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部肥胖、胰岛素抵抗和高血压有关。有证据表明，人体肌肉中快速抽搐纤维（%FT）的百分比与胰岛素抵抗呈负相关，也与体脂肪积累呈正相关。然而，Suwa等人培育出的%FT纤维基因水平较高的大鼠是否具有更高的基因水平还有待阐明。j .杂志。小鼠的胰岛素敏感性较对照组低。FT纤维优势模型大鼠（FFDR）腓肠肌和比目鱼肌的FT%纤维均明显高于对照组大鼠（CR）。本研究的主要目的是研究8 ~ 9周龄大鼠的胰岛素敏感性水平、纤维组成和毛细血管密度等肌肉特征，以及FFDR和CR之间的自主跑轮距离。用正糖高胰岛素钳钳评价胰岛素敏感性90min，以60 ~ 90min的平均葡萄糖输注速率（GIR; mg/ kg/ min）计算。两组在此期间的平均血浆胰岛素浓度无显著差异。除FFDR中比目鱼的体重较高外，FFDR的体重、脂肪含量和个体肌肉重量均与CR无显著差异。与CR相比，FFDR中腓肠肌和比目鱼肌深层的慢抽动纤维百分比（%ST）明显降低，而腓肠肌深层的%FTb纤维和比目鱼肌的%FTa纤维水平较高。另一方面，FFDR和CR在毛细血管密度、毛细血管与纤维之比和肌肉纤维周围的平均毛细血管数方面没有显著差异。FFDR组的GIR （4.9mg/kg/min）不显著低于CR组（4.6mg/kg/min）。8 - 9周龄时，FFDR组的跑轮距离也明显长于CR组。从这些结果来看，肌纤维成分并不是年轻雄性大鼠全身葡萄糖摄取的单一决定因素。本研究的第二个目的是研究高脂肪饮食对腹部脂肪积累的影响，以及低脂肪和高脂肪饮食后FFDR和CR之间的肌肉组织化学和生化特征。本研究采用低脂饮食的FFDR （FL, n=8）、高脂饮食的FFDR （FH, n=9）、低脂饮食的CR （CL, n=7）和高脂饮食的CR （CH, n=7）。每种饮食在8周龄开始，并维持6周。CH组体重增加和腹部脂肪积累显著高于FL和FH组。各组间能量摄取量无显著差异。虽然CH组的腓肠肌支原体重量高于FL组和FH组，但4组间比目鱼支原体和植物支原体重量无显著差异。FFDR组腓肠肌1型纤维的百分比明显低于CR组，而2DX型纤维的百分比明显高于CR组。在腓肠肌深层，2A型和2DX型纤维的琥珀酸脱氢酶（SDH）活性显著高于各组1型纤维。从这些结果来看，CR和FFDR在高脂肪饮食后脂肪积累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。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