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...

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Published in:Obesity (Silver Spring, Md.) Md.), 2010-07, Vol.18 (7), p.1289-1296
Main Authors: Vrang, Niels, Meyre, David, Froguel, Phillippe, Jelsing, Jacob, Tang‐Christensen, Mads, Vatin, Vincent, Mikkelsen, Jens D., Thirstrup, Kenneth, Larsen, Leif K., Cullberg, Karina B., Fahrenkrug, Jan, Jacobson, Per, Sjöström, Lars, Carlsson, Lena M.S., Liu, Yongjun, Liu, Xiaogang, Deng, Hong‐Wen, Larsen, Philip J.
Format: Article
Language:English
Subjects:
Adipose Tissue - physiology
Amino acids
Animals
Brain research
Cloning
Energy Metabolism - genetics
Experiments
Gene Expression Profiling
Genes
Genomic Imprinting - physiology
Genotype
Homeostasis
Homeostasis - genetics
Hypothalamus - physiology
Immunization
Laboratory animals
Leptin - genetics
Leptin - metabolism
Male
Medical Genetics
Medical research
Medicinsk genetik
Membrane Proteins - genetics
Membrane Proteins - metabolism
Metabolism
Mice
Mice, Inbred C57BL
Mice, Obese
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Obesity
Obesity - genetics
Obesity - physiopathology
Pancreas - physiology
PC12 Cells
Peptides
Physiology
Pituitary Gland - physiology
Polymorphism, Single Nucleotide
Proteins
Rats
Rats, Wistar
RNA, Messenger - metabolism
Signal Transduction - physiology
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Summary: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.
ISSN:1930-7381
1930-739X
DOI:10.1038/oby.2009.361