論文 - 詳細
| RRC ID | 88438 |
|---|---|
| 著者 | 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. |
| タイトル | Identification of ALK in Thinness. |
| ジャーナル | 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. |
| 巻・号 | 181(6) |
| ページ | 1246-1262.e22 |
| 公開日 | 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 350 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| 実験動物マウス | RBRC02411 RBRC02422 |