Single-Nucleus RNA Sequencing of the Hypothalamic Arcuate Nucleus of C57BL/6J Mice After Prolonged Diet-Induced Obesity.
Adiposity
/ physiology
Agouti-Related Protein
/ genetics
Animals
Arcuate Nucleus of Hypothalamus
/ metabolism
Cyclic AMP Response Element-Binding Protein
/ metabolism
Diet, High-Fat
/ adverse effects
Leptin
/ blood
Male
Mice
Neurons
/ metabolism
Obesity
/ etiology
Phosphorylation
Sequence Analysis, RNA
Signal Transduction
/ physiology
biology
hypothalamus
leptin
metabolism
obesity
Journal
Hypertension (Dallas, Tex. : 1979)
ISSN: 1524-4563
Titre abrégé: Hypertension
Pays: United States
ID NLM: 7906255
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
pubmed:
9
6
2020
medline:
17
4
2021
entrez:
9
6
2020
Statut:
ppublish
Résumé
Prolonged obesity is associated with blunted feeding and thermogenic autonomic responses to leptin, but cardiovascular responses to leptin are maintained. This state of selective leptin resistance is, therefore, proposed to contribute to the pathogenesis and maintenance of obesity-associated hypertension. Cells of the arcuate nucleus of the hypothalamus detect leptin, and although the cellular and molecular mechanisms remain unclear, altered arcuate nucleus biology is hypothesized to contribute to selective leptin resistance. Male C57BL/6J mice were fed a high-fat diet (HFD) or chow from 8 to 18 weeks of age, as this paradigm models selective leptin resistance. Nuclei were then isolated from arcuate nucleus for single-nucleus RNA sequencing. HFD caused expected gains in adiposity and circulating leptin. Twenty-three unique cell-type clusters were identified, and Ingenuity Pathway Analysis was used to explore changes in gene expression patterns due to chronic HFD within each cluster. Notably, gene expression signatures related to leptin signaling exhibited suppression predominantly in neurons identified as the Agouti-related peptide (
Identifiants
pubmed: 32507042
doi: 10.1161/HYPERTENSIONAHA.120.15137
pmc: PMC7347451
mid: NIHMS1592952
doi:
Substances chimiques
Agouti-Related Protein
0
Agrp protein, mouse
0
Cyclic AMP Response Element-Binding Protein
0
Leptin
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
589-597Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL134850
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007638
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL144807
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL084207
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001436
Pays : United States
Organisme : BLRD VA
ID : I01 BX004249
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL127673
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008629
Pays : United States
Références
Curr Hypertens Rep. 2018 Mar 19;20(3):25
pubmed: 29556733
Cell Metab. 2016 May 10;23(5):797-810
pubmed: 27166944
Sci Rep. 2020 Jan 30;10(1):1535
pubmed: 32001747
J Neurosci. 2014 Apr 16;34(16):5486-96
pubmed: 24741039
Mol Metab. 2018 Feb;8:1-12
pubmed: 29289646
Am J Physiol Regul Integr Comp Physiol. 2013 Sep 15;305(6):R566-81
pubmed: 23883674
Neurosci Lett. 2015 Sep 14;604:113-8
pubmed: 26254161
Nature. 2018 Apr;556(7702):505-509
pubmed: 29670283
Am J Physiol Regul Integr Comp Physiol. 2013 Dec;305(11):R1215-67
pubmed: 23904103
Science. 2019 May 17;364(6441):685-689
pubmed: 31097668
Nat Neurosci. 2017 Feb;20(2):176-188
pubmed: 27991900
Diabetes. 2006 Aug;55(8):2220-30
pubmed: 16873684
Cell Metab. 2007 Mar;5(3):181-94
pubmed: 17339026
Nat Rev Nephrol. 2019 Jun;15(6):367-385
pubmed: 31015582
J Neurosci. 2017 Apr 5;37(14):3875-3886
pubmed: 28275162
Mol Cell Biol. 2013 Oct;33(19):3826-34
pubmed: 23897430
Endocrinology. 2006 Sep;147(9):4486-95
pubmed: 16763061
Diabetes. 2005 Jul;54(7):2012-8
pubmed: 15983201
J Clin Invest. 2017 Apr 3;127(4):1414-1424
pubmed: 28263184
Mol Cell Endocrinol. 2009 Aug 13;307(1-2):99-108
pubmed: 19524132
Bioinformatics. 2014 Feb 15;30(4):523-30
pubmed: 24336805
Nat Commun. 2015 Sep 18;6:8237
pubmed: 26381935
Cell Rep. 2014 Nov 20;9(4):1495-506
pubmed: 25456138
Cell. 2012 Jun 8;149(6):1314-26
pubmed: 22682251
Front Neurosci. 2019 Nov 19;13:1217
pubmed: 31803004
Am J Physiol Endocrinol Metab. 2013 Dec;305(12):E1512-20
pubmed: 24169048
PLoS One. 2018 Dec 26;13(12):e0209648
pubmed: 30586455
Brain Behav Immun. 2020 Jul;87:272-285
pubmed: 31863824
Am J Physiol Regul Integr Comp Physiol. 2016 Oct 1;311(4):R764-R770
pubmed: 27534878
Mol Metab. 2012 Jul 26;1(1-2):61-9
pubmed: 24024119
Ann N Y Acad Sci. 2017 Mar;1391(1):35-53
pubmed: 27768821
Peptides. 2009 Feb;30(2):181-90
pubmed: 19059445
Nat Neurosci. 2017 Mar;20(3):484-496
pubmed: 28166221
Nat Methods. 2017 Oct;14(10):955-958
pubmed: 28846088
Elife. 2018 Mar 12;7:
pubmed: 29528284
Med Oncol. 2019 Jan 21;36(2):20
pubmed: 30666499
Am J Physiol Endocrinol Metab. 2002 Jun;282(6):E1352-9
pubmed: 12006366
Biochem Biophys Res Commun. 2018 Sep 10;503(3):1409-1414
pubmed: 30025893
Cell. 2018 Feb 22;172(5):1091-1107.e17
pubmed: 29474909
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
J Am Soc Nephrol. 2019 Jan;30(1):23-32
pubmed: 30510133
Obes Rev. 2015 Mar;16(3):207-24
pubmed: 25589226
Curr Hypertens Rep. 2019 Apr 26;21(6):46
pubmed: 31028563
J Neuroendocrinol. 2019 Aug;31(8):e12752
pubmed: 31136029
Circ Res. 2015 Mar 13;116(6):991-1006
pubmed: 25767285
Diabetes. 2009 Mar;58(3):536-42
pubmed: 19066310