Identification of ALK in Thinness.
Cell
; 181(6): 1246-1262.e22, 2020 06 11.
Article
en En
| MEDLINE
| ID: mdl-32442405
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Delgadez
/
Quinasa de Linfoma Anaplásico
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Animals
/
Female
/
Humans
/
Male
País/Región como asunto:
Europa
Idioma:
En
Revista:
Cell
Año:
2020
Tipo del documento:
Article
País de afiliación:
Austria