TY - JOUR
T1 - Leptin reduces food intake via adopamine D2 receptor-dependent mechanism
AU - Billes, Sonja K
AU - Simonds, Stephanie Elise
AU - Cowley, Michael Alexander
PY - 2012
Y1 - 2012
N2 - Food intake is generally accepted to be regulated by the melanocortin system, however recent data suggests that mesolimbic dopaminergic neurons also influence food intake. Whether dopamine signaling is crucial for the acute effect of leptin on feeding is unknown. Using pharmacological and genetic strategies, we tested the hypothesis that the acute inhibitory effect of leptin on food intake is partially mediated by dopamine. Dopamine D2 but not D1 receptor blockade attenuated the acute hypophagic effect of leptin in fasted mice. Additionally, mice lacking the D2R (D2R KO) exhibited an attenuated response to leptin. Conversely, dopamine receptor blockade had no effect on the acute hypophagic effect of melanocortin stimulation or the hyperphagic effect of ghrelin. These findings suggest that dopaminergic pathways do not constitute a normal part of melanocortin-dependent feeding regulation and that the dopaminergic neurocircuitry typically associated with regulation of hedonic feeding likely contributes to feeding regulation by leptin
AB - Food intake is generally accepted to be regulated by the melanocortin system, however recent data suggests that mesolimbic dopaminergic neurons also influence food intake. Whether dopamine signaling is crucial for the acute effect of leptin on feeding is unknown. Using pharmacological and genetic strategies, we tested the hypothesis that the acute inhibitory effect of leptin on food intake is partially mediated by dopamine. Dopamine D2 but not D1 receptor blockade attenuated the acute hypophagic effect of leptin in fasted mice. Additionally, mice lacking the D2R (D2R KO) exhibited an attenuated response to leptin. Conversely, dopamine receptor blockade had no effect on the acute hypophagic effect of melanocortin stimulation or the hyperphagic effect of ghrelin. These findings suggest that dopaminergic pathways do not constitute a normal part of melanocortin-dependent feeding regulation and that the dopaminergic neurocircuitry typically associated with regulation of hedonic feeding likely contributes to feeding regulation by leptin
UR - http://download.journals.elsevierhealth.com/pdfs/journals/2212-8778/PIIS2212877812000063.pdf
U2 - 10.1016/j.molmet.2012.07.003
DO - 10.1016/j.molmet.2012.07.003
M3 - Article
VL - 13
SP - 86
EP - 93
JO - Molecular Metabolism
JF - Molecular Metabolism
SN - 2212-8778
ER -