Die Rolle der Opioid-Peptide bei Essverhalten und Adipositas
Molekulare Biologie und Physiologie von Nerven- und Gliazellen
Zusammenfassung der Projektergebnisse
In the present study the contribution of the two major classes of endogenous opioids, namely enkephalin and dynorphin in the modulation of hedonic control of feeding behaviour was investigated. This behaviour was assessed using palatable food pellets and standard normal food pellets in an operant conditioning task. Another aim of the study focused on the role of dynorphin in modulation of metabolic changes associated with high-fat diet consumption using ad libitum and time restricted feeding regimen in constitutive dynorphin-deficient and wild-type animals. Learning behaviour in mice with enkephalin or dynorphin deficiency remained unchanged, thus operant conditioning was not affected by the KO. In summary our results using conditioning paradigms support the hypothesis that the endogenous opioids can modulate palatable food intake, however, are not absolutely necessary for the hedonic aspect of feeding behaviour. In line with the current results, opioid peptide knockout studies have previously showed that enkephalin and dynorphin modulate sucrose preference, but are not necessary to support sucrose consumption (20), therefore suggesting that these endogenous opioids may contribute to food and drug reinforcement via different neuronal pathways. In the further course of our studies we saw that Dyn KO mice showed an interesting phenotype in our studies using different feeding regimens. We conclude here that a lack of dynorphin causes dysregulation of body weight and food intake in animals when maintained on a high-fat diet. Our data suggest that dynorphin modulates metabolic changes associated with high-fat diet consumption and TR feeding regimen. Thus, using kappa opioid receptor agonists against obesity could be considered as a potential treatment strategy.
Projektbezogene Publikationen (Auswahl)
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Modulation of feeding behavior and metabolism by dynorphin. Sci Rep. 2020 Mar 2;10(1):3821
Ghule A, Rácz I, Bilkei-Gorzo A, Leidmaa E, Sieburg M, Zimmer A
