The imprinted gene neuronatin is regulated by metabolic status and associated with obesity

Niels Vrang, David Meyre, Phillippe Froguel, Jacob Jelsing, Mads Tang-Christensen, Vincent Vatin, Jens D Mikkelsen, Kenneth Thirstrup, Leif K Larsen, Karina B Cullberg, Jan Fahrenkrug, Per Jacobson, Lars Sjöström, Lena M S Carlsson, Yongjun Liu, Xiaogang Liu, Hong-Wen Deng, Philip J Larsen

57 Citationer (Scopus)

Abstract

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.
OriginalsprogEngelsk
TidsskriftObesity
Vol/bind18
Udgave nummer7
Sider (fra-til)1289-96
Antal sider8
ISSN1930-7381
DOI
StatusUdgivet - 1 jul. 2010

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