[非诺贝特对输注脂肪乳大鼠骨骼肌中过氧化物酶体增殖物激活受体γ辅激活因子-1α表达的影响]

[Effects of fenofibrate on the expression of peroxisome proliferator-activated-gamma coactivator-1α in skeletal muscle of rats infused with intralipid].

作者信息

Bai Xiu-ping, Li Hong-liang, Yang Wen-ying, Xiao Jian-zhong, Wang Bing

机构信息

Department of Endocrinology, China-Japan Friendship Hospital, Beijing 100029, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2010 Nov 2;90(40):2856-9.

PMID:21162799

Abstract

OBJECTIVE

To observe the effects of fenofibrate on the expression of peroxisome proliferator-activated (PPAR)-gamma coactivator-1α (PGC-1α) in skeletal muscle of rats with insulin resistance (IR) induced by elevated plasma free fatty acid (FFA) levels.

METHODS

Male Sprague-Dawley (SD) rats were randomly divided into three groups: control group (Con, infused with saline), lipid infusion group (FFA) and fenofibrate treatment plus lipid infusion group (F-FFA). Plasma glucose, insulin and FFA were measured. Glucose infusion rate (GIR) was used to evaluate the insulin sensitivity by euglycemic-hyperinsulinemic clamp. The gene expression of PGC-1α in skeletal muscle was determined by real-time polymerase chain reaction (PCR).

RESULTS

Compared with the control group, the levels of plasma FFA and insulin were elevated significantly in rats infused with lipid, but they decreased significantly in rats pretreated with fenofibrate then infused with lipid [FFA, Con: 0.46 (0.08 - 0.72) mmol/L, FFA: 1.45(0.87-1.70) mmol/L, F-FFA: 0.54 (0.06 - 0.84) mmol/L, all P < 0.01; Insulin, Con: (6.56 ± 0.78) µIU/ml, FFA: (10.54 ± 0.86) µIU/ml, F-FFA: (6.69 ± 0.84) µIU/ml, all P < 0.01]. In addition, the plasma glucose levels did not change markedly after lipid infusion; GIR was significantly reduced by 55.6% in lipid infusion group, but fenofibrate-pretreatment increased glucose infusion rate (GIR) [Con: (25.13 ± 2.10) mg×kg(-1)×min(-1), FFA: (10.16 ± 0.75) mg×kg(-1)×min(-1), F-FFA: (21.72 ± 2.89) mg×kg(-1)×min(-1), all P < 0.01]; the mRNA expression of PGC-1α decreased by about 71% in lipid infusion group but fenofibrate increased the gene expression by about 150% as compared with FFA group (all P < 0.01).

CONCLUSION

The elevation of plasma FFA levels may induce IR, and it also decreases the mRNA expression of PGC-1α in skeletal muscle. And fenofibrate pretreatment reverses these changes.

摘要

目的

观察非诺贝特对血浆游离脂肪酸（FFA）水平升高所致胰岛素抵抗（IR）大鼠骨骼肌中过氧化物酶体增殖物激活受体（PPAR）-γ共激活因子-1α（PGC-1α）表达的影响。

方法

雄性Sprague-Dawley（SD）大鼠随机分为三组：对照组（Con，输注生理盐水）、脂质输注组（FFA）和非诺贝特治疗加脂质输注组（F-FFA）。检测血浆葡萄糖、胰岛素和FFA水平。采用正常血糖高胰岛素钳夹技术，通过葡萄糖输注速率（GIR）评估胰岛素敏感性。采用实时聚合酶链反应（PCR）检测骨骼肌中PGC-1α的基因表达。

结果

与对照组相比，脂质输注大鼠血浆FFA和胰岛素水平显著升高，但非诺贝特预处理后再输注脂质的大鼠血浆FFA和胰岛素水平显著降低[FFA，Con：0.46（0.08 - 0.72）mmol/L，FFA：1.45（0.87 - 1.70）mmol/L，F-FFA：0.54（0.06 - 0.84）mmol/L，均P < 0.01；胰岛素，Con：（6.56 ± 0.78）µIU/ml，FFA：（10.54 ± 0.86）µIU/ml，F-FFA：（6.69 ± 0.84）µIU/ml，均P < 0.01]。此外，脂质输注后血浆葡萄糖水平无明显变化；脂质输注组GIR显著降低55.6%，但非诺贝特预处理可提高葡萄糖输注速率（GIR）[Con：（25.13 ± 2.10）mg×kg⁻¹×min⁻¹，FFA：（10.16 ± 0.75）mg×kg⁻¹×min⁻¹，F-FFA：（21.72 ± 2.89）mg×kg⁻¹×min⁻¹，均P < 0.01]；脂质输注组PGC-1α的mRNA表达降低约71%，但与FFA组相比，非诺贝特使基因表达增加约150%（均P < 0.01）。