Tanaka Shizuyo, Yamazaki Tohru, Asano Satoshi, Mitsumoto Atsushi, Kobayashi Daisuke, Kudo Naomi, Kawashima Yoichi
Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
Lipids. 2013 Nov;48(11):1115-34. doi: 10.1007/s11745-013-3839-6. Epub 2013 Sep 18.
SHR/NDmcr-cp (cp/cp) rats (SHR/NDcp) are an animal model of metabolic syndrome. A previous study of ours revealed drastic increases in the mass of palmitic (16:0), oleic (18:1n-9), palmitoleic (16:1n-7), cis-vaccenic (18:1n-7) and 5,8,11-eicosatrienoic acids in the liver of SHR/NDcp. However, detailed information on the class of lipid accumulated and the mechanism responsible for the overproduction of the accumulated lipid in the liver was not obtained. This study aimed to characterize the class of lipid accumulated and to explore the mechanism underlying the lipid accumulation in the liver of SHR/NDcp, in comparison with SHR/NDmcr-cp (+/+) (lean hypertensive littermates of SHR/NDcp) and Wistar Kyoto rats. In the liver of SHR/NDcp, de novo synthesis of fatty acids (16:0, 18:1n-9 and 16:1n-7) and triacylglycerol (TAG) synthesis were up-regulated and fatty acid β-oxidation was down-regulated. These perturbations of lipid metabolism caused fat accumulation in hepatocytes and accumulation of TAG, which were enriched with 16:0, 18:1n-9 and 16:1n-7, in the liver of SHR/NDcp. On the other hand, no changes were found in hepatic contents of diacylglycerol and unesterified fatty acid (FFA); among FFA, there were no differences in the hepatic concentrations of unesterified 16:0 and stearic acid between SHR/NDcp and two other groups of rats. Moreover, little change was brought about in the expression of genes responsive to endoplasmic reticulum stress in the liver of SHR/NDcp. These results may reinforce the pathophysiological role of stearoyl-CoA desaturase 1 and fatty acid elongase 6 in the liver of SHR/NDcp.
SHR/NDmcr-cp (cp/cp) 大鼠（SHR/NDcp）是代谢综合征的动物模型。我们之前的一项研究表明，SHR/NDcp 大鼠肝脏中棕榈酸（16:0）、油酸（18:1n-9）、棕榈油酸（16:1n-7）、顺式- vaccenic 酸（18:1n-7）和 5,8,11-二十碳三烯酸的含量急剧增加。然而，关于肝脏中积累的脂质类别以及导致肝脏中积累脂质过度产生的机制的详细信息尚未获得。本研究旨在表征积累的脂质类别，并与 SHR/NDmcr-cp (+/+)（SHR/NDcp 的瘦型高血压同窝仔鼠）和 Wistar Kyoto 大鼠相比，探索 SHR/NDcp 大鼠肝脏脂质积累的潜在机制。在 SHR/NDcp 大鼠的肝脏中，脂肪酸的从头合成（16:0、18:1n-9 和 16:1n-7）和三酰甘油（TAG）合成上调，脂肪酸β-氧化下调。这些脂质代谢紊乱导致肝细胞中脂肪积累以及 SHR/NDcp 大鼠肝脏中富含 16:0、18:1n-9 和 16:1n-7 的 TAG 积累。另一方面，二酰甘油和未酯化脂肪酸（FFA）的肝脏含量未发现变化；在 FFA 中，SHR/NDcp 与其他两组大鼠之间未酯化 16:0 和硬脂酸的肝脏浓度没有差异。此外，SHR/NDcp 大鼠肝脏中对内质网应激有反应的基因表达变化不大。这些结果可能会加强硬脂酰辅酶 A 去饱和酶 1 和脂肪酸延长酶 6 在 SHR/NDcp 大鼠肝脏中的病理生理作用。
