Defining high-fat-diet rat models:: metabolic and molecular effects of different fat types
Defining high-fat-diet rat models:: metabolic and molecular effects of different fat types
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DOI：
10.1677/jme.1.01909
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发表时间：
2006-06-01
影响因子：
3.5
通讯作者：
Bollheimer, L. C.
中科院分区：
文献类型：
--
作者：
Buettner, R.;Parhofer, K. G.;Bollheimer, L. C.
高脂饮食(HF)啮齿动物模型对胰岛素抵抗综合征的病理生理学分析做出了重要贡献，但不同研究的表型明显不同。在这里，我们系统地比较了不同脂肪酸组成的不同HF的代谢和分子效应。雄性Wistar大鼠饲喂HF饲料(42%能量；脂肪来源：HF-L猪油；HF-O-橄榄油；HF-C-椰子油；HF-F-鱼油)。在12周的饮食过程中测量体重、食物摄入量、全身胰岛素耐量和血浆糖脂代谢参数。利用Affymetrix GeneChips获得肝脏组织学和肝脏基因表达谱。HF-L和HF-O喂养的大鼠表现出最明显的肥胖和胰岛素抵抗；HF-C和HF-F的胰岛素敏感性接近正常。HF-F和HF-C动物血浆omega-3多不饱和脂肪酸(omega-3-PUFA)和饱和脂肪酸(C-12-C-14，SFA)水平分别升高。肝组织学检查显示，HF-L、HF-O和HF-C组大鼠肝脏脂肪变性，未见明显炎症反应。肝脏SREBP1c依赖基因在这些饮食中上调，而PPARα依赖基因在HF-F喂养的大鼠中主要上调。我们只在猪油和橄榄油(主要是长链饱和脂肪酸(LC-SFA)和单不饱和脂肪酸(MUFA))的饮食中检测到经典的HF效应。富含PUFA或MC-SFA的饮食不会导致胰岛素抵抗。以LC-SFA和MUFA为基础的日粮可诱导肝脏脂肪变性，并激活SREBP1c。这表明，尽管对胰岛素的代谢作用有抵抗，但肝脏胰岛素的转录效应是完整的。
High-fat (HF)-diet rodent models have contributed significantly to the analysis of the pathophysiology of the insulin resistance syndrome, but their phenotype varies distinctly between different studies. Here, we have systematically compared the metabolic and molecular effects of different HF with varying fatty acid compositions. Male Wistar rats were fed HF diets (42% energy; fat sources: HF-L - lard; HF-O - olive oil; HF-C - coconut fat; HF-F - fish oil). Weight, food intake, whole-body insulin tolerance and plasma parameters of glucose and lipid metabolism were measured during a 12-week diet course. Liver histologies and hepatic gene expression profiles, using Affymetrix GeneChips, were obtained. HF-L and HF-O fed rats showed the most pronounced obesity and insulin resistance; insulin sensitivity in HF-C and HF-F was close to normal. Plasma omega 3 polyunsaturated fatty acid (omega-3-PUFA) and saturated fatty acid (C-12-C-14, SFA) levels were elevated in HF-F and HF-C animals respectively. The liver histologies showed hepatic steatosis in HF-L, HF-O and HF-C without major inflammation. Hepatic SREBP1c-dependent genes were upregulated in these diets, whereas PPAR alpha-dependent genes were predominantly upregulated in HF-F fed rats. We detected classical HF effects only in diets based on lard and olive oil (mainly long-chain, saturated (LC-SFA) and monounsaturated fatty acids (MUFA)). PUFA- or MC-SFA-rich diets did not induce insulin resistance. Diets based on LC-SFA and MUFA induced hepatic steatosis with SREBP1c activation. This points to an intact transcriptional hepatic insulin effect despite resistance to insulin's metabolic actions.