摘要
目的探讨2型糖尿病肥胖状态下肝脏脂肪酸代谢的变化规律。方法30只SD大鼠随机均分为对照组和糖尿病(DM)组,分别喂以标准饲料和髙脂饲料,8周后通过口服糖耐量试验(OGTT)、胰岛素敏感指数(ISI)证实是否产生胰岛素抵抗,出现明显胰岛素抵抗的大鼠注射小剂量链脲佐菌素(STZ)以诱导2型糖尿病。成模后继续用高脂饲料喂养6周,每组随机取8只大鼠动脉采血,并留取肝脏组织。RT-PCR法检测脂肪酸代谢相关基因二酰基甘油酰基转移酶(DGAT1)、肉毒碱脂酰转移酶Ⅰ(CPTⅠ)、软脂酰辅酶A氧化酶(ACOX1)、过氧化物酶体D-双功能蛋白(DBP)和L-双功能蛋白(LBP)的mRNA水平,Western blotting检测DBP的蛋白表达,分光光度法检测过氧化物酶体脂肪酸β-氧化的活力,气相色谱法分析血液和肝脏脂肪酸谱的变化,油红染色法检测肝脏脂肪的沉积情况。结果与对照组比较,DM组DGAT1、CPTⅠ、ACOX1和LBP mRNA表达增加(P<0.01或P<0.05),DBP mRNA和蛋白表达量明显下降(P<0.05),血游离脂肪酸增加(P<0.01);肝中C22∶6、C26∶0等脂肪酸含量增多(P<0.01),C22∶0、C24∶0等脂肪酸含量减少(P<0.01);肝组织出现脂肪沉积。结论糖尿病大鼠在肥胖状态下肝脏出现脂肪沉积,且DBP参与的β-氧化途径减弱,引起肝组织C26∶0等脂肪酸含量增多,可能是造成糖尿病脂毒性的重要因素之一。
Objective To investigate the metabolic changes in free fatty acids in the livers of obese rats with type 2 diabetes. Methods Thirty male SD rats were randomly divided into control group （Con group） and diabetes mellitus group （DM group）, with 15 in each group. Rats in Con group and DM group were fed with normal diet and high-fat diet, respectively. Eight weeks later, OGTT and ISI test were performed to identify insulin resistance. Then the insulin-resistant rats received intraperitoneal injection of low-dose streptozocin （STZ） to induce type 2 diabetes. After giving high-fat diet further for six more weeks, 8 rats of each group were sacrificed and artery blood and liver sample were obtained for further analysis. The mRNA levels of diacylglycerol Oacyltransferase 1 （DGAT1）, earnitine pa/mitoyltransferaseⅠ（CPTD, palmitoyl CoA oxidase （ACOX1）, D-bifunctional protein （DBP） and L-bifunctional protein （LBP）, which were involved in fatty acids metabolism, were evaluated by RT-PCR. The protein level of DBP was evaluated by Western blotting Peroxisome fatty acids β-oxidation was measured by spectrophotometry. Free fatty acids in blood and liver were determined by gas chromatography. Oil red staining was used to determine the fat accumulation in liver. Results The mRNA expressions of DGAT1, CPT Ⅰ, ACOX1 and LBP increased （P〈0. 01, P〈0.01, P〈0. 05, P〈0. 05） in DM group, while mRNA and protein expressions of DBP decreased （P〈0. 05） in liver of diabetic rats. The concentration of free fatty acids in serum increased （P〈0. 0]）. The concentrations of some free fatty acids, such as C22：6 and C26：0 increased in the livers of DM group （P〈0.01）, while the concentrations of some other free fatty acids, such as C22：0 and C24：0 decreased （P〈0. 01 ）. Disordered fat storage was found in diabetic livers. Conclusions The abnormal fat storage and the weakening of DBP involved β-oxidation pathway leading to the increase in fatty acids, such as C26：0, may contribute to the lipotoxicity in type 2 diabetes.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2009年第9期1062-1065,共4页
Medical Journal of Chinese People's Liberation Army
