title: 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.
abstract: BACKGROUND
  A 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.
  
  
  METHODS
  Male 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.
  
  
  RESULTS
  HFC-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.
  
  
  CONCLUSIONS
  These data suggest that HFC-fed Tibetan minipigs develop IR and AS and that PPARs are involved in cardiovascular remodeling and impaired function.
authors.affiliation: Experimental Animal Research Center, Zhejiang Chinese Medical University, No. 548 Binwen Road, Binjiang District, Hangzhou, 310053, China. pym918@126.com.
authors.forename: Pan
authors.initials: P
authors.lastname: Yongming
authors.affiliation: Experimental Animal Research Center, Zhejiang Chinese Medical University, No. 548 Binwen Road, Binjiang District, Hangzhou, 310053, China. czw1234@163.com.
authors.forename: Cai
authors.initials: C
authors.lastname: Zhaowei
authors.affiliation: Experimental Animal Research Center, Zhejiang Chinese Medical University, No. 548 Binwen Road, Binjiang District, Hangzhou, 310053, China. OvOsp1@163.com.
authors.forename: Ma
authors.initials: M
authors.lastname: Yichao
authors.affiliation: Experimental Animal Research Center, Zhejiang Chinese Medical University, No. 548 Binwen Road, Binjiang District, Hangzhou, 310053, China. zjzygyz@126.com.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Keyan
authors.affiliation: Experimental Animal Research Center, Zhejiang Chinese Medical University, No. 548 Binwen Road, Binjiang District, Hangzhou, 310053, China. chl810@foxmail.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.affiliation: Experimental Animal Research Center, Zhejiang Chinese Medical University, No. 548 Binwen Road, Binjiang District, Hangzhou, 310053, China. ucika@sina.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Fangming
authors.affiliation: Experimental Animal Research Center, Zhejiang Chinese Medical University, No. 548 Binwen Road, Binjiang District, Hangzhou, 310053, China. xxp0001@126.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Xiaoping
authors.affiliation: Experimental Animal Research Center, Zhejiang Chinese Medical University, No. 548 Binwen Road, Binjiang District, Hangzhou, 310053, China. mqx1025@hotmail.com.
authors.forename: Ma
authors.initials: M
authors.lastname: Quanxin
authors.affiliation: Experimental Animal Research Center, Zhejiang Chinese Medical University, No. 548 Binwen Road, Binjiang District, Hangzhou, 310053, China. cmli991@aliyun.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Minli
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D002784:Cholesterol / Q000008:administration & dosage / Q000009:adverse effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D047492:Peroxisome Proliferator-Activated Receptors / Q000096:biosynthesis*; D013552:Swine; D013556:Swine, Miniature; D066253:Vascular Remodeling / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D047492:Peroxisome Proliferator-Activated Receptors; D002784:Cholesterol