Loss of Glp2r signaling activates hepatic stellate cells and exacerbates diet-induced steatohepatitis in mice.
JCI Insight
; 5(8)2020 04 23.
Article
in En
| MEDLINE
| ID: mdl-32191643
ABSTRACT
A glucagon-like peptide-2 (GLP-2) analog is used in individuals with intestinal failure who are at risk for liver disease, yet the hepatic actions of GLP-2 are not understood. Treatment of high-fat diet-fed (HFD-fed) mice with GLP-2 did not modify the development of hepatosteatosis or hepatic inflammation. In contrast, Glp2r-/- mice exhibited increased hepatic lipid accumulation, deterioration in glucose tolerance, and upregulation of biomarkers of hepatic inflammation. Both mouse and human liver expressed the canonical GLP-2 receptor (GLP-2R), and hepatic Glp2r expression was upregulated in mice with hepatosteatosis. Cell fractionation localized the Glp2r to hepatic stellate cells (HSCs), and markers of HSC activation and fibrosis were increased in livers of Glp2r-/- mice. Moreover, GLP-2 directly modulated gene expression in isolated HSCs ex vivo. Taken together, these findings define an essential role for the GLP-2R in hepatic adaptation to nutrient excess and unveil a gut hormone-HSC axis, linking GLP-2R signaling to control of HSC activation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glucagon-Like Peptide 2
/
Hepatic Stellate Cells
/
Fatty Liver
/
Glucagon-Like Peptide-2 Receptor
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
JCI Insight
Year:
2020
Document type:
Article
Affiliation country:
Canada
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
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US
/
USA