The obesity gene, TMEM18, is of ancient origin, found in majority of neuronal cells in all major brain regions and associated with obesity in severely obese children
-
Published:2010-04-09
Issue:1
Volume:11
Page:
-
ISSN:1471-2350
-
Container-title:BMC Medical Genetics
-
language:en
-
Short-container-title:BMC Med Genet
Author:
Almén Markus Sällman,Jacobsson Josefin A,Shaik Jafar HA,Olszewski Pawel K,Cedernaes Jonathan,Alsiö Johan,Sreedharan Smitha,Levine Allen S,Fredriksson Robert,Marcus Claude,Schiöth Helgi B
Abstract
Abstract
Background
TMEM18 is a hypothalamic gene that has recently been linked to obesity and BMI in genome wide association studies. However, the functional properties of TMEM18 are obscure.
Methods
The evolutionary history of TMEM18 was inferred using phylogenetic and bioinformatic methods. The gene's expression profile was investigated with real-time PCR in a panel of rat and mouse tissues and with immunohistochemistry in the mouse brain. Also, gene expression changes were analyzed in three feeding-related mouse models: food deprivation, reward and diet-induced increase in body weight. Finally, we genotyped 502 severely obese and 527 healthy Swedish children for two SNPs near TMEM18 (rs6548238 and rs756131).
Results
TMEM18 was found to be remarkably conserved and present in species that diverged from the human lineage over 1500 million years ago. The TMEM18 gene was widely expressed and detected in the majority of cells in all major brain regions, but was more abundant in neurons than other cell types. We found no significant changes in the hypothalamic and brainstem expression in the feeding-related mouse models. There was a strong association for two SNPs (rs6548238 and rs756131) of the TMEM18 locus with an increased risk for obesity (p = 0.001 and p = 0.002).
Conclusion
We conclude that TMEM18 is involved in both adult and childhood obesity. It is one of the most conserved human obesity genes and it is found in the majority of all brain sites, including the hypothalamus and the brain stem, but it is not regulated in these regions in classical energy homeostatic models.
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Genetics
Reference45 articles.
1. Maes HH, Neale MC, Eaves LJ: Genetic and environmental factors in relative body weight and human adiposity. Behavior genetics. 1997, 27: 325-351. 10.1023/A:1025635913927. 2. Hofker M, Wijmenga C: A supersized list of obesity genes. Nature genetics. 2009, 41: 139-140. 10.1038/ng0209-139. 3. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, et al: A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science (New York, NY). 2007, 316: 889-894. 4. Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Bruning JC, Ruther U: Inactivation of the Fto gene protects from obesity. Nature. 2009, 458: 894-898. 10.1038/nature07848. 5. Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM, Berndt SI, Elliott AL, Jackson AU, Lamina C, Lettre G, Lim N, Lyon HN, McCarroll SA, Papadakis K, Qi L, Randall JC, Roccasecca RM, Sanna S, Scheet P, Weedon MN, Wheeler E, Zhao JH, Jacobs LC, Prokopenko I, Soranzo N, Tanaka T, Timpson NJ, Almgren P, Bennett A, et al: Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nature genetics. 2009, 41: 25-34. 10.1038/ng.287.
Cited by
62 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|