Gudbrandsen Oddrun Anita, Wergedahl Hege, Bohov Pavol, Berge Rolf Kristian
The Lipid Research Group, Institute of Medicine, University of Bergen, 5021 Bergen, Norway.
Chem Biol Interact. 2009 May 15;179(2-3):227-32. doi: 10.1016/j.cbi.2008.10.004. Epub 2008 Oct 15.
It has been demonstrated that the absorption of EPA and DHA is significantly lower for ethyl esters than for the corresponding free fatty acids. Since these fatty acids exist in nature and are catabolized by beta-oxidation, we instead wanted to investigate the absorption, distribution and biological effects of a non-beta-oxidizable modified fatty acid. The modified fatty acid tetradecylthioacetic acid (TTA) and the ethyl ester of TTA (EtTTA) were administered to rats for 10 days, in doses corresponding to 150 mg TTA/kg BW/day. No significant differences were found between the accumulated amounts of TTA or its Delta9 desaturated metabolite in plasma, liver, heart and epididymal white adipose tissue between EtTTA and TTA treated rats. EtTTA and TTA increased the activities of carnitine palmitoyltransferase-II and fatty acyl-CoA oxidase in liver, with no differences between the two treatment groups, but did not affect these activities in heart. EtTTA and TTA treatment decreased the plasma levels of triacylglycerols, cholesterol and phospholipids to similar extents, but no significant effects were seen in hepatic and cardiac lipid levels. EtTTA and TTA had similar effects on the fatty acid composition in plasma, liver, heart and epididymal white adipose tissue. Based on changes in fatty acid indexes it seems that these drugs had comparable stimulating effects on stearoyl-CoA desaturase and Delta6 desaturase, and reduced the Delta5 desaturase activity in liver. From the presented results we conclude that the absorption and distribution of the ethyl ester and the free form of TTA are not significantly different, and that the two administered forms of TTA have similar effects on lipid metabolism in rats.
已证实，二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）乙酯的吸收显著低于相应的游离脂肪酸。由于这些脂肪酸天然存在并通过β-氧化进行分解代谢，因此我们转而研究一种不可进行β-氧化的修饰脂肪酸的吸收、分布及生物学效应。将修饰脂肪酸十四烷基硫代乙酸（TTA）及其乙酯（EtTTA）以相当于150 mg TTA/kg体重/天的剂量给予大鼠，持续10天。在EtTTA组和TTA组大鼠的血浆、肝脏、心脏及附睾白色脂肪组织中，TTA及其Δ9去饱和代谢产物的累积量未发现显著差异。EtTTA和TTA均可提高肝脏中肉碱棕榈酰转移酶-II和脂肪酰辅酶A氧化酶的活性，两组间无差异，但对心脏中的这些酶活性无影响。EtTTA和TTA处理可使血浆中甘油三酯、胆固醇和磷脂水平降低至相似程度，但对肝脏和心脏脂质水平无显著影响。EtTTA和TTA对血浆、肝脏、心脏及附睾白色脂肪组织中的脂肪酸组成具有相似影响。基于脂肪酸指数的变化，似乎这些药物对硬脂酰辅酶A去饱和酶和Δ6去饱和酶具有相当的刺激作用，并降低了肝脏中Δ5去饱和酶的活性。根据所呈现的结果，我们得出结论，TTA乙酯和游离形式的吸收与分布无显著差异，且两种给药形式的TTA对大鼠脂质代谢具有相似作用。
