Hikita M, Bujo H, Yamazaki K, Taira K, Takahashi K, Kobayashi J, Saito Y
Second Department of Internal Medicine, Chiba University School of Medicine, Chiba, 260-0856, Japan.
Biochem Biophys Res Commun. 2000 Oct 22;277(2):423-9. doi: 10.1006/bbrc.2000.3695.
Postprandial hyperlipidemia is frequently accompanied with intra-abdominal visceral accumulation in human subjects. We have found that the decreased lipoprotein lipase (LPL) mass and activity is negatively associated with the amount of visceral fat accumulation. Here, we studied the postprandial hyperlipidemia using the OLETF rat, a model with visceral obesity, in order to clarify the molecular mechanism causing postprandial hyperlipidemia accompanied with visceral obesity. At the same age of 32 weeks, the OLETF rats showed obviously higher plasma leptin, total cholesterol, triglyceride, and HDL-cholesterol levels than the control LETO rats, although the plasma glucose level was not significantly different. Fat-loading test revealed the delayed metabolism of exogenous fat in the OLETF rats compared to the LETO rats, similar to human subjects with visceral obesity. In the obese rats, plasma levels of LPL mass and activities were 60 and 49% of control rats. The expression of LPL gene was decreased in subcutaneous adipose tissues and skeletal muscle of OLETF rats to 40 and 52% compared to those of LETO rats. In OLETF rats, plasma tumor necrosis factor-alpha (TNF-alpha) and insulin levels were increased to 2.0- and 2.3-folds compared to those in control rats. Furthermore, plasma insulin and TNF-alpha levels in OLETF rats were negatively correlated with the expression levels of LPL gene in subcutaneous fat and muscle. These results indicate that decreased LPL mass and activity in the animal model with visceral obesity is possibly caused by decreased expression of LPL gene in tissues mediated by the increased levels of insulin and TNF-alpha. The different expression of LPL gene in tissues associated with the increased levels of insulin and TNF-alpha possibly elucidate the underlying mechanisms involving the postprandial hyperlipidemia observed in visceral obesity.
餐后高脂血症在人类受试者中常伴有腹内内脏脂肪堆积。我们发现脂蛋白脂肪酶（LPL）质量和活性的降低与内脏脂肪堆积量呈负相关。在此，我们使用OLETF大鼠（一种内脏肥胖模型）研究餐后高脂血症，以阐明导致伴有内脏肥胖的餐后高脂血症的分子机制。在32周龄时，OLETF大鼠的血浆瘦素、总胆固醇、甘油三酯和高密度脂蛋白胆固醇水平明显高于对照LETO大鼠，尽管血浆葡萄糖水平无显著差异。脂肪负荷试验显示，与LETO大鼠相比，OLETF大鼠中外源性脂肪的代谢延迟，类似于患有内脏肥胖的人类受试者。在肥胖大鼠中，LPL质量和活性的血浆水平分别为对照大鼠的60%和49%。与LETO大鼠相比，OLETF大鼠皮下脂肪组织和骨骼肌中LPL基因的表达分别降至40%和52%。在OLETF大鼠中，血浆肿瘤坏死因子-α（TNF-α）和胰岛素水平分别比对照大鼠升高至2.0倍和2.3倍。此外，OLETF大鼠的血浆胰岛素和TNF-α水平与皮下脂肪和肌肉中LPL基因的表达水平呈负相关。这些结果表明，内脏肥胖动物模型中LPL质量和活性的降低可能是由胰岛素和TNF-α水平升高介导的组织中LPL基因表达降低所致。胰岛素和TNF-α水平升高相关组织中LPL基因的不同表达可能阐明了内脏肥胖中观察到的餐后高脂血症的潜在机制。
