Liraglutide improves vascular dysfunction by regulating a cAMP-independent PKA-AMPK pathway in perivascular adipose tissue in obese mice.
Biomed Pharmacother
; 120: 109537, 2019 Dec.
Article
em En
| MEDLINE
| ID: mdl-31605951
ABSTRACT
BACKGROUND:
Perivascular adipose tissue (PVAT) attenuates its anti-contractile effect through an endothelial-dependent mechanism that aggravates endothelial dysfunction in obesity. The present study was conducted to explore whether liraglutide could improve vascular dysfunction, including the anti-contractile effect of PVAT and endothelial function, by modulating PVAT-related signaling pathways in obesity.METHODS:
C57BL/6 mice were fed a normal-chow diet or a high-fat diet (HFD) with or without liraglutide treatment. Vascular function of the thoracic aorta with or without PVAT were measured. Protein levels of components of the PKA-AMPK-PGC1α and antioxidant signaling pathway in PVAT were determined by western blotting. Brown adipose tissue-related gene in PVAT was measured by qRT-PCR.RESULTS:
Metabolic profiles of HFD-fed mice were improved after treatment with liraglutide. Liraglutide improved PVAT-induced anti-contractile capability and PVAT-induced endothelial dysfunction in HFD-fed mice both in vivo and ex vivo. However, blocking PKA, or AMPK, but not cAMP, attenuated these beneficial effects of liraglutide. Treating HFD-fed mice with liraglutide activated the AMPK/eNOS pathway and induced browning-related gene expression. Moreover, liraglutide increased antioxidant capability. The protective effects were related to activation of a cAMP-independent PKA-AMPK pathway, as demonstrated by western blot and PCR.CONCLUSIONS:
Liraglutide improved vascular dysfunction by modulating a cAMP-independent PKA-AMPK pathway in PVAT in HFD-induced obese mice. The findings provide a novel mechanism for the cardiovascular protection of liraglutide by modulating PVAT function in obesity.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
/
Vasos Sanguíneos
/
Tecido Adiposo Marrom
/
Transdução de Sinais
/
AMP Cíclico
/
Proteínas Quinases Ativadas por AMP
/
Liraglutida
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article