title: The effects of liraglutide in mice with diet-induced obesity studied by metabolomics.
abstract: Liraglutide is the glucagon-like peptide-1 receptor agonist widely used for the treatment of type 2 diabetes mellitus. Recently, it has been demonstrated to decrease cardiovascular morbidity and mortality in patients with type 2 diabetes and high cardiovascular risk. Although the major modes of liraglutide action are well-known, its detailed action at the metabolic level has not been studied. To this end, we explored the effect of 2-week liraglutide treatment in C57BL/6 male mice with obesity and diabetes induced by 13 weeks of high-fat diet using NMR spectroscopy to capture the changes in urine metabolic profile induced by the therapy. The liraglutide treatment decreased body and fat pads weight along with blood glucose and triglyceride levels. NMR spectroscopy identified 11 metabolites significantly affected by liraglutide treatment as compared to high-fat diet-fed control group. These metabolites included ones involved in nicotinamide adenine dinucleotide metabolism, β-oxidation of fatty acids and microbiome changes. Although majority of the metabolites changed after liraglutide treatment were similar as the ones previously identified after vildagliptin administration in a similar mouse model, the changes in creatinine, taurine and trigonelline were specific for liraglutide administration. The significance of these changes and its possible use in the personalization of antidiabetic therapy in humans requires further research.
authors.affiliation: Institute of MicrobiologyAcademy of Sciences of the Czech Republic, Prague, Czech Republic.|Faculty of Chemical TechnologyUniversity of Chemistry and Technology Prague, Prague, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Bugáňová
authors.affiliation: Institute of MicrobiologyAcademy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Helena
authors.initials: H
authors.lastname: Pelantová
authors.affiliation: Institute of Organic Chemistry and BiochemistryAcademy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Holubová
authors.affiliation: Faculty of Applied SciencesUniversity of West Bohemia, Plzeň, Czech Republic.
authors.forename: Blanka
authors.initials: B
authors.lastname: Šedivá
authors.affiliation: Institute of Organic Chemistry and BiochemistryAcademy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Maletínská
authors.affiliation: Institute of Organic Chemistry and BiochemistryAcademy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Blanka
authors.initials: B
authors.lastname: Železná
authors.affiliation: Institute of Organic Chemistry and BiochemistryAcademy of Sciences of the Czech Republic, Prague, Czech Republic.|Institute of PhysiologyAcademy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Kuneš
authors.affiliation: Institute of MicrobiologyAcademy of Sciences of the Czech Republic, Prague, Czech Republic.|Faculty of Chemical TechnologyUniversity of Chemistry and Technology Prague, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Kačer
authors.affiliation: Institute of MicrobiologyAcademy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Kuzma
authors.affiliation: Centre for Experimental Medicine and Diabetes CentreInstitute for Clinical and Experimental Medicine, Prague, Czech Republic mhalu@lf1.cuni.cz.|Institute of Medical Biochemistry and Laboratory Diagnostics1st Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Haluzík
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D059305:Diet, High-Fat; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000069450:Liraglutide / Q000494:pharmacology* / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics; D051379:Mice; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D014280:Triglycerides; D000069450:Liraglutide
keywords: NMR metabolomics; liraglutide; mouse urine; obesity; type 2 diabetes mellitus