Background Currently it is unclear whether lipid accumulation occurs in a particular sequence and its relationship with whole body insulin resistance （IR）. This study aimed to answer this question.Methods Male Sprague-Dawley （SD） rats were fed on a normal or a high-fat diet for 20 weeks. Serum triglycerides （TG）, serum free fatty acids （FFA）, fasting plasma glucose （FPG）, and liver and skeletal muscle TG were measured. The glucose infusion rate （GIR） and mRNA levels of acetyl-CoA carboxylase （ACC） and carnitine palmitoyltransferase-1 （CPT-1） in the liver and skeletal muscle were determined at different stages.Results Compared with rats fed on the normal diet, serum FFA was not significantly increased in rats fed on the high-fat diet until 20 weeks. In contrast, liver TG was significantly increased by the high-fat diet by four weeks （20-fold; P ＜0.01）,and remained elevated until the end of the study. However, skeletal muscle TG was not significantly increased by the high-fat diet until 20 weeks （10.6-fold; P＜0.01）, and neither was the FPG. The GIR was significantly reduced （1.6-fold; P ＜0.01） by the high-fat diet after 8 weeks. The mRNA levels of ACC gradually increased over time and CPT-1 decreased over time, in both the liver and skeletal muscle in rats fed the high-fat diet.Conclusions Lipid accumulation in the liver occurs earlier than lipid accumulation in the skeletal muscle. Fatty liver may be one of the early markers of whole body IR. Changes in the gene expression levels of ACC and CPT-1 may have important roles in the process of IR development.
BAI Xiu-pingLI Hong-liangYANG Wen-yingXIAO Jian-zhongWANG BingLOU Da-junDU Rui-qin
目的探讨高脂饲养SD大鼠脂肪分存的顺序及其与胰岛素抵抗的关系。方法将8周龄雄性SD大鼠随机分为2组:正常饲养组(NC,n=40)、高脂饲养组(HF,n=40)。在不同周龄测定血清、肝脏、肌肉组织中甘油三酯(TG)含量;进行正常血糖高胰岛素钳夹试验评估胰岛素的敏感性;并用定量PCR方法分析肝脏和肌肉中脂代谢调控基因mRNA表达的变化。结果(1)与NC组比较,高脂饲养4周、8周时血TG无明显变化,12周时明显增高[0.52(0.15-1.00)mmol/L vs 0.31(0.09-0.53)mmol/L,P<0.01],持续至20周。(2)HF组肝脏TG含量从高脂饲养4周始便明显增高[(34.38±11.12)mg/g vs(1.65±0.37)mg/g,p<0.01],一直持续至20周;肌肉TG在高脂饲养4、8、12周均无明显变化,高脂饲养20周时明显增高[(32.24±7.24)mg/g vs(2.77±0.76)mg/g,P<0.01]。(3)正常血糖高胰岛素钳夹试验表明,HF组高脂饲养4周始葡萄糖输注率(GIR)呈下降趋势,高脂饲养8周时明显下降[(21.81±7.20)mg·kg^(-1)·min^(-1)vs(8.44±1.77)mg·kg^(-1)·min^(-1),p<0.01],一直持续至20周。(4)脂代谢调控基因的检测表明,高脂饲养4周时肝脏中合成基因乙酰辅酶A羧化酶(ACCl)的表达无明显增高而氧化基因肉毒碱酰基转移酶(CPT-1)的表达下降20.3%(P<0.05),肌肉组织ACC2、CPT-1的表达均无明显变化(P>0.05);高脂饲养8周时肝脏中ACCl的表达增高20.6%、CPT-1的表达下降27.1%(P<0.05),肌肉组织ACC2的表达增高18.6%、CPT-1的表达下降19.2%(P<0.05);高脂饲养20周时肝脏ACCl表达增高48.3%(P<0.05)、CPT-l表达无明显变化(p>0.05),肌肉ACC2表达增高101.1%、CPT-1的表达下降71%(P<0.05)。结论高脂饲养SD大鼠脂肪分存过程中,肝脏早于肌肉,肝脏TG含量增加可能是胰岛素抵抗的早期标志之一。脂代谢调控基因的表达可能在其中起了重要作用。
