Central NMU signaling in body weight and energy balance regulation: evidence from NMUR2 deletion and chronic central NMU treatment in mice.
To investigate the role of the central neuromedin U (NMU) signaling system in body weight and energy balance regulation, we examined the effects of long-term intracerebroventricular (icv) infusion of NMU in C57Bl/6 mice and in mice lacking the gene encoding NMU receptor 2. In diet-induced obese male and female C57BL/6 mice, icv infusion of NMU (8 microg x day(-1) x mouse(-1)) for 7 days decreased body weight and total energy intake compared with vehicle treatment. However, these parameters were unaffected by NMU treatment in lean male and female C57BL/6 mice fed a standard diet. In addition, female (but not male) NMUR2-null mice had increased body weight and body fat mass when fed a high-fat diet but lacked a clear body weight phenotype when fed a standard diet compared with wild-type littermates. Furthermore, female (but not male) NMUR2-null mice fed a high-fat diet were protected from central NMU-induced body weight loss compared with littermate wild-type mice. Thus, we provide the first evidence that long-term central NMU treatment reduces body weight, food intake, and adiposity and that central NMUR2 signaling is required for these effects in female but not male mice.
Egecioglu
Emil
E
Dept. of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the Univ. of Gothenburg, Medicinaregatan, Gothenburg, Sweden. emil.egecioglu@medic.gu.se
Ploj
Karolina
K
Xu
Xiufeng
X
Bjursell
Mikael
M
Salomé
Nicolas
N
Andersson
Niklas
N
Ohlsson
Claes
C
Taube
Magdalena
M
Hansson
Caroline
C
Bohlooly-Y
Mohammad
M
Morgan
David G A
DG
Dickson
Suzanne L
SL
D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects; D000818:Animals; D001823:Body Composition / Q000187:drug effects / Q000235:genetics; D001835:Body Weight / Q000187:drug effects* / Q000235:genetics; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002149:Energy Intake / Q000187:drug effects / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects* / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D017981:Receptors, Neurotransmitter / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013997:Time Factors
D009479:Neuropeptides; D017981:Receptors, Neurotransmitter; C082444:neuromedin U receptor; C056900:neuromedin U