Hepatic Fibroblast Growth Factor 21 Is Involved in Mediating Functions of Liraglutide in Mice With Dietary Challenge.
Animals
Cells, Cultured
Diet, High-Fat
/ methods
Dipeptidyl-Peptidase IV Inhibitors
/ pharmacology
Disease Models, Animal
Fibroblast Growth Factors
/ metabolism
Glucagon-Like Peptide-1 Receptor
/ agonists
Hepatocytes
/ drug effects
Hypoglycemic Agents
/ pharmacology
Lipid Metabolism
/ drug effects
Liraglutide
/ pharmacology
Mice
Mice, Knockout
Non-alcoholic Fatty Liver Disease
/ metabolism
Sitagliptin Phosphate
/ pharmacology
Journal
Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
24
03
2021
received:
15
12
2020
accepted:
08
04
2021
pubmed:
15
4
2021
medline:
13
1
2022
entrez:
14
4
2021
Statut:
ppublish
Résumé
Several studies have shown that expression of hepatic fibroblast growth factor 21 (FGF21) can be stimulated by glucagon-like peptide 1 (GLP-1)-based diabetes drugs. As GLP-1 receptor (GLP-1R) is unlikely to be expressed in hepatocytes, we aimed to compare such stimulation in mice and in mouse hepatocytes, determine the involvement of GLP-1R, and clarify whether FGF21 mediates certain functions of the GLP-1R agonist liraglutide. Liver FGF21 expression was assessed in mice receiving a daily liraglutide injection for 3 days or in mouse primary hepatocytes (MPHs) undergoing direct liraglutide treatment. The effects of liraglutide on metabolic improvement and FGF21 expression were then assessed in high-fat diet (HFD)-fed mice and compared with the effects of the dipeptidyl-peptidase 4 inhibitor sitagliptin. Animal studies were also performed in Glp1r We suggest that liraglutide-stimulated hepatic Fgf21 expression may require GLP-1R to be expressed in extrahepatic organs. Importantly, we revealed that hepatic FGF21 is required for liraglutide to lower body weight and improve hepatic lipid homeostasis. These observations advanced our mechanistic understanding of the function of GLP-1-based drugs in NAFLD.
Sections du résumé
BACKGROUND AND AIMS
Several studies have shown that expression of hepatic fibroblast growth factor 21 (FGF21) can be stimulated by glucagon-like peptide 1 (GLP-1)-based diabetes drugs. As GLP-1 receptor (GLP-1R) is unlikely to be expressed in hepatocytes, we aimed to compare such stimulation in mice and in mouse hepatocytes, determine the involvement of GLP-1R, and clarify whether FGF21 mediates certain functions of the GLP-1R agonist liraglutide.
APPROACH AND RESULTS
Liver FGF21 expression was assessed in mice receiving a daily liraglutide injection for 3 days or in mouse primary hepatocytes (MPHs) undergoing direct liraglutide treatment. The effects of liraglutide on metabolic improvement and FGF21 expression were then assessed in high-fat diet (HFD)-fed mice and compared with the effects of the dipeptidyl-peptidase 4 inhibitor sitagliptin. Animal studies were also performed in Glp1r
CONCLUSIONS
We suggest that liraglutide-stimulated hepatic Fgf21 expression may require GLP-1R to be expressed in extrahepatic organs. Importantly, we revealed that hepatic FGF21 is required for liraglutide to lower body weight and improve hepatic lipid homeostasis. These observations advanced our mechanistic understanding of the function of GLP-1-based drugs in NAFLD.
Substances chimiques
Dipeptidyl-Peptidase IV Inhibitors
0
Glucagon-Like Peptide-1 Receptor
0
Hypoglycemic Agents
0
fibroblast growth factor 21
0
Fibroblast Growth Factors
62031-54-3
Liraglutide
839I73S42A
Sitagliptin Phosphate
TS63EW8X6F
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2154-2169Subventions
Organisme : CIHR
ID : PJT159735
Pays : Canada
Informations de copyright
© 2021 by the American Association for the Study of Liver Diseases.
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