Reference - Detail
| RRC ID | 88438 |
|---|---|
| Author | Orthofer M, Valsesia A, Mägi R, Wang QP, Kaczanowska J, Kozieradzki I, Leopoldi A, Cikes D, Zopf LM, Tretiakov EO, Demetz E, Hilbe R, Boehm A, Ticevic M, Nõukas M, Jais A, Spirk K, Clark T, Amann S, Lepamets M, Neumayr C, Arnold C, Dou Z, Kuhn V, Novatchkova M, Cronin SJF, Tietge UJF, Müller S, Pospisilik JA, Nagy V, Hui CC, Lazovic J, Esterbauer H, Hagelkruys A, Tancevski I, Kiefer FW, Harkany T, Haubensak W, Neely GG, Metspalu A, Hager J, Gheldof N, Penninger JM. |
| Title | Identification of ALK in Thinness. |
| Journal | Cell |
| 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. |
| Volume | 181(6) |
| Pages | 1246-1262.e22 |
| Published | 2020-6-11 |
| DOI | 10.1016/j.cell.2020.04.034 |
| PII | S0092-8674(20)30497-9 |
| PMID | 32442405 |
| MeSH | Adipose Tissue / metabolism Adult Anaplastic Lymphoma Kinase / genetics* Animals Cell Line Cohort Studies Drosophila / genetics Estonia Female Humans Leptin / genetics Lipolysis / genetics Male Mice Mice, Inbred C57BL Mice, Knockout Obesity / genetics RNA Interference / physiology Thinness / genetics* Young Adult |
| IF | 38.637 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 350 |
| Altmetric score changes over past 6months | 3.0 |
| Resource | |
| Mice | RBRC02411 RBRC02422 |