Ursodeoxycholic Acid (UDCA) Promotes Lactate Metabolism in Mouse Hepatocytes through Cholic Acid (CA) - Farnesoid X Receptor (FXR) Pathway.
Lactate
cholic acid
farnesoid X receptor
hepatocytes
hyperlactatemia
ursodeoxycholic acid
Journal
Current molecular medicine
ISSN: 1875-5666
Titre abrégé: Curr Mol Med
Pays: Netherlands
ID NLM: 101093076
Informations de publication
Date de publication:
2020
2020
Historique:
received:
16
08
2019
revised:
30
12
2019
accepted:
12
01
2020
pubmed:
24
1
2020
medline:
23
11
2021
entrez:
24
1
2020
Statut:
ppublish
Résumé
Persistent hyperlactatemia is associated with greater mortality in shock. Liver is the main site of lactate metabolism. In the first part, freshly isolated hepatocytes were incubated in 10% fetal bovine serum William's E medium supplemented with 10 mM lactate. Cells were then exposed to 100 μM ursodeoxycholic acid (UDCA), with no addition (control) for 2, 4, 6, 8 h. In the second part, hepatocytes were treated with Silencer select siRNA targeting FXR or scramble siRNA. The siRNA treatment was repeated twenty four hours later, and the cells were used in the experiments twenty-four hours after the second treatment. Then hepatocytes were incubated in 10% fetal bovine serum William's E medium supplemented with 10 mM lactate. Cells were then exposed to 100 μM UDCA for 2, 4, 6, 8 h. Lactate concentration was determined by ABL80 automatic blood gas analyzer. UDCA increased ability of hepatocytes to remove lactate. After the knockdown of FXR, effects caused by UDCA were weakened. These results demonstrate that UDCA promotes lactate metabolism in mouse hepatocytes through CA-FXR pathway.
Sections du résumé
BACKGROUND
Persistent hyperlactatemia is associated with greater mortality in shock. Liver is the main site of lactate metabolism.
METHOD
In the first part, freshly isolated hepatocytes were incubated in 10% fetal bovine serum William's E medium supplemented with 10 mM lactate. Cells were then exposed to 100 μM ursodeoxycholic acid (UDCA), with no addition (control) for 2, 4, 6, 8 h. In the second part, hepatocytes were treated with Silencer select siRNA targeting FXR or scramble siRNA. The siRNA treatment was repeated twenty four hours later, and the cells were used in the experiments twenty-four hours after the second treatment. Then hepatocytes were incubated in 10% fetal bovine serum William's E medium supplemented with 10 mM lactate. Cells were then exposed to 100 μM UDCA for 2, 4, 6, 8 h. Lactate concentration was determined by ABL80 automatic blood gas analyzer.
RESULTS
UDCA increased ability of hepatocytes to remove lactate. After the knockdown of FXR, effects caused by UDCA were weakened.
CONCLUSION
These results demonstrate that UDCA promotes lactate metabolism in mouse hepatocytes through CA-FXR pathway.
Identifiants
pubmed: 31971110
pii: CMM-EPUB-103882
doi: 10.2174/1566524020666200123161340
doi:
Substances chimiques
Fxr1h protein, mouse
0
Lactates
0
RNA-Binding Proteins
0
Ursodeoxycholic Acid
724L30Y2QR
Cholic Acid
G1JO7801AE
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
661-666Subventions
Organisme : National Natural Science Fund of China
ID : 81801901
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.