José K van den Heuvel1, Kara Furman2, Myrtille C R Gumbs3, Leslie Eggels3, Darren M Opland2, Benjamin B Land2, Sharon M Kolk4, Nandakumar S Narayanan5, Eric Fliers3, Andries Kalsbeek6, Ralph J DiLeone2, Susanne E la Fleur3. 1. Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Netherlands. Electronic address: j.k.vandenheuvel@amc.uva.nl. 2. Division of Molecular Psychiatry, Yale University School of Medicine, New Haven, Connecticut. 3. Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Netherlands. 4. Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands. 5. Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa. 6. Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Netherlands; Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Amsterdam, Netherlands.
Abstract
BACKGROUND: Neuropeptide Y (NPY) is a hypothalamic neuropeptide that plays a prominent role in feeding and energy homeostasis. Expression of the NPY Y1 receptor (Y1R) is highly concentrated in the nucleus accumbens (Acb), a region important in the regulation of palatable feeding. In this study, we performed a number of experiments to investigate the actions of NPY in the Acb. METHODS: First, we determined caloric intake and food choice after bilateral administration of NPY in the Acb in rats on a free-choice diet of saturated fat, 30% sucrose solution, and standard chow and whether this was mediated by the Y1R. Second, we measured the effect of intra-Acb NPY on neuronal activity using in vivo electrophysiology. Third, we examined co-localization of Y1R with enkephalin and dynorphin neurons and the effect of NPY on preproenkephalin messenger RNA levels in the striatum using fluorescent and radioactive in situ hybridization. Finally, using retrograde tracing, we examined whether NPY neurons in the arcuate nucleus projected to the Acb. RESULTS: In rats on the free-choice, high-fat, high-sugar diet, intra-Acb NPY increased intake of fat, but not sugar or chow, and this was mediated by the Y1R. Intra-Acb NPY reduced neuronal firing, as well as preproenkephalin messenger RNA expression in the striatum. Moreover, Acb enkephalin neurons expressed Y1R and arcuate nucleus NPY neurons projected to the Acb. CONCLUSIONS: NPY reduces neuronal firing in the Acb resulting in increased palatable food intake. Together, our neuroanatomical, pharmacologic, and neuronal activity data support a role and mechanism for intra-Acb NPY-induced fat intake.
BACKGROUND:Neuropeptide Y (NPY) is a hypothalamic neuropeptide that plays a prominent role in feeding and energy homeostasis. Expression of the NPY Y1 receptor (Y1R) is highly concentrated in the nucleus accumbens (Acb), a region important in the regulation of palatable feeding. In this study, we performed a number of experiments to investigate the actions of NPY in the Acb. METHODS: First, we determined caloric intake and food choice after bilateral administration of NPY in the Acb in rats on a free-choice diet of saturated fat, 30% sucrose solution, and standard chow and whether this was mediated by the Y1R. Second, we measured the effect of intra-AcbNPY on neuronal activity using in vivo electrophysiology. Third, we examined co-localization of Y1R with enkephalin and dynorphin neurons and the effect of NPY on preproenkephalin messenger RNA levels in the striatum using fluorescent and radioactive in situ hybridization. Finally, using retrograde tracing, we examined whether NPY neurons in the arcuate nucleus projected to the Acb. RESULTS: In rats on the free-choice, high-fat, high-sugar diet, intra-AcbNPY increased intake of fat, but not sugar or chow, and this was mediated by the Y1R. Intra-AcbNPY reduced neuronal firing, as well as preproenkephalin messenger RNA expression in the striatum. Moreover, Acbenkephalin neurons expressed Y1R and arcuate nucleus NPY neurons projected to the Acb. CONCLUSIONS:NPY reduces neuronal firing in the Acb resulting in increased palatable food intake. Together, our neuroanatomical, pharmacologic, and neuronal activity data support a role and mechanism for intra-AcbNPY-induced fat intake.
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