Transgenic overexpression of neuromedin U promotes leanness and hypophagia in mice.
Recent work has shown that neuromedin U (NmU), a peptide initially identified as a smooth muscle contractor, may play a role in regulating food intake and energy homeostasis. To further evaluate this putative function, we measured food intake, body weight, energy expenditure and glucose homeostasis in transgenic mice that ubiquitously overexpress murine proNmU. NmU transgenic mice were lighter and had less somatic and liver fat, were hypophagic, and had improved insulin sensitivity as judged by an intraperitoneal insulin tolerance test. Transgenic mice had higher levels of hypothalamic NPY, POMC and MCH mRNA. There was no difference in O2 consumption between genotypes; however, NmU transgenic mice displayed a modest increase in respiratory quotient during food deprivation and refeeding. There were no behavioral disturbances in the NmU transgenic mice that could account for the results (e.g. changes in locomotor activity). When placed on a high-fat diet, transgenic mice remained lighter than wild-type mice and ate less, but gained weight at a rate similar to wild-type mice. Despite the increased weight gain with high-fat feeding, glucose tolerance was significantly improved in the transgenic mice. These findings support the hypothesized role of NmU as an endogenous anorexigenic peptide.
Kowalski
T J
TJ
Department of CV/Metabolic Diseases, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA. timonthy.kowalski@spcorp.com
Spar
B D
BD
Markowitz
L
L
Maguire
M
M
Golovko
A
A
Yang
S
S
Farley
C
C
Cook
J A
JA
Tetzloff
G
G
Hoos
L
L
Del Vecchio
R A
RA
Kazdoba
T M
TM
McCool
M F
MF
Hwa
J J
JJ
Hyde
L A
LA
Davis
H
H
Vassileva
G
G
Hedrick
J A
JA
Gustafson
E L
EL
D000818:Animals; D000855:Anorexia / Q000235:genetics*; D001823:Body Composition; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D002153:Calorimetry, Indirect; D004435:Eating; D004734:Energy Metabolism; D005818:Genetic Engineering; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006706:Homeostasis; D017403:In Situ Hybridization / Q000379:methods; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods
D007328:Insulin; D020738:Leptin; D009479:Neuropeptides; C056900:neuromedin U; D005947:Glucose