Neural adaption in midbrain GABAergic cells contributes to high-fat diet-induced obesity.
Sci Adv
; 9(44): eadh2884, 2023 11 03.
Article
en En
| MEDLINE
| ID: mdl-37910621
ABSTRACT
Overeating disorders largely contribute to worldwide incidences of obesity. Available treatments are limited. Here, we discovered that long-term chemogenetic activation of ventrolateral periaqueductal gray (vlPAG) GABAergic cells rescue obesity of high-fat diet-induced obesity (DIO) mice. This was associated with the recovery of enhanced mIPSCs, decreased food intake, increased energy expenditure, and inguinal white adipose tissue (iWAT) browning. In vivo calcium imaging confirmed vlPAG GABAergic suppression for DIO mice, with corresponding reduction in intrinsic excitability. Single-nucleus RNA sequencing identified transcriptional expression changes in GABAergic cell subtypes in DIO mice, highlighting Cacna2d1 as of potential importance. Overexpressing CACNA2D1 in vlPAG GABAergic cells of DIO mice rescued enhanced mIPSCs and calcium response, reversed obesity, and therefore presented here as a potential target for obesity treatment.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Calcio
/
Dieta Alta en Grasa
Límite:
Animals
Idioma:
En
Revista:
Sci Adv
Año:
2023
Tipo del documento:
Article
País de afiliación:
China