Buettner R, Parhofer K G, Woenckhaus M, Wrede C E, Kunz-Schughart L A, Schölmerich J, Bollheimer L C
Department of Internal Medicine I, University of Regensburg, 93042 Regensburg, Germany.
J Mol Endocrinol. 2006 Jun;36(3):485-501. doi: 10.1677/jme.1.01909.
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 PPARalpha-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.
高脂（HF）饮食啮齿动物模型对胰岛素抵抗综合征病理生理学的分析有显著贡献，但不同研究中其表型差异明显。在此，我们系统比较了不同脂肪酸组成的不同高脂饮食的代谢和分子效应。给雄性Wistar大鼠喂食高脂饮食（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）。在为期12周的饮食过程中测量体重、食物摄入量、全身胰岛素耐受性以及葡萄糖和脂质代谢的血浆参数。使用Affymetrix基因芯片获得肝脏组织学和肝脏基因表达谱。喂食HF-L和HF-O的大鼠表现出最明显的肥胖和胰岛素抵抗；HF-C和HF-F中的胰岛素敏感性接近正常。HF-F和HF-C动物的血浆ω-3多不饱和脂肪酸（ω-3-PUFA）和饱和脂肪酸（C(12)-C(14)，SFA）水平分别升高。肝脏组织学显示HF-L、HF-O和HF-C中有肝脂肪变性但无严重炎症。这些饮食中肝脏SREBP1c依赖性基因上调，而在喂食HF-F的大鼠中PPARα依赖性基因主要上调。我们仅在基于猪油和橄榄油的饮食（主要是长链饱和（LC-SFA）和单不饱和脂肪酸（MUFA））中检测到典型的高脂效应。富含多不饱和脂肪酸（PUFA）或中链饱和脂肪酸（MC-SFA）的饮食不会诱导胰岛素抵抗。基于LC-SFA和MUFA的饮食通过SREBP1c激活诱导肝脂肪变性。这表明尽管对胰岛素的代谢作用有抵抗，但肝脏胰岛素转录效应仍完整。
