Parkes J G, Auerbach W, Goldberg D M
Department of Clinical Biochemistry, Banting Institute, University of Toronto, Canada.
Enzyme. 1990;43(1):47-55. doi: 10.1159/000468704.
The mechanism by which alcohol increases plasma total high density lipoproteins (HDLs) and HDL-cholesterol is unknown, but it may involve modulation of the lipolytic enzymes, hepatic triglyceride lipase (HTGL) and/or lipoprotein lipase (LPL) in hepatic and extrahepatic tissues. The modulation of HDL metabolism by alcohol may also be related to its potential to induce mixed function oxidases in liver microsomes. These possibilities were examined by a pair-feeding protocol in which rats were fed diets with 35% of the caloric content as ethanol; control groups received a diet with an isocaloric amount of sucrose or were fed chow ad libitum. Alcohol caused a significant decrease in HTGL activity of liver microsomes, but there was no significant effect of alcohol upon the activities of LPL in adipose tissue and heart muscle. The relative rates of mixed function oxidases, assayed in control liver microsomes using ethoxy-,pentoxy- and benzyloxy-resorufin as substrates, were benzyloxy greater than ethoxy greater than pentoxy. This order was not affected by alcohol, but the oxidation of ethoxy- and pentoxyresorufin was reduced in liver microsomes from the ethanol-fed group. HTGL synthesis and secretion were also measured using primary rat hepatocyte cultures isolated from animals on the above dietary regimes and maintained for up to 3 days in basal medium alone or supplemented with 10 mmol/l ethanol. In basal media the order of activity of extracellular HTGL, released by the addition of heparin, was sucrose-fed greater than chow-fed greater than ethanol-fed. The rate of HTGL secretion from hepatocytes was stimulated in ethanol-containing medium, and was greater in hepatocytes from the sucrose-fed controls.(ABSTRACT TRUNCATED AT 250 WORDS)
酒精增加血浆总高密度脂蛋白（HDL）和HDL胆固醇的机制尚不清楚，但可能涉及对肝及肝外组织中脂解酶、肝甘油三酯脂肪酶（HTGL）和/或脂蛋白脂肪酶（LPL）的调节。酒精对HDL代谢的调节也可能与其诱导肝微粒体中混合功能氧化酶的能力有关。通过配对喂养方案对这些可能性进行了研究，在该方案中，给大鼠喂食热量含量为35%乙醇的饲料；对照组接受等热量蔗糖饲料或随意喂食普通饲料。酒精导致肝微粒体HTGL活性显著降低，但对脂肪组织和心肌中LPL的活性没有显著影响。以乙氧基、戊氧基和苄氧基试卤灵为底物在对照肝微粒体中测定的混合功能氧化酶相对活性顺序为苄氧基＞乙氧基＞戊氧基。该顺序不受酒精影响，但乙醇喂养组肝微粒体中乙氧基和戊氧基试卤灵的氧化减少。还使用从上述饮食方案的动物中分离的原代大鼠肝细胞培养物，在单独的基础培养基中或补充10 mmol/l乙醇的培养基中培养长达3天，来测量HTGL的合成和分泌。在基础培养基中，添加肝素后释放的细胞外HTGL活性顺序为蔗糖喂养组＞普通饲料喂养组＞乙醇喂养组。含乙醇培养基刺激了肝细胞HTGL的分泌速率，且蔗糖喂养对照组的肝细胞中该速率更高。（摘要截短于250字）
