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BioMed Research International
Volume 2014, Article ID 751930, 8 pages
Research Article

Liraglutide Suppresses Obesity and Hyperglycemia Associated with Increases in Hepatic Fibroblast Growth Factor 21 Production in KKAy Mice

Department of Lifestyle Medicine, Translational Research Center, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan

Received 12 February 2014; Accepted 5 March 2014; Published 7 April 2014

Academic Editor: Ruxana Sadikot

Copyright © 2014 Katsunori Nonogaki et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Social isolation contributes to the development of obesity and insulin-independent diabetes in KK 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 KK 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 Ppar (1.8-fold increase), while having no effects on the expression of hepatic Ppar and Fgf21 in white adipose tissue. Moreover, systemic administration of liraglutide over 3 days significantly suppressed food intake, body weight gain, and hyperglycemia in KK 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 KK 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 KK mice.