SKELETAL MUSCLEAS A ETIOLOGY OF OBESITY AND INSULIN RESISTANCE : INVESTIGATION BY USING FAST-TWITCH FIBER DOMINANT MODEL RATS (FFDR)

最近的研究报道，骨骼肌特征与腹型肥胖、胰岛素抵抗和高血压有关。有证据表明，人体肌肉中快抽动(%FT)纤维的百分比与胰岛素抵抗呈负相关，与体脂积累也呈正相关。然而，它尚未阐明是否具有遗传更高水平的%FT纤维的大鼠是由Suwa等人(Am.J.Physiol，271：R432-R436,1996)的胰岛素敏感性水平低于对照组。FT纤维显性模型大鼠(FFDR)腓肠肌和比目鱼肌的FT%纤维均显著高于对照组(CR)。本研究的主要目的是调查胰岛素敏感性水平，一些肌肉特征，包括纤维组成和毛细血管密度，以及自由车轮在FFDR和CR之间的距离。8~9周龄FFDR(n=6)和CR(n=8)为…在这项研究中使用更多的e。胰岛素敏感性由正常血糖高胰岛素钳夹90min评估，以60~90min的平均葡萄糖输注率(GIR；mg/kg/min)计算。两组患者在此期间的平均血浆胰岛素浓度无显著差异。FFDR的体重、脂肪含量和个体肌肉重量与CR没有显著差异，但FFDR的比目鱼体重比CR高。与CR组相比，FFDR组腓肠肌和比目鱼肌深部的慢收缩(%ST)纤维明显减少，而腓肠肌深部的%FTB纤维和比目鱼肌的%FTA纤维明显增多。另一方面，FFDR和CR在毛细血管密度、毛细血管与纤维的比例以及肌纤维周围的平均毛细血管数量方面没有显著差异。FFDR组GIR(4.9 mg/kg/min)与CR组(4.6 mg/kg/min)无显著差异。8~9周龄FFDR组车轮行走距离也显著长于CR组。由此可见，肌纤维成分不是幼年雄性大鼠摄取葡萄糖的单一决定因素。本研究的第二个目的是研究高脂饮食对腹脂蓄积的影响，以及低脂和高脂饮食后FFDR和CR之间肌肉组织化学和生化特性的变化。FFDR+低脂饮食(FL；n=8)、FFDR+高脂饮食(FH；n=9)、CR+低脂饮食(CL；n=7)、CR+高脂饮食(CH；n=7)。每组8周龄开始饲喂，维持6周。体重增长和腹部脂肪积累量，CH组显著高于FL和FH组。4组间能量摄入量差异无统计学意义。虽然CH组的腓肠肌重量高于FL组和FH组，但比目鱼肌和足底肌重在4组间无显著差异。FFDR组腓肠肌I型纤维百分率明显低于CR组，而2DX类纤维百分率显著高于FFDR组。在腓肠肌深层，2A型和2DX型纤维的琥珀酸脱氢酶(SDH)活性均显著高于1型纤维。这些结果表明，高脂饮食后，CR和FFDR在脂肪积累方面的差异取决于每种纤维类型的氧化能力的差异，而不是肌肉体积的差异。较少

Recent studies reported skeletal muscle characteristics to be related to abdominal obesity, insulin resistance, and hyper tension. There is some evidences that the percentage of fast-twitch (%FT) fibers in human muscle is inversely associated with insulin resistance and is also positively related with body fat accumulation. However, it has yet to be elucidated as to whether rats with genetically higher levels of %FT fibers developed by Suwa et al (Am. J. Physiol., 271 : R432 - R436, 1996) had lower levels of insulin sensitivity than control rats. The FT% fiber in both the M. gastrocnemius and soleus in FT fiber dominant model rat (FFDR) were demonstrated to be significantly higher than in control rats (CR). The main purposes of present study was to investigate the levels of insulin sensitivity, some muscle characteristics including fiber composition and capillary density, and the distance for voluntary wheel running between FFDR and CR. FFDR (n=6) and CR(n=8) aged from 8 to 9 weeks wer … More e used in this study. Insulin sensitivity was evaluated by the euglycemic hyper insulinemic clamp for 90min and was calculated as the mean glucose infusion rate (GIR ; mg/ kg/ min) from 60 to 90 min. The mean plasma insulin concentration in both groups during this period showed no significant differences. Neither the body weight, fat contents, and individual muscle weight of FFDR were observed to be significantly different from CR, except for higher the weight of M. soleus in FFDR. A significantly lower levels of percentage of slow-twitch (%ST) fibers in the deep portion of the M. gastrocnemius and soleus, and higher levels of %FTb fibers in the deep portion of M. gastrocnemius and %FTa fibers in M. soleus were observed in FFDR when compared with CR. On the other hand, no significant differences between FFDR and CR were observed regarding the capillary density, capillary to fiber ratio, and the mean number of capillaries around the muscle fiber. The GIR in FFDR (4.9mg/kg/min) was not significantly lower than that in CR (4.6mg/kg/min). Distance covered by wheel running in FFDR at aged from 8 to 9 weeks was also significantly longer than that in CR. From these results, the muscle fiber composition is thus suggested to not be the single determinant of the whole-body glucose uptake in young male rats. The second purpose of present study was to investigate the effect of high-fat diet on abdominal fat accumulation, and histochemical and biochemical muscle characteristics between FFDR and CR after low- and high-fat diet. The FFDR with low-fat diet (FL ; n=8), FFDR with high-fat diet (FH ; n=9), CR with low-fat diet (CL ; n=7) and CR with high-fat diet (CH ; n=7) were used in this study. Each diet were started at age of 8 weeks and were maintained for 6 weeks. Increasing in body weight and abdominal fat accumulation in CH were significantly higher than in FL and FH. No significant Difference was observed in energy intake among 4 groups. Although weight of M. gastrocnemius in CH was higher than in FL and FH, no significant difference were observed in the weight of M. soleus and M. plantaris among 4 groups. The %type1 fibers in M. gastrocnemius in FFDR was significantly lower than in CR, but %type 2DX fibers in FFDR was significantly higher than that in FFDR. In the deep portion of M. gastrocnemius, succinate dehydrogenase (SDH) activity in type 2A and type 2DX fibers is significantly higher than that in type1 fibers in each group. From these results, it is suggested that the difference in fat accumulation after high-fat diet between CR and FFDR is dependent on difference in oxidative capacity of each fiber type but not in the muscles volume. Less