Melanocortin 1 receptor regulates cholesterol and bile acid metabolism in the liver.
bile acid
cell biology
cholesterol
fibrosis
medicine
melanocortin 1 receptor
mouse
steatosis
triglyceride
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
25 07 2023
25 07 2023
Historique:
received:
08
11
2022
accepted:
13
07
2023
medline:
26
7
2023
pubmed:
25
7
2023
entrez:
25
7
2023
Statut:
epublish
Résumé
Melanocortin 1 receptor (MC1-R) is widely expressed in melanocytes and leukocytes and is thus strongly implicated in the regulation of skin pigmentation and inflammation. MC1-R has also been found in the rat and human liver, but its functional role has remained elusive. We hypothesized that MC1-R is functionally active in the liver and involved in the regulation of cholesterol and bile acid metabolism. We generated hepatocyte-specific MC1-R knock-out (Mc1r LKO) mice and phenotyped the mouse model for lipid profiles, liver histology, and bile acid levels. Mc1r LKO mice had significantly increased liver weight, which was accompanied by elevated levels of total cholesterol and triglycerides in the liver as well as in the plasma. These mice demonstrated also enhanced liver fibrosis and a disturbance in bile acid metabolism as evidenced by markedly reduced bile acid levels in the plasma and feces. Mechanistically, using HepG2 cells as an in vitro model, we found that selective activation of MC1-R in HepG2 cells reduced cellular cholesterol content and enhanced uptake of low- and high-density lipoprotein particles
Identifiants
pubmed: 37490042
doi: 10.7554/eLife.84782
pii: 84782
pmc: PMC10368426
doi:
pii:
Substances chimiques
Receptor, Melanocortin, Type 1
0
Cholesterol
97C5T2UQ7J
Bile Acids and Salts
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : GM-104080
Pays : United States
Informations de copyright
© 2023, Thapa et al.
Déclaration de conflit d'intérêts
KT, JK, KS, IP, BG, MC, ES, PR No competing interests declared
Références
Hepatology. 2015 Jun;61(6):2100-3
pubmed: 25503476
Peptides. 1996;17(4):675-9
pubmed: 8804079
J Gastroenterol. 2006 Oct;41(10):971-80
pubmed: 17096066
J Endocrinol. 2018 Mar;236(3):111-123
pubmed: 29317531
Mol Metab. 2021 Jun;48:101206
pubmed: 33684608
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
N Engl J Med. 2017 Nov 23;377(21):2063-2072
pubmed: 29166236
Cell Mol Life Sci. 2015 Apr;72(7):1331-45
pubmed: 25504085
Pharmacol Rev. 2004 Mar;56(1):1-29
pubmed: 15001661
Toxicol Appl Pharmacol. 2013 Apr 15;268(2):132-40
pubmed: 23391614
Histochem Cell Biol. 2012 Mar;137(3):279-91
pubmed: 22183812
Am J Physiol. 1983 Jul;245(1):E47-54
pubmed: 6869528
Atherosclerosis. 2015 Mar;239(1):192-202
pubmed: 25617860
Clin Chim Acta. 2007 Jul;382(1-2):82-8
pubmed: 17482152
Compr Physiol. 2013 Jan;3(1):541-65
pubmed: 23720296
Epidemiol Rev. 2007;29:1-5
pubmed: 17569676
Nutrients. 2013 Apr 12;5(4):1218-40
pubmed: 23584084
Arterioscler Thromb Vasc Biol. 2015 Jul;35(7):1678-86
pubmed: 25931512
Mol Cell Endocrinol. 1994 Jun;102(1-2):R7-11
pubmed: 7926261
Arthritis Res Ther. 2022 Sep 1;24(1):210
pubmed: 36050717
Invest Ophthalmol Vis Sci. 2007 Mar;48(3):1219-27
pubmed: 17325166
Front Cell Dev Biol. 2022 Mar 21;10:819281
pubmed: 35386193
Physiol Rev. 2009 Jul;89(3):1025-78
pubmed: 19584320
Ann N Y Acad Sci. 1999 Oct 20;885:188-95
pubmed: 10816652
Science. 1992 Aug 28;257(5074):1248-51
pubmed: 1325670
J Biol Chem. 1999 Jan 1;274(1):305-15
pubmed: 9867845
J Biol Chem. 2004 May 21;279(21):22404-11
pubmed: 14988395
J Immunol. 1997 Aug 15;159(4):1930-7
pubmed: 9257858
Nucleic Acids Res. 2013 May 1;41(10):e108
pubmed: 23558742
Endocr Rev. 1988 Feb;9(1):159-79
pubmed: 3286233
J Hepatol. 2009 Apr;50(4):789-96
pubmed: 19231010
Anal Bioanal Chem. 2014 Dec;406(30):7799-815
pubmed: 25384335
Liver Res. 2019 May 21;3(2):88-98
pubmed: 32015930
Neuroimmunomodulation. 2006;13(1):51-5
pubmed: 16864968
Pharmacol Biochem Behav. 1978 Aug;9(2):207-12
pubmed: 714971
J Clin Endocrinol Metab. 2004 Jun;89(6):2595-600
pubmed: 15181029
Nat Rev Drug Discov. 2008 Apr;7(4):307-23
pubmed: 18323849
J Biol Chem. 2002 Dec 13;277(50):48158-64
pubmed: 12368294
Cell. 1993 Oct 8;75(1):187-97
pubmed: 8402897
J Mol Endocrinol. 2015 Oct;55(2):R11-22
pubmed: 26363062
J Lipid Res. 2003 May;44(5):1001-9
pubmed: 12588950
Biochim Biophys Acta. 2014 Oct;1842(10):1431-9
pubmed: 25048193
Cell Metab. 2012 May 2;15(5):665-74
pubmed: 22560219
J Am Chem Soc. 2010 Jun 16;132(23):8115-28
pubmed: 20496895
J Hepatol. 2011 Jan;54(1):153-9
pubmed: 20947198
Semin Immunol. 2022 Jan;59:101603
pubmed: 35341670
Am J Physiol Endocrinol Metab. 2003 Mar;284(3):E468-74
pubmed: 12556347
Exp Dermatol. 2014 Jun;23(6):431-3
pubmed: 24698097
Hepatol Commun. 2018 Nov 12;3(1):84-98
pubmed: 30619997
Hepatology. 2004 Oct;40(4):910-7
pubmed: 15382124
Transl Neurodegener. 2022 Apr 13;11(1):22
pubmed: 35418104
J Hepatol. 2004 Mar;40(3):539-51
pubmed: 15123373
J Hepatol. 2021 Jun;74(6):1429-1441
pubmed: 33515644
Proc Natl Acad Sci U S A. 2020 Jul 14;117(28):16492-16499
pubmed: 32601222
Sci Transl Med. 2020 Dec 2;12(572):
pubmed: 33268509
Cell Metab. 2014 Sep 2;20(3):512-25
pubmed: 25043817
EMBO J. 1990 Aug;9(8):2439-46
pubmed: 2369897
Arterioscler Thromb Vasc Biol. 2018 Feb;38(2):313-323
pubmed: 29284608
Cell Rep. 2016 May 10;15(6):1291-302
pubmed: 27134165
Circulation. 2017 Jul 4;136(1):83-97
pubmed: 28450348
Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11603-7
pubmed: 7903453
Nat Med. 2018 Jul;24(7):908-922
pubmed: 29967350
J Lipid Res. 2009 Dec;50(12):2340-57
pubmed: 19498215
J Clin Invest. 2002 Jul;110(1):109-17
pubmed: 12093894
Prog Lipid Res. 2011 Oct;50(4):403-10
pubmed: 21801748