title: Gemigliptin ameliorates Western-diet-induced metabolic syndrome in mice.
abstract: Dipeptidyl peptidase 4 (DPP-4) inhibitors are widely used antihyperglycemic agents for type 2 diabetes mellitus. Recently, increasing attention has been focused on the pleiotropic actions of DPP-4 inhibitors. The aim of the present study was to examine whether gemigliptin, a recently developed DPP-4 inhibitor, could ameliorate features of metabolic syndrome. Mice were fed a Western diet (WD) for 12 weeks and were subsequently divided into 2 groups: mice fed a WD diet alone or mice fed a WD diet supplemented with gemigliptin for an additional 4 weeks. Gemigliptin treatment attenuated WD-induced body mass gain, hypercholesterolemia, adipocyte hypertrophy, and macrophage infiltration into adipose tissue, which were accompanied by an increased expression of uncoupling protein 1 in subcutaneous fat. These events contributed to improved insulin sensitivity, as assessed by the homeostasis model assessment of insulin resistance and intraperitoneal insulin tolerance test. Furthermore, gemigliptin reduced WD-induced hepatic triglyceride accumulation via inhibition of de novo lipogenesis and activation of fatty acid oxidation, which was accompanied by AMP-dependent protein kinase activation. Gemigliptin ameliorated WD-induced hepatic inflammation and fibrosis through suppression of oxidative stress. These results suggest that DPP-4 inhibitors may represent promising therapeutic agents for metabolic syndrome beyond their current role as antihyperglycemic agents.
authors.affiliation: a Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Choi
authors.affiliation: b Department of Immunology, School of Medicine, Catholic University of Daegu, Daegu, Republic of Korea.
authors.forename: Jaechan
authors.initials: J
authors.lastname: Leem
authors.affiliation: c Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Sungmi
authors.initials: S
authors.lastname: Park
authors.affiliation: b Department of Immunology, School of Medicine, Catholic University of Daegu, Daegu, Republic of Korea.
authors.forename: Chong-Kee
authors.initials: CK
authors.lastname: Lee
authors.affiliation: c Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University, Daegu, Republic of Korea.|d Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Keun-Gyu
authors.initials: KG
authors.lastname: Park
authors.affiliation: c Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University, Daegu, Republic of Korea.|d Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.|e BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Lee
mesh_terms: D017667:Adipocytes / Q000473:pathology; D000818:Animals; D066273:Diet, Western / Q000009:adverse effects*; D005234:Fatty Liver / Q000188:drug therapy; D005355:Fibrosis / Q000188:drug therapy; D006937:Hypercholesterolemia / Q000517:prevention & control; D006984:Hypertrophy / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy; D007333:Insulin Resistance; D008099:Liver / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010881:Piperidones / Q000494:pharmacology* / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use*; D050151:Subcutaneous Fat / Q000378:metabolism; D000071256:Uncoupling Protein 1 / Q000096:biosynthesis; D015430:Weight Gain / Q000187:drug effects
chemical_list: C534891:LC15-0444; D010881:Piperidones; D011743:Pyrimidines; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1
keywords: AMP-dependent protein kinase; DPP-4 inhibitor; Western diet; adipocyte hypertrophy; adipose inflammation; hypertrophie des adipocytes; inflammation adipeuse; inhibiteur de la DPP-4; metabolic syndrome; nonalcoholic steatohepatitis; oxidative stress; protéine kinase dépendante de l’AMP; régime alimentaire occidental; stress oxydant; stéatose hépatique non alcoolique; syndrome métabolique