Identification of ALK in Thinness.
Cell
; 181(6): 1246-1262.e22, 2020 06 11.
Article
in 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thinness
/
Anaplastic Lymphoma Kinase
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Animals
/
Female
/
Humans
/
Male
Country/Region as subject:
Europa
Language:
En
Journal:
Cell
Year:
2020
Document type:
Article
Affiliation country:
Austria