参与肝脏能量代谢的关键转录因子的失调,如过氧化物酶体增殖物激活受体γ辅激活因子-1α(PGC-1α)和肝X受体α(LXRα),在T2DM中观察到。本研究旨在探讨有氧训练和补充维生素D对肝酶水平以及肝细胞中PGC-1α和LXRα蛋白水平的影响。在T2DM大鼠模型中。这项研究涉及56只雄性Wistar大鼠,分为两组:一组是非糖尿病患者,作为对照组(n=8),另一个诱发了糖尿病(n=48)。然后将糖尿病大鼠分为六个亚组:两组接受高或中等剂量的维生素D和有氧训练(D+AT+HD和D+AT+MD);两组单独接受高或中等剂量的维生素D(D+HD和D+MD);一组接受载剂(芝麻油;D+AT+油)的有氧训练,一组是糖尿病对照组,仅接受芝麻油(接受油)。D+AT+HD和D+HD组接受了10,000IU的维生素D,而D+AT+MD和D+MD组每周一次注射5000IU维生素D。D+AT+油组和假手术组接受芝麻油。经过八周的治疗,体重,BMI,食物摄入量,血清胰岛素,葡萄糖,25-羟基维生素D,ALT,AST,测量内脏脂肪。通过蛋白质印迹法评估肝脏中PGC-1α和LXRα蛋白的水平。采用配对t检验进行统计学分析,单向方差分析(ANOVA),和Tukey事后检验在P<0.05的显著性水平。体重,食物摄入量,D+AT+HD组BMI显著下降,D+AT+MD,D+AT+滑油,D+HD,和D+MD组,在D+AT+HD组中,观察到体重和BMI降低最高。D+AT+HD组胰岛素水平最低,葡萄糖,和HOMA-IR,而DC组在糖尿病组中表现出最高水平。与其他组相比,DATHD和DATMD组的ALT和AST酶水平较低,DATHD和DATMD之间无显着差异。D+AT+HD(p=0.001),D+AT+MD(p=0.001),D+HD(p=0.023),D+MD(p=0.029),与D+C相比,D+AT+油(p=0.011)上调LXRα。D+AT+HD表现出比D+AT+MD更明显的LXRα上调,D+AT+滑油,D+HD,和D+MD(分别为p=0.005;p=0.002,p=0.001和p=0.001)。同样,与D+AT+油相比,D+AT+HD显示PGC-1α的上调更为显著,D+HD,和D+MD(分别为p=0.002;p=0.001和p=0.001)。Pearson相关性检验显示,血清25-羟基维生素水平与内脏脂肪(r=-0.365;p=0.005)和HOMA-IR(r=-0.118;p=0.009)之间存在显着负相关;而ALT和AST酶的肝脏体重比之间以及QUICKI水平与LXRα(r=0.578;p=0.001)和PGC-1p=0.001之间存在正相关。有氧训练和补充维生素D的联合施用可能会改善2型糖尿病大鼠的肝酶,同时上调肝细胞中PGC-1α和LXRα蛋白的水平。当运动与高剂量维生素D补充剂相结合时,这些改善更为显著。这项研究强调了这种联合疗法作为一种新的糖尿病治疗策略的潜力。
Dysregulation of key transcription factors involved in hepatic energy metabolism, such as peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and liver X receptor alpha (LXRα), has been observed in T2DM. The present study aims to investigate the effects of aerobic training and vitamin D supplementation on liver enzyme levels and the levels of PGC-1α and LXRα proteins in hepatocytes, in a rat model of T2DM. The study involved 56 male Wistar rats, divided into two groups: one was non-diabetic and acted as a control group (n = 8), and the other had induced diabetes (n = 48). The diabetic rats were then split into six subgroups: two groups received high or moderate doses of vitamin D and aerobic training (D + AT + HD and D + AT + MD); two groups received high or moderate doses of vitamin D alone (D + HD and D + MD); one group underwent aerobic training with vehicle (sesame oil; D + AT + oil), and one group was a diabetic control receiving only sesame oil (oil-receiving). The D + AT + HD and D + HD groups received 10,000 IU of vitamin D, while the D + AT + MD and D + MD groups received 5000 IU of vitamin D once a week by injection. The D + AT + oil group and the sham group received sesame oil. After eight weeks of treatment, body weight, BMI, food intake, serum insulin, glucose, 25-hydroxyvitamin D, ALT, AST, and visceral fat were measured. The levels of PGC-1α and LXRα proteins in the liver was assessed by western blotting. Statistical analysis was performed using the paired t-test, one-way analysis of variance (ANOVA), and the Tukey post hoc test at a significance level of P < 0.05. Body weight, food intake, and BMI decreased significantly in the D + AT + HD, D + AT + MD, D + AT + oil, D + HD, and D + MD groups with the highest reduction being observed in body weight and BMI in the D + AT + HD group. The D + AT + HD group exhibited the lowest levels of insulin, glucose, and HOMA-IR while the D + C group exhibited the highest levels among the diabetic groups. The D + AT + HD and D + AT + MD groups had lower levels of ALT and AST enzymes compared to the other groups with no significant difference between D + AT + HD and D + AT + MD. D + AT + HD (p = 0.001), D + AT + MD (p = 0.001), D + HD (p = 0.023), D + MD (p = 0.029), and D + AT + oil (p = 0.011) upregulated LXRα compared to D + C. Among these groups, D + AT + HD exhibited a more profound upregulation of LXRα than D + AT + MD, D + AT + oil, D + HD, and D + MD (p = 0.005; p = 0.002, p = 0.001, and p = 0.001, respectively). Similarly, D + AT + HD showed a more notable upregulation of PGC-1α compared to D + AT + oil, D + HD, and D + MD (p = 0.002; p = 0.001, and p = 0.001, respectively). Pearson correlation tests showed significant and negative correlations between serum 25-hydroxyvitamin levels and both visceral fat (r = - 0.365; p = 0.005) and HOMA-IR (r = - 0.118; p = 0.009); while positive and significant correlations between the liver-to-bodyweight ratio with both ALT and AST enzymes and also between QUICKI levels with LXRα (r = 0.578; p = 0.001) and PGC-1α (r = 0.628; p = 0.001). Combined administration of aerobic training and vitamin D supplementation potentially improves liver enzymes in type-2 diabetic rats that were simultaneous with upregulating the levels of PGC-1α and LXRα proteins in hepatocytes. These improvements were more significant when combining exercise with high-dose vitamin D supplementation. This study highlights the potential of this combination therapy as a new diabetes treatment strategy.