Obesity-associated gene TMEM18 has a role in the central control of appetite and body weight regulation.
Proc Natl Acad Sci U S A
; 114(35): 9421-9426, 2017 08 29.
Article
em En
| MEDLINE
| ID: mdl-28811369
ABSTRACT
An intergenic region of human chromosome 2 (2p25.3) harbors genetic variants which are among those most strongly and reproducibly associated with obesity. The gene closest to these variants is TMEM18, although the molecular mechanisms mediating these effects remain entirely unknown. Tmem18 expression in the murine hypothalamic paraventricular nucleus (PVN) was altered by changes in nutritional state. Germline loss of Tmem18 in mice resulted in increased body weight, which was exacerbated by high fat diet and driven by increased food intake. Selective overexpression of Tmem18 in the PVN of wild-type mice reduced food intake and also increased energy expenditure. We provide evidence that TMEM18 has four, not three, transmembrane domains and that it physically interacts with key components of the nuclear pore complex. Our data support the hypothesis that TMEM18 itself, acting within the central nervous system, is a plausible mediator of the impact of adjacent genetic variation on human adiposity.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Apetite
/
Peso Corporal
/
Proteínas de Membrana
/
Obesidade
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article