Targeted deletion of the Vgf gene indicates that the encoded secretory peptide precursor plays a novel role in the regulation of energy balance

Seung Hahm, Tooru M. Mizuno, T. John Wu, Jonathan P. Wisor, Catherine A. Priest, Christine A. Kozak, Carol N. Boozer, Bonnie Peng, Robert C. McEvoy, Paul Good, Kevin A. Kelley, Joseph S. Takahashi, John E. Pintar, James L. Roberts, Charles V. Mobbs, Stephen R.J. Salton

Research output: Contribution to journalArticle

174 Scopus citations

Abstract

To determine the function of VGF, a secreted polypeptide that is synthesized by neurons, is abundant in the hypothalamus, and is regulated in the brain by electrical activity, injury, and the circadian clock, we generated knockout mice lacking Vgf. Homozygous mutants are small, hypermetabolic, hyperactive, and infertile, with markedly reduced leptin levels and fat stores and altered hypothalamic proopiomelanocortin (POMC), neuropeptide Y (NPY), and agouti-related peptide (AGRP) expression. Furthermore, VGF mRNA synthesis is induced in the hypothalamic arcuate nuclei of fasted normal mice. VGF therefore plays a critical role in the regulation of energy homeostasis, suggesting that the study of lean VGF mutant mice may provide insight into wasting disorders and, moreover, that pharmacological antagonism of VGF action(s) might constitute the basis for treatment of obesity.

Original languageEnglish (US)
Pages (from-to)537-548
Number of pages12
JournalNeuron
Volume23
Issue number3
DOIs
StatePublished - Jul 1999
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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    Hahm, S., Mizuno, T. M., Wu, T. J., Wisor, J. P., Priest, C. A., Kozak, C. A., Boozer, C. N., Peng, B., McEvoy, R. C., Good, P., Kelley, K. A., Takahashi, J. S., Pintar, J. E., Roberts, J. L., Mobbs, C. V., & Salton, S. R. J. (1999). Targeted deletion of the Vgf gene indicates that the encoded secretory peptide precursor plays a novel role in the regulation of energy balance. Neuron, 23(3), 537-548. https://doi.org/10.1016/S0896-6273(00)80806-5