A BASIC APPROACH TO ASSOCIATION OF INSULIN RESISTANCE WITH TNF α IN COWS WITH FATTY LIVER

最近有报道称，围产期有时会观察到患有胰岛素抵抗的奶牛，它们的产奶量显著减少。指出脂肪肝与其发病机制密切相关。脂肪细胞分泌的肿瘤坏死因子α被认为是导致胰岛素抵抗的最重要因素。我们设计了两个诱导脂肪肝的实验。试验一将奶牛禁食4天，进入负能量平衡状态。此外，作为实验2，奶牛被给予乙硫氨酸，蛋氨酸的类似物质，以减少肝脏中蛋白质的产生。在每个实验中分析使用过的奶牛的胰岛素抵抗和肿瘤坏死因子α。结果1.禁食后大鼠肝脏甘油三酯(TG)含量明显升高。在脂肪肝的发生发展过程中观察到胰岛素抵抗的增加。禁食牛血清肿瘤坏死因子α浓度无明显变化。在肝脏的微形态分析中，脂肪肝奶牛的肝脏基底膜明显增厚。结果：1.乙硫氨酸处理的黄牛肝脏甘油三酯含量显著升高。在脂肪肝的发生发展过程中，血清载脂蛋白B-100浓度明显降低。肝脏脂肪沉积明显诱导胰岛素抵抗。试验牛出现高血糖和高胰岛素血症。未发现脂肪肝与血清肿瘤坏死因子α浓度的明显相关性。从这些结果中，两个实验被认为是有效的脂肪肝诱导。虽然对采集的肝组织进行了生化和组织学分析，但未检测到其与肝脏脂肪沉积的相关性。我们计划改进肿瘤坏死因子α的测定和组织标本，以仔细检查这些实验。

It has been recently reported that cows with insulin resistance are sometime observed during the periparturient period, and their milk production are remarkably decreased. It is pointed out that fatty liver is closely linked to that pathogenesis. Tumor necrosis factor ct (TNFα) secreted from fatty cell is considered to be the most important factor in the insulin resistance. We designed two experiments for induction of fatty liver. In experiment-1, cows were fasted for 4 day to be fallen into negative energy balance. Moreover, as experiment-2, cows were administrated ethionine, analogous substance of methionine, to reduce the production of proteins in the liver. Insulin resistance and TNF α of used cows were analyzed in each experiment.Experiment-11. Liver triglyceride (TG) content was apparently increased after fasting.2. The increase of insulin resistance was observed in the development of fatty liver.3. Serum concentration of TNFα was not significantly changed in the fasted cow.4. In micromorphological analysis of liver, hepatic basal lamina in the cow with fatty liver remarkably became thicker compared to that in control.Experiment-21. Liver TG contents were remarkably increased in ethionine-treated cows.2. Serum concentration of apolipoprotein B-100 was significantly decreased in the development of fatty liver.3. Hepatic lipidosis apparently induced insulin resistance.4. Hyperglycemia and hyperinsulinism were observed in treated cows.5. The apparent association of fatty liver with serum concentration of TNFα was not detected.From these results, two experiments were suggested to be effective for induction of fatty liver. Although TNFα of sampled liver tissues were analyzed biochemically and histologically, its relevance to hepatic lipidosis was not detected. We are planning to improve TNFα determination and histological specimens to scrutinize these experiments.