title: Liraglutide suppresses obesity and hyperglycemia associated with increases in hepatic fibroblast growth factor 21 production in KKAy mice.
abstract: Social isolation contributes to the development of obesity and insulin-independent diabetes in KKA(y) mice. Here we show that systemic administration of liraglutide, a long-acting human glucagon-like peptide-1 (GLP-1) analog, significantly decreased food intake, body weight, and blood glucose levels at 24 h after its administration while having no significant effects on plasma insulin and glucagon levels in individually housed KKA(y) mice. In addition, the systemic administration of liraglutide significantly increased plasma fibroblast growth factor (Fgf) 21 levels (1.8-fold increase) associated with increases in the expression of hepatic Fgf21 (1.9-fold increase) and Pparγ (1.8-fold increase), while having no effects on the expression of hepatic Pparα and Fgf21 in white adipose tissue. Moreover, systemic administration of liraglutide over 3 days significantly suppressed food intake, body weight gain, and hyperglycemia in KKA(y) mice. On the other hand, despite remarkably increased plasma active GLP-1 levels (4.2-fold increase), the ingestion of alogliptin, a selective dipeptidyl peptidase-4 inhibitor, over 3 days had no effects on food intake, body weight, blood glucose levels, and plasma Fgf21 levels in KKA(y) mice. These findings suggest that systemic administration of liraglutide induces hepatic Fgf21 production and suppresses the social isolation-induced obesity and diabetes independently of insulin, glucagon, and active GLP-1 in KKA(y) mice.
authors.affiliation: Department of Lifestyle Medicine, Translational Research Center, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Nonogaki
authors.affiliation: Department of Lifestyle Medicine, Translational Research Center, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Hazama
authors.affiliation: Department of Lifestyle Medicine, Translational Research Center, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Satoh
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000096:biosynthesis*; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000069450:Liraglutide; D051379:Mice; D009765:Obesity / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D001786:Blood Glucose; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1