Cell proliferation and neuroblast differentiation in the dentate gyrus of high-fat diet-fed mice are increased after rosiglitazone treatment

In this study, we determined how rosiglitazone (RSG) differentially affected hippocampal neurogenesis in mice fed a low-fat diet (LFD) or high-fat diet (HFD; 60% fat). LFD and HFD were given to the mice for 8 weeks. Four weeks after initiating the LFD and HFD feeding, vehicle or RSG was administered orally once a day to both groups of mice. We measured cell proliferation and neuroblast differentiation in the subgranular zone of the dentate gyrus using Ki67 and doublecortin (DCX), respectively, as markers. In addition, we monitored the effects of RSG on the levels of DCX and brain-derived neurotrophic factor (BDNF) in hippocampal homogenates. At 8 weeks after the LFD feeding, the numbers of Ki67- and DCX-positive cells as well as hippocampal levels of DCX and BDNF were significantly decreased in the RSG-treated group compared to the vehicle-treated animals. In contrast, the numbers of Ki67- and DCX-positive cells along with hippocampal levels of DCX and BDNF in the HFD fed mice were significantly increased in the RSG-treated mice compared to the vehicle-treated group. Our data demonstrate that RSG can modulate the levels of BDNF, which could play a pivotal role in cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus.     

罗格列酮对异育银鲫血清生化指标和糖代谢的影响

研究罗格列酮对异育银鲫血清生化指标和糖代谢指标的影响。选取480尾初始体重(5.30±0.38)g的异育银鲫,随机分为4个组,每组4个重复,每个重复30尾鱼。对照组饲喂基础日粮,试验Ⅰ组、试验Ⅱ组、试验Ⅲ组在基础日粮基础上分别添加10、15 mg/kg和20 mg/kg罗格列酮,试验期为30 d。结果表明:与对照组相比,试验Ⅱ组和试验Ⅲ组血清中的谷丙转氨酶(GPT)活性显著升高(P<0.05);Ⅲ组血清中的谷草转氨酶(GOT)和乳酸脱氢酶(LDH)活性显著升高(P<0.05);各试验组血清中的总蛋白(TP)含量均显著增加(P<0.05),血糖浓度和胰岛素水平显著降低(P<0.05),肌糖原含量显著增加(P<0.05)。结果说明,日粮中添加10、15 mg/kg和2 0 mg/kg的罗格列酮均能够显著降低血糖的浓度,添加水平为10 mg/kg对异育银鲫肝胰脏无损伤。     

Protective influence of rosiglitazone against time‐dependent deterioration of boar spermatozoa preserved at 17°C

Spermatozoa are highly specialized cells, and energy metabolism plays an important role in modulating sperm viability and function. Rosiglitazone is an antidiabetic drug in the thiazolidinedione class that regulates metabolic flexibility and glucose uptake in various cell types, but its effects on boar sperm metabolism are unknown. In this study, we investigated the potential effect of rosiglitazone against time‐dependent deterioration of boar spermatozoa during liquid preservation at 17°C. Freshly ejaculated semen was diluted with Beltsville Thawing Solution (BTS) containing different concentrations of rosiglitazone, and the motility, membrane and acrosome integrity of sperm were detected. Besides, we measured glucose uptake capacity, l ‐lactate production level, mitochondrial membrane potential, adenosine triphosphate (ATP) content and mitochondrial reactive oxygen species (mROS) production of sperm after boar semen had been incubated with or without rosiglitazone, iodoacetate (glycolysis inhibitor) and rotenone (electron transport chain inhibitor) for 5 days. The addition of rosiglitazone significantly enhanced sperm quality and had a strong protective effect on the sperm membrane and acrosome integrity during storage. BTS containing 50 μM rosiglitazone maintained the total motility of liquid‐preserved sperm above 60% for 7 days. Rosiglitazone improved sperm quality by regulating energy metabolism manner of preserved sperm, protected the sperm mitochondrial membrane potential, enhanced sperm ATP production and in the meanwhile reduced mROS through enhancing glycolysis but not oxidative phosphorylation. The data suggested the practical feasibility of using rosiglitazone for improving boar spermatozoa quality during semen preservation.     

猪脂肪前体细胞的原代培养及诱导分化

以2日龄仔猪皮下脂肪组织为材料,采用胶原酶消化法分离培养出细胞成分均一、增殖旺盛的原代脂肪前体细胞。对所获细胞采用含50 nmol/L胰岛素+100 nmol/L地塞米松+0.25 mmol/L 3-异丁基-1-甲基黄嘌呤+100nmol/L罗格列酮的分化培养液进行诱导分化培养,少量细胞第2 d开始出现脂滴,大多细胞第3 d出现脂滴,分化率达95%以上,第4~7 d小脂滴逐步融合为大脂滴。在脂滴出现及汇聚快慢上本实验所采用诱导方法明显快于其他诱导方式。     

烟酰胺削弱罗格列酮诱导猪前体脂肪细胞凋亡的作用与分子机制

【目的】探讨烟酰胺（nicotinamide, NIC）和罗格列酮（rosiglitazone, RSG）对猪前体脂肪细胞凋亡的作用及分子机制,寻找通过凋亡方式调控脂肪细胞数目进而控制生脂的新途径。【方法】分别用含有 0、0.2、0.4、0.6、0.8 和 1.0 mmol•L-1 RSG的培养基处理猪前体脂肪细胞,在处理后的48 h,对不同处理组细胞进行Hoechst33258和Annexin-V-FITC/PI染色以观察细胞形态,流式细胞仪分析细胞凋亡情况;并收集细胞总蛋白,用Western blotting方法检测细胞凋亡关键基因的蛋白表达水平;基于RSG促凋亡的浓度梯度结果,选用1.0 mmol•L-1 RSG分别与含0、0.1、0.2和0.3 mmol•L-1 NIC的培养基共处理细胞,在处理后的48 h,染色并观察细胞形态,流式细胞仪分析细胞凋亡情况;并收集细胞总蛋白、细胞质蛋白和细胞核蛋白,检测细胞凋亡关键基因的蛋白水平。【结果】 RSG以浓度依赖方式诱导猪前体脂肪细胞凋亡,减少了细胞数目;Bcl-2和cleaved Caspase-3凋亡关键蛋白水平随RSG浓度增加而上升,Bax则下降;0.1（P＜0.05）、0.2（P＜0.01）和0.3 mmol•L-1 （P＜0.01）NIC显著削弱1 mmol•L-1 RSG诱导猪前体脂肪细胞凋亡,Bcl-2和cleaved Caspase-3水平显著被下调（P＜0.05）,Bax则被上调（P＜0.05）;0.3 mmol•L-1 NIC明显有助于1 mmol•L-1 RSG处理的猪前体脂肪细胞中的Sirt1由细胞质向核转移,且抑制核中cleaved Caspase-3水平。【结论】NIC通过促进Sirt1由细胞质到核的转位以及下调核中cleaved Caspase-3水平削弱RSG诱导的猪前体脂肪细胞凋亡。     

罗格列酮对2型糖尿病患者血脂水平和血浆PAI-1活性的影响

目的观察罗格列酮对2型糖尿病患者血脂水平和血浆纤溶酶原激活物抑制剂1(PAI-1)活性的影响。方法60例2型糖尿病患者随机分为常规治疗组和罗格列酮治疗组,每组30例,另选择20例健康体检者作为正常对照组。常规治疗组和罗格列酮治疗组分别于治疗前和治疗后12周检测空腹血糖(FPG)、血脂水平,采用发光底物法测定全部观察对象的PAI-1的活性。结果治疗12周后罗格列酮治疗组的血清甘油三酯(TG)下降、高密度脂蛋白胆固醇(HDL-C)升高,血浆PAI-1活性明显降低,差异有统计学意义(P<0.05)。结论罗格列酮可改善糖尿病患者的代谢紊乱,减少血浆PAI-1的表达,有助于改善或延缓糖尿病合并动脉粥样硬化的发生。     

PPARs调控剂对加州鲈生长及糖脂代谢的影响

为研究PPARs(过氧化物酶体增殖物激活受体)调控剂对加州鲈(Micropterus salmoides)生长及糖脂代谢的影响,试验采用单因素梯度设计,以基础饲料为对照组,在基础饲料中分别添加调控剂罗格列酮0.3、1.5、7.5和37.5 mg/kg,饲喂初始体重为(3.90±0.04)g的加州鲈56 d后,测定了PPARs调控剂罗格列酮对加州鲈生长和糖脂代谢相关血液生化指标的影响。结果显示:与对照组相比,饲料中添加罗格列酮对加州鲈增重率、特定生长率、饲料系数和蛋白质效率无显著性影响(P>0.05)。添加7.5 mg/kg罗格列酮试验组加州鲈鱼体脂肪和肝脏脂肪含量显著低于对照组及其它试验组(P<0.05)。添加7.5 mg/kg和37.5 mg/kg罗格列酮试验组血清甘油三酯的水平显著低于对照组(P<0.05);随着饲料中罗格列酮添加水平的增加,试验各组鱼体血糖和谷丙转氨酶的水平呈下降趋势,但试验各组鱼体血糖和血清谷丙转氨酶的水平与对照组之间差异不显著(P>0.05)。结果表明,添加罗格列酮可预防加州鲈糖脂代谢混乱,防止加州鲈脂肪肝的发生。     

梧桐籽油和罗格列酮对绵羊组织中脂代谢相关酶基因表达的影响

为研究饲粮中添加硬脂酰辅酶A去饱和酶(SCD)的抑制剂(梧桐籽油)和促进剂(罗格列酮)对育肥绵羊背最长肌及皮下脂肪中脂代谢关键调节因子和相关酶mRNA表达量的影响,选用18只平均体重为27.71±2.64kg、生理状况相似的杂交公羊(美利奴♂×小尾寒羊♀)随机分为3组,每组6只,进行单栏饲养(2.0m长×1.2m宽)。对照组(C组)饲喂含4.8%胡麻籽的饲粮,梧桐籽油组(W组)饲喂对照组饲粮+15g/d梧桐籽油,罗格列酮组(L组)饲喂对照组饲粮+8mg/d罗格列酮。试验期50d,其中过渡期10d,预饲期5d,正式试验期为35d。结果表明:1)与对照组相比,W组背最长肌和皮下脂肪中PPAR-γmRNA表达量分别上调了42%和28%,背最长肌中SREBP-1和SCD mRNA表达量分别下降了20%和24%(P0.05);2)与对照组相比,L组背最长肌中PPAR-γ和SREBP-1mRNA表达量均有不同程度的提高,分别提高了93%和35%(P0.05),FAS、LPL和SCD mRNA表达量分别提高了36%、56%和22%(P0.05),L组皮下脂肪中PPAR-γ和FAS mRNA的表达量分别提高了25%和32%(P0.05)。研究表明梧桐籽油可以提高背最长肌及皮下脂肪中PPAR-γmRNA的表达量,降低背最长肌中SREBP-1和SCD mRNA的表达量;罗格列酮可以提高背最长肌中PPAR-γ、SREBP-1、FAS、LPL和SCD mRNA的表达量,提高皮下脂肪中SREBP-1和FAS mRNA的表达量。     

日粮中添加罗格列酮和梧桐子油对绵羊脂代谢相关酶活性的影响

为研究日粮中添加硬脂酰辅酶A去饱和酶(SCD)的活性促进剂(罗格列酮)和抑制剂(梧桐子油)对绵羊背最长肌及皮下脂肪组织中的脂肪酸合成酶(FAS)、脂蛋白脂酶(LPL)、乙酰辅酶A羧化酶(ACC)以及SCD酶活性的影响,选18只体重为27.71±2.64kg、生理状态相似的杂交公羊(美利奴♂×小尾寒羊♀),将其随机分为3组,每组6只,单栏饲养。对照组饲喂基础日粮,梧桐子油组饲喂基础日粮+15g/d梧桐子油,罗格列酮组(L组)饲喂基础日粮+8mg/d罗格列酮。结果表明:1)与对照组相比,罗格列酮可以显著提高绵羊背最长肌中LPL、SCD和皮下脂肪中FAS酶的活性(P0.05),然而,对背最长肌和皮下脂肪中ACC酶的活性没有影响。2)与对照组相比,梧桐子油抑制了绵羊背最长肌中ACC和SCD酶的活性,但对皮下脂肪中的ACC、FAS、LPL和SCD酶活性没有影响。本试验表明罗格列酮可以通过增强机体对胰岛素的敏感性,进而提高SCD和FAS的活性,另外罗格列酮还可以通过激活PPAR-γ,进而提高组织中LPL的活性;富含不饱和脂肪酸的梧桐子油可以通过抑制ACC的基因表达而影响组织中其酶活性的变化,SCD的活性受到梧桐子油中苹婆酸和其他多不饱和脂肪酸的抑制作用而表现出活性降低的结果。     

罗格列酮对断奶仔猪肠黏膜结构和抗氧化能力的影响

试验研究罗格列酮(ROS)对脂多糖(LPS)刺激的断奶仔猪肠黏膜结构和抗氧化能力的影响。试验包括3个处理组,对照组注射生理盐水,LPS组注射100μg/kg体重的LPS,ROS组在注射LPS之前的30min注射3mg/kg体重的ROS。注射LPS3h后取样。结果表明:ROS提高了十二指肠和回肠DNA的含量(P0.05);ROS缓解了LPS导致的十二指肠、空肠和回肠隐窝深度的增加(P0.10)和绒毛高度/隐窝深度的降低(P0.01);ROS降低了空肠丙二醛含量(P0.10),提高了十二指肠和空肠SOD活性(P0.05)。结果表明,ROS可能是通过提高肠道抗氧化功能而对LPS刺激的断奶仔猪小肠形态结构的损伤起到一定保护作用。