Lack of adipocyte purinergic P2Y6 receptor greatly improves whole body glucose homeostasis.
Proc Natl Acad Sci U S A
; 117(48): 30763-30774, 2020 12 01.
Article
em En
| MEDLINE
| ID: mdl-33199639
ABSTRACT
Uridine diphosphate (UDP)-activated purinergic receptor P2Y6 (P2Y6R) plays a crucial role in controlling energy balance through central mechanisms. However, P2Y6R's roles in peripheral tissues regulating energy and glucose homeostasis remain unexplored. Here, we report the surprising finding that adipocyte-specific deletion of P2Y6R protects mice from diet-induced obesity, improving glucose tolerance and insulin sensitivity with reduced systemic inflammation. These changes were associated with reduced JNK signaling and enhanced expression and activity of PPARα affecting downstream PGC1α levels leading to beiging of white fat. In contrast, P2Y6R deletion in skeletal muscle reduced glucose uptake, resulting in impaired glucose homeostasis. Interestingly, whole body P2Y6R knockout mice showed metabolic improvements similar to those observed with mice lacking P2Y6R only in adipocytes. Our findings provide compelling evidence that P2Y6R antagonists may prove useful for the treatment of obesity and type 2 diabetes.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores Purinérgicos P2
/
Adipócitos
/
Glucose
/
Homeostase
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article