The imprinted gene neuronatin is regulated by metabolic status and associated with obesity.
Using restriction fragment differential display (RFDD) technology, we have identified the imprinted gene neuronatin (Nnat) as a hypothalamic target under the influence of leptin. Nnat mRNA expression is decreased in several key appetite regulatory hypothalamic nuclei in rodents with impaired leptin signaling and during fasting conditions. Furthermore, peripheral administration of leptin to ob/ob mice normalizes hypothalamic Nnat expression. Comparative immunohistochemical analysis of human and rat hypothalami demonstrates that NNAT protein is present in anatomically equivalent nuclei, suggesting human physiological relevance of the gene product(s). A putative role of Nnat in human energy homeostasis is further emphasized by a consistent association between single nucleotide polymorphisms (SNPs) in the human Nnat gene and severe childhood and adult obesity.
Vrang
Niels
N
Rheoscience, Rødovre, Denmark. niels@gubra.dk
Meyre
David
D
Froguel
Phillippe
P
Jelsing
Jacob
J
Tang-Christensen
Mads
M
Vatin
Vincent
V
Mikkelsen
Jens D
JD
Thirstrup
Kenneth
K
Larsen
Leif K
LK
Cullberg
Karina B
KB
Fahrenkrug
Jan
J
Jacobson
Per
P
Sjöström
Lars
L
Carlsson
Lena M S
LM
Liu
Yongjun
Y
Liu
Xiaogang
X
Deng
Hong-Wen
HW
Larsen
Philip J
PJ
D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D004734:Energy Metabolism / Q000235:genetics; D020869:Gene Expression Profiling; D018392:Genomic Imprinting / Q000502:physiology*; D005838:Genotype; D006706:Homeostasis / Q000235:genetics; D007031:Hypothalamus / Q000502:physiology; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology*; D016716:PC12 Cells; D010179:Pancreas / Q000502:physiology; D010902:Pituitary Gland / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology
D020738:Leptin; D008565:Membrane Proteins; C490237:NNAT protein, human; D009419:Nerve Tissue Proteins; C490239:Nnat protein, mouse; D012333:RNA, Messenger; C088089:Nnat protein, rat