Luan Yang, Hirashima Tsukasa, Man Zhi-Wei, Wang Min-Wei, Kawano Kazuya, Sumida Takumi
Biological Research Institute, Otsuka Pharmaceutical Co. Ltd., 463-10 kagasuno Kawauchi-cho, Tokushima 771-0192, Japan.
Diabetes Res Clin Pract. 2002 Aug;57(2):75-82. doi: 10.1016/s0168-8227(02)00026-8.
Obesity was considered to be one of the causes of non-insulin-dependent diabetes mellitus (NIDDM). However, the mechanism responsible for obesity has not yet been fully elucidated. In this study, we first examined the relationship between food intake amount and obesity in a NIDDM model animal, and then we focused on triacylglycerol (TG) synthetase activity, which play important roles in hypertriglyceridemia (HTG) associated with obesity. Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model of NIDDM, characterized by obesity, HTG and insulin resistance. In this study, OLETF rats were allocated to a food-satiated group (satiated) or food-restricted group (to eliminate the effects of hyperphagia on obesity, amount of daily food intake was the same as that in their control strain Long-Evans Tokushima Otsuka (LETO) rats). Changes in body weight, body fat, intraabdominal fat weight, and TG content in liver were measured and biochemical blood tests and activity assay of TG synthetase (monoacylglycerol acyltransferase (MGAT) and diacylglycerol acyltransferase (DGAT)) were performed.
(1) The body weight in the restricted OLETF rats was significantly decreased to 71.7% of that in the satiated OLETF rats, which was almost the same value as that in the LETO rats. However, body fat and intraabdominal fat weight were significantly increased in restricted OLETF rats and satiated OLETF rats compared with LETO rats. (2) Plasma TG, insulin, glucose, leptin and hepatic TG content were significantly higher in OLETF rats than the values in LETO rats. (3) MGAT activity in the small intestine from both satiated and restricted OLETF rats was significantly higher than that in LETO rats. DGAT activity in OLETF rats was not significantly different from that in LETO rats. In conclusion, the body fat weight and plasma TG were still significantly accelerated in OLETF rats at the same food intake as LETO rats. MGAT activity in the small intestine from OLETF rats was also significantly higher than those of LETO rats. Therefore, high MGAT activity in the small intestine may play an important role in HTG and obesity, subsequently hastening the development of NIDDM in OLETF rats.
肥胖被认为是非胰岛素依赖型糖尿病（NIDDM）的病因之一。然而，导致肥胖的机制尚未完全阐明。在本研究中，我们首先在NIDDM模型动物中研究了食物摄入量与肥胖之间的关系，然后聚焦于甘油三酯（TG）合成酶活性，其在与肥胖相关的高甘油三酯血症（HTG）中起重要作用。大冢长 - Evans 德岛肥胖（OLETF）大鼠是NIDDM的动物模型，其特征为肥胖、HTG和胰岛素抵抗。在本研究中，将OLETF大鼠分为食物饱足组（饱足组）和食物限制组（为消除多食对肥胖的影响，每日食物摄入量与对照品系大冢长 - Evans 德岛（LETO）大鼠相同）。测量体重、体脂、腹内脂肪重量和肝脏中TG含量的变化，并进行血液生化检测以及TG合成酶（单酰甘油酰基转移酶（MGAT）和二酰甘油酰基转移酶（DGAT））活性测定。
（1）食物限制的OLETF大鼠体重显著下降至饱足的OLETF大鼠体重的71.7%，这与LETO大鼠的体重几乎相同。然而，与LETO大鼠相比，食物限制的OLETF大鼠和饱足的OLETF大鼠的体脂和腹内脂肪重量均显著增加。（2）OLETF大鼠的血浆TG、胰岛素、葡萄糖、瘦素和肝脏TG含量显著高于LETO大鼠的值。（3）饱足和食物限制的OLETF大鼠小肠中的MGAT活性均显著高于LETO大鼠。OLETF大鼠的DGAT活性与LETO大鼠无显著差异。总之，在与LETO大鼠相同食物摄入量的情况下，OLETF大鼠的体脂重量和血浆TG仍显著升高。OLETF大鼠小肠中的MGAT活性也显著高于LETO大鼠。因此，小肠中高MGAT活性可能在HTG和肥胖中起重要作用，随后加速OLETF大鼠NIDDM的发展。
