Effect of diets with different fat content on metabolic syndrome of rats and mice

目的 探讨不同脂肪含量的高脂纯化配方饲料对大、小鼠体重、血糖、血胰岛素、血脂、脂肪肝及白蛋白尿的影响.方法 雄性SD大鼠及C57BL/6小鼠随机分为MD10％、MD45％和MD60％脂肪含量饲料组,喂养3个月,检测动物体重、血糖、血胰岛素水平、血脂和蛋白尿水平,以及主要脏器重量及肝脏脂质含量.结果 与正常组(MD10％脂肪含量)相比,高脂组(MD45％和MD60％脂肪含量)动物体重显著增加,出现明显的糖耐量异常、胰岛素抵抗和血脂水平升高,同时伴有肝脏脂质含量和蛋白尿水平的增加,并且以MD45％高脂组体重增加及胰岛素抵抗更加显著.结论 MD45％和MD60％高脂配方饲料均可在大、小鼠较好地诱导代谢综合征的发生,而且前者优于后者.     

谷氨酰胺对高脂饮食诱导C57BL/6J小鼠肥胖和胰岛素抵抗的影响

目的:探讨谷氨酰胺(L-glutamine,Gln)对高脂饮食(high-fat diet,HFD)诱导小鼠肥胖和胰岛素抵抗的影响。方法:60只雄性C57BL/6J小鼠随机分为正常对照(normal control,NC)组、HFD组、HFD+丙氨酸(Lalanine,Ala)组和HFD+Gln组,每组15只。每周记录小鼠体重,给药16周后禁食不禁水12 h测定空腹血糖(fasting blood glucose,FBG),处死后剖腹取附睾脂肪垫并称重。采用酶联免疫法检测小鼠胰岛素(insulin,INS)、瘦素(leptin,LEP)、脂联素(adiponectin,APN)和胰高血糖素样肽1(glucagon-like peptide-1,GLP-1)的水平,并计算胰岛素抵抗指数(insulin resistance index,IRI)和胰岛素敏感指数(insulin sensitivity index,ISI)。结果:与NC组比较,HFD组小鼠体重和附睾脂肪垫重量明显升高,FBG、INS、IRI和LEP水平均明显升高,ISI和APN水平明显降低(P0.05);与HFD组比较,HFD+Gln组小鼠体重明显下降,FBG和LEP水平明显降低,IRI明显减小(P0.05)。4组小鼠血清的GLP-1水平差异无统计学显著性。结论:谷氨酰胺减轻高脂饮食诱导的肥胖小鼠体重和胰岛素抵抗。     

高脂饲养致小鼠胰岛素抵抗对脂肪肝形成的影响

目的:探讨高脂饲养致小鼠脂肪肝形成的机制。方法:随机将8周雄性C57BL/6J小鼠分成高脂饲养组(给予含60%卡路里的高饱和脂肪酸饲养)和正常对照组,饲养12周。监测体重、肝重、血甘油三酯、血总胆固醇、血糖和血胰岛素水平,通过高胰岛素正葡萄糖钳夹实验反映胰岛素敏感性,HE染色、苏丹IV染色及肝脂含量反映肝组织脂质沉积情况,确定高脂饲养致小鼠脂肪肝的形成。通过Western blot法检测磷酸化胰岛素受体底物1(IRS1)和蛋白激酶B(Akt)水平反映胰岛素信号通路激活情况,检测固醇调节元件结合蛋白1(SREBP-1)和脂肪酸合成酶(FAS)蛋白水平反映肝内脂质合成的情况。结果:高脂饲养组小鼠体重及肝重较正常对照组小鼠明显增加。与正常对照组相比,高脂组血和肝组织内甘油三酯和总胆固醇含量显著升高,血清胰岛素水平升高,葡萄糖输注率减少,磷酸化IRS1和Akt水平降低。肝组织HE染色可见高脂组肝细胞胞浆内充满大量脂肪空泡,苏丹IV染色可见肝细胞内存在大量大小不一的红色脂滴;SREBP-1和FAS蛋白水平明显升高。给予外源性油酸干预原代正常肝细胞48 h,磷酸化IRS1和Akt水平呈浓度依赖性减低,而SREBP-1和FAS蛋白表达明显升高。结论:高脂饲养导致小鼠肝脏发生胰岛素抵抗,并通过激活SREBP-FAS脂肪合成途径,促进肝脏脂质沉积,从而诱发脂肪肝。     

罗格列酮对非糖尿病代谢综合征患者血清脂联素水平和胰岛素抵抗的影响

目的：观察罗格列酮（ROS）对非糖尿病代谢综合征（MS）患者血清脂联素水平和胰岛素抵抗性的影响。方法：选择92例非糖尿病MS患者随机分为两组,A组40例,给予常规治疗;B组52例,在常规治疗上的基础上,加用罗格列酮（ROS）口服。用药前及用药后8周,应用酶联免疫吸附法测定血清脂联素水平、计算胰岛素抵抗指数、胰岛素敏感指数。结果：A组治疗前后脂联素水平（1．49±0．59mg／L vs 1．21±0．66mg／L,P〉0．05）及胰岛素抵抗指数（1．44±0．51 vs 1．32±0．57,P〉0．05）、胰岛素敏感指数（-4．56±0．51vs -4．44±0．57,P〉0．05）比较无显著性差异;B组治疗前后比较,脂联素水平升高（0．89±0．73mg／L vs 2．52±1．37mg／L,P〈0．01）、胰岛素抵抗指数降低（1．50±0．45 vs 0．99±0．35,P〈0．01）、胰岛素敏感指数升高（-4．61±0．45 vs -4．10±0．46,P〈0．01）均有统计学意义。结论：非糖尿病MS患者经口服ROS后脂联素水平明显升高、胰岛素抵抗指数降低、胰岛素敏感指数升高。     

厚朴酚对高脂饮食性肥胖大鼠体重及胰岛素抵抗的影响

目的 观察厚朴酚对高脂饮食性肥胖大鼠体重和血清生化指标的影响,并探讨其机制.方法 将SD大鼠随机分成4组:对照组,高脂组和厚朴酚高、低二个剂量组.每天定时称量食水、灌胃,每周测体重,第8周末各组大鼠禁食12 hA股动脉取血测定血清生化指标.结果 低剂量厚朴酚组从第4周开始体重比高脂组显著降低(P＜0.05),高、低剂量厚朴酚组的胰岛素、游离脂肪酸、丙二醛以及低剂量组的血糖、三酰甘油比高脂组都显著下降(P＜0.05).结论 厚朴酚能降低高脂饮食性肥胖大鼠的体重,并对胰岛素抵抗和糖脂代谢紊乱等有一定的改善作用.     

长程高脂饲料对雌雄大鼠非酒精性脂肪肝差异的影响及机制的初步探讨

目的 观察SD雌雄大鼠肝脏脂质沉积情况,探讨形成雌雄大鼠脂肪肝差异的可能机制.方法 肝脏组织石蜡切片HE染色,用光镜观察肝脏脂质沉积情况.测定第14个月大鼠肝脏组织甘油三酯水平.测定第14个月大鼠的空腹血糖和空腹胰岛素,计算胰岛素抵抗指数.测定第14个月大鼠肝脏组织匀浆液中线粒体和微粒体的丙二醛和过氧化氢酶的含量,检测大鼠肝脏组织氧化应激和抗氧化应激水平.结果 ①长程高脂喂养14个月后雌雄大鼠高脂组肝脏组织出现弥散性的脂肪滴沉积,但无明显的炎性细胞浸润,未见纤维化形成,也未观察到明显的局部性肝细胞坏死或细胞凋亡等现象;②雄性高脂组大鼠肝脏组织的脂肪泡比雌性大鼠的面积大并且数量多,且雄性高脂组肝脏甘油三酯水平显著高于雌性高脂组(P<0.001);③第14个月,雌雄大鼠空腹血糖水平无显著差异,高脂雄性大鼠空腹胰岛素水平显著高于高脂雌性大鼠(P<0.05).高脂雄性大鼠胰岛素抵抗水平(HOMA-IR)亦显著高于高脂雌性大鼠(P<0.05);④雌性高脂组大鼠肝脏组织中丙二醛水平都低于雄性大鼠高脂组,过氧化氢酶水平都高于雄性高脂组大鼠,有显著性差异(P<0.05).结论 单纯长程高脂饲料喂养SD雌雄大鼠能引起典型的脂肪肝的形成,并且雄性高脂组大鼠脂肪肝的程度比雌性高脂组严重,其机制可能与雌性大鼠的外周胰岛素抵抗水平和肝脏组织的氧化应激水平低于雄性大鼠有关.     

高脂和高果糖饲料喂养大鼠肌细胞内长链酯酰辅酶A的含量及其与胰岛素抵抗的关系

 摘要: 目的 观察高果糖饮食喂养对大鼠骨骼肌内长链酯酰辅酶A(LCACoAs)含量的影响,并探讨高果糖与高脂两种不同饮食诱导的动物模型肌细胞内LCACoAs与胰岛素抵抗的关系。方法 Wistar雄性大鼠分为对照组、高脂组及高果糖组喂养3周,测定各组大鼠空腹血糖、血胰岛素、HOMA指数、血甘油三酯、肌肉甘油三酯及肌细胞内LCACoAs的含量。结果 与对照组相比,高脂组、高果糖组的血葡萄糖、血胰岛素浓度、HOMA指数、 血甘油三酯明显增高;高脂组肌TG含量明显高于对照组和高果糖组,分别为4.5±0.2对3.0±0.1和3.1±0.4（mmol/g）(p<0.01) ;高脂组、高果糖组的肌细胞内总LCACoA含量分别为30.73.4和32.32.7(nmol/g),明显高于对照组20.62.1 (nmol/g)(p<0.01)。肌肉总LCACoA含量与HOMA指数呈正相关。结论 高果糖饮食同高脂饮食一样均可引起机体的胰岛素抵抗及脂肪酸活性形式LCACoA的堆积,肌肉LCACoA含量与胰岛素抵抗密切相关。     

代谢综合征诊断的全球定义的启示

代谢综合征（metabolic syndrome，MS）是指伴有胰岛素抵抗的一组疾病，但是MS一直缺乏统一的定义．1988年Reaven用“x综合征”描述了各种成人代谢病的综合状态．1989年Kaplan将同时具有中心性肥胖、IGT、高血压和高甘油三酯血症称为“死亡四重奏”．此后，曾有学者称之为“胰岛素抵抗综合征”、“多代谢综合征”等．流行病学和临床研究表明MS的每一种成分都是发生心血管病变的危险因素，同时合并多种异常时发生心血管病的危险性更大，严重影响人们的健康和生活质量，成为社会的沉重负担．胰岛素抵抗（IR）是MS中的重要中心环节，中心性肥胖通过影响胰岛素的敏感性参与IR的发生和发展．引起MS的原因是多方面的，主要是遗传易感性和环境因素互相作用的结果．不良的生活方式（高热量、高脂饮食、体力活动减少等）是主要的外来因素．     

血清脂联素水平与慢性乙型肝炎患者伴发代谢综合征的相关性研究

目的 研究脂联素及其受体2与慢性乙型肝炎感染伴发MS患者的肝脂肪变、纤维化和炎症的相关性.方法 收集138例慢性乙型肝炎(chronic hepatitis B,CHB)患者资料,根据患者有无代谢综合征(metabolic syndrome,MS)分为MS组(65例)和非MS组(73例),检测两组患者血清脂联素(adiponectin,Adi)水平,并比较血清酶学、糖脂类代谢相关指标水平以及HBeAg阳性率等指标是否有组间差异.结果 CHB伴发MS患者血清酶学、糖脂类代谢相关指标水平以及HBeAg阳性率明显高于非MS组.体重指数和稳态模型评估指数是CHB伴发MS患者的独立危险因素.结论 CHB患者伴发的MS与胰岛素抵抗相关,肝脏脂联素表达水平与CHB伴发MS患者疾病进展密切相关.     

妊娠期代谢综合征对母亲健康及后代生长发育影响的研究进展

妊娠期女性为满足妊娠过程母体和胎儿的需要,体内各系统发生不同程度的改变.但由于个体的差异,部分妊娠期女性会出现2型糖尿病(T2D)、脂质紊乱和高血压等代谢性异常,影响母亲健康及后代神经及心血管等系统的发育.因此,控制各种代谢异常有利于改善妊娠结局.     

Fetuin-A levels in obesity: differences in relation to metabolic syndrome and correlation with clinical and laboratory variables

Introduction

Fetuin-A is an important player in the enhancement of insulin resistance. There are very limited data available concerning the relationships between fetuin-A, weight status and features of the metabolic syndrome (Met S) in obese Egyptian subjects, and especially in children. The aim of the study was to evaluate fetuin-A serum level in subjects with obesity and its possible association with other laboratory and clinical variables.

Material and methods

A total of 140 obese subjects and 50 controls aged 10-40 years were recruited. Demographic, anthropometric and biochemical features were collected according to a standard protocol. Serum fetuin-A levels were measured using ELISA and the modified Third Report of the National Cholesterol Education Program (NCEP-ATP III) criteria were adopted to diagnose Met S.

Results

A higher level of serum fetuin-A was detected in obese subjects. Met S cases were also significantly associated with higher serum fetuin-A. Fetuin-A correlated significantly with BMI (r = 0.437), systolic (r = 0.228) and diastolic blood pressure (r = 0.295), waist circumference (r = 0.332), insulin resistance calculated by the homeostasis model (HOMA-IR) (r = 0.295) and high-density lipoprotein (HDL) (r = 0.362).

Conclusions

Fetuin-A levels were higher in adults and children with obesity and Met S. They were related to insulin resistance and to features of the Met S in cross-sectional analyses. Our study demonstrates a novel association between human fetuin-A and the Met S among obese subject. Therefore, fetuin-A might be a new promising link between obesity and its comorbidities.     

Circulating visfatin level and visfatin/insulin ratio in obese women with metabolic syndrome

Introduction

Visfatin is an adipokine secreted by visceral adipose tissue with insulin-mimetic properties. Higher circulating visfatin levels were reported in type 2 diabetes. The aim of this study was to analyse circulating visfatin and insulin levels and the visfatin/insulin ratio in obese women with and without metabolic syndrome (MetS).

Material and methods

The study involved 92 obese women. Subjects were diagnosed with MetS according to IDF 2005 criteria. The MetS group consisted of 71 subjects (age: 52.8 ±9.4 years, body mass index [BMI]: 39.1 ±5.6 kg/m², waist circumference: 109.6 ±11.4 cm and fat mass: 52.0 ±12.8 kg) while the non-MetS group consisted of 21 subjects (age: 51.7 ±9.5 years, BMI: 36.3 ±5.2 kg/m², waist circumference: 104.7 ±11.0 cm and fat mass: 45.2 ±10.7 kg). In addition to anthropometric measurements and assessment of serum glucose and lipids, plasma concentrations of visfatin were estimated by enzyme-linked immunosorbent assay (ELISA) and of insulin by radioimmunoassay (RIA). Homeostatic model assessment insulin resistance (HOMA-IR) and visfatin/insulin ratio were calculated.

Results

In the MetS group significantly higher (p < 0.01) plasma concentrations of insulin and HOMA-IR values but similar visfatin levels were observed than in the non-MetS group. As a consequence of the significantly higher plasma insulin concentration the visfatin/insulin ratio was significantly lower in the MetS group (p < 0.05). The visfatin/insulin ratio correlated inversely with anthropometric parameters such as body mass, BMI, body fat and waist circumference (r = –0.41, p = 0.0003; r = –0.42, p = 0.0002; r = –0.29, p = 0.01; r = –0.23, p = 0.04, respectively).

Conclusions

We conclude that the visfatin/insulin ratio declining with increasing visceral obesity may predispose to the development of insulin resistance.     

Correlation of obstructive sleep apnea hypopnea syndrome with metabolic syndrome in snorers

Though obstructive sleep apnea hypopnea syndrome (OSAHS) and metabolic syndrome (MS) are correlated; the contributing factors for the occurrence of MS in Chinese snorers remain largely undefined. We aimed to investigate the associated pathogenesis of coexistence of OSAHS and MS in Chinese snorers. A total of 144 Chinese habitual snorers were divided into 3 groups, the control group (simple snorers) (n  =  36), the mild OSAHS group (n  =  52) and the moderate-to-severe OSAHS group (n  =  56). The incidence of MS in the moderate-to-severe OSAHS group (26.8%) was significantly higher than that in the control group (8.3%), the mild OSAHS group (11.1%) and all the OSAHS patients (19.45%) (all P < 0.05). Homeostatic model assessment (HOMA) index and proinsulin (PI) were negatively correlated with nocturnal meanSpO₂ and miniSpO₂. Meanwhile, nocturnal SpO₂ were negatively correlated with body mass index, waist and neck circumferences and diastolic blood pressure, but positively correlated with total cholesterol and high-density lipoprotein cholesterol. The study indicated that in Chinese snorers, moderate-to-severe OSAHS was closely associated with MS via nocturnal hypoxemia.     

Comparing the effects of inorganic nitrate and allopurinol in renovascular complications of metabolic syndrome in rats: role of nitric oxide and uric acid

Introduction

The epidemic of metabolic syndrome is increasing worldwide and correlates with elevation in serum uric acid and marked increase in total fructose intake. Fructose raises uric acid and the latter inhibits nitric oxide bioavailability. We hypothesized that fructose-induced hyperuricemia may have a pathogenic role in metabolic syndrome and treatment of hyperuricemia or increased nitric oxide may improve it.

Material and methods

Two experiments were performed. Male Sprague-Dawley rats were fed a control diet or a high-fructose diet to induce metabolic syndrome. The latter received either sodium nitrate or allopurinol for 10 weeks starting with the 1^st day of fructose to evaluate the preventive role of the drugs or after 4 weeks to evaluate their therapeutic role.

Results

A high-fructose diet was associated with significant (p < 0.05) hyperuricemia (5.9 ±0.5 mg/dl), hypertension (125.2 ±7.8 mm Hg), dyslipidemia and significant decrease in tissue nitrite (27.4 ±2.01 mmol/l). Insulin resistance, as manifested by HOMAIR (20.6 ±2.2) and QUICKI (0.23 ±0.01) indices, as well as adiposity index (12.9 ±1.1) was also significantly increased (p < 0.1). Sodium nitrate or allopurinol was able to reverse these features significantly (p < 0.05) in the preventive study better than the therapeutic study.

Conclusions

Fructose may have a major role in the epidemic of metabolic syndrome and obesity due to its ability to raise uric acid. Either sodium nitrate or allopurinol can prevent this pathological condition by different mechanisms of action.     

Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles

IntroductionMetabolic syndrome arises from abnormal adipose function accompanied by insulin resistance. As early factors reflecting/impacting lipid storage dysfunction of adipose tissues, we sought to determine adipokine levels in subcutaneous and visceral adipose tissues (SAT and VAT).Material and methodsGene and protein expression levels of leptin, adiponectin, and resistin were analysed in SAT and VAT of normal-weight and overweight/obese women, subclassified according to insulin resistance index, triglyceride, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels into metabolically healthy and “at risk” groups.ResultsCompared with normal-weight women, obese women had higher serum leptin levels (p < 0.05), as well as increased leptin gene and protein expression in VAT. Conversely, expression levels of leptin were lower in SAT of obese women, and minor in the SAT of “at risk” groups of women, compared with weight-matched healthy groups. In addition, lower adiponectin levels were detected in SAT of metabolically healthy obese women (p < 0.01), and lower in SAT and VAT (p < 0.05) of “at risk” obese women compared to healthy, obese women. Significant differences in resistin levels were only observed in obese women; resistin gene expression was higher in VAT and SAT of obese, compared to normal-weight women. However, higher gene expression was not consistent with protein expression of resistin.ConclusionsLow adiponectin in both examined adipose tissues and inappropriate leptin expression levels in SAT appear to be important characteristics of obesity-related metabolic syndrome. Intriguingly, this adipokine dysregulation is primary seen in SAT, suggesting that endocrine dysfunction in this abdominal depot may be an early risk sign of metabolic syndrome.     

An approach to the etiology of metabolic syndrome

Increased prevalence of obesity in the world, especially accumulation of abnormal amounts of visceral fat predisposes to insulin resistance, which is the central role of metabolic syndrome (MS). Obesity can deregulate the intracellular signaling of insulin due to the production of inflammatory substances, chemoattractant proteins, adipokines and molecules that trigger hormonal mediator potentials for destabilization of signal transduction, leading to metabolic disorders such as hyperglycemia, hypertension, and dyslipidemia. The complexity of the MS and of the genetic mechanisms involved in its etiology derives from the combination of variants on genes involved and environmental factors that predispose it. The purpose of this paper is to review the effects of obesity in molecular and biochemical responses that trigger insulin resistance and its relation to some candidate genes and the ancestral component of the population.     

Obesity and metabolic syndrome: pathological effects on the gastrointestinal tract

Obesity is an increasingly common problem worldwide and a risk factor for a variety of gastrointestinal (GI) diseases, both non‐neoplastic (e.g. gastro‐oesophageal reflux and Barrett's oesophagus) and neoplastic (e.g. oesophageal adenocarcinoma, colorectal carcinoma, and gallbladder cancer). Furthermore, obesity is associated with worse GI cancer outcomes. Body mass index is a commonly used measure of fat accumulation, although specific patterns such as abdominal/central obesity and visceral fat quantity sometimes predict disease risk more accurately. Metabolic syndrome (MS) is a related condition characterized by central adiposity and insulin resistance. The reasons for the associations with neoplasia are diverse. Established cancer‐related conditions that have a higher prevalence in overweight subjects include Barrett's oesophagus and gallstones. Preneoplastic lesions such as colorectal adenoma, colorectal serrated lesions and pancreatic intraepithelial neoplasia are also associated with obesity/MS. At the cellular level, adipocytes can release carcinogens such as adipokines, insulin‐like growth factor, and vascular endothelial growth factor. Inflammatory cells constitute a further potential source of carcinogens; in obese subjects, their numbers are increased systemically and in adipose tissue. Animal studies have contributed additional information. For example, mice with a genetic predisposition to develop colorectal carcinoma given a high‐fat diet have larger and more numerous intestinal adenomas than controls, and there may be demonstrably higher levels of mucosal oncogenic factors. The associations between obesity and GI disease are of variable strength, and the underlying mechanisms are incompletely understood, but it is clear that obesity and MS have a significant, potentially avoidable and often under‐recognized impact on the population burden of GI disease.     

代谢综合征和胰岛素抵抗的认识进展

代谢综合征是一组复杂的代谢紊乱症候群,是导致糖尿病、心脑血管疾病的危险因素,胰岛素抵抗在其发病机制中可能起重要作用。至今对它认识争议颇多,本文就MS的定义、发病机制和治疗以及对IR认识方面的进展作简要介绍。