Gamma-aminobutyric acid supplementation improves olanzapine-induced insulin resistance by inhibiting macrophage infiltration in mice subcutaneous adipose tissue.
Diabetes Obes Metab
; 26(7): 2695-2705, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38660748
ABSTRACT
AIMS:
To investigate whether gamma-aminobutyric acid (GABA) supplementation improves insulin resistance during olanzapine treatment in mice and to explore the underlying mechanisms. MATERIALS ANDMETHODS:
Insulin resistance and body weight gain were induced in mice by 10 weeks of olanzapine treatment. Simultaneously, the mice were administered GABA after 4 weeks of olanzapine administration.RESULTS:
We found that mice treated with olanzapine had lower GABA levels in serum and subcutaneous white adipose tissue (sWAT). GABA supplementation restored GABA levels and improved olanzapine-induced lipid metabolism disorders and insulin resistance. Chronic inflammation in adipose tissue is one of the main contributors to insulin resistance. We found that GABA supplementation inhibited olanzapine-induced adipose tissue macrophage infiltration and M1-like polarization, especially in sWAT. In vitro studies showed that stromal vascular cells, rather than adipocytes, were sensitive to GABA. Furthermore, the results suggested that GABA improves olanzapine-induced insulin resistance at least in part through a GABAB receptor-dependent pathway.CONCLUSIONS:
These findings suggest that targeting GABA may be a potential therapeutic approach for olanzapine-induced metabolic disorders.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Gordura Subcutânea
/
Olanzapina
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Ácido gama-Aminobutírico
/
Macrófagos
Limite:
Animals
Idioma:
En
Revista:
Diabetes Obes Metab
Assunto da revista:
ENDOCRINOLOGIA
/
METABOLISMO
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China