Reduced vascular responsiveness to adiponectin in hyperlipidemic rats--mechanisms and significance.

Authors

• Rong Li
• Ming Xu
• Xiaoliang Wang
• Yajing Wang
• Wayne Bond Lau
• Yuexing Yuan
• Wei Yi
• Xuefeng Wei
• Bernard L Lopez
• Theodore A Christopher
• Xiao-Ming Wang
• Xin-Liang Ma

Publication/Presentation Date

9-1-2010

Abstract

Deficiency of adiponectin (APN), an adipocyte-derived vascular protective molecule, contributes to diabetic vascular injury. The current study determined whether obesity/hyperlipidemia may alter the vascular response to APN, and investigated the involved mechanisms and pathologic significance. Adult male Sprague-Dawley rats were fed a regular or high-fat diet (HF) for 4-16 weeks. Circulating APN levels, aortic pAMPK/AMPK, peNOS/eNOS, and APN receptor expression levels were determined. Compared to time-matched animals fed control diet, plasma APN levels in HF-diet animals were significantly increased at 8 weeks, and rapidly declined thereafter. Despite unchanged or elevated circulating APN levels, phosphorylated AMPK and eNOS in vascular tissue were significantly reduced at all observed time points. Recombinant full-length APN (rAPN)-induced AMPK/eNOS phosphorylation and vasodilatation were significantly reduced in 16-week obese/hyperlipidemic aortic segments. Vascular APN receptor 1 (AdipoR1) and receptor 2 (AdipoR2) expression were significantly reduced 16 weeks after HF-diet. Pre-incubation of rAPN with obese/hyperlipidemic plasma, but not with normal plasma, significantly reduced its AMPK and eNOS activation effect, and blunted its protective effect against TNFalpha-induced HUVEC apoptosis. This study demonstrated for the first time that obesity/hyperlipidemia reduces vascular responsiveness to APN. Modification/inactivation of APN by unidentified factors present in obese/hyperlipidemic plasma, decreased vascular AdipoR1/R2 expression, and reduced circulating APN levels contribute to reduced vascular responsiveness to APN at different stages of the obese condition. Reduced APN bioactivity allows unmitigated TNFalpha pro-apoptotic and pro-inflammatory actions, contributing to vascular injury in obesity/hyperlipidemia.

Volume

49

Issue

3

First Page

508

Last Page

515

ISSN

1095-8584

Published In/Presented At

Li, R., Xu, M., Wang, X., Wang, Y., Lau, W. B., Yuan, Y., Yi, W., Wei, X., Lopez, B. L., Christopher, T. A., Wang, X. M., & Ma, X. L. (2010). Reduced vascular responsiveness to adiponectin in hyperlipidemic rats--mechanisms and significance. Journal of molecular and cellular cardiology, 49(3), 508–515. https://doi.org/10.1016/j.yjmcc.2010.03.002

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

20303976

Department(s)

Administration and Leadership

Document Type

Article