Effect of early nutrition on intestine development of intrauterine growth retardation in rats and its correlation to leptin

AIM: To investigate the intestine and body development of intrauterine growth retardation (IUGR) rats under early different protein diet and to analyze the correlation between leptin and intestine and body development. METHODS: An IUGR rat model was established by food restriction of pregnant female rats. Fifty-six neonatal IUGR rats and 24 neonatal normal rats were randomly divided into normal control group (C group), IUGR model group (SC group), low protein diet IUGR group (SL group), and high protein diet IUGR group (SH group). Eight rats were killed per group at wk 0, 4, and 12. Serum leptin, body weight (BW), body length (BL), intestinal weight (IW), intestinal length (IL), and intestinal disaccharidase (including lactase, maltase, and saccharase) were detected. RESULTS: BW (4.50±0.41 g), BL (5.96±0.40 cm), IW (0.05±0.01 g), and IL (15.9±2.8 cm) in neonatal IUGR rats were much lower than those in C group (6.01±0.55 g, 6.26±0.44 cm, 0.10±0.02 g, 21.8±2.7 cm, P<0.05), while intestinal lactase and maltase activities were higher than those in C group. SH group showed the fastest catch up growth and their BW, BL, IW, and IL reached the C group level at wk 4. SC group showed relatively slower catch up growth than SH group, and their BW, BL, IW did not reach the C group level at wk 4. SL group did not show intestine and body catch up growth. Intestinal maltase [344±33 μmol/(min·g)] and saccharase activities [138±32 μmol/(min·g)] in SL group were both markedly lower than those in C group [751±102, 258±27 μmol/(min·g), P<0.05]. There were no significant differences in lactase activities at wk 4 and disaccharidase activities at wk 12 among all groups (P>0.05). The leptin level in SL. group (0.58±0.12 ng/mL) was the highest in all groups, and much lower in SH group (0.21±0.03 ng/mL) than that in any other IUGR groups at wk 4 (P<0.05). Leptin was negatively related to BW (r=-0.556, P= 0.001), IW (r=-0.692, P=0.001) and IL (r=-0.738, P= 0.000) at wk 4, while no correlation was found at wk 12. CONCLUSION: High protein diet is a reasonable early nutritional mode to IUGR rats in promoting intestine and body catch up growth.     

Leptin inhibition of insulin secretion from isolated human islets

Leptin is a hormone produced and secreted from the adipose tissue. Its physiological actions include the regulation of satiety, food intake and energy balance. The production of leptin is increased by high insulin levels. Here, we demonstrate that leptin acts as an inhibitor of glucose-induced (20 mM) insulin secretion from isolated human islets. No effect was observed in the presence of lower glucose levels (2.8 and 10 mM glucose). The pancreatic β-cell might represent a target of a direct physiological action of leptin. We suggest the presence of an “adipo-insular axis” in which leptin mediates negative feedback from the adipose tissue to the endocrine pancreas. Received: 21 July 1997 / Accepted in revised form: 1 October 1997     

口服糖耐量试验中血糖和胰岛素动态变化对瘦素的影响

目的　利用口服葡萄糖耐量试验（ＯＧＴＴ）中体内血糖和胰岛素浓度的改变,探讨血糖和胰岛素对瘦素可能存在的即时和短时效应。方法　５０ 例Ⅱ型糖尿病和５０ 例非糖尿病个体（ 年龄、性别和体重指数相匹配）做ＯＧＴＴ,测定０、３０、６０、１２０、１８０ 分钟时相的血浆葡萄糖、血清胰岛素和瘦素水平。结果　糖尿病组空腹血清瘦素水平男性为（３．８８ ±０．６４） μｇ／Ｌ,女性为（８．３０ ±１．０６） μｇ／Ｌ ;非糖尿病组男性为（５ ．０１ ±０．６４） μｇ／Ｌ,女性为（１０．４８±１．３０） μｇ／Ｌ ,两组差别无显著性。与非糖尿病组相比,糖尿病组ＯＧＴＴ血糖升高明显,而胰岛素释放曲线呈反应低平,高峰不明显或延迟相。瘦素释放曲线两组均呈下降趋势,糖尿病组这种趋势更为明显。结论　血瘦素水平未曾随着胰岛素浓度的升高而升高,相反表现为昼夜节律性的下降,提示胰岛素促瘦素分泌的效应相对较弱,未能影响瘦素白天下降的趋势。     

血清可溶性肿瘤坏死因子受体与胰岛素抵抗的关系

目的　了解血清可溶性肿瘤坏死因子受体 (STNFR) 1,2与胰岛素抵抗 (IR)的关系。方法　测定 43名男性和 41名绝经期前女性的STNFR1,2。以稳态模型 (HomaModel)公式评估IR。结果　肥胖男、女组STNFR1与非肥胖男、女组相近 ,而其STNFR2高于非肥胖男、女组 ,差异有显著性 (P <0 .0 5 )。所有男性STNFR1和STNFR2水平高于女性 (P <0 .0 1)。所有对象相关分析示STNFR2与臀腰比 (WHR)、空腹血糖、体重指数 (BMI)、HomaIR、空腹胰岛素正相关。STNFR1与上述指标无相关性。在男性中 ,STNFR2与瘦素正相关 (r =0 .34 ,P <0 .0 5 ) ,调整BMI、WHR影响后 ,STNFR2仍与瘦素正相关 (r=0 .30 ,P <0 .0 5 )。逐步回归分析示WHR和STNFR2对HomaIR的影响达 41.3%。结论　STNFR2与IR相关 ,在人类TNF系统对IR的影响可能主要通过TNFR2起作用。     

男性乙型肝炎肝硬化患者血清瘦素及血脂水平的研究

目的检测男性乙型肝炎肝硬化患者血清瘦素及血脂水平，探讨其异常变化的临床意义。方法男性乙型肝炎肝硬化患者64例，男性健康受试者28名，用ELISA法检测血清瘦素水平，用全自动生化分析仪检测肝功能和血脂。对血清瘦素、血脂与肝功能的关系进行分析。结果各组乙型肝炎肝硬化Child-Pugh分级患者与对照组比，血清瘦素水平无显著性差异（P〉0．05）；与正常对照组比，乙型肝炎肝硬化患者血CHO和LDL水平显著降低（P〈0．01），按Child分级由A到C级各组CHO和LDL水平逐渐降低，差异有显著性（P〈0．01）。无腹水肝硬化患者血清瘦素水平与BMI及Fat％均呈显著正相关。结论血清瘦素水平不能作为评价男性乙型肝炎肝硬化患者病情严重程度的指标，血清胆固醇、低密度脂蛋白是肝功能减退的指标。瘦素可能参与了男性乙型肝炎肝硬化患者的营养不良。     

Promoter Methylation of LEP and LEPR before and after Bariatric Surgery: A Cross-Sectional Study

IntroductionDNA methylation constitutes one important epigenetic mechanism that regulates gene expression in human cells. With regard to obesity, bariatric surgery-induced weight loss has been associated with promoter methylation changes in several genes. Hyperleptinemia is a characteristic feature of obesity. The underlying regulating mechanisms have not yet been completely elucidated.MethodsWe investigated the methylation of the promoters of the leptin gene (LEP) and the leptin receptor gene (LEPR) as well as leptin expression in pre- and postbariatric surgery patients using a comparative cross-sectional design.ResultsOur results revealed significantly higher LEP promoter methylation patterns in prebariatric surgery patients compared to postoperatively. DNA methylation of the LEPR promoter was significantly higher in the postoperative group. Moreover, we found significantly higher leptin serum levels in patients before the bariatric surgery than afterwards.DiscussionThese findings strengthen the suggestion that there is an association between LEP expression and LEP methylation in obesity. We suggest that the epigenetic profile of LEP might be influenced by leptin serum levels in the form of a regulating feedback mechanism.     

KIF1B在瘦素促进妊娠早期绒毛滋养细胞MMP-2表达中的作用

 目的 观察瘦素对妊娠早期绒毛滋养细胞基质金属蛋白酶2（MMP-2）表达的影响,探讨驱动蛋白家族成员1B（KIF1B）在瘦素对MMP-2调控中的作用。方法 正常妊娠妇女人工流产绒毛组织（6~9周）,按常规分离获得滋养细胞,分为对照组、leptin（100 和500 μg/L）刺激组以及KIF1B-siRNA、leptin（100 和500 μg/L）分别+KIF1B-siRNA组,24 h后,明胶酶谱检测上清MMP-2的表达,RT-PCR检测MMP-2 mRNA、瘦素长型受体（OB-Rl）mRNA及KIF1B mRNA表达,Western blot检测KIF1B蛋白表达。结果 与对照组相比,瘦素（100 和500 μg/L）显著促进滋养细胞MMP-2表达（100 μg/L: mRNA水平由0.11±0.02增至0.18±0.05,P<0.05）;瘦素以剂量依赖方式促进OB-Rl及KIF1B表达（P<0.05）;KIF1B-siRNA部分抑制瘦素对MMP-2分泌的促进作用。结论 瘦素可能通过leptin R-KIF1B途径促进MMP-2分泌,从而促进妊娠早期滋养细胞侵袭,为阐明滋养细胞侵袭调控机制提供了新的基础数据。     

慢性胆囊炎患者血清瘦素及可溶性瘦素受体与血脂水平的变化及关系

目的:探讨慢性胆囊炎患者血清瘦素(Lep)、可溶性瘦素受体(s LR)与血脂水平的变化及其相互关系。方法:选择103例慢性胆囊炎患者,以91例健康体检者为对照,测定所有受试者空腹血清Lep、s LR、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL),分析慢性胆囊炎患者血清Lep、s LR水平与血脂水平的关系。结果:与对照组比较,慢性胆囊炎组患者血清TC、LDL和Lep水平均明显升高,而s LR水平明显降低(均P0.05)。单因素分析显示,Lep水平与TC、TG和HDL水平呈明显正相关(均P0.05),而s LR水平与各血脂指标无明显相关性(均P0.05);多元回归分析显示,Lep水平与TC水平呈明显正相关(P0.05)。结论:慢性胆囊炎患者血清Lep明显升高、s LR水平降低以及血脂代谢紊乱,其中,Lep升高所致胆固醇代谢障碍可能是主要原因。     

瘦素、脂肪酸对大鼠胰岛细胞解偶联蛋白2 mRNA表达的影响

以瘦素、脂肪酸作用于体外培养的大鼠胰岛细胞，以甘油三酯含量，解偶联蛋白2 mRNA表达水平为指标，显示瘦素通过外周途径调节产热，脂肪酸可损害胰岛功能。