The online version of this article (doi:10.1186/1475-2840-11-48) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
PS, IH, AL designed research; PS, IH, CB, AS, MR, CB, DE, GR and AL performed research; CB, AS, GR and DE revised the manuscript critically for intellectual content; PS, IH, CB, AS and AL analyzed data; PS and AL wrote the paper. All authors have read and approved submission of the final manuscript.
Genome-wide association studies (GWAS) are useful to reveal an association between single nucleotide polymorphisms and different measures of obesity. A multitude of new loci has recently been reported, but the exact function of most of the according genes is not known. The aim of our study was to start elucidating the function of some of these genes.
We performed an expression analysis of fourteen genes, namely BDNF, ETV5, FAIM2, FTO, GNPDA2, KCTD15, LYPLAL1, MCR4, MTCH2, NEGR1, NRXN3, TMEM18, SEC16B and TFAP2B, via real-time RT-PCR in adipose tissue of the kidney capsule, the mesenterium and subcutaneum as well as the hypothalamus of obese Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats at an age of 22 weeks.
All of our target genes except for SEC16B showed the highest expression in the hypothalamus. This suggests a critical role of these obesity-related genes in the central regulation of energy balance. Interestingly, the expression pattern in the hypothalamus showed no differences between obese ZDF and lean ZL rats. However, LYPLAL1, TFAP2B, SEC16B and FAIM2 were significantly lower expressed in the kidney fat of ZDF than ZL rats. NEGR1 was even lower expressed in subcutaneous and mesenterial fat, while MTCH2 was higher expressed in the subcutaneous and mesenterial fat of ZDF rats.
The expression pattern of the investigated obesity genes implies for most of them a role in the central regulation of energy balance, but for some also a role in the adipose tissue itself. For the development of the ZDF phenotype peripheral rather than central mechanisms of the investigated genes seem to be relevant.
Elks CE, Loos RJ, Sharp SJ, Langenberg C, Ring SM, Timpson NJ, Ness AR, Davey Smith G, Dunger DB, Wareham NJ, Ong KK: Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. PLoS Med. 2010, 7: e1000284-10.1371/journal.pmed.1000284. PubMedCentralCrossRefPubMed
Heid IM, Jackson AU, Randall JC, Winkler TW, Qi L, Steinthorsdottir V, Thorleifsson G, Zillikens MC, Speliotes EK, Magi R, et al: Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat Genet. 2010, 42: 949-960. 10.1038/ng.685. PubMedCentralCrossRefPubMed
Lindgren CM, Heid IM, Randall JC, Lamina C, Steinthorsdottir V, Qi L, Speliotes EK, Thorleifsson G, Willer CJ, Herrera BM, et al: Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution. PLoS Genet. 2009, 5: e1000508-10.1371/journal.pgen.1000508. PubMedCentralCrossRefPubMed
Ng MC, Tam CH, So WY, Ho JS, Chan AW, Lee HM, Wang Y, Lam VK, Chan JC, Ma RC: Implication of genetic variants near NEGR1, SEC16B, TMEM18, ETV5/DGKG, GNPDA2, LIN7C/BDNF, MTCH2, BCDIN3D/FAIM2, SH2B1, FTO, MC4R, and KCTD15 with obesity and type 2 diabetes in 7705 Chinese. J Clin Endocrinol Metab. 2010, 95: 2418-2425. 10.1210/jc.2009-2077. CrossRefPubMed
Renstrom F, Payne F, Nordstrom A, Brito EC, Rolandsson O, Hallmans G, Barroso I, Nordstrom P, Franks PW: Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden. Hum Mol Genet. 2009, 18: 1489-1496. 10.1093/hmg/ddp041. PubMedCentralCrossRefPubMed
Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, Styrkarsdottir U, Gretarsdottir S, Thorlacius S, Jonsdottir I, et al: Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet. 2009, 41: 18-24. 10.1038/ng.274. CrossRefPubMed
Trayhurn P, Bing C, Wood IS: Adipose tissue and adipokines–energy regulation from the human perspective. J Nutr. 2006, 136: 1935S-1939S. PubMed
Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, et al: A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007, 316: 889-894. 10.1126/science.1141634. PubMedCentralCrossRefPubMed
Almen MS, Jacobsson JA, Shaik JH, Olszewski PK, Cedernaes J, Alsio J, Sreedharan S, Levine AS, Fredriksson R, Marcus C, Schioth HB: 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. BMC Med Genet. 2010, 11: 58. PubMedCentralCrossRefPubMed
Walley AJ, Jacobson P, Falchi M, Bottolo L, Andersson JC, Petretto E, Bonnefond A, Vaillant E, Lecoeur C, Vatin V, et al: Differential coexpression analysis of obesity-associated networks in human subcutaneous adipose tissue. Int J Obes (Lond). 2012, 36: 137-147. 10.1038/ijo.2011.22. CrossRef
Gelb BD: Char Syndrome. GeneReviews [Internet] Seattle (WA): University of Washington, Seattle; 1993–2003 Aug 15 [updated 2008 Mar 19]. 1993
Ugi S, Nishio Y, Yamamoto H, Ikeda K, Kobayashi M, Tsukada S, Kondo M, Morino K, Obata T, Yoshizaki T, et al: Relation of the expression of transcriptional factor TFAP2B to that of adipokines in subcutaneous and omental adipose tissues. Obesity (Silver Spring). 2010, 18: 1277-1282. 10.1038/oby.2009.442. CrossRef
Morrow CM, Hostetler CE, Griswold MD, Hofmann MC, Murphy KM, Cooke PS, Hess RA: ETV5 is required for continuous spermatogenesis in adult mice and may mediate blood testes barrier function and testicular immune privilege. Ann N Y Acad Sci. 2007, 1120: 144-151. 10.1196/annals.1411.005. PubMedCentralCrossRefPubMed
Kulyte A, Ryden M, Mejhert N, Dungner E, Sjolin E, Arner P, Dahlman I: MTCH2 in Human White Adipose Tissue and Obesity. J Clin Endocrinol Metab. 2011, 96: 1661-1665. 10.1210/jc.2010-3050. CrossRef
Razny U, Kiec-Wilk B, Wator L, Polus A, Dyduch G, Solnica B, Malecki M, Tomaszewska R, Cooke JP, Dembinska-Kiec A: Increased nitric oxide availability attenuates high fat diet metabolic alterations and gene expression associated with insulin resistance. Cardiovasc Diabetol. 2011, 10: 68-10.1186/1475-2840-10-68. PubMedCentralCrossRefPubMed
- Expression of fourteen novel obesity-related genes in zucker diabetic fatty rats
Peter M Schmid
Dierk H Endemann
Guenter A Riegger
- BioMed Central
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