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

S Hahm; T M Mizuno; T J Wu; J P Wisor; C A Priest; C A Kozak; C N Boozer; B Peng; R C McEvoy; P Good; K A Kelley; J S Takahashi; J E Pintar; J L Roberts; C V Mobbs; S R Salton

doi:10.1016/s0896-6273(00)80806-5

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

Neuron. 1999 Jul;23(3):537-48. doi: 10.1016/s0896-6273(00)80806-5.

Authors

S Hahm¹, T M Mizuno, T J Wu, J P Wisor, C A Priest, C A Kozak, C N Boozer, B Peng, R C McEvoy, P Good, K A Kelley, J S Takahashi, J E Pintar, J L Roberts, C V Mobbs, S R Salton

Affiliation

¹ Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, New York 10029, USA.

PMID: 10433265
DOI: 10.1016/s0896-6273(00)80806-5

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Aggression / physiology
Animals
Arcuate Nucleus of Hypothalamus / chemistry
Arcuate Nucleus of Hypothalamus / cytology
Arcuate Nucleus of Hypothalamus / metabolism
Body Weight / physiology
Catecholamines / metabolism
Circadian Rhythm / physiology
Energy Metabolism / physiology*
Fasting / physiology
Female
Fertility
Gene Deletion*
Gene Expression / physiology
Gonadotropins / metabolism
Homeostasis / physiology
In Situ Hybridization
Leptin
Male
Mammary Glands, Animal / chemistry
Mammary Glands, Animal / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Growth Factors
Neurons / chemistry
Neurons / metabolism*
Neuropeptides
Ovary / chemistry
Ovary / metabolism
Oxygen Consumption / physiology
Phenotype
Pituitary Gland / chemistry
Pituitary Gland / metabolism
Protein Precursors / genetics
Protein Precursors / metabolism
Proteins / genetics*
Proteins / metabolism*
RNA, Messenger / analysis
Thyrotropin / genetics

Substances

Catecholamines
Gonadotropins
Leptin
Nerve Growth Factors
Neuropeptides
Protein Precursors
Proteins
RNA, Messenger
Vgf protein, mouse
Thyrotropin