Zheng Xiaozhong, Rivabene Roberto, Cavallari Claudio, Napolitano Mariarosaria, Avella Michael, Bravo Elena, Botham Kathleen M
Department of Veterinary Basic Sciences, The Royal Veterinary College, London, UK.
Free Radic Biol Med. 2002 Jun 1;32(11):1123-31. doi: 10.1016/s0891-5849(02)00830-4.
The influence of chylomicron remnants enriched in n-6 or n-3 polyunsaturated fatty acids (PUFA) on the expression of mRNA for the low density lipoprotein receptor (LDLr), LDLr-related protein (LRP), and peroxisome proliferator activated receptor alpha (PPAR(alpha)) was investigated in normal hepatocytes and after manipulation of the cellular oxidative state by incubation with N-acetyl cysteine (NAC) or CuSO(4). In normal cells, mRNA levels for the LDLr were unaffected by incubation with chylomicron remnants, but those for the LRP and PPAR(alpha) were downregulated by remnants enriched in n-3 as compared to n-6 PUFA, suggesting that the transcription of these genes are influenced directly by the type of fatty acid delivered to the liver from the diet. Treatment with NAC or CuSO(4) was found to shift the hepatocytes into a pro-reducing or pro-oxidizing state, respectively. The abundance of mRNA for the LDLr, LRP, and PPAR(alpha) was increased after incubation with remnants enriched in n-3, but not n-6, PUFA in pro-reducing as compared to pro-oxidizing cells, and PPAR(alpha) mRNA levels were also decreased by remnants high in n-6 PUFA in the more reduced cells. These results indicate that the effects of fatty acids from the diet delivered to the liver in chylomicron remnants on the expression of hepatic genes regulating their uptake and metabolism are modulated by the redox state of the cells, and that the type of fatty acid carried by the particles also plays a part in determining the response observed.
富含n-6或n-3多不饱和脂肪酸（PUFA）的乳糜微粒残粒对低密度脂蛋白受体（LDLr）、LDLr相关蛋白（LRP）和过氧化物酶体增殖物激活受体α（PPAR(α)）mRNA表达的影响，在正常肝细胞以及通过与N-乙酰半胱氨酸（NAC）或CuSO₄孵育来调控细胞氧化状态后进行了研究。在正常细胞中，与乳糜微粒残粒孵育不影响LDLr的mRNA水平，但与富含n-6 PUFA的残粒相比，富含n-3的残粒会下调LRP和PPAR(α)的mRNA水平，这表明这些基因的转录直接受从饮食中输送到肝脏的脂肪酸类型影响。发现用NAC或CuSO₄处理分别使肝细胞转变为促还原或促氧化状态。与促氧化细胞相比，在促还原细胞中，与富含n-3而非n-6 PUFA的残粒孵育后，LDLr、LRP和PPAR(α)的mRNA丰度增加，并且在还原性更强的细胞中，富含n-6 PUFA的残粒也会降低PPAR(α)的mRNA水平。这些结果表明，乳糜微粒残粒中从饮食输送到肝脏的脂肪酸对调节其摄取和代谢的肝脏基因表达的影响受细胞氧化还原状态调节，并且颗粒携带的脂肪酸类型在决定观察到的反应中也起作用。
