TY - JOUR
T1 - Targeted deletion of the Vgf gene indicates that the encoded secretory peptide precursor plays a novel role in the regulation of energy balance
AU - Hahm, Seung
AU - Mizuno, Tooru M.
AU - Wu, T. John
AU - Wisor, Jonathan P.
AU - Priest, Catherine A.
AU - Kozak, Christine A.
AU - Boozer, Carol N.
AU - Peng, Bonnie
AU - McEvoy, Robert C.
AU - Good, Paul
AU - Kelley, Kevin A.
AU - Takahashi, Joseph S.
AU - Pintar, John E.
AU - Roberts, James L.
AU - Mobbs, Charles V.
AU - Salton, Stephen R J
N1 - Funding Information:
We thank Dr. David Colman for critically reading the manuscript; Drs. Mariann Blum, Marie Gibson, Patrick Hof, Brett Morrison, Phyllis Wise, and Hai Yan for advice; Ellen L. Ziemer for fecal fat analysis; and Christopher DiPalma and Larry Ross (Amgen) for pathological analysis. This work was supported by grants from the National Institutes of Health and the Dysautonomia Foundation. J. T. is an investigator of the Howard Hughes Medical Institute. S. R. J. S. was supported in part by a Pew Scholars Award and a Career Scientist Award from the Irma T. Hirschl and Monique Weill-Caulier Trusts.
PY - 1999/7
Y1 - 1999/7
N2 - 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.
AB - 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.
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U2 - 10.1016/S0896-6273(00)80806-5
DO - 10.1016/S0896-6273(00)80806-5
M3 - Article
C2 - 10433265
AN - SCOPUS:0001398513
SN - 0896-6273
VL - 23
SP - 537
EP - 548
JO - Neuron
JF - Neuron
IS - 3
ER -