Pharmacologic stimulation of central GLP-1 receptors has opposite effects on the alterations of plasma FGF21 levels induced by feeding and fasting

• Published in: Neuroscience letters 2016-01, Vol.612, p.14-17
• Main Authors: Nonogaki, Katsunori, Kaji, Takao, Yamazaki, Tomoe, Murakami, Mari
• Format: Article
• Language: English
• Subjects: Animals; Body weight; Body Weight - drug effects; Eating - drug effects; FGF21; Fibroblast Growth Factors - blood; Fibroblast Growth Factors - metabolism; Food Deprivation; Food intake; GLP-1receptor; Glucagon-Like Peptide-1 Receptor - agonists; Glucagon-Like Peptide-1 Receptor - metabolism; Injections, Intraventricular; Liraglutide; Liraglutide - pharmacology; Liver - metabolism; Male; Mice, Inbred C57BL
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2015.12.011

•Central injection of liraglutide decreased body weight by inhibiting food intake.•Central injection of liraglutide increased plasma FGF21 levels in free-feeding mice.•Central injection of liraglutide reduced plasma FGF21 levels in food-deprived mice.•Liraglutide alters plasma FGF21 levels independently of body weight reduction.•There may be a central feedback system in the regulation of circulating FGF21. Fibroblast growth factor 21 (FGF21) functions as an endocrine hormone to regulate energy metabolism. Circulating FGF21 is derived from the liver and is produced in response to alterations of nutritional status. Here we show the effects of liraglutide, a human glucagon-like-peptide-1 (GLP-1) receptor agonist, injected into the third cerebral ventricle on body weight and plasma FGF21 levels in free-feeding mice, food-deprived mice, and mice provided 1g after the injection. In free-feeding mice, liraglutide (5–100μg/kg) injected into the third cerebral ventricle suppressed food intake and body weight after 24h in a dose-dependent manner. Liraglutide (50 and 100μg/kg) significantly increased plasma FGF21 levels and hepatic FGF21 expression, whereas smaller doses (5 and 10μg/kg) had no effect. In food-deprived mice, body weight did not differ significantly between the saline control and liraglutide-treated groups, but liraglutide (100μg/kg) significantly decreased plasma FGF21 levels at 24h compared with the saline control. In mice provided 1g food, body weight did not differ significantly between the saline control and liraglutide-treated groups, but liraglutide (50μg/kg) significantly decreased plasma FGF21 levels at 24h compared with the saline control. These findings suggest that intracerebral injection of liraglutide decreases body weight by inhibiting food intake and increases plasma FGF21 levels in free-feeding mice, whereas it suppresses the elevations of plasma FGF21 levels induced by fasting or the restricted feeding. Thus, pharmacologic stimulation of central GLP-1 receptors has opposite effects on the alterations of plasma FGF21 levels induced by feeding and fasting.