Influence of endogenous glucagon-like peptide-2 on lipid disorders in mice fed a high-fat diet

ABSTRACT

Aim: The purpose of the present study was to investigate the influence of endogenous glucagon-like peptide-2 (GLP-2) on lipid profile in mice fed a standard diet (STD) or a high-fat diet (HFD). Materials and methods: HFD- and age-matched STD mice were injected once a day with GLP-2 (3–33), a GLP-2 receptor (GLP-2R) antagonist, or vehicle for 4 weeks. Results: HFD mice displayed increased intrahepatic lipid concentration and hepatic steatosis and higher plasma concentrations of cholesterol, LDL, AST, and ALT than STD mice. No difference was observed in lipid fecal elimination. In STD mice, the chronic treatment with GLP-2 (3–33) did not affect any parameter, while in HFD mice, it enhanced plasma triglycerides, cholesterol, ALT, and AST and reduced HDL, it increased intrahepatic lipid concentration, and it worsened the hepatic steatosis degree, without affecting lipid fecal elimination. Conclusions: The present results suggest that GLP-2R antagonism worsens lipid disorders in HFD mice, and endogenous GLP-2 might even exert a defensive role against lipid imbalance.

KEYWORDS:

• GLP-2
• insulin resistance
• lipids
• liver
• obesity

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This work was supported by a grant from Ministero dell’Istruzione, dell’Università e della Ricerca, Italy (FFR2012, University of Palermo).

Additional information

Funding

This work was supported by a grant from Ministero dell’Istruzione, dell’Università e della Ricerca, Italy (FFR2012, University of Palermo).

Notes on contributors

Sara Baldassano

Sara Baldassano conceived the idea of study, carried out the experiments and data analysis, and wrote the manuscript; Antonella Amato researched data and contributed to the discussion; Francesco Cappello and Francesca Rappa performed the morphological analysis; Flavia Mulè designed the study, reviewed, and refined the manuscript.

Antonella Amato

Sara Baldassano conceived the idea of study, carried out the experiments and data analysis, and wrote the manuscript; Antonella Amato researched data and contributed to the discussion; Francesco Cappello and Francesca Rappa performed the morphological analysis; Flavia Mulè designed the study, reviewed, and refined the manuscript.

Francesca Rappa

Sara Baldassano conceived the idea of study, carried out the experiments and data analysis, and wrote the manuscript; Antonella Amato researched data and contributed to the discussion; Francesco Cappello and Francesca Rappa performed the morphological analysis; Flavia Mulè designed the study, reviewed, and refined the manuscript.

Francesco Cappello

Sara Baldassano conceived the idea of study, carried out the experiments and data analysis, and wrote the manuscript; Antonella Amato researched data and contributed to the discussion; Francesco Cappello and Francesca Rappa performed the morphological analysis; Flavia Mulè designed the study, reviewed, and refined the manuscript.

Flavia Mulè

Sara Baldassano conceived the idea of study, carried out the experiments and data analysis, and wrote the manuscript; Antonella Amato researched data and contributed to the discussion; Francesco Cappello and Francesca Rappa performed the morphological analysis; Flavia Mulè designed the study, reviewed, and refined the manuscript.