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Comment
. 2016 Apr 14;374(15):1486-8.
doi: 10.1056/NEJMcibr1601693.

Obesity--On or Off?

Fredrik Karpe  1 , Cecilia M Lindgren  1
Affiliations
Comment

Obesity--On or Off?

Fredrik Karpe et al. N Engl J Med. .
No abstract available

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Figures

Figure 1
Figure 1. Trim, Not So Trim, and Trim28.
A stable complex involving tripartite motif-containing 28 and the ZFP57 zinc-finger protein (TRIM28-ZFP57) is required for chromatin stability during embryonic development. Mutations in Trim28 appear to have downstream epigenetic consequences that are linked to a concerted down-regulation of a network of imprinted genes (IGN1), as described by Dalgaard et al. The down-regulation of genes in this network, in particular Nnat and Peg3, appear to cause an obese (“on”) phenotype in mice with a Trim28 mutation in which a single copy of Trim28 is inactivated. This polyphenism, a random phenotypic switch in the genetically identical mice carrying the Trim28 mutation, shows a bimodal distribution (“on” or “off”) of obesity with no intermediate phenotype. Since these mice are genetically identical, environmental signals (e.g., temperature, hormones, and diet) could be influencing the phenotype switch and polyphenism.
See this image and copyright information in PMC

Comment on

  • Trim28 Haploinsufficiency Triggers Bi-stable Epigenetic Obesity.
    Dalgaard K, Landgraf K, Heyne S, Lempradl A, Longinotto J, Gossens K, Ruf M, Orthofer M, Strogantsev R, Selvaraj M, Lu TT, Casas E, Teperino R, Surani MA, Zvetkova I, Rimmington D, Tung YC, Lam B, Larder R, Yeo GS, O'Rahilly S, Vavouri T, Whitelaw E, Penninger JM, Jenuwein T, Cheung CL, Ferguson-Smith AC, Coll AP, Körner A, Pospisilik JA. Dalgaard K, et al. Cell. 2016 Jan 28;164(3):353-64. doi: 10.1016/j.cell.2015.12.025. Cell. 2016. PMID: 26824653 Free PMC article.

References

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    1. Locke AE, Kahali B, Berndt SI, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518:197–206. doi: 10.1056/NEJMcibr1601693. - DOI - PMC - PubMed