奥地利科学院分子生物技术研究所Josef M. Penninger、瑞士洛桑联邦理工学院Nele Gheldof、Jorg Hager等研究人员合作发现人类体瘦基因ALK。相关论文于2020年5月21日在线发表在《细胞》杂志上。

Title: Identification of ALK in Thinness

Author: Michael Orthofer, Armand Valsesia, Reedik Mgi, Qiao-Ping Wang, Joanna Kaczanowska, Ivona Kozieradzki, Alexandra Leopoldi, Domagoj Cikes, Lydia M. Zopf, Evgenii O. Tretiakov, Egon Demetz, Richard Hilbe, Anna Boehm, Melita Ticevic, Margit Nukas, Alexander Jais, Katrin Spirk, Teleri Clark, Sabine Amann, Maarja Lepamets, Christoph Neumayr, Cosmas Arnold, Zhengchao Dou, Volker Kuhn, Maria Novatchkova, Shane J.F. Cronin, Uwe J.F. Tietge, Simone Müller, J. Andrew Pospisilik, Vanja Nagy, Chi-Chung Hui, Jelena Lazovic, Harald Esterbauer, Astrid Hagelkruys, Ivan Tancevski, Florian W. Kiefer, Tibor Harkany, Wulf Haubensak, G. Gregory Neely, Andres Metspalu, Jorg Hager, Nele Gheldof, Josef M. Penninger

Issue&Volume: 2020-05-21

Abstract: There is considerable inter-individual variability in susceptibility to weight gaindespite an equally obesogenic environment in large parts of the world. Whereas manystudies have focused on identifying the genetic susceptibility to obesity, we performeda GWAS on metabolically healthy thin individuals (lowest 6th percentile of the population-wide BMI spectrum) in a uniquely phenotyped Estoniancohort. 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-inducedobesity. Mechanistically, we found that ALK expression in hypothalamic neurons controlsenergy expenditure via sympathetic control of adipose tissue lipolysis. Our geneticand mechanistic experiments identify ALK as a thinness gene, which is involved in the resistance to weight gain.

DOI: 10.1016/j.cell.2020.04.034

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30497-9