胆固醇在高脂高胆固醇诱导非酒精性脂肪性肝炎发生发展过程中的动态作用

目的探讨胆固醇在高脂高胆固醇诱导的非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)发生发展过程中的动态作用。方法将SD大鼠随机分为CON组(正常饮食)、HFC0组(20%脂肪)、HFC1组(20%脂肪+1%胆固醇)、HFC2组(20%脂肪+2%胆固醇)及HFC5组(20%脂肪+5%胆固醇)。饲喂第4、6、8及12周末,采血并取肝脏组织;采用油酸(oleic acid,OA)及OA+低密度脂蛋白-胆固醇(low-density lipoprotein-cholesterol,LDL-C)诱导人肝脏正常细胞(HL-7702)5 d后,构建NASH模型,同时以RPMI1640培养基(含10%FBS)为对照组。分别检测大鼠血浆及HL-7702细胞培养液中丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转氨酶(AST)的含量,大鼠肝脏组织及HL-7702细胞中总胆固醇(total cholesterol,TC)及甘油三酯(triglyceride,TG)的含量;HE及Masson染色观察肝脏组织病理改变;油红O及菲律宾菌素染色观察HL-7702细胞内脂滴及胆固醇含量;Western blot法检测活性n-固醇调节元件结合蛋白-2(n-sterol regulatory element binding protein 2,n-SREBP-2)、低密度脂蛋白受体(low-density lipoproteins receptors,LDLR)及3-羟基3-甲基戊二酰辅酶A还原酶(3-hydroxy-3-methylglutaryl-CoA reductase,HMGCR)的蛋白表达水平。结果动物水平:12周末,与CON组比较,HFC2组、HFC5组血浆中ALT、AST及肝脏组织中TC、TG含量均显著升高(P均<0.05),肝细胞脂肪变性、气球样变性及纤维化病变明显,HFC2组、HFC5组大鼠NASH诱导成功;经Western blot分析,4、6及8周末,HFC2组、HFC5组较CON组LDLR蛋白表达水平均显著升高(P均<0.05),12周末,HFC5组较CON组LDLR蛋白表达水平显著降低(P<0.05);4、6及8周末,各组n-SREBP-2蛋白表达水平与CON组比较差异均无统计学意义(P均>0.05),12周末,HFC2组、HFC5组较CON组n-SREBP-2蛋白表达水平均显著升高(P均<0.05);4、6及12周末各组HMGCR蛋白表达水平与CON组比较差异均无统计学意义(P均>0.05),8周末,HFC5组较CON组HMGCR蛋白表达水平显著降低(P<0.05)。细胞水平:OA+LDL-C组较对照组及OA组细胞内胆固醇含量、n-SREBP-2及HMGCR蛋白表达水平均显著升高(P均<0.05);OA组及OA+LDL-C组较对照组LDLR蛋白表达水平均显著降低(P均<0.05)。结论胆固醇摄入量和摄入时间的长短与NASH肝损伤呈正相关;胆固醇可诱导肝细胞高表达LDLR,促使胆固醇进入肝脏增加,抑制HMGCR调控的内源性胆固醇合成;随着肝内胆固醇堆积增多,肝细胞LDLR表达减少,使肝内胆固醇相对不足,反馈性调节n-SREBP-2及HMGCR表达升高,打破肝脏胆固醇代谢稳态,促进了NASH的发生发展。     

高脂喂养SD大鼠体内花生四烯酸乙醇胺水平及Ⅰ型大麻素受体表达的变化

目的探讨高脂饮食诱导肥胖SD大鼠脂肪代谢紊乱对内源性大麻素系统(endocannabinoid system,ECS)的影响及其机制。方法建立高脂饮食诱导肥胖SD大鼠模型,每周称量大鼠体重;采用酶比色法测定大鼠血清中总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)和低密度脂蛋白(low-density lipoprotein cholesterol,LDL-C)水平;高效液相色谱法检测大鼠血浆中大麻内源性配体花生四烯酸乙醇胺(anandamide,AEA)的含量;Western blot法检测大鼠附睾脂肪组织中Ⅰ型大麻素受体(cannabinoid receptorⅠ,CB1)的表达。结果大鼠经高脂饮食持续喂养8周,体重均不同程度增加;血清中TC、TG、LDL-C和血浆中AEA水平均显著升高(P0.05);附睾脂肪组织中CB1的表达量也显著增加(P0.05)。结论通过高脂饲料成功诱导SD大鼠的TC、TG和LDL-C升高,使大鼠产生高脂血症;大鼠血清AEA水平和血浆中CB1表达的显著变化表明肥胖大鼠体内ECS在肥胖过程中发生了显著改变,本研究在一定程度上建立了ECS与肥胖之间的联系。     

α-硫辛酸对糖尿病大鼠血糖、血脂及肝脏内AMPKα表达及活性的影响

目的探讨α-硫辛酸对糖尿病大鼠血糖、血脂及肝脏内腺苷酸活化蛋白激酶(Adenosine monophosphate activated protein kinase,AMPK)α亚基(AMPKα)表达及活性的影响。方法应用高脂饮食联合腹腔单次注射小剂量的链脲佐菌素(STZ)复制2型糖尿病合并脂代谢紊乱的Wistar大鼠模型,再将模型大鼠随机分为糖尿病对照(DC)组和α-硫辛酸治疗(LA)组,并设正常对照(NC)组。NC组和DC组每只给予生理盐水2ml/d,LA组经腹腔注射α-硫辛酸60mg/kg·d,共4周。分别测定各组大鼠的体重、血糖、血脂、糖化血红蛋白(HbA1c)和肝脏内AMPKα及磷酸化AMPKα(pAMPKα)的表达水平。结果建模后、给药前及给药后,NC组大鼠血糖水平均显著低于DC和LA组(P<0.01),给药后,LA组显著低于DC组(P<0.05)。给药4周后,DC组大鼠甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)和HbA1c水平均显著高于NC组(P<0.01),而高密度脂蛋白(HDL)、肝脏内AMPKα及pAMPKα的表达水平均显著降低(P<0.05);LA组大鼠TG、TC、LDL和HbA1c水平均较DC组显著下降(P<0.05),而HDL、AMPKα及pAMPKα表达水平均显著升高(P<0.05);DC组肝脏内AMPKα表达较NC组明显下降(P<0.05),LA组无明显变化(P>0.05)。结论α-硫辛酸可以通过调节肝脏内AMPKα的表达水平,进而改善糖尿病状态下的"糖脂毒性"。     

橙皮苷对载脂蛋白E基因敲除小鼠动脉粥样硬化斑块形成的影响

目的研究橙皮苷对ApoE~(-/-)小鼠AS斑块形成的影响。方法 10周龄的雄性ApoE~(-/-)小鼠,分为对照组(ApoE~(-/-))和橙皮苷给药组(ApoE~(-/-)+HES-100mg/kg/d),每组10只,所有小鼠喂饲高脂饲料14周后收集各组织样本。采用酶学试剂盒检测各组的血脂(TC、TG、LDL-C);采用油红O染色观察各组全血管及主动脉根部的斑块面积及斑块分布;采用HE染色观察各组主动脉根部病理形态学变化。结果高脂饲料喂养ApoE~(-/-)小鼠14周后,两组之间体重无明显差异,橙皮苷给药组的总胆固醇(TC)和甘油三酯(TG)明显低于对照小鼠(P0.05);同时橙皮苷给药组的LDL-C明显小于对照组小鼠(P0.001);全血管和主动脉根部油红O染色结果表明橙皮苷减少了AS斑块面积(P0.001,P0.01);对照组斑块有大量泡沫细胞及炎症细胞形成,并伴有胆固醇结晶,发生脂纹期病变和纤维期病变,而橙皮苷能降低斑块中的炎性细胞和纤维成分,没有胆固醇结晶,多为脂纹期病变。结论橙皮苷能抑制ApoE~(-/-)小鼠AS斑块形成。     

人参煎方对2型糖尿病大鼠糖代谢及脂代谢的影响

目的:研究人参煎方对2型糖尿病大鼠糖脂代谢的影响。方法:SD大鼠高糖高脂饲料喂养4周后,结合腹腔注射链脲佐菌素(STZ)_35mg·kg~(-1),建立2型糖尿病大鼠模型,将成模的大鼠按血糖随机分为模型组,阳性对照组(盐酸二甲双胍0.15 g·kg~(-1)·d~(-1)),人参煎方高、中、低剂量组(按生药量计为3.76,1.88,0.94 g·kg~(-1)·d~(-1)),并设正常对照组。给药3周后,观察治疗期间大鼠的一般情况,检测空腹血糖(FBG),糖化血清蛋白(GSP),血清甘油三酯(TG),总胆固醇(CHO),高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)的含量。结果:与正常组比较,模型组大鼠血糖,糖化血清蛋白含量明显增高(P0.01),血清甘油三酯(TG),总胆固醇(CHO),低密度脂蛋白胆固醇(LDL-C)含量增高(P0.05),高密度脂蛋白胆固醇(HDL-C)含量明显下降(P0.05)。人参煎方可降低2型糖尿病大鼠的FBG、GSP、TG、CHO及LDL-C的含量,提高HDL-C的水平,与模型组比较有明显改善(P0.05),人参煎方与盐酸二甲双胍药物治疗组无显著性差异。结论:人参煎方能有效地降低2型糖尿病大鼠的血糖,纠正糖尿病大鼠脂代谢紊乱,调节血脂。     

沙棘油番茄红素软胶囊对大鼠的辅助降血脂实验研究

目的:探究沙棘油番茄红素软胶囊对试验性高脂大鼠的降血脂作用。方法:将试验性大鼠随机的分为正常组、模型组、低剂量组、中剂量组、高剂量组和辛伐他汀阳性组。通过饲喂高脂饲料建立高脂模型,分别灌胃给予不同受试物30天,测定总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白(LDL-C)含量。结果:沙棘油番茄红素软胶囊和辛伐他汀片均能显著降低高血脂大鼠血清TC、TG、LDL-C水平,对HDL-C水平无明显影响,证明,沙棘油番茄红素软胶囊具有降血脂作用,其中高剂量组降血脂效果与辛伐他汀阳性组作用相当。结论:沙棘油番茄红素软胶囊具辅助降血脂的作用。     

高脂、胰岛素抵抗合并高脂高糖对大鼠肝脏Angptl3和LPL基因mR-NA转录的影响

目的探讨高脂、胰岛素抵抗合并高脂高糖对大鼠肝脏血管生成素样蛋白3(Angptl3)和脂蛋白脂肪酶(LPL)基因mRNA转录的影响。方法建立高脂(HL)、胰岛素抵抗合并高脂高糖(IR-HLG)大鼠模型,采用自动分析仪检测模型大鼠空腹血糖(BG)、总三酰甘油(TG)和胆固醇(TC)含量,采用Realtime PCR定量检测各组大鼠肝组织Angptl3和LPL基因的mRNA转录水平。结果模型组大鼠血清TG、TC含量及肝脏Angptl3和LPL基因mRNA转录水平均较对照组明显升高;IR-HLG组大鼠的BG水平和Angptl3水平较对照组和HL组均明显升高,LPL水平较HL组明显下降。结论随血脂的增高,Angptl3和LPL的表达均增强;在高糖、胰岛素抵抗状态下,Angptl3的表达增高,而LPL的表达则部分受到抑制。     

原花青素经肠道微生态途径对脂质代谢的调节

目的研究原花青素(Proanthocyanidin,PC)经肠道微生态途径调节脂质代谢。方法取成年雄性SD大鼠和长爪沙鼠,经基础饲料适应性喂养1周后,采集尾静脉血,收集血清,检测血清总胆固醇(Total cholesterol,TC)水平,并按TC及体重分为基础对照组、模型对照组、低剂量组(25 mg/kg PC)、中剂量组(100 mg/kg PC)、高剂量组(150 mg/kg PC)、阳性对照组(非诺倍特80 mg/kg),基础对照组饲以普通基础饲料,其余各组均饲以高脂饲料,每天灌胃1次,大鼠连续灌胃8周,沙鼠连续灌胃2周。大鼠8周末、沙鼠2周末,经股动脉采血,分离血清,处死前3 d收集72 h粪便。采用全自动生化仪检测TC、甘油三酯(Triglyceride,TG)、高密度脂蛋白胆固醇(High-density lipopro-tein cholesterol,HDL-C)、低密度脂蛋白胆固醇(Low-density lipoprotein cholesterol,LDL-C)、血总胆汁酸(Total bileacid,TBA)水平;循环酶法试剂盒测定粪TBA排出量水平;双抗体两步夹心ELISA法测定卵磷脂胆固醇酰基转移酶(Lecithin-cholesterol acyltransferase,LCAT)活性。解剖处死的大鼠和沙鼠,进行病理组织学分析。提取大鼠、沙鼠小肠、盲肠细菌基因组DNA,采用PCR-变性梯度凝胶电泳(Denatured gradient gel electrophoresis,DGGE)进行动物模型肠道微生态菌群多样性变化分析。结果模型对照组大鼠和沙鼠TC、TG水平明显高于基础对照组,差异有统计学意义(P<0.05),表明高脂模型建模成功。与模型对照组相比,各剂量组和阳性对照组大鼠、沙鼠TC、TG、LDL-C、血TBA水平均降低,LCAT活性、粪TBA排出量均明显升高,差异有统计学意义(P<0.05);各剂量组大鼠肝脏损伤、肝细胞肿胀、变性等病变程度明显减轻,肝组织病理变化明显改善。DGGE检测及图像分析显示,大鼠各剂量组肠道优势菌群多样性明显增加,随着PC干预剂量加大,中、高剂量组肠道菌群多样性明显减少;沙鼠低剂量组与模型对照组的肠道菌群结构基本相似,而中、高剂量组肠道菌群多样性明显减少,肠道优势菌群结构明显恢复。结论 100、150 mg/kg PC干预的实验动物模型中,肠道菌群结构多样性明显恢复,提示PC可通过肠道菌群这一靶标,进行脂质代谢的调节。     

富含硅的天然矿泉水降血脂活性研究

探讨富含硅的天然矿泉水(富硅水)对大鼠饲喂高脂饲料造成的高脂血症预防作用。将成年雄性Wistar大鼠做模型测定各组大鼠的体重及肝指数,检测血清中丙氨酸氨基转移酶(ALT)、天门冬氨基转移酶(AST)、总胆固醇(TC)和甘油三酯(TG),并做肝脏病理学检查。结果表明,富硅水各剂量组血清甘油三酯显著降低(P0.01);血清中ALT与AST极显著降低(P0.01);均显著降低肝指数(3.99±0.19)%,(4.07±0.19)%,(3.97±0.29)%;同时病理组织学显示富硅水能明显改善大鼠的肝细胞脂肪变性。富硅水能够有效预防高脂模型引起的高脂血症的发生或发展。     

福辛普利对非酒精性脂肪性肝炎大鼠肝组织ACE和ACE2基因mRNA转录水平的影响

目的探讨福辛普利对高脂饮食诱导的非酒精性脂肪性肝炎(Nonalcoholic steatohepatitis,NASH)大鼠肝组织ACE和ACE2基因mRNA转录水平的影响,为阐明NASH的发病机制及探索新的治疗策略提供实验依据。方法将40只雄性SD大鼠用普通饲料喂养1周后,随机分为4组:正常对照组(NC组,普通饲料+生理盐水1 ml灌胃)、高脂组(HC组,高脂饲料+生理盐水1 ml灌胃)、药物对照组[NF组,正常饲料+福辛普利3.6 mg/(kg.d)灌胃]和药物干预组[HF组,高脂饲料+福辛普利3.6 mg/(kg.d)灌胃],每组10只。给药24周后,分析各组大鼠肝组织病理学变化,检测各组大鼠血清中谷丙转氨酶(Alanine aminotransferase,ALT)、碱性磷酸酶(Alkaline phosphatase,ALP)、甘油三酯(Triglycerides,TG)、低密度脂蛋白(Low-density lipoprotein,LDL)、转化生长因子-β(Transforming growth factor-β,TGF-β)、血管紧张素转换酶(Angiotensin-convert ingenzyme,ACE)、ACE2、血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)和Ang(-1-7)的水平;RT-PCR检测各组大鼠肝组织ACE和ACE2基因mRNA的转录水平;Western blot检测各组大鼠肝组织Ⅰ型胶原蛋白(CollagenⅠ)的表达水平。结果给药24周后,HF组非酒精脂肪性肝病活动度评分和肝纤维化程度与HC组相比,均明显下降(P<0.001);HF组血清中ALT、ALP、TG、LDL、TGF-β、ACE和AngⅡ的水平均明显低于HC组(P<0.05),而ACE2和Ang(-1-7)的水平均明显高于HC组(P<0.05);福辛普利可显著降低肝组织ACE基因mRNA的转录水平(P<0.001)和CollagenⅠ蛋白的表达水平(P<0.01),升高ACE2基因mRNA的转录水平(P<0.01)。结论福辛普利可能通过下调ACE和上调ACE2的生成和表达,从而降低AngⅡ和升高Ang(-1-7)的生成,具有改善NASH和抗肝纤维化作用。本实验为阐明NASH的发病机制及探索新的治疗策略提供了实验依据。     

High-Fat Diet Aggravates Cerebral Infarct,Hemorrhagic Transformation and Neuroinflammation in a Mouse Stroke Model

Background: Stroke in context of type 2 diabetes (T2D) is associated with a poorer outcome than in non-diabetic conditions. We aimed at creating a new reproducible mouse model of stroke in impaired glucose tolerance conditions induced by high-fat diet. Methods: Adult C57BL6 mice were fed for 2 months with either normal diet (ND) or high-fat diet (HFD). We used a model of Middle Cerebral Artery Occlusion (MCAO) for 90 min. Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT) were used to assess pre-diabetic status. Brain infarct volume, hemorrhagic transformation (HT) as well as systemic and cerebral inflammatory markers were evaluated. Results: HFD was associated with an increased body weight and glycemia following OGTT. The HFD group presented a significant increase in brain infarct volume (38.7 (IQR 30–46.7%) vs. 28.45 (IQR 21–30%); p = 0.016) and HT (HFD: 2 (IQR 1–5) vs. ND: 0 (IQR 0–1); p = 0.012) and higher levels of IL-6 and MCP-1 in infarcted hemisphere compared to the ND group. Conclusion: Two months of HFD in adult mice were sufficient to alter the lipid profile and the control of hyperglycemia. These metabolic perturbations were significantly associated with increased infarct volume and hemorrhagic complications.     

Theophylline-Based KMUP-1 Improves Steatohepatitis via MMP-9/IL-10 and Lipolysis via HSL/p-HSL in Obese Mice

KMUP-1 (7-[2-[4-(2-chlorobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) has been reported to cause hepatic fat loss. However, the action mechanisms of KMUP-1 in obesity-induced steatohepatitis remains unclear. This study elucidated the steatohepatitis via matrix metallopeptidase 9 (MMP-9) and tumor necrosis factor α (TNFα), and related lipolysis via hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) by KMUP-1. KMUP-1 on steatohepatitis-associated HSL/p-HSL/ATGL/MMP-9/TNFα/interleukin-10 (IL-10) and infiltration of M1/M2 macrophages in obese mice were examined. KMUP-1 was administered by oral gavage from weeks 1–14 in high-fat diet (HFD)-supplemented C57BL/6J male mice (protection group) and from weeks 8–14, for 6 weeks, in HFD-induced obese mice (treatment group). Immunohistochemistry (IHC) and hematoxylin and eosin (H&E) staining of tissues, oil globules number and size, infiltration and switching of M1/M2 macrophages were measured to determine the effects on livers. IL-10 and MMP-9 proteins were explored to determine the effects of KMUP-1 on M1/M2 macrophage polarization in HFD-induced steatohepatitis. Long-term administration of KMUP-1 reversed HFD-fed mice increased in body weight, sGOT/sGPT, triglyceride (TG) and glucose. Additionally, KMUP-1 decreased MMP-9 and reactive oxygen species (ROS), and increased HSL/p-HSL and IL-10 in HFD mice livers. In conclusion, KMUP-1, a phosphodiesterase inhibitor (PDEI), was shown to reduce lipid accumulation in liver tissues, suggesting that it could be able to prevent or treat steatohepatitis induced by HFD.     

(?)-Epicatechin-3-O-β-d-allopyranoside from Davallia formosana,Prevents Diabetes and Hyperlipidemia by Regulation of Glucose Transporter 4 and AMP-Activated Protein Kinase Phosphorylation in High-Fat-Fed Mice

The purpose of this experiment was to determine the antidiabetic and lipid-lowering effects of (−)-epicatechin-3-O-β-d-allopyranoside (BB) from the roots and stems of Davallia formosana in mice. Animal treatment was induced by high-fat diet (HFD) or low-fat diet (control diet, CD). After eight weeks of HFD or CD exposure, the HFD mice were treating with BB or rosiglitazone (Rosi) or fenofibrate (Feno) or water through gavage for another four weeks. However, at 12 weeks, the HFD-fed group had enhanced blood levels of glucose, triglyceride (TG), and insulin. BB treatment significantly decreased blood glucose, TG, and insulin levels. Moreover, visceral fat weights were enhanced in HFD-fed mice, accompanied by increased blood leptin concentrations and decreased adiponectin levels, which were reversed by treatment with BB. Muscular membrane protein levels of glucose transporter 4 (GLUT4) were reduced in HFD-fed mice and significantly enhanced upon administration of BB, Rosi, and Feno. Moreover, BB treatment markedly increased hepatic and skeletal muscular expression levels of phosphorylation of AMP-activated (adenosine monophosphate) protein kinase (phospho-AMPK). BB also decreased hepatic mRNA levels of phosphenolpyruvate carboxykinase (PEPCK), which are associated with a decrease in hepatic glucose production. BB-exerted hypotriglyceridemic activity may be partly associated with increased mRNA levels of peroxisome proliferator activated receptor α (PPARα), and with reduced hepatic glycerol-3-phosphate acyltransferase (GPAT) mRNA levels in the liver, which decreased triacylglycerol synthesis. Nevertheless, we demonstrated BB was a useful approach for the management of type 2 diabetes and dyslipidemia in this animal model.     

A Perinatal Palatable High-Fat Diet Increases Food Intake and Promotes Hypercholesterolemia in Adult Rats

The main goal of the present study was to evaluate the long-term effects of a perinatal palatable high-fat diet on the food intake and cholesterol profile of adult rats. Male Wistar rats (aged 22 days) were divided into two groups according to their mother’s diet during gestation and lactation (C _p, n = 10; pups from control mothers; and HL_p n = 10; pups from mothers fed a palatable high-fat diet). At the 76th day, pups were housed individually for 14 days, and daily food consumption was determined during a period of 6 days. Blood from 100-day-old rats was sampled by cardiac puncture. Fasting (12 h) serum glucose, total cholesterol, LDL-C, HDL-C, triglycerides (TG), and VLDL-C levels were determined. The measurement of food intake was higher in the animals submitted to a hyperlipidic diet during the perinatal period. Serum total cholesterol, LDL-C, HDL-C, TG, VLDL-C and glycemia were increased in the HL_p group compared to the control group. Our findings show that an early life environment with a high-fat diet can contribute to metabolic disease in later life.     

Effects of polyphenolic natural products on the lipid profiles of rats fed high fat diets

Male Wistar rats were fed a high fat diet (HFD) containing 2.5% cholesterol and 16% lard supplemented with polyphenolic natural products namely quercetin, morin or tannic acid (100 mg/rat/day) for 4, 7 and 10 wk. Rats fed HFD without the supplements served as control. The effects of these compounds on blood lipid profiles, enzymes, liver fat and aorta of the rat were studied. In rats fed HFD containing tannic acid, plasma total cholesterol (TC), low density lipoprotein cholesterol (LDLC) and triglyceride (TG) were reduced by 33.3%, 29.6% and 65.1%, respectively, at week 10. High density lipoprotein cholesterol (HDLC) concentration was not altered. Fat deposition was also decreased in the liver of these rats. Morin significantly reduced plasma TG (65.1%) and liver fat only at week 7 while at week 10 it reduced plasma TC and LDLC by 30.9% and 29.3% respectively. The plasma HDLC concentration was increased by 47.3% at week 4 but no effect was seen at weeks 7 and 10. In the rats fed HFD containing quercetin, plasma HDLC was increased by 28.6% at week 7 but at week 10, plasma LDLC was increased by 21.2%. Quercetin did not cause any significant changes on the plasma TC, TG and liver fat at weeks 4, 7 and 10. Plasma alanine aminotransferase, alkaline phosphatase and bilirubin in control and treated groups were not significantly different. However, hepatic lipase activity in rats fed tannic acid was significantly lower. Aortae of all groups of rats showed no abnormalities. The present report indicates that tannic acid and morin are effective in reducing plasma and liver lipids when supplemented with a high fat diet in rats.     

Supplementation with Docosahexaenoic Acid and Vitamin E Improves Hepatic Triglyceride Accumulation Induced by High-Fat Diet in Mice

The study aims to investigate the effect of combined supplementation with docosahexaenoic acid (C22:6 n-3, DHA) and vitamin E (VE) on the oxidative stress and liver triglycerides (TG) accumulation induced by high-fat diet (HFD) in mice. C57BL/6J mice are fed either a control diet or an HFD for 8 weeks. Animals are supplemented with DHA, VE, or DHA + VE, respectively. Supplementation with DHA alone shows significant improvement in oxidative stress and hepatic steatosis in mice. Supplementation with DHA significantly reduces the liver TG and total cholesterol contents, and the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, compared with the HFD. Supplementation with DHA also significantly decreases the mRNA expression level of sterol regulatory element-binding protein 1C. However, supplementation with VE alone does not show improvement in oxidative stress and hepatic steatosis. DHA + VE supply obtains a superior effect in alleviation of hepatic steatosis than DHA supplementation alone in mice fed by HFD. The efficacy of DHA potentiated by VE can be due to that VE enhances the effect of DHA in decrease of ALT and AST levels and increase of antioxidant enzyme activity and glutathione level in mice fed by HFD. Practical Applications: Supplementation with DHA significantly improves the oxidative stress and hepatic steatosis induced by HFD in mice. The efficacy of DHA in the alleviation of hepatic steatosis induced by HFD is potentiated by VE. These findings may provide a rational basis for the use of DHA and VE co-supplementation in patients with liver steatosis.     

The prevention of alcoholic fatty liver using dietary supplements: Dihydroxyacetone,pyruvate and riboflavin compared to arachidonic acid in pair-fed rats

Male Sprague-Dawley rats were fed for 30 days a high-fat liquid ethanol diet with dihydroxyacetone, pyruvate and riboflavin added as supplements (AMA-). Plasma triglyceride (TG) levels were 6-fold greater in these rats than in those fed and alcohol with without the supplements (AA-). The liver TG content in rats fed the AMA-diet was similar to that of rats fed a control diet (CA-) in which alcohol was replaced with isocaloric amounts of dextrose. Livers of rats fed the AA- diet had 3 times more TG than controls. Alcohol ingestion also enhanced the hepatic content of cholesteryl esters (CE) and phospholipids (PL). These lipids were reduced to levels found in livers of rats fed the control diet (CA-) when dihydroxyacetone, pyruvate and riboflavin were included in the alcohol diet. The fatty acid compositions of TG, CE and PL from livers of rats fed the AMA-diet were similar to those of corresponding lipids from rats fed the control diet (CA-) but differed from compositions when fed the alcohol diet (AA-). Regardless of the diet fed, TG had the same fatty acid composition in plasma and liver. The same was true of PL fatty acid composition. However, the fatty acid composition of CE differed between liver and plasma. The major fatty acid in liver CE was 18∶1 whereas in plasma it was arachidonic acid (20∶4). Reduced fatty liver was observed in an earlier study when rats were fed ad libitum an ethanol diet containing 20∶4. In the present study, we pair-fed the same diet and fatty liver was not reduced. Dihydroxyacetone, pyruvate and riboflavin did not prevent alcohol-induced fatty liver when 20∶4 was included in the AMA-diet. Our results confirm that dietary dihydroxyacetone, pyruvate and riboflavin prevent alcohol-induced fatty liver, and show that this effect may result from increased mobilization of fat from liver.     

Metabolomic Profiles in Adipocytes Differentiated from Adipose-Derived Stem Cells Following Exercise Training or High-Fat Diet

Controlling the differentiation potential of adipose-derived stem cells (ADSCs) is attracting attention as a new strategy for the prevention and treatment of obesity. Here, we aimed to observe the effect of exercise training (TR) and high-fat diet (HFD) on the metabolic profiles of ADSCs-derived adipocytes. The rats were divided into four groups: normal diet (ND)-fed control (ND-SED), ND-fed TR (ND-TR), HFD-fed control (HFD-SED), and HFD-fed TR (HFD-TR). After 9 weeks of intervention, ADSCs of epididymal and inguinal adipose tissues were differentiated into adipocytes. In the metabolome analysis of adipocytes after isoproterenol stimulation, 116 metabolites were detected. The principal component analysis demonstrated that ADSCs-derived adipocytes segregated into four clusters in each fat pad. Amino acid accumulation was greater in epididymal ADSCs-derived adipocytes of ND-TR and HFD-TR, but lower in inguinal ADSCs-derived adipocytes of ND-TR, than in the respective controls. HFD accumulated several metabolites including amino acids in inguinal ADSCs-derived adipocytes and more other metabolites in epididymal ones. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that TR mainly affected the pathways related to amino acid metabolism, except in inguinal ADSCs-derived adipocytes of HFD-TR rats. These findings provide a new way to understand the mechanisms underlying possible changes in the differentiation of ADSCs due to TR or HFD.