To the top

Page Manager: Webmaster
Last update: 9/11/2012 3:13 PM

Tell a friend about this page
Print version

Central actions of glucag… - University of Gothenburg, Sweden Till startsida
To content Read more about how we use cookies on

Central actions of glucagon-like peptide-1 on food intake and reward: Novel neurological targets and sex divergent effects

Doctoral thesis
Authors Jennifer E. Richard
Date of public defense 2020-01-10
ISBN 978-91-7833-507-7
Publisher Göteborgs universitet
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Physiology
Language en
Keywords Glucagon-like peptide-1, Food reward, Food intake, GLP-1, Sex differences
Subject categories Physiology


Obesity is one of the biggest health risks of our society; however, treatment options are sparse and often result in suboptimal weight-loss. The glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonist liraglutide was recently approved for treatment of obesity in the US. GLP-1, and synthetic analogues, reduce body weight by suppressing food intake and food reward through actions on GLP-1Rs in the CNS. Regulation of homeostatic and hedonic feeding, by GLP-1, was previously attributed to actions specifically within the hypothalamus or limbic system, respectively. Our studies chal-lenge this view and demonstrate novel central areas mediating the effects of GLP-1R stimulation on food intake and reward. Using standard food intake and body weight measurements, and reward behavior tests, we demonstrate that GLP-1R stimulation, using GLP-1R agonist exendin-4 (Ex4), reduces food intake and food reward behavior through actions in the nucleus of the solitary tract (NTS) and lateral hypothalamus (LH). In addition, NTS GLP-1 neurons were found in close proximity to noradrenergic neurons, and intra-NTS Ex4 injection increased dopamine-related genes in the ventral tegmental area, suggesting a link between the NTS and the reward system. Furthermore, the parabrachial nucleus (PBN) was identified as a novel area mediating the anorexic effects of GLP-1R stimulation. This thesis also demonstrates potential sex differences in the effects of GLP-1, and its agonists, as central GLP-1R stimulation suppresses food-motivated behavior to a larger degree in females compared to males. In addition, central estrogen, and estrogen receptor-α (ERα), blockade attenuate the effects of Ex4 on food reward, but not food intake. However, specifically within the LH, GLP-1R stimulation is sufficient to reduce food-motivated behavior in both sexes, while it is only necessary in males. In conclusion, effects of GLP-1R stimulation on food intake and food reward are not bound to actions on GLP-1Rs exclusively within homeostatic or hedonic feeding cen-ters. Furthermore, GLP-1-mediated food reward, but not food intake, suppression is dependent on estrogen signaling. However, GLP-1 may also act differently within specific brain nuclei, as LH GLP-1R stimulation is sufficient to reduce food-reward in both sexes, while it is only necessary for its actions in males.

Page Manager: Webmaster|Last update: 9/11/2012

The University of Gothenburg uses cookies to provide you with the best possible user experience. By continuing on this website, you approve of our use of cookies.  What are cookies?