胆汁酸对代谢性疾病的调控

胆汁酸作为一种信号分子通过激活肝、肠道和外周组织中的胆汁酸受体影响体内葡萄糖和脂质的代谢平衡,对于调节肥胖、2型糖尿病和非酒精性脂肪肝等代谢性疾病具有非常重要的意义。胆汁酸与相应核受体,如法尼醇X受体(farnesoid X receptor, FXR)和Takeda G蛋白偶联受体5 (Takeda G protein-coupled receptor 5,TGR5)的相互作用影响了这些代谢性疾病。FXR主要通过影响胆汁酸的合成及转运对非酒精性脂肪肝发挥作用,TGR5则是间接增加褐色脂肪组织中的生热作用,改善肥胖和2型糖尿病。这些调控机制的研究是非常必要的。本文综述了胆汁酸代谢及其对代谢性疾病调控的分子机制的研究进展,以期为科研工作者提供一定的参考。     

自噬与代谢及代谢性疾病

细胞自噬是真核生物中一种高度保守的代谢过程,可以清除受损的细胞器,降解糖原、脂类、蛋白质等生物大分子物质供细胞重新利用,对维持细胞内代谢平衡有重要意义。自噬障碍常被发现与代谢性疾病相关,如酸性麦芽糖酶缺乏症、肥胖和神经退行性疾病等。该文就近年来关于自噬与代谢及代谢性疾病的研究作一综述。     

溶血磷脂酰胆碱在肥胖相关代谢性疾病中的研究进展

溶血磷脂酰胆碱(lysophosphatidylcholines, LPCs)是人体丰度最高的溶血甘油磷脂,可直接作用于靶蛋白,或转换为其他磷脂,在神经系统和周围代谢器官中发挥重要的生理功能.临床研究表明,肥胖、糖尿病、非酒精性脂肪肝病患者血液中多种LPCs浓度下降,且LPCs浓度与身体测量指标及血液检测指标存在相关性,可有效鉴别肥胖及其相关代谢性疾病,预测疾病严重程度,具有潜在的生物标记物功能. LPCs还具有改善肥胖表型、缓解炎症、抑制脂肪从头合成的作用.本文将系统整理LPCs的基本代谢和生理功能,深入探究LPCs在肥胖相关代谢性疾病中的浓度变化和生物学作用,为肥胖及相关代谢性疾病的诊疗提供新思路.     

运动调控FGF21在改善肥胖相关代谢性疾病中的作用

肥胖是糖尿病、脂肪肝、心血管疾病等慢性代谢性疾病发生发展的重要风险因素。运动可以改善肥胖,对相关代谢性疾病的预防与康复具有积极作用。成纤维细胞生长因子21 (fibroblast growth factor 21,FGF21)是一种对机体能量稳态、糖脂代谢有积极调控作用的内分泌因子,是代谢性疾病预防和治疗的有效靶点之一。FGF21抵抗是机体对FGF21反应性减弱的现象,表现为靶组织生物学效应降低,机体FGF21代偿性合成增加。这可能是由FGF21受体(fibroblast growth factor receptors,FGFRs)和β-klotho蛋白(β-klotho,KLB)表达减少或敏感性降低所致。肥胖患者常出现FGF21抵抗,改善FGF21抵抗是治疗肥胖及相关代谢性疾病的新思路。运动不仅可以增加部分组织FGF21表达量,还可以刺激FGFRs与KLB的表达来敏化FGF21的作用,改善FGF21抵抗。     

阻塞型睡眠呼吸暂停低通气综合征与代谢综合征组分关系探讨

目的：探讨阻塞型睡眠呼吸暂停低通气综合征（OSAHS）与代谢综合征（MS）组分关系。方法：对我院2003年1月至2010年7月39例诊断为0SAHS住院患者进行回顾性调查,30例同期住院病人为对照组,均记录年龄、性别,测量身高、体重、血压,检测空腹血糖、血脂,分析OSAHS患者合并MS组分情况。结果：1．OSAHS组与对照组比较,体重指数（BMI）、血压、血清甘油三酯、总胆固醇、低密度脂蛋白胆固醇、载脂蛋白Al升高,高密度脂蛋白胆固醇降低（P〈0．05）;2．OSAHS组与对照组相比较,无MS组分比例低于对照组,差异有统计学意义（P〈0．05）;3．OSAHS组与对照组相比较,OSAHS组合并MS组分,包括BMI〉25Kg／m2,血脂紊乱的比例,均高于对照组,差异有统计学意义（P〈0．05）。结论：OSAHS患者易合并代谢综合征组分。     

阻塞型睡眠呼吸暂停低通气综合征与代谢综合征组分关系探讨

目的:探讨阻塞型睡眠呼吸暂停低通气综合征(OSAHS)与代谢综合征(MS)组分关系。方法:对我院2003年1月至2010年7月39例诊断为OSAHS住院患者进行回顾性调查,30例同期住院病人为对照组,均记录年龄、性别,测量身高、体重、血压,检测空腹血糖、血脂,分析OSAHS患者合并MS组分情况。结果:1.OSAHS组与对照组比较,体重指数(BMI)、血压、血清甘油三酯、总胆固醇、低密度脂蛋白胆固醇、载脂蛋白A1升高,高密度脂蛋白胆固醇降低(P<0.05);2.OSAHS组与对照组相比较,无MS组分比例低于对照组,差异有统计学意义(P<0.05);3.OSAHS组与对照组相比较,OSAHS组合并MS组分,包括BMI≥25Kg/m2,血脂紊乱的比例,均高于对照组,差异有统计学意义(P<0.05)。结论:OSAHS患者易合并代谢综合征组分。     

慢性代谢性疾病的环境与遗传交互作用以及早期预防

随着我国经济的发展和营养与生活方式的迅速变迁,近年来我国居民肥胖、2型糖尿病等慢性代谢性疾病患病率激增,已成为影响国民健康最主要的威胁。有研究显示:与白种人相比,亚洲人具有较高的2型糖尿病遗传易感性,这可能与"代谢性肥胖"表型和遭遇营养转型中的"致肥胖环境"有关。大量的研究结果表明,此类慢性代谢性疾病是遗传和环境因素交互作用的结果。随着全基因组关联研究开展,目前已发现了20多个肥胖和2型糖尿病易感基因,不仅揭示了不同种族人群在基因结构和效应值方面存在着差异,但同时也发现遗传方面的差异仍无法完全解释东西方人在发病风险方面的不同。膳食、生活方式等环境因素仍被认为是2型糖尿病发病中的重要决定因素。在全基因组关联研究后时代,国际上的研究将更加强调基因—基因、基因—环境、基因—表型之间的交互作用对代谢性疾病的影响和相关的机制。事实上,有研究表明,各种基因多态性、炎性因子和脂肪细胞因子等都可能成为早期诊断的生物标记物,而通过改变膳食和生活方式则是目前国际公认的预防和控制慢性代谢性疾病最有效的方法。然而,我国尤为缺乏在大规模前瞻性流行病学研究中对导致慢性代谢性疾病流行的主要遗传和环境因素,以及基因—环境相互作用对健康的影响方面的系统的研究。而这类研究将为建立适用于中国人群遗传和表型特征的早期诊断生物标记物和有效预防干预策略奠定基础。     

代谢性疾病肠道菌群研究现状及其与中医诊疗关系的探讨

代谢性疾病的发生与肠道菌群有着密切的关系.当机体由于饮食、药物等因素引起肠道菌群紊乱时,会造成有益菌的减少和有害菌的增多,肠道菌群释放的炎性物质进入血液中,容易引发肥胖症和2型糖尿病等代谢性疾病.本文通过分析以往文献中肠道菌群在肥胖症、2型糖尿病以及非酒精性脂肪性肝病患者中的变化,以及中药或方剂对其干预后的菌群变化,为...     

FGF21与代谢性疾病防治及其运动干预

成纤维细胞生长因子21(fibroblast growth factor 21, FGF21)属于成纤维细胞生长因子家族FGF19(fibroblast growth factor 19, FGF19)的亚型,不具有促成纤维细胞生长活性,且不与肝素特异性结合,是一种调节机体代谢的分泌型蛋白。在骨骼肌、肾脏、心脏以及血管和脂肪组织中 fgf21 表达比肝脏中高约7~10倍。FGF21可靶向脑、心脏、骨骼肌以及肾脏和肠等多种组织器官发挥作用。近来证实,FGF21已广泛应用于肝脂、糖脂代谢以及心血管疾病等代谢性疾病的预防与康复,可能成为代谢性疾病预防和康复的有效靶点之一。急性运动后骨骼肌FGF21表达显著升高,耐力运动可改善FGF21对肝脏脂肪调节的抵抗,有氧运动和抗阻运动可显著提高肝脏FGF21表达水平,单次急性运动后小鼠血清FGF21水平呈上升趋势。表明运动可显著提高循环和靶器官FGF21水平。积极开展运动介导的FGF21表达与肝脂、糖脂代谢紊乱及心血管等疾病康复研究,将为代谢性疾病预防与康复及其相关药物筛选提供新思路和新靶点。     

NLRP3炎性体与代谢性疾病的研究进展

代谢性疾病是由体内氨基酸、葡萄糖和脂质代谢紊乱引起的一类疾病,慢性炎症反应是其重要特征之一.Nod样受体蛋白3(Nod-like receptor protein 3,NLRP3)炎性体是位于细胞内的一种蛋白质复合体,主要功能为活化半胱氨酸天冬氨酸蛋白酶1(caspase-1)以间接调控白介素1β(IL-1β)、IL-18和IL-33等的成熟和分泌.NLRP3炎性体是炎性体相关研究的热点,多种内源性或外源性危险信号通过激活这一蛋白质复合体上调炎性因子的表达水平,从而促进多种代谢性疾病的发生发展.本文对NLRP3炎性体的结构、功能、调节以及在代谢性疾病中的作用做一综述,以期为代谢性疾病的防治提供新靶点.     

冠心病患者血清CRP的变化及其临床意义

目的:探讨冠心病(CAD)患者血清C-反应蛋白(CRP)的变化及其临床意义.方法:运用全自动生化分析仪检测97例CAD患者和28例对照组人群的血清CRP,将CAD患者进一步分为稳定性心绞痛组(SAP)、不稳定心绞痛(UAP)、心肌梗死组(AMI)三组.另外,将97例CAD惠者分为1支病变组、2支病变组和3支病变组.所有研究对象均行选择性冠状动脉造影检查.结果:(1)与对照组比较,CAD患者血清CRP显著升高(P<0.05);(2)与对照组比较,SAP组、UAP组和AMI组患者血清CRP均显著升高(P<0.05);与SAP组比较,UAP组和AMI组患者血清CRP亦显著升高(P<0.05);(3)与对照组比较,1支病变组、2支病变组和3支病变组患者血清CRP均显著升高(P<0.05);与1支病变组比较,2支病变组和3支病变组患者血清CRP亦显著升高(P<0.05);与2支病变组比较,3支病变组患者血清CRP亦显著升高(P<0.05).结论:(1)CRP可能与CAD有关;(2)CRP异常升高可能反映冠状动脉斑块的不稳定和CAD的严重程度.     

Body Mass Index and Coronary Artery Disease in African-Americans

There are limited data available concerning the influence of obesity, a major cardiovascular disease risk factor, in relationship to coronary artery disease (CAD). This is of considerable importance to African-Americans since African-Americans have one of the world's highest CAD mortality rates coupled with the fact that obesity is extremely prevalent in this population. The present study assessed the relationship between body mass index and CAD in African-Americans undergoing coronary angiography. Eight hundred sixty-six available cardiac catheterization reports between the years 1983 through 1990 were retrospectively reviewed at Howard University Hospital in Washington, D.C. CAD was prevalent in 59.6% and 41.2%, males and females, respectively. Among the males overweight and obesity were found in 22.4% and 20.9%, respectively, compared to 39.6% and 30.6% for females. An upside-down U-shaped relationship between BMI and CAD was found. The interpretation of this finding is that being overweight is associated with increased risk of CAD compared to the lean and obese.     

体质指数与直肠癌的关系探讨

目的：探讨体质指数（bodymassindex,BMI）与我国直肠癌发病的关系,为直肠癌的预防提供参考。方法：用病例．对照研究方法分析353例首次确诊的直肠癌患者和354名健康人的BMI,比较两组人群BMI的情况。结果：首次确诊的直肠癌患者平均BMI为（24．54±4．48）kg／m^2,健康对照人群平均BMI为（23．58±3．12）kg／m^2,直肠癌患者的BMI明显高于健康对照人群,其差别具有统计学意义（P〈0．001）。根据性别的不同进行分组后,可以看出不同性别直肠癌患者的BMI均比健康对照组高。logistic回归分析,BMI的升高是直肠癌发生的危险因素,OR值为1．056（95％CI,1．027±1．089）。结论：直肠癌的发生与BMI有关。     

The Relationship of Body Mass Index to Reproductive Factors in Pre- and Postmenopausal African-American Women With and Without Breast Cancer

To date, there are virtually no existing data on the relationship between obesity, menopausal status, and breast cancer in African-Americans. Therefore, the present study was designed to test the following hypotheses in an African-American population: (1) there exists a positive association between BMI and breast cancer among postmenopausal women; (2) there exists an inverse association between BMI and breast cancer among premenopausal women; and (3) similar associations between BMI and reproductive factors exist for both pre- and postmenopausal breast cancer cases. The study population comprised 357 African-American women (n=193 breast cancer cases; n=164 controls). No significant differences were observed between premenopausal cases and controls for BMI, obesity categories, and reproductive factors. Among the postmenopausal women, the cases had significantly lower weight and BMI levels than the controls. Age at first pregnancy and parity were significantly lower among postmenopausal cases than their controls. No significant associations were revealed between body mass index and breast cancer for pre- and postmenopausal women. In the present study, early age at menarche was the only reproductive factor that was an independent predictor of BMI for both pre- and postmenopausal women, irrespective of breast cancer status. Also, these findings strongly suggest the need to consider reproductive factors, particularly age at menarche, as a covariate of BMI and other obesity-related diseases.     

Growth and Body Mass Index of Brazilians Ages 9 Through 17 Years

Obesity during adolescence is considered a strong predictor of adult obesity, and obesity and overweight have been increasing among Brazilian adults. To gauge the relative frequency of overweight among adolescents in Brazil, we compared the distributions of body mass index (kg/m²) and stature in national population based samples of the U.S. and Brazil. U.S. adolescents were on average about 10 cm taller than Brazilians, although growth spurts occurred at the same age for both populations. Brazilian adolescents were leaner than their U.S. counterparts. This difference was reduced among girls in the postpubertal period. At age 17 years, U.S. boys were about 10 kg heavier than Brazilian boys, but the difference among girls was only 2 kg. In families above the poverty level in the more developed South region, body mass index distribution for boys was closer to that of the U.S., and older girls tended to have higher body mass index than U.S. girls. Within Brazil, body mass index varied by ethnicity with Mulattos, but not Blacks, of both sexes having lower body mass index than Whites of the same age. Urban adolescents had higher body mass index than those living in rural areas. In general, the patterns seen among Brazilian adults were found among children. Among girls, in particular, overweight has become an identifiable problem during adolescence.     

Comparisons for Body Mass Index and Body Fat Percent Among Puerto Ricans,Blacks, Whites and Asians Living in the New York City Area

The latest data (NHANES III) from the National Center for Health Statistics (NCHS) show that the black population has the highest proportion of overweight among all adult populations in the United States. The present study compared the body mass index (BMI) and body fat percent from dual-photon absorptiometry in 1,324 healthy adults aged 18 to 107 years recruited from four ethnic groups in the New York City area; 523 whites, 280 blacks, 267 Asians and 254 Puerto Ricans. Puerto Ricans had the largest BMI and the largest percent of subjects with body weight more than 120% of their ideal weight, and the largest fat percent of the four ethnic groups: 76% of Puerto Rican males had fat percent above the median value for white males (fat percent = 19.6%) and 95% of Puerto Rican females had fat percent above the median for white females (fat percent = 30.8%). Asians had the smallest BMI, but 63% of them had fat percent above the median values for whites in each gender. Puerto Ricans also had the largest waist-to-hip ratios among the four ethnic groups. In blacks, the percent of subjects with fat percent larger than the median for whites was slightly smaller than that for Puerto Ricans, 64% and 82% of males and females respectively. These results differ from the latest NCHS data and show that Puerto Ricans in this sample are heavier and fatter than blacks.     

Genetic Influences on Changes in Body Mass Index: A Longitudinal Analysis of Women Twins

AUSTIN, MELISSA A, YECHIEL FRIEDLANDER, BETH NEWMAN, KAREN EDWARDS, ELIZABETH J MAYER-DAVIS, MARY-CLAIRE KING. Genetic influences on changes in body mass index: a longitudinal analysis of women twins. Numerous studies have demonstrated genetic influences on body fat, but there also may be genetic effects on its intraindividual variation over time. This study examined changes in body mass index (BMI) using longitudinal data from two examinations of the Kaiser Permanente Women Twins Study, performed a decade apart. The analysis included 630 women, 185 monozygotic and 130 dizygotic twin pairs, with average ages of 41 years and 51 years at the two examinations, respectively. Age adjusted heritability estimates for the change in BMI over the decade ranged from 0.57 to 0.86 (all ρ≤0.001) using three different statistical analysis approaches, indicating that at least half, and possibly as much as 85%, of the variance in the change in BMI is attributable to genetic influences under a polygenic model. These estimates remained statistically significant after adjusting for environmental factors (ranging from 0.57 to 0.78) and with additional adjustment for BMI at baseline (ranging from 0.41 to 0.79), although dizygotic intraclass correlations were low after these adjustments. Thus, in addition to known environmental and behavioral influences, these results provide evidence for genetic influences on changes in BMI over a decade in women.     

产甲烷常温古细菌和嗜热古细菌代谢网络拓扑结构与功能间的关联性研究

根据从KEGG数据库获得的产甲烷的常温古细菌Methanosarcina acetivorans(MAC)和嗜热古细菌Methanopyrus kandleri(MKA)的代谢网络,通过不同的网络属性特征的比较,发现常温古细菌MAC的代谢网络比嗜热古细菌MKA有更长的平均路径长度,更大的直径,这表明常温古细菌MAC的总体结构是相对低密度、松散的网络结构.同时为了从系统水平上分析这些特征蕴含的功能意义,采用了Grivan和Newman提出的模块算法(简称GN算法)分析这两个生物体的功能模块,并将所得的结果与KEGG数据库中的途径信息进行比较研究,发现大部分模块对应2~4个KEGG途径,表明这些网络模块均具有一定功能意义.