Targeted deletion of the Vgf gene indicates that the encoded secretory peptide precursor plays a novel role in the regulation of energy balance.
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.
Hahm
S
S
Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Mizuno
T M
TM
Wu
T J
TJ
Wisor
J P
JP
Priest
C A
CA
Kozak
C A
CA
Boozer
C N
CN
Peng
B
B
McEvoy
R C
RC
Good
P
P
Kelley
K A
KA
Takahashi
J S
JS
Pintar
J E
JE
Roberts
J L
JL
Mobbs
C V
CV
Salton
S R
SR
D000374:Aggression / Q000502:physiology; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D005215:Fasting / Q000502:physiology; D005260:Female; D005298:Fertility; D017353:Gene Deletion; D015870:Gene Expression / Q000502:physiology; D006062:Gonadotropins / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D017403:In Situ Hybridization; D020738:Leptin; D008297:Male; D008321:Mammary Glands, Animal / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D009479:Neuropeptides; D010053:Ovary / Q000737:chemistry / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology; D010641:Phenotype; D010902:Pituitary Gland / Q000737:chemistry / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013972:Thyrotropin / Q000235:genetics
D002395:Catecholamines; D006062:Gonadotropins; D020738:Leptin; D009414:Nerve Growth Factors; D009479:Neuropeptides; D011498:Protein Precursors; D011506:Proteins; D012333:RNA, Messenger; C512697:Vgf protein, mouse; D013972:Thyrotropin