红芪多糖对实验性大鼠糖尿病胰岛素抵抗瘦素的影响

目的探讨红芪多糖(HPS)对实验性大鼠糖尿病胰岛素抵抗瘦素的影响。方法随机抽取正常大鼠为正常对照组,剩余大鼠使用高脂高糖饲料和注射小剂量链脲佐菌素诱导糖尿病胰岛素抵抗大鼠模型。造模成功的大鼠随机分为模型组、二甲双胍组、HPS小剂量组、HPS大剂量组,并分别予以生理盐水、二甲双胍、HPS高剂量、HPS低剂量灌胃治疗4周。检测各组大鼠空腹血糖(FPG)、血清胰岛素(INS)、胰岛素敏感性指数(ISI)、血脂、血清瘦素、脂肪瘦素。结果 HPS高、低剂量组以及二甲双胍组与模型组相比,FPG、INS、总胆固醇、三酰甘油、血清瘦素、脂肪瘦素降低,高密度脂蛋白胆固醇、ISI升高,差异均有统计学意义(P0.05或P0.01)。结论 HPS可改善糖尿病胰岛素抵抗大鼠血清瘦素、脂肪瘦素及其相关指标。     

黄芩苷对2型糖尿病大鼠模型胰岛素抵抗的影响

目的 观察中药黄芩苷对实验性2型糖尿病(T2DM)大鼠空腹血糖(FBG)、空腹胰岛素(FINS)、胰岛素敏感指数(ISI)、尿白蛋白和脂肪因子的影响.方法 Wistar雄性大鼠40只随机分为4组:正常对照组、模型组、黄芩苷治疗组、罗格列酮治疗组.用高热量饲料加小剂量链脲佐菌素(30 mg/kg)建立实验性T2DM大鼠模型后,各组按要求进行处置,12 w后测定肿瘤坏死因子-α(TNF-α)、瘦素、脂联素、尿白蛋白、FBG、FINS,计算出ISI.结果 与模型组相比,黄芩苷可使大鼠TNF-α、瘦素水平降低,脂联素水平升高,尿白蛋白降低,ISI升高,其作用与典型噻唑烷二酮类制剂罗格列酮相似.结论 黄芩苷可改善实验性T2DM大鼠的胰岛素抵抗(IR),推测黄芩苷可能通过改善脂肪因子水平达到改善IR的作用.     

血脂康胶囊对高脂喂养大鼠内脏脂肪及代谢指标的影响

目的探讨血脂康胶囊对高脂喂养大鼠内脏脂肪及代谢指标的影响。方法选择6周龄健康雄性Wistar大鼠36只,随机分为对照组(n=12)组和高脂组(n=24),分别饲以基础饲料和高脂饲料,高脂组大鼠再随机分成两组:高脂模型组(n=12)和血脂康组(n=12),分别给予等剂量0.5%纤维素钠安慰剂和血脂康300 mg/(kg·d)灌胃,共观察12周后,检测各组大鼠附睾、肾周脂肪等内脏脂肪重量,计算体脂比,同时检测各组大鼠空腹血糖、胰岛素、总胆固醇、三酰甘油,计算胰岛素抵抗指数(HOMA-IR)。结果高脂喂养组大鼠12周后的体重和附睾、肾周脂肪重量及体脂比均显著高于正常对照组(P0.01),血脂康组虽较正常对照组大鼠也有增加(P0.05),但仍显著低于高脂喂养组大鼠(P0.01);高脂喂养组大鼠空腹血糖、空腹胰岛素、总胆固醇、三酰甘油及HOMA IR均显著高于正常对照组大鼠(P0.01)。血脂康组空腹血糖高于正常对照组(P0.01),空腹胰岛素和HOMA IR与正常对照组比较差异无统计学意义,而较高脂喂养组显著降低(P0.05);总胆固醇、三酰甘油虽较正常对照组有明显增加(P0.05或P0.01),但也显著低于高脂喂养组(P0.05或P0.01)。结论血脂康胶囊干预可以有效减少高脂喂养大鼠内脏脂肪聚集,从而显著改善糖脂代谢异常和胰岛素抵抗。     

成年期追赶生长对大鼠胰岛素敏感性与应激水平的影响

目的 观察成年期追赶生长对大鼠胰岛素敏感性和应激水平的影响,并探讨其胰岛素抵抗形成的可能机制。方法 将7周龄雄性SD大鼠分为6组（共2个时间点）,即4周时间点2组：热卡限制4周组(R4),正常饮食4周组(NC4)作为R4组对照;8周时间点4组：正常饮食追赶生长组(RN4)、高脂饮食追赶生长组(RH4)、持续高脂饮食8周组（HF8）、持续正常饮食8周组(NC8)。通过先热卡限制后恢复饮食的方法建立追赶生长大鼠模型。检测大鼠高胰岛素-正糖钳夹试验过程中葡萄糖输注率和骨骼肌2-脱氧葡萄糖摄取、胰岛素刺激后的骨骼肌胰岛素信号通路、血皮质酮、骨骼肌11β-羟类固醇脱氢酶1(11β-HSD1)表达水平。结果 热卡限制4周时,R4组大鼠血皮质酮和骨骼肌11β-HSD1 mRNA表达水平明显高于NC4组(P＜0.05),骨骼肌蛋白激酶B( Akt) Ser473磷酸化和糖摄取与NC4组相比差异无统计学意义。热卡限制后恢复饮食4周时,血皮质酮和骨骼肌11β-HSD1表达水平RN4组明显高于NC8组,RH4组明显高于NC8和HF8组,而骨骼肌Akt磷酸化和糖摄取RN4组明显低于NC8组,RH4组明显低于NC8组、HF8组和RN4组（均P＜0.05）。结论正常饮食和高脂饮食追赶生长大鼠均可导致整体和骨骼肌应激水平上调及胰岛素抵抗,尤以高脂饮食追赶生长大鼠更为明显。应激和饮食状况的交互作用可能是追赶生长胰岛素抵抗形成的重要原因。     

代谢综合征大鼠中血清瘦素和肿瘤坏死因子α与胰岛素抵抗的关系

目的探讨瘦素与肿瘤坏死因子-α(TNF-α)在代谢综合征的发生发展过程中扮演的角色.方法高糖高脂饮食喂养SD大鼠12周后分别测血糖、血脂、血清胰岛素的水平,胰岛素抵抗(IR)的程度用稳态模型(Homa-IR)的IR指数(IAI)评估,血清中瘦素的水平用放免法测定TNF-α用ELISA方法检测,另取大鼠腹内脂肪组织,用免疫组化的方法观测脂肪细胞中瘦素表达的情况.结果高糖高脂饮食喂养12周的大鼠体重、空腹血糖、血脂以及空腹血清胰岛素的水平均高于正常对照组(P＜0.01),IAI与正常对照组相比有显著性升高[(4.44±0.27)∶(5.45±0.51),P＜0.05],血清瘦素和TNF-α与正常对照组相比也有明显升高[(0.15±0.05)∶(0.41±0.23),P＜0.01].结论高糖高脂饮食可诱导大鼠代谢综合征模型的建立,IR与血清瘦素和TNF-α的关系密切,瘦素和TNF-α的水平升高可作为代谢综合征的临床特征之一,以此通过代谢综合征的发展情况预测心血管疾病的发生和发展.     

长期脂肪含量较高饲料喂养对大鼠胰岛素抵抗的影响

目的探讨脂肪含量较高饲料长期喂养对大鼠胰岛素抵抗的影响。方法大鼠随机分为两组,对照组以普通饲料喂养16 w,高脂组以脂肪热量比38.5%的饲料喂养12 w,再以脂肪热量比51.3%的饲料喂养4 w。实验结束时,测定空腹血糖(FBG)、空腹血浆胰岛素(FINS)并计算胰岛素敏感指数(ISI)和胰岛素抵抗指数(HOMA-IR);另外进行口服葡萄糖耐量试验(OGTT),计算血糖曲线下面积(AUC)。结果两组大鼠能量摄取相似,体重差别不大。高脂组大鼠FINS显著高于对照组(P<0.01),但FBG无显著差别。高脂组大鼠ISI显著下降(P<0.01),HOMA-IR显著上升(P<0.01),血糖AUC显著升高(P<0.01)。结论脂肪含量较高的饲料喂养大鼠16 w后引起了胰岛素抵抗和糖耐量异常。     

宫内发育迟缓大鼠第36周胰岛素合成相关基因的表达

目的研究宫内发育迟缓（IUGR）大鼠第36周胰腺组织中胰岛素合成相关基因表达的变化。方法将20只体重250-270g的8-10周健康雌性SD大鼠,饲养于无特定病原体（SPF）级动物房,适应性饲养2周后将雌雄鼠合笼,以发现阴栓当天记为雌鼠受孕第1天,雌鼠受孕后随机数字表法分为造模组（n=10）和对照组（n=10）。采用孕中晚期热量限制的方法建立IUGR大鼠模型。造模组孕鼠自妊娠11d起给予对照组总热量50％饲料,新生鼠出生体重低于对照组新生鼠平均体重2个标准差者人选为IUGR组;对照组新生鼠即为正常组,对照组孕鼠自由进食。两组每窝各保留8只新生鼠继续饲养,仔鼠21d断奶后以标准饲料喂养至36周。选取第36周（中老年阶段）雄鼠为研究对象,实施腹腔葡萄糖耐量及胰岛素释放试验,运用逆转录聚合酶链反应（RT-PCR）方法检测胰腺组织中胰岛素合成相关基因[胰岛素基因1（Insulinl）、胰岛素基因2（Insulin2）以及胰-十二指肠同源盒基因-1（PDX-I）]的表达情况。两组间比较采用t检验分析。结果第36周,IUGR组大鼠胰重及胰重／体重比值明显低于正常组[分别为（4971±525）比（5844±398）mg和（0．58±0．05）％比（0．69±0．04）％,t=-2．65、-3．39,均P〈0．05]。糖负荷后各时点（30、60、120、180min）血糖值IUGR组均明显高于正常组[分别为30min：（17．9±1．5）比（16．1±1．1）mmol／L,60min：（13．4±1．1）比（11．7±1．4）mmol／L,120min：（10．1±0．8）比（8．6±1．0）mmol／L,180min：（8．9±1．0）比（7．6±0．9）mmol／L,t=2．31、2．37、2．77、2．34,均P〈0．05];糖负荷后各时点胰岛素分泌水平两组大鼠差异无统计学意义（t=1．66、-0．10、-0．65、-0．83、-0．58,均P〉0．05）。IUGR组大鼠胰腺组织中Insulinl基因表达较正常组明显减少（0．79±0．17比1．25±0．28,t=-2．78,P〈0．05）,而Insulin2、PDX-1基因表达差异均无统计学意义（t=-1．65、-1．46,均P〉0．05）。结论IUGR大鼠第36周糖耐量减退,胰腺组织中Insulinl基因表达下调。     

胰岛素抵抗大鼠视黄醇结合蛋白4骨骼肌磷脂酰肌醇3激酶的表达及吡格列酮的干预作用

目的 观察胰岛素抵抗(IR)大鼠体内视黄醇结合蛋白4(RBP4)、骨骼肌磷脂酰肌醇3激酶( P13K)和晚期氧化蛋白产物(AOPP)的水平,以及给予吡格列酮干预后其活性的变化,探讨RBP4与IR的关系及其可能的机制。 方法 将SPF级雄性Wistar大鼠35只随机分为2组,正常对照组（对照组）11只,饲以普通饲料;模型组24只,饲以高糖高脂饲料。模型组造模成功后再随机分为2个亚组,IR组和IR+吡格列酮干预组（干预组）,每组12只;IR组和干预组继续饲以高糖高脂饲料,干预组大鼠同时给予吡格列酮20mg·kg 1·d-1灌胃,持续8周。第16周末处死大鼠取血检测三酰甘油(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)及空腹血糖(FBG)、空腹胰岛素(FINS),计算胰岛素抵抗指数(HOME-IR);酶联免疫吸附法(ELISA)检测血清RBP4水平,RT-PCR测定附睾脂肪组织RBP4表达;免疫组织化学染色检测骨骼肌PI3K水平;紫外分光光度计法测定AOPP水平;并取大鼠腹腔内肠系膜、附睾、腹膜反折处的脂肪组织称质量,计算腹部脂肪含量与体质量的比值。 结果 (1)IR组大鼠体质量16周后明显增加,TG、LDL-C、FINS以及脂体比较对照组均明显升高,而HDL-C则明显降低;吡格列酮干预后,干预组体质量、TG、LDL-C、FINS以及脂体比较IR组有明显下降,HDL-C明显升高;(2)IR组大鼠血清及附睾脂肪组织RBP4水平和血清AOPP水平明显高于对照组,干预组水平明显降低;(3)IR组大鼠骨骼肌组织PI3K表达水平明显低于对照组,吡格列酮干预其表达水平升高;(4)相关分析表明大鼠血清RBP4与FINS、脂体比、LDL-C呈正相关;与HDL-C、骨骼肌组织PI3K水平呈负相关。 结论 (1)IR大鼠RBP4、AOPP水平升高,RBP4是致IR的脂肪细胞因子,并可引起机体脂代谢紊乱及氧化应激增强;(2)RBP4降低大鼠胰岛素敏感性可能与其削弱胰岛素信号转导作用有关;(3)吡格列酮可降低IR大鼠RBP4及血清AOPP水平,增加骨骼肌PI3K表达,从而提高机体对胰岛素的敏感性。     

替米沙坦上调胰岛素抵抗大鼠心肌脂联素及其受体的表达

目的:探讨胰岛素抵抗(IR)大鼠心肌脂联素(APN)及其受体(AdipoRI和AdipoR2)表达改变和替米沙坦(TMST)的影响.方法:雄性SD大鼠50只随机选择10只作为对照组(用普通饲料喂养8周),其余40只大鼠用高果糖饮食喂养4周建立IR模型.从IR大鼠中随机选择10只作为IR组(用生理盐水灌胃4周,继续用高果...     

高脂喂养的胰岛素抵抗大鼠骨骼肌蛋白激酶B mRNA表达的改变

目的研究高脂饮食喂养的胰岛素抵抗(IR)大鼠胰岛素敏感性及骨骼肌中蛋白激酶B(PKB)mRNA表达改变。方法 70只大鼠随机分为正常对照组和高脂饮食组,高脂饮食组采用高脂喂养的方法建立IR大鼠模型,用高胰岛素-正常葡萄糖钳夹实验测定葡萄糖输注率(GIR),同时测定各组大鼠空腹血糖(FPG)、空腹胰岛素(FINS)等指标的水平,实时荧光定量RT-PCR测定大鼠骨骼肌PKB mRNA表达。结果①高脂喂养4 w后,高脂组FPG、FINS、胰岛素抵抗指数(HOMA-IR)均较正常对照组显著升高,而胰岛素敏感指数(ISI)下降(P<0.05),GIR显著低于正常对照组(P<0.01),说明高脂组存在IR,IR模型制造成功。②与正常对照组相比高脂组PKB mRNA表达明显减弱(P<0.05)。结论高脂饮食喂养的IR大鼠IR的产生与骨骼肌胰岛素刺激PKB表达明显降低有关。     

Development of high fat diet-induced obesity and leptin resistance in C57Bl/6J mice

OBJECTIVE: To investigate the development of high fat diet-induced obesity and leptin resistance. DESIGN: Two experiments were carried out in this study. Firstly, we fed the mice with a high- or low-fat diet for up to 19 weeks to examine a progressive development of high fat diet-induced obesity. Secondly, we examined peripheral and central exogenous leptin sensitivity in mice fed high- or low-fat diets for 1, 8 or 19 weeks. SUBJECTS: A total of 168 C57BL/6J mice (3 weeks old) were used in this study. MEASUREMENTS: In the first experiment, we measured the body weight, energy intake, adipose tissue mass, tibia bone length, and plasma leptin in mice fed either a high- or low-fat diet for 1, 8, 15 and 19 weeks. In the second experiment, body weight change and cumulative energy intake were measured at 6 h intervals for 72 h after leptin injection in mice fed a high- or low-fat diet for 1, 8 or 19 weeks. RESULTS: The results from the first experiment suggested that the development of high fat diet-induced obesity in mice could be divided into early, middle and late stages. Compared with the mice fed a low-fat diet, the mice fed a high-fat diet showed a gradually increased body weight (+5.2%), fat storage (epididymal plus perirenal; +6.7%) and plasma leptin (+18%) at 1 week; +11.4%, +68.1%, and +223%, respectively, at 8 weeks; and +30.5%, +141%, and +458%, respectively, at 19 weeks. Energy intake of high fat diet-fed mice was equal to that of low fat diet-fed controls for the first 3 weeks; it fell below control levels over the next 5 week period, but began to increase gradually after 8 weeks of high-fat diet feeding and then increased dramatically from 15 weeks to be 14% higher than that of controls after 19 weeks. The results from our second experiment showed that: (1) after 1 week of feeding, the mice fed a high-fat diet were sensitive to a 2 microg/g (body weight) intraperitoneal (i. p.) injection of leptin, with no differences in body weight change or cumulative energy intake post-injection; (2) after 8 weeks of feeding, the mice fed a high-fat diet were insensitive to 2 microg/g (body weight) i.p. leptin, but were sensitive to a 0.1 microg intracerebroventricular (i.c.v.) injection of leptin; (3) after 19 weeks of feeding, the mice fed a high-fat diet were insensitive to 0. 1 microg i.c.v. leptin, but were sensitive to a high dose of 2 microg i.c.v. leptin. CONCLUSIONS: The present study demonstrated that the development of high fat diet-induced obesity (19 weeks) in C57 B1/6J mice could be divided into three stages: (1) an early stage in response to high-fat diet that mice were sensitive to exogenous leptin; (2) a reduced food intake stage when mice had an increase in leptin production and still retained central leptin sensitivity; and (3) an increased food intake stage, accompanied by a reduction of central leptin sensitivity.     

Augmenting leptin circadian rhythm following a weight reduction in diet-induced obese rats: short- and long-term effects

The current study sought to examine whether leptin injections following a weight reduction in diet-induced obese rats would reduce both the enhanced food intake and body weight (BW) regain observed during the refeeding phase. Female Wistar rats (n = 100, 20 per group) were divided into 5 groups: (1) LEP rats were fed a high-fat (HF) diet (35% wt/wt) for 8 weeks to induce obesity and were then food-restricted (50% ad libitum) with a fortified high-fat diet for 2 weeks to induce a 20% BW loss. These rats were then refed the HF diet ad libtum for another 11 weeks. They were given leptin injections (200 microg/kg BW, twice daily, intraperitoneally ) for 19 days concomitant with the onset of refeeding. (2) SAL rats were treated in the same manner as LEP rats except that they were given saline injections; (3) PF rats were treated like SAL rats except that they were pair-fed with the LEP rats; (4) HFC rats were fed HF diet ad libitum; and (5) LFC rats were fed a low-fat (LF) diet (AIN-93M) ad libitum. Ten rats from each group were killed after leptin treatment and at the end of the study. Food and caloric intakes were monitored, and body composition and plasma glucose, insulin, and leptin levels were assessed at death. Leptin injections after a weight reduction briefly reduced energy intake during the first week only. After 19 days of treatment and to the end of the study, LEP and SAL rats were similar in energy intake, BW (LEP: 393 +/- 11.2 g, SAL: 371 +/- 14.1; difference not significant [NS]) and total body fat percent (LEP: 19.3 +/- 1.5, SAL: 17.6 +/- 1.5; NS). Leptin treatment induced hyperinsulinemia and insulin resistance. All of the metabolic abnormalities observed at the end of treatment period disappeared at the end of the study (8 weeks post-leptin injection). We conclude that bolus leptin injections to manipulate leptin circadian rhythm in diet-induced obese rats after a weight reduction caused temporary insulin resistance and hyperinsulinemia, and were ineffective in influencing food intake, BW, and fat content. Leptin resistance was evident following 1 week of treatment in this study. Leptin treatment had no effect on body fat content both short-term and long-term. Exogenous leptin treatment may, in the long run, increase leptin resistance in diet-induced obese animals. Hence, long-term leptin treatment may not be beneficial to obese individuals consuming a HF diet.     

High serum leptin concentrations during catch-up growth of children born with intrauterine growth retardation.

The aim of the study was to investigate how leptin could be involved in catch-up growth of children born with intrauterine growth retardation (IUGR). The study population was made up of 70 newborns with IUGR longitudinally studied during the first 2 yr of life and 35 newborns and 32, 66, and 61 children with normal birth weight aged 3 days, 12 months, and 24 months, respectively. Postnatal patterns of body mass index (BMI) were similar in the 2 groups, but BMI remained significantly lower in IUGR over the study period. In contrast, children born with IUGR aged 1 yr had significantly higher serum leptin levels than normal children (P < 0.0001) independently of BMI. The correlation observed between BMI and serum leptin at birth in both groups and in the control group thereafter disappeared in children born with IUGR. Similarly, sexual dimorphism observed in normal children over the study period was not observed in the IUGR group during the first 2 yr of life. In summary, serum leptin is effective and regulated during the first years of life as it is in older children. Children born with IUGR demonstrate high serum leptin values during the first year of life, with a loss of the regulatory effect of BMI and gender. We suggest that these children develop an adaptative leptin resistance beneficial for their catch-up growth. An alternative hypothesis is that these observations could reflect an adipocyte dysfunction, a consequence of the special time course of adipose tissue development in children born with IUGR.     

Characterization of the resistance to the anorectic and endocrine effects of leptin in obesity-prone and obesity-resistant rats fed a high-fat diet

Leptin produced by adipocytes controls body weight by restraining food intake and enhancing energy expenditure at the hypothalamic level. The diet-induced increase in fat mass is associated with the presence of elevated circulating leptin levels, suggesting the development of resistance to its anorectic effect. Rats, like humans, show different susceptibility to diet-induced obesity. The aim of the present study was to compare the degree of leptin resistance in obesity-prone (OP) vs obesity-resistant (OR) rats on a moderate high-fat (HF) diet and to establish if the effects of leptin on hypothalamo-pituitary endocrine functions were preserved. Starting from 6 weeks after birth, male Sprague-Dawley rats were fed on either a commercial HF diet (fat content: 20% of total calorie intake) or a standard pellet chow (CONT diet, fat content: 3%). After 12 weeks of diet, rats fed on HF diet were significantly heavier than rats fed on CONT diet. Animals fed on HF diet were ranked according to body weight; the two tails of the distribution were called OP and OR rats respectively. A polyethylene cannula was implanted into the right ventricle of rats 1 week before central leptin administration. After 12 weeks of HF feeding, both OR and OP rats were resistant to central leptin administration (10 mug, i.c.v.) (24 h calorie intake as a percent of vehicle-treated rats: CONT rats, 62 [50; 78]; OR, 93 [66; 118]; OP, 90 [70; 120] as medians and 95% confidence intervals (CIs) of six rats for each group). Conversely, after 32 weeks of diet both OR and OP rats were partially responsive to 10 mug leptin i.c.v. as compared with CONT rats (24 h calorie intake as a percent of vehicle-treated rats: CONT rats, 60 [50; 67]; OR, 65 [50; 80]; OP, 80 [60; 98] as medians and 95% CIs of six rats for each group); the decrease of food intake following 200 mug leptin i.p. administration was similar in all the three groups (calorie intake as a percent of vehicle-treated rats: 86 [80; 92] as median and 95% CI). The long-term intake of HF diet caused hyperleptinemia, hyperinsulinemia and higher plasma glucose levels in OP rats as compared with CONT rats. Plasma thyroxine (T4) was lower in all the rats fed the HF diet as compared with CONT. i.c.v. administration of leptin after 32 weeks of diet restored normal insulin levels in OP rats. Moreover, leptin increased plasma T4 concentration and strongly enhanced GH mRNA expression in the pituitary of OP as well as OR rats (180+/-10% vs vehicle-treated rats). In conclusion, long-term intake of HF diet induced a partial central resistance to the anorectic effect of leptin in both lean and fat animals; the neuroendocrine effects of leptin on T4 and GH were preserved.     

The effect of high-fat and high-fructose diets on glucose tolerance and plasma lipid and leptin levels in rats

Aim: High‐fat and high‐fructose diets are usually used to induce animal model diabetes mellitus. The purposes of this research were to compare the abnormalities of glucose metabolism caused by high‐fructose diet and a high‐fat diet and the effects of the high‐fructose diet and high‐fat diet on plasma leptin. Methods: In this research, 24 Sprague–Dawley rats were used as the experimental animals, which were divided into three groups: chow diet (control group), high‐fructose diet (60% fructose w/w) and high‐fat diet (20% lard w/w). They were fed for a period of 8 weeks, during which an oral glucose tolerance test was conducted in the seventh week, and after completion of the eighth week, the abdominal adipose tissue and liver of the rats were excised and weighed, and the plasma cholesterol, triglyceride, insulin and leptin concentrations were assayed. Results: The high‐fat diet group presented a fasting blood glucose concentration that was higher than that of the control group. Furthermore, after 2 h of glucose challenge, the rats in the high‐fat and high‐fructose diet groups all presented higher plasma glucose concentrations than did the control group. The high‐fat diet group showed higher body weight, higher relative liver weight, a higher plasma cholesterol concentration and higher amylase activity than did the other groups, whereas the high‐fructose diet group showed higher fasting insulin and triglyceride concentrations. As for adipose tissue, the high‐fat diet group presented an amount that was higher than that of the high‐fructose and control groups, but the plasma leptin concentration of the high‐fructose group was higher than that of the control group. Conclusions: It can be concluded from the above‐mentioned experimental results that a high‐fructose diet can cause hyperinsulinaemia, while a high‐fat diet can result in impaired pancreatic function of insulin secretion and glucose intolerance, indicating that high‐fructose diet and a high‐fat diet may exert divergent effects on glucose metabolism in rats.     

Determinants of fetal leptin synthesis,fat mass,and circulating leptin concentrations in well-nourished ewes in late pregnancy

We have investigated the factors regulating leptin synthesis, fat deposition, and circulating leptin concentrations in fetuses of well nourished ewes in late pregnancy. Vascular catheters were surgically inserted in 17 pregnant ewes and their fetuses at 103-120 d gestation (term = 147 +/- 3 d). Ewes were fed a diet providing either 100% (control; n = 9) or approximately 155% (well fed; n = 8) of the maintenance energy requirements and fetal perirenal and interscapular fat depots were collected at 139-141 d gestation. There was a significant relationship between the relative mass of fetal unilocular fat and fetal glucose (relative mass of unilocular fat, 1.14; fetal glucose, +0.16; r = 0.50; P < 0.04; n = 17), but not insulin, concentrations in the control and well-fed groups. In contrast to the controls, there was a positive relationship between the relative abundance of leptin mRNA and fetal insulin, but not glucose, concentrations in fetal perirenal adipose tissue in the well-fed group. A moderate increase in maternal nutrition also resulted in a strong reciprocal relationship between uncoupling protein 1 and leptin expression in fetal perirenal adipose tissue in late gestation (well-fed group: uncoupling protein 1 mRNA:18S rRNA, -0.51; leptin mRNA:beta-actin mRNA, +1.53; r = 0.80; P < 0.02; n = 8). These studies provide evidence that fetal glucose and insulin differentially regulate fetal fat deposition and leptin mRNA expression within the fetal perirenal fat depot in the well nourished animal during late gestation.     

Nutritional effects on the lifespan of Syrian hamsters

Syrian hamsters were fed one of nine semipurified diets composed of three casein levels (9, 18, and 36 g/385 Kcal), with each of three corn oil levels (4.5, 9.0, and 18.0 g/385 Kcal). These diets were given either for five weeks and were followed by control diet (18 g casein and 9 g corn oil/385 Kcal) or control diet was fed for the first five weeks and was followed by the nine diets. Calorie consumption, maximum body weight and length of growth period and of life are reported. Calorie consumption was directly related to dietary fat levels. Maximum body weights increased with increasing dietary fat and protein when the various diets were fed during weeks 1–5. This result was not due to a conditioning of the animals fed high-fat or high-protein levels during weeks 1–5 to consume more calories after week 5, since after this time consumption was the same in all groups fed the control diet. When diets were fed from week 6 body weight increased in both sexes with increased dietary fat; however, higher dietary protein increased female and decreased male maximum body weight. Males took longer to reach these maximum weights than females, and were not affected by receiving the various diets during weeks 1–5. However, when diets were fed from week 6 until death, the growth period increased with higher dietary fat or protein. Male hamsters survived longer than females with each experimental treatment. Animals fed low-fat, low-protein diet or high-fat, high-protein diet during the first 5 weeks of the study survived longest. When diets were fed from 6 weeks until death, survival increased as dietary fat rose for both sexes. In contrast, survival improved as dietary protein rose for females or decreased for males. These studies establish a basis for further investigations on the link between nutrition and longevity in the Syrian hamster.     

胰岛素抵抗大鼠肝脏SREBP-1c mRNA表达及罗格列酮的干预作用

目的 探讨固醇调控元件结合蛋白-1c（SREBP-1c）在胰岛素抵抗（IR）发病中的作用及罗格列酮（RSG）的干预机制.方法 将27只大鼠适应性喂养1周后随机分为对照组、模型组及观察组各9只,模型组及观察组均予高脂饲料喂养8周建立IR模型,对照组予普通饲料喂养8周;其后观察组予RSG 3 mg/（kg·d）＋生理盐水至2 ml灌胃,模型组和对照组均予2 ml生理盐水灌胃.三组均同前喂养6周后取静脉血测定空腹胰岛素、空腹血糖、TG、游离脂肪酸（FFA）、TNF-α、瘦素,计算胰岛素敏感指数（ISI）;处死动物后测定体脂比,取肝脏组织采用RT-PCR法检测SREBP-1c mRNA表达.同时对相关指标进行Pearson相关分析.结果 SREBP-1c mRNA表达水平观察组为0.75±0.06、模型组为0.92±0.05、对照组为0.72±0.03,观察组及对照组均显著低于模型组,P均〈0.01.Pearson相关分析显示,SREBP-1c mRNA与TG（r=0.802,P〈0.01）、FFA（r=0.666,P〈0.01）、TNF-α（r=0.749,P〈0.01）、瘦素（r=0.708,P〈0.01）、体脂比（r=0.495,P〈0.01）均呈明显正相关,与ISI（r=-0.677,P〈0.01）呈负相关.结论 SREBP-1c mRNA过表达与IR发生有关,RSG可能通过降低SREBP-1c mRNA表达改善IR和脂代谢紊乱;此为IR及相关疾病的治疗提供了新的靶点.     

The effects of a new soluble dietary fiber on weight gain and selected blood parameters in rats

This study was designed to investigate a new dietary fiber, alpha-cyclodextrin, marketed under the trade name FBCx (Wacker Biochem, Adrian, MI), for beneficial effects on weight reduction and the improvement of certain blood parameters in rats. Male Wistar rats were divided into 4 groups and fed ad libitum for a period of 6 weeks: (1) a normal low-fat diet (LF; 4% fat wt/wt); (2) an LF diet with FBCx added; (3) a high-fat diet (HF, 40% fat wt/wt); and (4) an HF diet with FBCx. The FBCx was added at the rate of 10% (wt/wt) of the fat in the diet. Body weight and food intake were recorded 3 times per week. Plasma constituent levels and liver and fecal lipid contents, as well as body composition were determined at sacrifice. Adding FBCx to the diet significantly reduced weight gain in rats fed with an HF diet relative to rats fed with the HF control diet (P < .05). FBCx also elicited a reduction in plasma triglyceride levels of 30%, total cholesterol of 9%, and increased the fat content of the feces in the rats fed with the HF diet with FBCx. In addition, the serum leptin levels were normalized, and the calculated insulin sensitivity was improved. No adverse effects were observed in the rats consuming FBCx. It would appear that FBCx might be effective in reducing body weight gain and improving metabolic syndrome.