Profile of the bile acid FXR-FGF15 pathway in the glucolipid metabolism disorder of diabetic mice suffering from chronic stress.
Bile acids
Depression
FGF15
FXR
Glucolipid metabolism
High fed diet
Insulin
Streptozotocin
Journal
PeerJ
ISSN: 2167-8359
Titre abrégé: PeerJ
Pays: United States
ID NLM: 101603425
Informations de publication
Date de publication:
2023
2023
Historique:
received:
01
05
2023
accepted:
13
10
2023
medline:
1
12
2023
pubmed:
29
11
2023
entrez:
29
11
2023
Statut:
epublish
Résumé
Imbalances in bile acid (BA) synthesis and metabolism are involved in the onset of diabetes and depression in humans and rodents. However, the role of BAs and the farnesoid X receptor (FXR)/fibroblast growth factor (FGF) 15 signaling pathway in the development of diabetes and depression is still largely unknown. Therefore, we investigated the potential molecular mechanisms of BAs that may be associated with glucolipid metabolism disorders in diabetic mice subjected to chronic stress. The type 2 diabetes mellitus (T2DM) mouse model was induced by feeding mice a high-fat diet and administering an intraperitoneal injection of streptozotocin (STZ). The chronic unpredictable mild stress (CUMS) procedure was performed by introducing a series of mild stressors. Forty mice were randomly divided into the regular chow feeding group and the high-fat diet feeding group. After two weeks of feeding, the mice were randomly divided into four groups: the Control group, CUMS group, T2DM group, and T2DM+CUMS group. The T2DM group and T2DM+CUMS group received an intraperitoneal injection of STZ to induce the T2DM model. The CUMS and T2DM+CUMS groups were exposed to CUMS to induce depressive-like phenotypes. Blood and tissue samples were obtained for pertinent analysis and detection. Compared with the T2DM mice, T2DM+CUMS mice had higher blood glucose and lipid levels, insulin resistance, inflammation of the liver and pancreas, impaired liver function, and increased total bile acids. These changes were accompanied by attenuated FXR signaling. Chronic stress was found to attenuate FXR expression and its downstream target, FGF15, in the ileum when compared with the T2DM group. FXR may play a role in the diabetic disorder of glucolipid metabolism when aggravated by chronic stress. FXR and its downstream target, FGF15, may be therapeutic targets for treating comorbid T2DM and depression.
Sections du résumé
Background
UNASSIGNED
Imbalances in bile acid (BA) synthesis and metabolism are involved in the onset of diabetes and depression in humans and rodents. However, the role of BAs and the farnesoid X receptor (FXR)/fibroblast growth factor (FGF) 15 signaling pathway in the development of diabetes and depression is still largely unknown. Therefore, we investigated the potential molecular mechanisms of BAs that may be associated with glucolipid metabolism disorders in diabetic mice subjected to chronic stress.
Methods
UNASSIGNED
The type 2 diabetes mellitus (T2DM) mouse model was induced by feeding mice a high-fat diet and administering an intraperitoneal injection of streptozotocin (STZ). The chronic unpredictable mild stress (CUMS) procedure was performed by introducing a series of mild stressors. Forty mice were randomly divided into the regular chow feeding group and the high-fat diet feeding group. After two weeks of feeding, the mice were randomly divided into four groups: the Control group, CUMS group, T2DM group, and T2DM+CUMS group. The T2DM group and T2DM+CUMS group received an intraperitoneal injection of STZ to induce the T2DM model. The CUMS and T2DM+CUMS groups were exposed to CUMS to induce depressive-like phenotypes. Blood and tissue samples were obtained for pertinent analysis and detection.
Results
UNASSIGNED
Compared with the T2DM mice, T2DM+CUMS mice had higher blood glucose and lipid levels, insulin resistance, inflammation of the liver and pancreas, impaired liver function, and increased total bile acids. These changes were accompanied by attenuated FXR signaling. Chronic stress was found to attenuate FXR expression and its downstream target, FGF15, in the ileum when compared with the T2DM group.
Conclusion
UNASSIGNED
FXR may play a role in the diabetic disorder of glucolipid metabolism when aggravated by chronic stress. FXR and its downstream target, FGF15, may be therapeutic targets for treating comorbid T2DM and depression.
Identifiants
pubmed: 38025699
doi: 10.7717/peerj.16407
pii: 16407
pmc: PMC10656902
doi:
Substances chimiques
Bile Acids and Salts
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e16407Informations de copyright
©2023 Cai et al.
Déclaration de conflit d'intérêts
The authors declare there are no competing interests.
Références
PLoS One. 2014 Mar 20;9(3):e92574
pubmed: 24651118
J Biol Chem. 2006 Apr 21;281(16):11039-49
pubmed: 16446356
Nat Med. 2018 Dec;24(12):1919-1929
pubmed: 30397356
FASEB J. 2022 Jan;36(1):e22100
pubmed: 34939244
J Med Life. 2016 Apr-Jun;9(2):120-5
pubmed: 27453739
Psychopharmacology (Berl). 2020 Mar;237(3):695-705
pubmed: 31786648
Dig Dis. 2015;33(3):327-31
pubmed: 26045265
Medicine (Baltimore). 2016 Mar;95(10):e2778
pubmed: 26962776
Pharmacol Ther. 2021 Oct;226:107867
pubmed: 33895191
Diabet Med. 2008 Sep;25(9):1096-101
pubmed: 19183314
Mol Biosyst. 2010 May;6(5):852-61
pubmed: 20567771
Nat Metab. 2022 Apr;4(4):416-423
pubmed: 35338368
Prim Care Diabetes. 2022 Feb;16(1):1-10
pubmed: 34810141
Metabolism. 1998 Jun;47(6):663-8
pubmed: 9627363
Mol Cell Endocrinol. 2013 Apr 10;368(1-2):17-29
pubmed: 22609541
Horm Res Paediatr. 2022;95(2):149-166
pubmed: 34915489
Mamm Genome. 2013 Jun;24(5-6):240-51
pubmed: 23712496
J Cachexia Sarcopenia Muscle. 2022 Apr;13(2):1177-1196
pubmed: 35060352
Lancet Diabetes Endocrinol. 2015 Jun;3(6):461-471
pubmed: 25995124
Physiol Rev. 2018 Jan 1;98(1):117-214
pubmed: 29212789
Front Behav Neurosci. 2015 Mar 30;9:70
pubmed: 25870546
Food Funct. 2015 Feb;6(2):558-65
pubmed: 25518825
J Biol Chem. 2005 Aug 19;280(33):29971-9
pubmed: 15899888
J Clin Invest. 2006 Apr;116(4):1102-9
pubmed: 16557297
Mol Med Rep. 2019 Apr;19(4):2953-2959
pubmed: 30720089
Curr Protoc. 2021 Apr;1(4):e78
pubmed: 33905609
Genes Dev. 2012 Feb 15;26(4):312-24
pubmed: 22302876
Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):1006-11
pubmed: 16410358
Neurosci Biobehav Rev. 2022 Aug;139:104758
pubmed: 35777578
Mol Endocrinol. 2003 Feb;17(2):259-72
pubmed: 12554753
Liver Int. 2015 Apr;35(4):1133-1144
pubmed: 25156247
Curr Opin Clin Nutr Metab Care. 2012 Jul;15(4):386-91
pubmed: 22617565
Cell. 2000 Sep 15;102(6):731-44
pubmed: 11030617
Curr Protoc. 2021 Aug;1(8):e208
pubmed: 34406704
J Affect Disord. 2012 Oct;142 Suppl:S56-66
pubmed: 23062858
Neuropharmacology. 2018 Jul 1;136(Pt B):327-334
pubmed: 29180223
Mol Cell Biol. 2013 Jun;33(11):2202-11
pubmed: 23530060
Hepatology. 2017 Dec;66(6):1854-1865
pubmed: 28586124
Front Neurosci. 2017 Nov 07;11:617
pubmed: 29163019
Lancet Diabetes Endocrinol. 2015 Jun;3(6):472-485
pubmed: 25995125
Ann Fam Med. 2006 Jan-Feb;4(1):46-53
pubmed: 16449396
Int J Epidemiol. 2011 Jun;40(3):804-18
pubmed: 21335614
Diabetes. 2009 Apr;58(4):773-95
pubmed: 19336687
Diabetes Res Clin Pract. 2022 Jan;183:109119
pubmed: 34879977
J Clin Invest. 2004 May;113(10):1408-18
pubmed: 15146238
Biochem Pharmacol. 2021 Jun;188:114561
pubmed: 33857491
Neuromolecular Med. 2021 Mar;23(1):99-117
pubmed: 33085065
Cell Metab. 2011 Jun 8;13(6):729-38
pubmed: 21641554
Proteomics. 2022 Aug;22(15-16):e2100324
pubmed: 35731901
Int J Mol Sci. 2018 Dec 11;19(12):
pubmed: 30544908
J Gen Intern Med. 2010 Jun;25(6):524-9
pubmed: 20182815
J Ethnopharmacol. 2020 Oct 5;260:112832
pubmed: 32387465
Diabetologia. 2019 Jan;62(1):3-16
pubmed: 30171279
Diabetes Res Clin Pract. 2010 Mar;87(3):302-12
pubmed: 20181405
Dialogues Clin Neurosci. 2018 Mar;20(1):47-52
pubmed: 29946211
Exp Diabetes Res. 2011;2011:416254
pubmed: 22164157
Diabet Med. 2006 Nov;23(11):1165-73
pubmed: 17054590
Trends Endocrinol Metab. 2015 Jan;26(1):22-9
pubmed: 25476453
Curr Vasc Pharmacol. 2020;18(2):110-116
pubmed: 30961498
Biomolecules. 2019 Jun 15;9(6):
pubmed: 31208099
Science. 2011 Mar 25;331(6024):1621-4
pubmed: 21436455
World Psychiatry. 2016 Jun;15(2):166-74
pubmed: 27265707
Drugs. 2015 Apr;75(6):577-87
pubmed: 25851098
J Clin Endocrinol Metab. 2016 Aug;101(8):3002-9
pubmed: 27270475