CAJ | 학술논문

目的观察高脂饮食和罗格列酮干预对老年大鼠骨骼肌过氧化物酶体增生物激活受体γ共激活因子1α(PGC-1α)和线粒体融合蛋白2(Mfn2)表达的影响. 方法 21～23月龄Wistar大鼠分为老年对照组、高脂组和高脂+罗格列酮干预组(干预组),并设4～5月龄Wistar大鼠作为青年对照组.应用正常葡萄糖高胰岛素钳夹技术评价胰岛素敏感性,高脂喂养第8周时,检测骨骼肌PGC-1α和Mfn2的mRNA及蛋白表达.结果高脂喂养8周后,青年对照组、老年对照组和高脂组空腹血游离脂肪酸[(0.68±0.18)mmol/L、(0.82±0.23)mmol/L和(1.53±0.40)mmol/L],三酰甘油[(0.53±0.13)mmol/L、(0.63±0.17)mmol/L和(1.08±0.30)mmol/L],骨骼肌三酰甘油[(1.09±0.17)mmol/L、(1.34±0.20)mmol/L和(2.07±0.30)mmol/L]均升高,葡萄糖输注率((30.4±4.2)mg·kg~(-1)·min~(-1)、(20.9±2.2)mg·kg~(-1)·min~(-1)和(12.0±1.9)mg·kg~(-1)·min~(-1)]下降;经过罗格列酮干预后游离脂肪酸[(0.93±0.29)mmol/L]、三酰甘油[(0.62±0.12)mmol/L]及骨骼肌三酰甘油[(1.68±0.28)mmol/L)]均明显下降,葡萄糖输注率[(16.7±1.7)mg·kg~(-1)·min~(-1)]升高.与青年对照组比较,老年对照组骨骼肌PGC-1α和Mfn2的表达下降,经高脂喂养后PGc-1α和Mfn2的表达进一步下降,干预组上述基因的表达均显著高于高脂组(P<0.05),但仍比老年对照组降低(P<0.05). 结论高脂饮食可诱导老年大鼠产生IR,推测可能与骨骼肌PGC-1α和Mfn2的表达下降有关;罗格列酮可通过改变骨骼肌PGC-1α和Mfn2的表达增加胰岛素敏感性.
목적 관찰고지음식화라격렬동간예대노년대서골격기과양화물매체증생물격활수체γ공격활인자1α(PGC-1α)화선립체융합단백2(Mfn2)표체적영향. 방법 21～23월령Wistar대서분위노년대조조、고지조화고지+라격렬동간예조(간예조),병설4～5월령Wistar대서작위청년대조조.응용정상포도당고이도소겸협기술평개이도소민감성,고지위양제8주시,검측골격기PGC-1α화Mfn2적mRNA급단백표체.결과고지위양8주후,청년대조조、노년대조조화고지조공복혈유리지방산[(0.68±0.18)mmol/L、(0.82±0.23)mmol/L화(1.53±0.40)mmol/L],삼선감유[(0.53±0.13)mmol/L、(0.63±0.17)mmol/L화(1.08±0.30)mmol/L],골격기삼선감유[(1.09±0.17)mmol/L、(1.34±0.20)mmol/L화(2.07±0.30)mmol/L]균승고,포도당수주솔((30.4±4.2)mg·kg~(-1)·min~(-1)、(20.9±2.2)mg·kg~(-1)·min~(-1)화(12.0±1.9)mg·kg~(-1)·min~(-1)]하강;경과라격렬동간예후유리지방산[(0.93±0.29)mmol/L]、삼선감유[(0.62±0.12)mmol/L]급골격기삼선감유[(1.68±0.28)mmol/L)]균명현하강,포도당수주솔[(16.7±1.7)mg·kg~(-1)·min~(-1)]승고.여청년대조조비교,노년대조조골격기PGC-1α화Mfn2적표체하강,경고지위양후PGc-1α화Mfn2적표체진일보하강,간예조상술기인적표체균현저고우고지조(P<0.05),단잉비노년대조조강저(P<0.05). 결론 고지음식가유도노년대서산생IR,추측가능여골격기PGC-1α화Mfn2적표체하강유관;라격렬동가통과개변골격기PGC-1α화Mfn2적표체증가이도소민감성.
Objective To investigate the effects of high-fat diets and rosiglitazone treatment on the expressions of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and mitofusin-2 (Mfn2) in skeletal muscle of aged rats. Methods Male wistar rats aged 21-23 months were randomly divided into old control group (OC; n=20), high-fat diets group (HF; n=20) and high-fat diets plus rosiglitazone treatment group (RSG; n=20). Male wistar rats aged 4-5 months were selected as young control group (YC; n=20). Insulin sensitivity was evaluated by hyperinsulinemic-euglycemic clamp technique at the end of the 4th and 8th week. The expressions at mRNA and protein levels of PGC-1α and Mfn2 in skeletal muscle were determined by polymerase chain reaction and Western blotting technique. Results (1)After 8 weeks, the levels of free fatty acid [(0. 68±0. 18)mmol/L, (0.82±0. 23) mmol/L and (1. 53±0.40) mmol/L], triglyceride [(0.53±0.13) mmol/L,(0. 63±0. 17) mmol/L and (1.08±0.30) mmol/L]and muscle triglyceride [(1.09±0.17) mmol/L,(1.34±0. 20) mmol/L and (2.07±0. 30) mmol/L]in YC group, OC group and HF group were significantly increased and glucose infusion rate [(30.4±4. 2) mg·kg~(-1)·min~(-1), (20.9±2.2) mg·kg~(-1)·min~(-1) and (12. 0±1.9) mg·kg~(-1)·min~(-1)]was significantly decreased as compared with pre-high fat diet, respectively. The levels of fasting free fatty acid [(0.93±0.29) mmol/L], triglyceride [(0.62±0.12) mmol/L]and music triglyceride [(1.68±0.28) mmol/L]in RSG group were significantly decreased and glucose infusion rate [(16.7±1.7) mg·kg~(-1)·min~(-1)]was significantly higher than in HF group. (2)In skeletal muscle, the expressions at mRNA and protein levels of PGC-1α and Mfn2 decreased in OC group compared with YC group (all P<0.01). The expressions of PGC-1α and Mfn2 were lower significantly in HF group than in OC group, and were higher significantly in RSG group than in HF group (all P<0.01). Conclusions The aged rats fed the high-fat diets develop insulin resistance with decreased expressions of PGC-1α and Mfn2 in skeletal muscle. Insulin sensitivity is improved with rosiglitazone treatment by increasing expressions of PGC-1α and Mfn2 in skeletal muscle.