Identification of ALK in Thinness

Identification of ALK in Thinness.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1016/j.cell.2020.04.034
Journal or Publication Title: Cell
Volume: 181
Number: 6
Page Range: 1246-1262.e22
Date: 2020
Divisions: Directed Evolution
Depositing User: General Admin
Identification Number: 10.1016/j.cell.2020.04.034
ISSN: 00928674
Date Deposited: 04 Jan 2021 03:39
Abstract:

There is considerable inter-individual variability in susceptibility to weight gain despite an equally obesogenic environment in large parts of the world. Whereas many studies have focused on identifying the genetic susceptibility to obesity, we performed a GWAS on metabolically healthy thin individuals (lowest 6th percentile of the population-wide BMI spectrum) in a uniquely phenotyped Estonian cohort. We discovered anaplastic lymphoma kinase (ALK) as a candidate thinness gene. In Drosophila, RNAi mediated knockdown of Alk led to decreased triglyceride levels. In mice, genetic deletion of Alk resulted in thin animals with marked resistance to diet- and leptin-mutation-induced obesity. Mechanistically, we found that ALK expression in hypothalamic neurons controls energy expenditure via sympathetic control of adipose tissue lipolysis. Our genetic and mechanistic experiments identify ALK as a thinness gene, which is involved in the resistance to weight gain.

Creators:
Creators
Email
Orthofer, Michael
UNSPECIFIED
Valsesia, Armand
UNSPECIFIED
Mägi, Reedik
UNSPECIFIED
Wang, Qiao-Ping
UNSPECIFIED
Kaczanowska, Joanna
UNSPECIFIED
Kozieradzki, Ivona
UNSPECIFIED
Leopoldi, Alexandra
UNSPECIFIED
Cikes, Domagoj
UNSPECIFIED
Zopf, Lydia M.
UNSPECIFIED
Tretiakov, Evgenii O.
UNSPECIFIED
Demetz, Egon
UNSPECIFIED
Hilbe, Richard
UNSPECIFIED
Boehm, Anna
UNSPECIFIED
Ticevic, Melita
UNSPECIFIED
Nõukas, Margit
UNSPECIFIED
Jais, Alexander
UNSPECIFIED
Spirk, Katrin
UNSPECIFIED
Clark, Teleri
UNSPECIFIED
Amann, Sabine
UNSPECIFIED
Lepamets, Maarja
UNSPECIFIED
Neumayr, Christoph
UNSPECIFIED
Arnold, Cosmas
UNSPECIFIED
Dou, Zhengchao
UNSPECIFIED
Kuhn, Volker
UNSPECIFIED
Novatchkova, Maria
UNSPECIFIED
Cronin, Shane J.F.
UNSPECIFIED
Tietge, Uwe J.F.
UNSPECIFIED
Müller, Simone
UNSPECIFIED
Pospisilik, J. Andrew
UNSPECIFIED
Nagy, Vanja
UNSPECIFIED
Hui, Chi-Chung
UNSPECIFIED
Lazovic, Jelena
UNSPECIFIED
Esterbauer, Harald
UNSPECIFIED
Hagelkruys, Astrid
UNSPECIFIED
Tancevski, Ivan
UNSPECIFIED
Kiefer, Florian W.
UNSPECIFIED
Harkany, Tibor
UNSPECIFIED
Haubensak, Wulf
UNSPECIFIED
Neely, G. Gregory
UNSPECIFIED
Metspalu, Andres
UNSPECIFIED
Hager, Jorg
UNSPECIFIED
Gheldof, Nele
UNSPECIFIED
Penninger, Josef M.
UNSPECIFIED
Last Modified: 04 Jan 2021 03:39
URI: https://eprints.centenary.org.au/id/eprint/735

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