Fr. De Fonseca et al., Peripheral versus central effects of glucagon-like peptide-1 receptor agonists on satiety and body weight loss in Zucker obese rats, METABOLISM, 49(6), 2000, pp. 709-717
The present study explores the potential utility of peripheral versus centr
al administration of glucagon-like peptide-1 (GLP-1) receptor agonists in t
he regulation of feeding behavior in Wistar and Zucker obese rats. Acute ce
ntral (intracerebroventricular [ICV]) and peripheral (subcutaneous [SC]) ad
ministration of both GLP-1 (7-36) amide and exendin-4 resulted in a reducti
on in food intake for at least 4 hours, exendin-4 being much more potent th
an GLP-1 (7-36) amide, especially after peripheral administration. Both Zuc
ker obese rats (fa/fa) and their lean littermates (Fa/-) responded to acute
central and peripheral administration of exendin-4. Moreover, in situ hybr
idization revealed specific labeling for the mRNA for GLP-1 receptors in se
veral brain areas of both the obese and lean rats. The presence of this rec
eptor was also detected by affinity cross-linking assays. Long-term SC admi
nistration of exendin-4 (1 single injection per day, 1 hour prior to the on
set of the dark phase of the cycle) decreased daily food intake and practic
ally blocked weight gain in obese rats. In contrast to previous studies, th
ese findings show that peripheral (SC) administration of both GLP-1 recepto
r agonists also induces satiety and weight loss in rats, and suggest the po
tential usefulness of exendin-4 as a therapeutic tool for the treatment of
diabetes and/or obesity. Copyright (C) 2000 by W.B. Saunders Company.