Central NMU signaling in body weight and energy balance regulation: evidence from NMUR2 deletion and chronic central NMU treatment in mice

• Published in: American journal of physiology: endocrinology and metabolism Vol. 297; no. 3; pp. E708 - E716
• Main Authors: Egecioglu, Emil, Ploj, Karolina, Xu, Xiufeng, Bjursell, Mikael, Salome, Nicolas, Andersson, Niklas, Ohlsson, Claes, Taube, Magdalena, Hansson, Caroline, Bohlooly-Y, Mohammad, Morgan, David G. A, Dickson, Suzanne L
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.09.2009
• Subjects: Adipose Tissue; Adipose Tissue - anatomy & histology; Adipose Tissue - drug effects; administration & dosage; anatomy & histology; Animals; Body Composition; Body Composition - drug effects; Body Composition - genetics; Body Weight; Body Weight - drug effects; Body Weight - genetics; Central Nervous System; Central Nervous System - drug effects; Central Nervous System - metabolism; Central Nervous System - physiology; Comparative analysis; Diet; drug effects; Effects; Energy Intake; Energy Intake - drug effects; Energy Intake - genetics; Energy Metabolism; Energy Metabolism - drug effects; Energy Metabolism - genetics; Female; Fysiologi; Gene Deletion; genetics; Genotype & phenotype; Inbred C57BL; Injections; Injections, Intraventricular; Intraventricular; Knockout; Male; Medical treatment; metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuropeptides; Neuropeptides - administration & dosage; Neuropeptides - pharmacology; Neurotransmitter; Obesity; pharmacology; Physiology; Receptors; Receptors, Neurotransmitter - genetics; Receptors, Neurotransmitter - metabolism; Receptors, Neurotransmitter - physiology; Rodents; Signal Transduction; Signal Transduction - drug effects; Signal Transduction - genetics; Time Factors; Weight
• ISSN: 0193-1849; 1522-1555; 1522-1555
• DOI: 10.1152/ajpendo.91022.2008

1 Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg; 2 AstraZeneca Research and Development, Mölndal; and 3 Department of Internal Medicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden Submitted 22 December 2008 ; accepted in final form 2 July 2009 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 µg·day –1 ·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. neuromedin U; appetite; anorexic; energy expenditure; obesity; food intake; neuromedin U receptor 2; FM4; GRP66 Address for reprint requests and other correspondence: E. Egecioglu, Dept. of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the Univ. of Gothenburg, Medicinaregatan 11, P. O. Box 434, SE-405 30 Gothenburg, Sweden (e-mail: emil.egecioglu{at}medic.gu.se )