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The Journal of Neuroscience, December 19, 2007, 27(51):14139-14146; doi:10.1523/JNEUROSCI.3280-07.2007

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Neurobiology of Disease
Differential Effects of Recombinant Adeno-Associated Virus-Mediated Neuropeptide Y Overexpression in the Hypothalamic Paraventricular Nucleus and Lateral Hypothalamus on Feeding Behavior

Birgitte Tiesjema,¹ Roger A. H. Adan,¹ Mieneke C. M. Luijendijk,¹ Andries Kalsbeek,² and Susanne E. la Fleur¹

¹Rudolf Magnus Institute of Neuroscience, Department of Pharmacology and Anatomy, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands, and ²Netherlands Institute for Neuroscience, 1105 AZ Amsterdam, The Netherlands

Correspondence should be addressed to Dr. Roger A. H. Adan, Rudolf Magnus Institute of Neuroscience, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. Email: r.a.h.adan{at}umcutrecht.nl

It is well known that neuropeptide Y (NPY) increases food intake. The hypothalamic paraventricular nucleus (PVN) and the lateral hypothalamus (LH) are both involved in the acute, hyperphagic effects of NPY. Although it is obvious that increased energy intake may lead to obesity, it is less understood which aspects of feeding behavior are affected and whether one or multiple neural sites mediate the effects of long-term increased NPY signaling. By long-term overexpressing NPY in either the PVN or the LH, we uncovered brain site-specific effects of NPY on meal frequency, meal size, and diurnal feeding patterns. In rats injected with adeno-associated virus-NPY in the PVN, increased food intake resulted from an increase in the amount of meals consumed, whereas in rats injected in the LH, increased food intake was attributable to increased meal size. Interestingly, food intake and body weight gain were only temporarily increased in PVN-injected rats, whereas in LH-injected rats hyperphagia and body weight gain remained for the entire 50 d. Moreover, in LH-NPY rats, but not in PVN-NPY rats, diurnal rhythmicity with regard to food intake and body core temperature was lost. These data clearly show that the NPY system differentially regulates energy intake and energy expenditure in the PVN and LH, which together adjust energy balance.

Key words: rAAV; obesity; meal frequency; meal size; rhythmicity; lateral hypothalamus

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Received July 19, 2007; revised Sept. 26, 2007; accepted Nov. 11, 2007.

Correspondence should be addressed to Dr. Roger A. H. Adan, Rudolf Magnus Institute of Neuroscience, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. Email: r.a.h.adan{at}umcutrecht.nl

This article has been cited by other articles:

				L. Yang, K. A. Scott, J. Hyun, K. L. Tamashiro, N. Tray, T. H. Moran, and S. Bi Role of Dorsomedial Hypothalamic Neuropeptide Y in Modulating Food Intake and Energy Balance J. Neurosci., January 7, 2009; 29(1): 179 - 190. [Abstract] [Full Text] [PDF]

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