May;4(3):290-6
pubmed: 10395223
Obes Rev. 2013 Jan;14(1):2-18
pubmed: 23016694
Eur J Neurosci. 2001 Feb;13(4):773-80
pubmed: 11207812
J Neurosci Methods. 2007 Mar 15;160(2):231-45
pubmed: 17081618
Neuroscience. 2010 Dec 15;171(3):779-87
pubmed: 20875839
Pharmacol Ther. 1994;64(2):291-370
pubmed: 7878079
Curr Opin Behav Sci. 2016 Jun;9:126-135
pubmed: 28191490
Eur J Pharmacol. 2011 Jun 11;660(1):21-7
pubmed: 21211531
Brain Res. 2009 Nov 17;1298:111-22
pubmed: 19666014
Int J Obes (Lond). 2018 Mar;42(3):391-397
pubmed: 28990588
Pharmacol Rev. 2011 Mar;63(1):182-217
pubmed: 21303898
Trends Neurosci. 2007 May;30(5):228-35
pubmed: 17408758
Proc Natl Acad Sci U S A. 1988 Jul;85(14):5274-8
pubmed: 2899326
Science. 2008 Oct 17;322(5900):449-52
pubmed: 18927395
Chem Senses. 1996 Jun;21(3):323-34
pubmed: 8670711
J Neurosci. 2015 Jul 15;35(28):10316-24
pubmed: 26180206
Cell Metab. 2011 Jan 5;13(1):105-13
pubmed: 21195353
Cell. 2005 Jul 29;122(2):261-73
pubmed: 16051150
Mol Psychiatry. 2014 Oct;19(10):1095-105
pubmed: 24732670
Nat Commun. 2016 Jun 23;7:11829
pubmed: 27337658
Nature. 2012 Sep 20;489(7416):391-399
pubmed: 22996553
Brain Behav Immun. 2005 Jul;19(4):275-80
pubmed: 15944067
Lancet. 2001 Feb 3;357(9253):354-7
pubmed: 11210998
Front Neural Circuits. 2013 Oct 11;7:152
pubmed: 24130517
Wiley Interdiscip Rev Syst Biol Med. 2010 Sep-Oct;2(5):577-593
pubmed: 20836049
Neuropsychopharmacology. 2019 Nov 20;:
pubmed: 31747681
Neurochem Res. 2008 Mar;33(3):598-605
pubmed: 17940894
J Lipid Res. 1989 Oct;30(10):1569-77
pubmed: 2614260
Curr Opin Neurobiol. 2013 Aug;23(4):535-8
pubmed: 23726225
Behav Neurosci. 2008 Dec;122(6):1257-63
pubmed: 19045945
Neurosci Res. 2007 Jul;58(3):305-16
pubmed: 17499375
Psychoneuroendocrinology. 2015 Oct;60:206-16
pubmed: 26186250
J Neurosci. 2015 May 20;35(20):7964-76
pubmed: 25995480
J Neurosci. 2008 May 28;28(22):5671-85
pubmed: 18509028
J Lipid Res. 1993 Feb;34(2):229-38
pubmed: 8429258
Int Rev Psychiatry. 2012 Jun;24(3):211-8
pubmed: 22724642
Physiol Behav. 2013 Sep 10;121:103-11
pubmed: 23562867
Int J Obes (Lond). 2006 Sep;30(9):1322-31
pubmed: 16801931
Neuropsychopharmacology. 2011 Jan;36(1):133-52
pubmed: 20631684
Mol Psychiatry. 2014 Oct;19(10):1078-84
pubmed: 25199919
Mol Pharmacol. 1999 Feb;55(2):202-9
pubmed: 9927609
eNeuro. 2018 May 16;5(2):
pubmed: 29780881
Nat Rev Neurosci. 2016 Mar;17(3):183-95
pubmed: 26865020
Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):5099-104
pubmed: 15044694
Curr Top Behav Neurosci. 2012;11:1-24
pubmed: 22016109
J Abnorm Psychol. 2008 Nov;117(4):924-35
pubmed: 19025237
Neuroimage. 2007 Aug 15;37(2):410-21
pubmed: 17566768
Physiol Behav. 2014 Sep;136:63-73
pubmed: 24732416
Nat Neurosci. 2010 May;13(5):635-41
pubmed: 20348917
Mol Metab. 2013 Nov 20;3(2):167-76
pubmed: 24634821
J Neurosci. 2010 Feb 17;30(7):2428-32
pubmed: 20164326
Cell. 2014 Nov 6;159(4):896-910
pubmed: 25417164
Trends Pharmacol Sci. 2016 Oct;37(10):858-871
pubmed: 27546785
Physiol Behav. 2009 Jul 14;97(5):537-50
pubmed: 19336238
Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):7097-102
pubmed: 25964346
Sci Rep. 2018 Jul 9;8(1):10310
pubmed: 29985439
Nutrition. 2009 Jan;25(1):58-65
pubmed: 18834717
Nature. 2013 Feb 14;494(7436):238-42
pubmed: 23354054