Botham Kathleen M, Zheng Xiaozhong, Napolitano Mariarosaria, Avella Michael, Cavallari Claudio, Rivabene Roberto, Bravo Elena
Department of Veterinary Basic Sciences, Royal Veterinary College, London NW1 0TU, United Kingdom.
Exp Biol Med (Maywood). 2003 Feb;228(2):143-51. doi: 10.1177/153537020322800203.
The influence of chylomicron remnants enriched in n-3 or n-6 polyunsaturated fatty acids (PUFA) (derived from fish or corn oil, respectively) on the expression of mRNA for four genes involved in the regulation of the synthesis, assembly, and secretion of very-low-density lipoprotein (VLDL) in the liver was investigated in normal rat hepatocytes and after manipulation of the cellular oxidative state by incubation with N-acetyl cysteine (NAC) or CuSO(4). The four genes investigated were those encoding apolipoprotein B (apoB), the microsomal triacylglycerol transfer protein (MTP), and the enzymes acyl coenzyme A:diacylglycerol acyltransferase (DGAT) and acyl coenzyme A:cholesterol acyltransferase 2 (ACAT2), which play a role in the regulation of triacylglycerol and cholesteryl ester synthesis, respectively. mRNA levels for apoB, MTP, and DGAT were unaffected by either fish or corn oil chylomicron remnants, but the amount of ACAT2 mRNA was significantly reduced after incubation of the hepatocytes with fish oil remnants as compared with corn oil remnants or without remnants. These findings indicate that the delivery of dietary n-3 PUFA to hepatocytes in chylomicron remnants downregulates the expression of mRNA for ACAT2, and this may play a role in their inhibition of VLDL secretion. However, when the cells were shifted into a pro-oxidizing or pro-reducing state by pretreatment with CuSO(4) (1 mM) or NAC (5 mM) for 24 hr, levels of mRNA for MTP were increased by about 2- or 4-fold, respectively, by fish oil remnants, whereas corn oil remnants had no significant effect. Fish oil remnants also caused a smaller increase in apoB mRNA in comparison with corn oil remnants in NAC-treated cells (+38%). These changes would be expected to lead to increased VLDL secretion rather than the decrease associated with dietary n-3 PUFA in normal conditions. These findings suggest that relatively minor changes in cellular redox levels can have a major influence on important liver functions such as VLDL synthesis and secretion.
研究了富含n-3或n-6多不饱和脂肪酸（PUFA）（分别源自鱼油或玉米油）的乳糜微粒残粒对正常大鼠肝细胞以及在用N-乙酰半胱氨酸（NAC）或硫酸铜（CuSO₄）孵育以改变细胞氧化状态后，肝脏中参与极低密度脂蛋白（VLDL）合成、组装和分泌调控的四个基因的mRNA表达的影响。所研究的四个基因分别是编码载脂蛋白B（apoB）、微粒体三酰甘油转移蛋白（MTP）以及酰基辅酶A：二酰甘油酰基转移酶（DGAT）和酰基辅酶A：胆固醇酰基转移酶2（ACAT2）的基因，它们分别在三酰甘油和胆固醇酯合成的调控中发挥作用。apoB、MTP和DGAT的mRNA水平不受鱼油或玉米油乳糜微粒残粒的影响，但与玉米油残粒或无残粒相比，用鱼油残粒孵育肝细胞后，ACAT2 mRNA的量显著降低。这些发现表明，乳糜微粒残粒将膳食中的n-3 PUFA递送至肝细胞会下调ACAT2的mRNA表达，这可能在其对VLDL分泌的抑制中起作用。然而，当细胞通过用1 mM CuSO₄或5 mM NAC预处理24小时而转变为促氧化或促还原状态时，鱼油残粒分别使MTP的mRNA水平增加约2倍或4倍，而玉米油残粒则无显著影响。与NAC处理的细胞中的玉米油残粒相比，鱼油残粒还使apoB mRNA有较小程度的增加（+38%）。这些变化预期会导致VLDL分泌增加，而不是在正常条件下与膳食n-3 PUFA相关的减少。这些发现表明，细胞氧化还原水平的相对微小变化可能对诸如VLDL合成和分泌等重要肝功能产生重大影响。
