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The hypolipidemic benefits of trans-11 vaccenic acid in a rat model of dyslipidemia and metabolic syndrome.

机译：反式11疫苗酸对血脂异常和代谢综合征的大鼠模型具有降血脂作用。

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摘要

Trans-11 vaccenic acid (VA) is the predominant trans fatty acid in dairy fat and is the major precursor to endogenous synthesis of cis9,trans11-conjugated linoleic acid (CLA) in humans and animals. Epidemiological studies have shown the positive association between trans fat intake and incidence of coronary heart disease. Nevertheless, CLA, categorized as a group of trans fatty acids, has been shown to possess anti-carcinogenic, hypolipidemic and anti-diabetic benefits in several animal models as well as certain human populations, possibly via activating peroxisome proliferator-activated receptor (PPAR) related metabolic pathways. The subsequent effort in enriching CLA in dairy products (e.g. butter) has led to a concomitant increase in VA, whose bioactivity and health implications were not fully appreciated. Interestingly, VA is the major natural trans fat found in the diet. Therefore, the objectives of this thesis were to assess the effect of dietary supplementation of synthetic VA on lipid metabolism especially during conditions of dyslipidemia and metabolic syndrome, and to delineate the intestinal and hepatic metabolic pathways potentially modulated by VA. The JCR:LA-cp rat model, when homozygous for the cp trait (cp/cp), develop leptin receptor deficiency which leads to symptoms of metabolic syndrome and pre-diabetes including obesity, insulin resistance, hepatic steatosis, hypertriglyceridemia and exacerbated production of hepatic very low-density lipoproteins and intestinal chylomicrons (CM). Gas chromatography analysis on nascent lymph shows that VA was effectively absorbed into the intestine. In addition, VA from natural source (i.e. beef fat) showed higher intestinal bioavailability compared to synthetic VA. Dietary supplementation of 1.0% (w/w) synthetic VA to JCR:LA-cp rats (but not lean healthy controls) demonstrated a profound reduction in plasma triglyceride, total cholesterol, low-density lipoprotein-cholesterol, non-esterified fatty acid and haptoglobin concentrations (51%, p<0.001; 40%, p<0.001; 50%, p<0.05; 20%, p<0.05 and 50%, p<0.001; respectively), as well as improvement in hepatic steatosis and postprandial lipaemia. Gastric infusion of VA also resulted in an acute reduction in CM secretion in response to a fat load (p<0.05). We also found that the overall hypolipidemic benefits of VA might be partially contributed by suppression of hepatic de novo lipogenesis, activation of PPAR-α activity as well as up-regulation of PPAR-α and PPAR-γ expression in the intestine. In conclusion, VA as a natural trans fat, possesses beneficial properties in a rat model of dyslipidemia and metabolic syndrome, suggesting potential for the prevention of cardiovascular disease risk.
机译：反式11疫苗酸（VA）是乳制品脂肪中的主要反式脂肪酸，是人和动物内源合成cis9，trans11-共轭亚油酸（CLA）的主要前体。流行病学研究表明反式脂肪摄入与冠心病的发病率呈正相关。尽管如此，在几种动物模型以及某些人群中，CLA被归类为反式脂肪酸，已显示具有抗癌，降血脂和抗糖尿病的益处，可能是通过激活过氧化物酶体增殖物激活受体（PPAR）相关的代谢途径。随后在乳制品（例如黄油）中丰富CLA的努力导致了随之而来的VA的增加，其生物活性和健康影响并未得到充分认识。有趣的是，VA是饮食中主要的天然反式脂肪。因此，本论文的目的是评估饮食中补充合成VA对脂质代谢的影响，尤其是在血脂异常和代谢综合征时，并勾勒出VA可能调节的肠道和肝脏代谢途径。当JCR：LA-cp大鼠模型具有纯净的cp性状（cp / cp）时，会产生瘦素受体缺乏症，导致代谢综合征和糖尿病前期的症状，包括肥胖，胰岛素抵抗，肝脂肪变性，高甘油三酯血症和加重生产肝极低密度脂蛋白和肠乳糜微粒（CM）。气相色谱分析新生淋巴表明，VA被有效地吸收到肠中。另外，与合成VA相比，来自天然来源（即牛肉脂肪）的VA显示出更高的肠生物利用度。日粮向JCR：LA-cp大鼠（非瘦弱健康对照组）补充1.0％（w / w）合成VA证明血浆甘油三酸酯，总胆固醇，低密度脂蛋白胆固醇，非酯化脂肪酸和触珠蛋白浓度（分别为51％，p <0.001； 40％，p <0.001； 50％，p <0.05； 20％，p <0.05和50％，p <0.001），以及肝脂肪变性和餐后改善血脂过多。胃输注VA还可导致因脂肪负荷而导致CM分泌急剧减少（p <0.05）。我们还发现，VA的总体降血脂益处可能部分由抑制新生肝脏脂肪形成，激活PPAR-α活性以及上调PPAR-α和PPAR-γ表达而引起。总之，作为一种天然反式脂肪的VA在血脂异常和代谢综合征的大鼠模型中具有有益的特性，这表明其具有预防心血管疾病风险的潜力。

著录项

  • 作者

    Wang, Ye.;

  • 作者单位

    University of Alberta (Canada).;

  • 授予单位 University of Alberta (Canada).;
  • 学科 Health Sciences Nutrition.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 213 p.
  • 总页数 213
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 老年病学;
  • 关键词

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