LeBoeuf R C, Caldwell M, Kirk E
Department of Medicine, University of Washington, Seattle 98195.
J Lipid Res. 1994 Jan;35(1):121-33.
This study illustrates that genetic strain and feeding status can markedly influence tissue lipid concentrations and mRNA levels of apolipoprotein genes. C57BL/6 and BALB/c mice were maintained for 2 weeks on four test diets differing in amount of cholesterol and type of fat, and fasted for 4 h or 16 h prior to collection of tissues. For both strains, the primary effect of fasting from 4 h to 16 h was to paradoxically elevate triglyceride levels in plasma and liver, and to elevate hepatic apoA-IV mRNA levels. Triglyceride secretion rates, estimated after the injection of Triton WR-1339, suggested that elevations in plasma triglyceride levels were due to reduced clearance of very low density lipoproteins. Although plasma glucose levels decreased with fasting time for both strains, insulin levels decreased for BALB/c but not C57BL/6 mice regardless of diet. This suggests that factors thought to be mediated by insulin, (e.g., plasma free fatty acid concentrations; hepatic apoA-IV mRNA levels) may be influenced by local changes in insulin sensitivity, which are controlled genetically and are not reflected by plasma insulin levels. In summary, nutritional status influences a constellation of factors involved in lipid transport that also show strong genetic components and may influence subsequent analyses of gene expression in the mouse system.
本研究表明,遗传品系和喂养状态可显著影响组织脂质浓度和载脂蛋白基因的mRNA水平。将C57BL/6和BALB/c小鼠分别置于四种胆固醇含量和脂肪类型不同的试验饮食中饲养2周,并在采集组织前禁食4小时或16小时。对于这两种品系,禁食4小时至16小时的主要影响是反常地提高血浆和肝脏中的甘油三酯水平,并提高肝脏载脂蛋白A-IV的mRNA水平。注射Triton WR-1339后估算的甘油三酯分泌率表明,血浆甘油三酯水平升高是由于极低密度脂蛋白清除率降低所致。尽管两种品系的血浆葡萄糖水平均随禁食时间而降低,但无论饮食如何,BALB/c小鼠的胰岛素水平降低,而C57BL/6小鼠的胰岛素水平未降低。这表明,被认为由胰岛素介导的因素(如血浆游离脂肪酸浓度;肝脏载脂蛋白A-IV的mRNA水平)可能受胰岛素敏感性局部变化的影响,这些变化由基因控制,且未在血浆胰岛素水平中体现。总之,营养状态会影响一系列参与脂质转运的因素,这些因素也显示出很强的遗传成分,并且可能会影响小鼠系统中后续的基因表达分析。