Lateral hypothalamic GLP-1 receptors are critical for the control of food reinforcement, ingestive behavior and body weight
| Autor: | López-Ferreras, L, Richard, J E, Noble, E E, Eerola, K, Anderberg, R H, Olandersson, K, Taing, L, Kanoski, S E, Hayes, M R, Skibicka, K P |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
endocrine system Motivation digestive oral and skin physiology Body Weight Hypothalamus Feeding Behavior Diet High-Fat Glucagon-Like Peptide-1 Receptor Rats Rats Sprague-Dawley Eating Reward Glucagon-Like Peptide 1 Hypothalamic Area Lateral Animals Conditioning Operant Original Article Female Reinforcement Psychology |
| Zdroj: | Molecular Psychiatry |
| ISSN: | 1476-5578 1359-4184 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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