To the top

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

Tell a friend about this page
Print version

Lateral hypothalamic GLP-… - University of Gothenburg, Sweden Till startsida
To content Read more about how we use cookies on

Lateral hypothalamic GLP-1 receptors are critical for the control of food reinforcement, ingestive behavior and body weight

Journal article
Authors Lorena López-Ferreras
Jennifer E. Richard
E. E. Noble
Kim Eerola
Rozita H Anderberg
Kajsa Olandersson
Lilly Taing
S. E. Kanoski
M. R. Hayes
Karolina P Skibicka
Published in Molecular Psychiatry
Volume 23
Issue 5
Pages 1157-1168
ISSN 1359-4184
Publication year 2018
Published at Institute of Neuroscience and Physiology, Department of Physiology
Pages 1157-1168
Language en
Keywords glucagon-like peptide-1, ventral tegmental area, neural mechanisms, nucleus-accumbens, dopamine neurons, self-stimulation, energy-balance, reward, leptin, ghrelin, Biochemistry & Molecular Biology, Neurosciences & Neurology, Psychiatry
Subject categories Psychiatry, Neurosciences, Biochemistry and Molecular Biology


Increased motivation for highly rewarding food is a major contributing factor to obesity. Most of the literature focuses on the mesolimbic nuclei as the core of reward behavior regulation. However, the lateral hypothalamus (LH) is also a key reward-control locus in the brain. Here we hypothesize that manipulating glucagon-like peptide-1 receptor (GLP-1R) activity selectively in the LH can profoundly affect food reward behavior, ultimately leading to obesity. Progressive ratio operant responding for sucrose was examined in male and female rats, following GLP-1R activation and pharmacological or genetic GLP-1R blockade in the LH. Ingestive behavior and metabolic parameters, as well as molecular and efferent targets, of the LH GLP-1R activation were also evaluated. Food motivation was reduced by activation of LH GLP-1R. Conversely, acute pharmacological blockade of LH GLP-1R increased food motivation but only in male rats. GLP-1R activation also induced a robust reduction in food intake and body weight. Chronic knockdown of LH GLP-1R induced by intraparenchymal delivery of an adeno-associated virus-short hairpin RNA construct was sufficient to markedly and persistently elevate ingestive behavior and body weight and ultimately resulted in a doubling of fat mass in males and females. Interestingly, increased food reinforcement was again found only in males. Our data identify the LH GLP-1R as an indispensable element of normal food reinforcement, food intake and body weight regulation. These findings also show, for we believe the first time, that brain GLP-1R manipulation can result in a robust and chronic body weight gain. The broader implications of these findings are that the LH differs between females and males in its ability to control motivated and ingestive behaviors.

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?