Impaired Gut-Systemic Signaling Drives Total Parenteral Nutrition-Associated Injury.
Alanine Transaminase
/ metabolism
Animals
Cholestasis
Cholesterol 7-alpha-Hydroxylase
/ metabolism
Constitutive Androstane Receptor
Enteral Nutrition
Gastrointestinal Tract
/ drug effects
Intestinal Mucosa
Keratin-7
Liver
/ drug effects
Liver Diseases
Mitogen-Activated Protein Kinase 1
/ metabolism
Parenteral Nutrition
/ adverse effects
Parenteral Nutrition, Total
/ methods
Receptors, Cytoplasmic and Nuclear
Swine
gut injury
gut–systemic crosstalk
hepato-biliary receptors and transporters
liver disease
parenteral nutrition
Journal
Nutrients
ISSN: 2072-6643
Titre abrégé: Nutrients
Pays: Switzerland
ID NLM: 101521595
Informations de publication
Date de publication:
20 May 2020
20 May 2020
Historique:
received:
30
03
2020
revised:
11
05
2020
accepted:
13
05
2020
entrez:
24
5
2020
pubmed:
24
5
2020
medline:
17
2
2021
Statut:
epublish
Résumé
Total parenteral nutrition (TPN) provides all nutritional needs intravenously. Although lifesaving, enthusiasm is significantly tempered due to side effects of liver and gut injury, as well as lack of mechanistic understanding into drivers of TPN injury. We hypothesized that the state of luminal nutritional deprivation with TPN drives alterations in gut-systemic signaling, contributing to injury, and tested this hypothesis using our ambulatory TPN model. A total of 16 one-week-old piglets were allocated randomly to TPN ( TPN resulted in significant hyperbilirubinemia and cholestatic liver injury, We report significant alterations in key hepatobiliary receptors driving gut-systemic signaling in a TPN piglet model. This presents a major advancement to our understanding of TPN-associated injury and suggests opportunities for strategic targeting of the gut-systemic axis, specifically, FXR, TGR5, and EGF in developing ameliorative strategies.
Sections du résumé
BACKGROUND
BACKGROUND
Total parenteral nutrition (TPN) provides all nutritional needs intravenously. Although lifesaving, enthusiasm is significantly tempered due to side effects of liver and gut injury, as well as lack of mechanistic understanding into drivers of TPN injury. We hypothesized that the state of luminal nutritional deprivation with TPN drives alterations in gut-systemic signaling, contributing to injury, and tested this hypothesis using our ambulatory TPN model.
METHODS
METHODS
A total of 16 one-week-old piglets were allocated randomly to TPN (
RESULTS
RESULTS
TPN resulted in significant hyperbilirubinemia and cholestatic liver injury,
CONCLUSION
CONCLUSIONS
We report significant alterations in key hepatobiliary receptors driving gut-systemic signaling in a TPN piglet model. This presents a major advancement to our understanding of TPN-associated injury and suggests opportunities for strategic targeting of the gut-systemic axis, specifically, FXR, TGR5, and EGF in developing ameliorative strategies.
Identifiants
pubmed: 32443928
pii: nu12051493
doi: 10.3390/nu12051493
pmc: PMC7284746
pii:
doi:
Substances chimiques
Constitutive Androstane Receptor
0
Keratin-7
0
Receptors, Cytoplasmic and Nuclear
0
Cholesterol 7-alpha-Hydroxylase
EC 1.14.14.23
Alanine Transaminase
EC 2.6.1.2
Mitogen-Activated Protein Kinase 1
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : R03EB015955-01
Pays : United States
Organisme : NIDDK NIH HHS
ID : R03 DK121046
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK098623
Pays : United States
Organisme : NIH HHS
ID : R13DK109671-01
Pays : United States
Organisme : DeNardo Foundation
ID : DeNardo
Organisme : NIH HHS
ID : K08DK098623
Pays : United States
Références
Hepatology. 2008 Nov;48(5):1632-43
pubmed: 18972444
Clin Liver Dis. 2017 Nov;21(4):687-695
pubmed: 28987256
Acta Pharm Sin B. 2016 Sep;6(5):409-412
pubmed: 27709009
Dig Liver Dis. 2014 Apr;46(4):302-12
pubmed: 24411485
JPEN J Parenter Enteral Nutr. 2016 Jan;40(1):67-72
pubmed: 25921560
J Surg Res. 2019 Feb;234:13-19
pubmed: 30527464
JPEN J Parenter Enteral Nutr. 2017 Feb;41(2):198-207
pubmed: 27503935
Cell Mol Gastroenterol Hepatol. 2017 Jan 17;3(3):447-468
pubmed: 28462383
J Nutr. 1993 Feb;123(2 Suppl):395-8
pubmed: 8429393
JPEN J Parenter Enteral Nutr. 2018 Feb;42(2):279-295
pubmed: 29443403
Exp Biol Med (Maywood). 2020 Jun;245(12):1049-1057
pubmed: 32264693
Nutrients. 2017 Apr 14;9(4):
pubmed: 28420095
Med Sci (Basel). 2018 Sep 17;6(3):
pubmed: 30227645
Early Hum Dev. 2010 Nov;86(11):683-7
pubmed: 20923719
JPEN J Parenter Enteral Nutr. 2003 Jul-Aug;27(4):291-9
pubmed: 12903895
Adv Nutr. 2013 Nov 06;4(6):711-7
pubmed: 24228202
Science. 1999 May 21;284(5418):1362-5
pubmed: 10334992
Semin Liver Dis. 2010 May;30(2):186-94
pubmed: 20422500
Lab Invest. 2011 Aug;91(8):1136-45
pubmed: 21519326
J Pediatr. 2012 Mar;160(3):421-7
pubmed: 21982303
Curr Opin Gastroenterol. 2019 Mar;35(2):126-133
pubmed: 30585838
Int J Clin Exp Pathol. 2014 Jun 15;7(7):4076-85
pubmed: 25120786
Gastroenterology. 2012 Dec;143(6):1473-1481.e3
pubmed: 22982184
Curr Opin Organ Transplant. 2010 Jun;15(3):330-3
pubmed: 20386446
Surg Clin North Am. 2011 Jun;91(3):693-717
pubmed: 21621704
J Hum Nutr (Carson City). 2020;4(1):
pubmed: 32705087
Curr Med Chem. 2014;21(24):2822-9
pubmed: 24606522
J Pediatr Surg. 2005 Jun;40(6):1015-8
pubmed: 15991188
Clin Nutr. 2018 Dec;37(6 Pt A):1794-1797
pubmed: 30017241
Clin Nutr. 2016 Dec;35(6):1209-1218
pubmed: 27126711
J Nutr. 1993 Jul;123(7):1248-59
pubmed: 8320564
JPEN J Parenter Enteral Nutr. 2012 Mar;36(2):205-12
pubmed: 22190604
Clin Nutr. 2018 Dec;37(6 Pt A):1798-1809
pubmed: 30172658
Cell Metab. 2005 Oct;2(4):217-25
pubmed: 16213224
JPEN J Parenter Enteral Nutr. 2009 Nov-Dec;33(6):618-25; discussion 626
pubmed: 19675300
Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2020-30
pubmed: 16037564
Saudi J Gastroenterol. 2014 Sep-Oct;20(5):293-6
pubmed: 25253364
BMC Nurs. 2005 Feb 01;4(1):2
pubmed: 15686591
J Pediatr Surg. 2006 May;41(5):950-4
pubmed: 16677891
F1000Res. 2018 Jan 18;7:85
pubmed: 29399329
Ann Pharmacother. 2007 Nov;41(11):1867-72
pubmed: 17911205
Clin Nutr. 2017 Oct;36(5):1349-1354
pubmed: 27663542
JPEN J Parenter Enteral Nutr. 2014 Jul;38(5):538-57
pubmed: 24696095
Mediators Inflamm. 2016;2016:1927348
pubmed: 27524860
J Anim Sci. 2013 May;91(5):1991-2000
pubmed: 23729782
Dev Cell. 2002 Jun;2(6):721-31
pubmed: 12062085
Pediatr Dev Pathol. 2007 Sep-Oct;10(5):383-90
pubmed: 17929991
Children (Basel). 2018 Sep 25;5(10):
pubmed: 30257520
J Hepatol. 2018 Feb;68(2):280-295
pubmed: 29154964
Curr Opin Pediatr. 2017 Jun;29(3):363-370
pubmed: 28333693
Science. 1999 May 21;284(5418):1365-8
pubmed: 10334993
J Pediatr Gastroenterol Nutr. 2017 Nov;65(5):588-596
pubmed: 28837507
World J Gastroenterol. 2012 Nov 28;18(44):6357-75
pubmed: 23197881
J Pediatr. 2002 Aug;141(2):237-42
pubmed: 12183720
J Nutr. 2006 Oct;136(10):2547-52
pubmed: 16988124
Nutr Res. 2015 Feb;35(2):169-74
pubmed: 25649660
Pediatr Gastroenterol Hepatol Nutr. 2016 Mar;19(1):44-53
pubmed: 27066448
Clin Gastroenterol Hepatol. 2008 Aug;6(8):926-33
pubmed: 18674734
Physiology (Bethesda). 2008 Oct;23:286-95
pubmed: 18927204
MethodsX. 2015 Feb 21;2:124-34
pubmed: 26150980
JPEN J Parenter Enteral Nutr. 2018 Nov;42(8):1238-1251
pubmed: 29701901
Crit Rev Toxicol. 2014 Jan;44(1):64-82
pubmed: 24180433
Am J Physiol Gastrointest Liver Physiol. 2012 Jan 15;302(2):G218-24
pubmed: 22094603
Hepatol Int. 2018 Feb;12(Suppl 1):24-33
pubmed: 28550391
JPEN J Parenter Enteral Nutr. 2016 Sep;40(7):973-81
pubmed: 25837680
World J Gastroenterol. 2008 Oct 7;14(37):5630-40
pubmed: 18837078
J Biol Chem. 2005 Mar 4;280(9):7427-34
pubmed: 15590640
JPEN J Parenter Enteral Nutr. 2014 Jan;38(1):70-85
pubmed: 23894170
Children (Basel). 2015 Jul 31;2(3):358-70
pubmed: 27417369
Pediatr Int. 2012 Jun;54(3):434-6
pubmed: 22449297