Neuromedin U has a physiological role in the regulation of food intake and partially mediates the effects of leptin.
Intracerebroventricular (ICV) administration of Neuromedin U (NMU), a hypothalamic neuropeptide, or leptin, an adipostat hormone released from adipose tissue, reduces food intake and increases energy expenditure. Leptin stimulates the release of NMU in vitro, and NMU expression is reduced in models of low or absent leptin. We investigated the role of NMU in mediating leptin-induced satiety. ICV administration of anti-NMU immunoglobulin G (IgG) (5 nmol) to satiated rats significantly increased food intake 4 h after injection, an effect seen for </=8 h after injection. ICV administration of NMU (1 nmol) to fasted rats reduced food intake 1 h after injection compared with control, an effect attenuated by pretreatment with anti-NMU IgG. ICV administration of leptin (0.625 nmol) reduced 24-h food intake. This was partially attenuated by the administration of anti-NMU IgG [24 h after onset of dark phase: vehicle, 22.5 +/- 2.0 g; leptin, 13.7 +/- 2.3 g (P < 0.005 vs. vehicle), leptin/NMU IgG, 19.4 +/- 1.3 g (P < 0.05 vs. leptin)]. Intraperitoneal administration of leptin (1.1 mg/kg body wt) reduced 24-h food intake. This was partially attenuated by ICV administration of anti-NMU IgG [24 h after onset of dark phase: vehicle, 31.4 +/- 4.9 g; leptin, 20.8 +/- 2.6 g (P < 0.01 vs. vehicle); leptin/NMU IgG, 28.7 +/- 1.1 g (P < 0.01 vs. leptin)]. These results suggest that NMU plays a physiological role in the regulation of appetite and partially mediates the leptin-induced satiety.
Jethwa
Preeti H
PH
Dept. of Metabolic Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.
Small
Caroline J
CJ
Smith
Kirsty L
KL
Seth
Asha
A
Darch
Sarah J
SJ
Abbott
Caroline R
CR
Murphy
Kevin G
KG
Todd
Jeannie F
JF
Ghatei
Mohammad A
MA
Bloom
Stephen R
SR
D000704:Analysis of Variance; D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D004435:Eating / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D020738:Leptin / Q000008:administration & dosage / Q000502:physiology*; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric
D020738:Leptin; D009479:Neuropeptides; C056900:neuromedin U