Neuroscience lettersDec 20, 2015

Drugs activating brain GLP-1 receptors change blood FGF21 levels differently after eating and fasting

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 6, 2026

Abstract

Liraglutide injected into the third cerebral ventricle significantly increased plasma FGF21 levels in free-feeding mice.

Liraglutide (5-100μg/kg) reduced food intake and body weight in free-feeding mice after 24 hours in a dose-dependent manner.
Higher doses of liraglutide (50 and 100μg/kg) significantly raised plasma FGF21 levels and liver FGF21 expression.
Smaller doses of liraglutide (5 and 10μg/kg) did not affect FGF21 levels.
In food-deprived mice, liraglutide (100μg/kg) resulted in significantly lower plasma FGF21 levels compared to saline control after 24 hours.
In mice given 1g of food, liraglutide (50μg/kg) also significantly decreased plasma FGF21 levels at 24 hours compared to saline control.

Simplified

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.

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Drugs activating brain GLP-1 receptors change blood FGF21 levels differently after eating and fasting

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