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The Journal of Neuroscience, January 7, 2009, 29(1):179-190; doi:10.1523/JNEUROSCI.4379-08.2009

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Behavioral/Systems/Cognitive
Role of Dorsomedial Hypothalamic Neuropeptide Y in Modulating Food Intake and Energy Balance

Liang Yang, ^* Karen A. Scott, ^* Jayson Hyun, Kellie L. Tamashiro, Nancy Tray, Timothy H. Moran, and Sheng Bi

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Correspondence should be addressed to Sheng Bi, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 618, Baltimore, MD 21205. Email: sbi{at}jhmi.edu

Previous studies have suggested that neuropeptide Y (NPY) in the dorsomedial hypothalamus (DMH) serves as an important signaling peptide in the regulation of energy balance. To elucidate such actions, we used the adenoassociated virus (AAV) system to alter Npy gene expression in the DMH and examined the effects of these alterations on food intake and energy balance as well as explored its downstream signaling pathway. We found that AAV-mediated overexpression of NPY in the DMH of lean rats increased food intake and body weight, and exacerbated high-fat diet-induced obesity. Knockdown of NPY expression in the DMH via AAV-mediated RNA interference ameliorated the hyperphagia, obesity, and diabetes of Otsuka Long–Evans Tokushima Fatty (OLETF) rats. NPY knockdown in the DMH produced a nocturnal and meal size-specific feeding effect. Moreover, we found that knockdown of DMH NPY expression in intact rats reduced NPY content in the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus and affected within-meal satiation. DMH NPY knockdown increased the feeding inhibitory and NTS c-Fos responses to peripheral administration of cholecystokinin. Together, these results indicate that DMH NPY plays an important role in modulating food intake and energy balance and its dysregulation causes disordered energy balance leading to obesity.

Key words: hypothalamus; nucleus of the solitary tract; feeding; obesity; adenoassociated virus; RNAi

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Received Sept. 12, 2008; revised Oct. 13, 2008; accepted Nov. 17, 2008.

Correspondence should be addressed to Sheng Bi, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 618, Baltimore, MD 21205. Email: sbi{at}jhmi.edu

Related articles in J. Neurosci.:

Functional Implications for Modulating Neuropeptide Y Gene Expression in the Dorsomedial Hypothalamus

Nicole R. Kinzeler and Kristin S. Edwards
J. Neurosci. 2009 29: 7389-7391. [Full Text]  

This article has been cited by other articles:

				M. Schroeder, O. Zagoory-Sharon, L. Shbiro, A. Marco, J. Hyun, T. H. Moran, S. Bi, and A. Weller Development of obesity in the Otsuka Long-Evans Tokushima Fatty rat Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2009; 297(6): R1749 - R1760. [Abstract] [Full Text] [PDF]

				N. R. Kinzeler and K. S. Edwards Functional Implications for Modulating Neuropeptide Y Gene Expression in the Dorsomedial Hypothalamus J. Neurosci., June 10, 2009; 29(23): 7389 - 7391. [Full Text] [PDF]

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