Srivastava R A
Department of Internal Medicine, Washington University School of Medicine, Saint Louis, MO 63110.
Biochem Mol Biol Int. 1994 Sep;34(2):393-402.
The aim of the present study was to investigate the regulation of the apoAI gene by dietary saturated fat and cholesterol. Saturated fatty acids and cholesterol raise low density- and high density lipoprotein particles in humans. Increased LDL is attributed to the down-regulation of LDL-receptor gene, but the mechanism of increased plasma HDL levels is unknown. To study the mechanism of HDL elevation by saturated fat, male rats and male mice were employed as animal models, since they also raise their plasma HDL levels when fed high lipid diets. Animals were divided in four groups and fed the following diets: control (5% corn oil); high cholesterol (0.5%); high fat (20% coconut oil); and high fat plus cholesterol diets. The high cholesterol diet did not alter plasma and HDL-cholesterol levels. However, the high fat diet increased HDL levels by 20% in rats and 55% in mice. A combination of saturated fat and cholesterol diet raised plasma HDL levels by 36 and 67% in rats and mice, respectively. Plasma apoAI levels increased parallel to HDL concentrations. Mechanism of HDL elevation by saturated fat was investigated. Hepatic and intestinal apoAI mRNA did not change with any of the test diets in mice. Rat hepatic apoAI mRNA was also unchanged by the high cholesterol diet, but was decreased on high fat and fat-cholesterol combination diets. These results suggest that transcriptional regulation of the apoAI gene was not responsible for increased plasma apoAI and HDL. The translational efficiency of apoAI on isolated polysomes was also measured, and it was found that apoAI synthesis increased about 20% on high fat and fat-cholesterol combination diets. This partially explains the elevated levels of plasma HDL. Additional regulation through impaired catabolism of HDL particles by high fat diet feeding may be another pathway for increased HDL levels. Unlike apoAI mRNA, the mRNA of other HDL apoproteins, apoAII and apoAIV, were increased by high fat and combination diet feeding. These results suggest that saturated fatty acids regulate plasma HDL levels by translational and posttranslational mechanisms.
本研究的目的是探讨膳食饱和脂肪和胆固醇对载脂蛋白AI（apoAI）基因的调控作用。饱和脂肪酸和胆固醇可提高人体低密度脂蛋白和高密度脂蛋白颗粒水平。低密度脂蛋白升高归因于低密度脂蛋白受体基因的下调，但血浆高密度脂蛋白水平升高的机制尚不清楚。为研究饱和脂肪使高密度脂蛋白升高的机制，选用雄性大鼠和雄性小鼠作为动物模型，因为它们在高脂饮食时血浆高密度脂蛋白水平也会升高。将动物分为四组，分别给予以下饮食：对照组（5%玉米油）；高胆固醇组（0.5%）；高脂肪组（20%椰子油）；高脂肪加胆固醇组。高胆固醇饮食未改变血浆和高密度脂蛋白胆固醇水平。然而，高脂肪饮食使大鼠高密度脂蛋白水平升高20%，小鼠升高55%。饱和脂肪与胆固醇联合饮食使大鼠和小鼠血浆高密度脂蛋白水平分别升高36%和67%。血浆载脂蛋白AI水平与高密度脂蛋白浓度平行升高。对饱和脂肪使高密度脂蛋白升高的机制进行了研究。小鼠肝脏和肠道载脂蛋白AI信使核糖核酸（mRNA）在任何一种试验饮食下均未改变。大鼠肝脏载脂蛋白AI mRNA在高胆固醇饮食时也未改变，但在高脂肪和高脂肪加胆固醇联合饮食时降低。这些结果表明，载脂蛋白AI基因的转录调控与血浆载脂蛋白AI和高密度脂蛋白升高无关。还测定了分离多聚核糖体上载脂蛋白AI的翻译效率，发现高脂肪和高脂肪加胆固醇联合饮食时载脂蛋白AI合成增加约20%。这部分解释了血浆高密度脂蛋白水平升高的原因。高脂饮食导致高密度脂蛋白颗粒分解代谢受损的额外调控可能是高密度脂蛋白水平升高的另一条途径。与载脂蛋白AI mRNA不同，其他高密度脂蛋白载脂蛋白，即载脂蛋白AII和载脂蛋白AIV的mRNA在高脂肪和联合饮食时升高。这些结果表明，饱和脂肪酸通过翻译和翻译后机制调节血浆高密度脂蛋白水平。
