Liraglutide improves vascular dysfunction by regulating a cAMP-independent PKA-AMPK pathway in perivascular adipose tissue in obese mice

Biomedicine & Pharmacotherapy

Ningning Hou¹  Enwen Mao¹  Xiaodong Sun¹  Yongping Liu¹  Na Huang¹  Fang Han²  Ruiyan Pan³  Xing Zhang⁴ 

[1] Department of Endocrinology, Affiliated Hospital of Weifang Medical University, Weifang, China;Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China;Department of Pharmacology, Weifang Medical University, Weifang, China;Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, China;

关键词: Perivascular adipose tissue;    Obesity;    Glucagon-like peptide-1;    Endothelial function;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown