Involvement of peroxisome proliferator-activated receptors in cardiac and vascular remodeling in a novel minipig model of insulin resistance and atherosclerosis induced by consumption of a high-fat-cholesterol dietReport as inadecuate




Involvement of peroxisome proliferator-activated receptors in cardiac and vascular remodeling in a novel minipig model of insulin resistance and atherosclerosis induced by consumption of a high-fat-cholesterol diet - Download this document for free, or read online. Document in PDF available to download.

Cardiovascular Diabetology

, 14:6

First Online: 16 January 2015Received: 20 October 2014Accepted: 27 December 2014

Abstract

BackgroundA long-term high-fat-cholesterol HFC diet leads to insulin resistance IR, which is associated with inflammation, atherosclerosis AS, cardiac sympathovagal imbalance, and cardiac dysfunction. Peroxisome proliferator-activated receptors PPARs and nuclear factor ĸB NF-κB are involved in the development of IR-AS. Thus, we elucidated the pathological molecular mechanism of IR-AS by feeding an HFC diet to Tibetan minipigs to induce IR and AS.

MethodsMale Tibetan minipigs were fed either a normal diet or an HFC diet for 24 weeks. Thereafter, the minipigs were tested for physiological and biochemical blood indices, blood pressure, cardiac function, glucose tolerance, heart rate variability HRV, and PPAR-associated gene and protein expression levels.

ResultsHFC-fed minipigs exhibited IR through increased body weight, fasting blood glucose levels, plasma cholesterol and its composition, and insulin and free fatty acid FFA levels; decreased insulin sensitivity; impaired glucose tolerance; and hypertension. Increased C-reactive protein CRP levels, cardiac dysfunction, depressed HRV, and the up-regulation of PPAR expression in the abdominal aorta concomitant with down-regulation in the heart tissue were observed in HFC-fed minipigs. Furthermore, the levels of NF-κBp65, IL-1β, TNF-α, MCP-1, VCAM-1, ICAM-1, MMP-9, and CRP proteins were also significantly increased.

ConclusionsThese data suggest that HFC-fed Tibetan minipigs develop IR and AS and that PPARs are involved in cardiovascular remodeling and impaired function.

KeywordsTibetan minipig Insulin resistance Atherosclerosis Myocardial ischemia PPARs NF-ĸB High-fat-cholesterol diet Heart rate variability  Download fulltext PDF



Author: Pan Yongming - Cai Zhaowei - Ma Yichao - Zhu Keyan - Chen Liang - Chen Fangming - Xu Xiaoping - Ma Quanxin - Chen Minli

Source: https://link.springer.com/article/10.1186/s12933-014-0165-0



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