Osmundsen H, Braud H, Beauseigneur F, Gresti J, Tsoko M, Clouet P
Department of Physiology and Biochemistry, Institute for Oral Biology, University of Oslo, Box 1052, Blindern, 0316 Oslo, Norway.
Biochem J. 1998 Apr 1;331 ( Pt 1)(Pt 1):153-60. doi: 10.1042/bj3310153.
(1) Effects of dietary treatment of male albino rats with eicosapentaenoic acid (EPA) or docosahexaenoic acid on hepatic mitochondrial lipid metabolism have been investigated. (2) Mitochondria isolated from rats given these treatments were shown to have increased ability to respire on acyl-CoA esters in the presence of malonate. This effect was expressed with most of the long-chain acyl-CoA esters used as substrates. When malonate in the incubations was replaced with malate, mitochondria from treated animals were found to exhibit diminished rates of respiration on polyunsaturated acyl-CoA esters, in particular linolenoyl-, eicosapentaenoyl- and docosahexaenoyl-CoA. This phenomenon could not be attributed to changes in activity of carnitine palmitoyltransferase I or in peroxisomal beta-oxidation. (3) Uncoupled respiration on glutamate, malate or succinate was also affected by treatment with EPA. With liver mitochondria isolated from rats that had been treated with a omega-3 fatty acid in the fasted state, the respiratory rates were lower than those observed with mitochondria isolated from control rats. Respiratory rates with mitochondria isolated from rats given the omega-3 fatty acid in the fed state was not significantly different from control rates. (4) In rats treated with EPA in the fed state, the amount of EPA incorporated into mitochondrial lipids was markedly more increased as compared to rats given omega-3 fatty acid in the fasted state. Incorporation of dietary EPA into tissue lipids was investigated, also following mildronate treatment of rats (an inhibitor of carnitine biosynthesis). (5) A hypolipidaemic effect of dietary EPA was only observed when the fatty acid was given to fed rats. Rats treated with EPA in the fasted state, in contrast, exhibited hypoglycaemia, the hypolipidaemic effects now being absent. (6) These results suggest that hypolipidaemia is most pronounced when the metabolic state favours incorporation of dietary EPA into body lipids rather than its beta-oxidation, as mediated by the fed/fasted transition or by treatment with mildronate.
（1）研究了用二十碳五烯酸（EPA）或二十二碳六烯酸对雄性白化大鼠进行饮食治疗对肝脏线粒体脂质代谢的影响。（2）从接受这些治疗的大鼠中分离出的线粒体显示，在丙二酸存在下，其对酰基辅酶A酯的呼吸能力增强。这种效应在用作底物的大多数长链酰基辅酶A酯中都有体现。当孵育中的丙二酸被苹果酸取代时，发现经处理动物的线粒体对多不饱和酰基辅酶A酯，特别是亚麻酸酰基辅酶A、二十碳五烯酰基辅酶A和二十二碳六烯酰基辅酶A的呼吸速率降低。这种现象不能归因于肉碱棕榈酰转移酶I活性的变化或过氧化物酶体β氧化的变化。（3）用EPA处理也会影响谷氨酸、苹果酸或琥珀酸的解偶联呼吸。从禁食状态下用ω-3脂肪酸处理的大鼠中分离出的肝脏线粒体，其呼吸速率低于从对照大鼠中分离出的线粒体。从喂食状态下给予ω-3脂肪酸的大鼠中分离出的线粒体的呼吸速率与对照速率无显著差异。（4）在喂食状态下用EPA处理的大鼠中，与禁食状态下给予ω-3脂肪酸的大鼠相比，掺入线粒体脂质中的EPA量明显增加更多。还研究了在大鼠用米屈肼（肉碱生物合成抑制剂）处理后，饮食中EPA掺入组织脂质的情况。（5）仅在将脂肪酸给予喂食的大鼠时才观察到饮食中EPA的降血脂作用。相比之下，在禁食状态下用EPA处理的大鼠表现出低血糖，现在没有降血脂作用。（6）这些结果表明，当代谢状态有利于饮食中EPA掺入身体脂质而不是其β氧化时，降血脂作用最为明显，这是由进食/禁食转变或米屈肼处理介导的。
