Ochiai Masaru, Matsuo Tatsuhiro
Faculty of Agriculture, Kagawa University, Kagawa, Japan.
J Oleo Sci. 2013;62(9):745-54. doi: 10.5650/jos.62.745.
Muscular insulin resistance is a characteristic of obesity and type 2 diabetes, but little is known about fatty acid (FA) metabolism in insulin-resistant skeletal muscle. In this study, we investigated the effects of the repeated administration of the PPAR-γ agonist pioglitazone on fat accumulation, FA composition, and stearoyl-CoA desaturase (SCD) index in rat tissues. Seventeen 4-week-old male Wistar rats were divided into control (C, n = 9) and pioglitazone treatment (P, n = 8) groups, and all the rats were fed a high-fat and high-sucrose diet for 8 weeks. Vehicle or pioglitazone (3 mg/kg) was orally administered daily to rats in the C group and P group, respectively. In the eighth week of the test period, an oral glucose tolerance test (OGTT) was performed after 12 h fasting. At the end of the test period, serum, liver, perirenal adipose tissue, and skeletal muscles were removed after 12 h fasting. The fasting serum and plasma glucose concentrations and OGTT glucose and insulin levels were significantly lower, while the serum adiponectin concentration was significantly higher in the P group than in the C group. Pioglitazone administration increased fat accumulation in the various muscle types examined, perirenal adipose tissue, and brown adipose tissue (BAT), but decreased fat accumulation in the liver. Pioglitazone administration increased the SCD indices for the muscles, perirenal adipose tissue, and liver, but not those of BAT. The lipoprotein lipase (LPL) activity of the BAT and perirenal adipose tissue, but not the muscles, was higher in the P group than in the C group. These results indicate that pioglitazone administration improved glucose tolerance and increased fat accumulation and SCD indices in the muscles and adipose tissues of rats. The increased fat accumulation was closely correlated with LPL activity in both adipose tissues, but not in the muscles.
肌肉胰岛素抵抗是肥胖症和2型糖尿病的一个特征，但对于胰岛素抵抗的骨骼肌中的脂肪酸（FA）代谢了解甚少。在本研究中，我们调查了重复给予过氧化物酶体增殖物激活受体γ（PPAR-γ）激动剂吡格列酮对大鼠组织中脂肪堆积、FA组成和硬脂酰辅酶A去饱和酶（SCD）指数的影响。将17只4周龄雄性Wistar大鼠分为对照组（C组，n = 9）和吡格列酮治疗组（P组，n = 8），所有大鼠均给予高脂高糖饮食8周。分别给C组和P组大鼠每日口服溶剂或吡格列酮（3 mg/kg）。在试验期的第8周，禁食12小时后进行口服葡萄糖耐量试验（OGTT）。在试验期结束时，禁食12小时后取出血清、肝脏、肾周脂肪组织和骨骼肌。P组的空腹血清和血浆葡萄糖浓度以及OGTT葡萄糖和胰岛素水平显著较低，而血清脂联素浓度显著高于C组。给予吡格列酮增加了所检测的各种肌肉类型、肾周脂肪组织和棕色脂肪组织（BAT）中的脂肪堆积，但减少了肝脏中的脂肪堆积。给予吡格列酮增加了肌肉、肾周脂肪组织和肝脏的SCD指数，但未增加BAT的SCD指数。P组BAT和肾周脂肪组织而非肌肉的脂蛋白脂肪酶（LPL）活性高于C组。这些结果表明，给予吡格列酮改善了大鼠的葡萄糖耐量，并增加了肌肉和脂肪组织中的脂肪堆积及SCD指数。脂肪堆积增加与两个脂肪组织中的LPL活性密切相关，但与肌肉中的LPL活性无关。
