Relationship between β3-AR Gene and Obesity, Type 2 Diabetes, Insulin Resistance in Chinese Han Population

Objective: To explore the relationship between the β 3-adrenergic receptor(β 3-AR)gene and obesity, T2DM, insulin resistance in Chinese Han population. Methods: Fifty-three healthy subjects, 105 subjects with simple obesity, 63 type 2 diabetic patients without obesity, and 114 type 2 diabetic patients with obesity were studied with the technique of PCR-RFLP in codon 64 of the exon region of β 3-AR gene representing the variation Trp/Arg. Results: Compared with the subjects of Trp homozygous group, the individuals with Arg allele were more elevated in WHR,MBP,SBP,DBP,FBS,PBS,FINS,PINS,FCP,PCP and lower in ISI. Frequency of Arg allele was higher in HINS subgroup without T2DM. Conclusion: The results indicate that the Trp/Arg variation might lead to insulin resistance, obesity and T2DM.β 3-AR gene is supposed to be the candidate gene of insulin resistance, obesity and T2DM in Chinese Han population.

Involvement of Cbl-b-mediated macrophage inactivation in insulin resistance

Aging and overnutrition cause obesity in rodents and humans. It is well-known that obesity causes various diseases by producing insulin resistance(IR). Macrophages infiltrate the adipose tissue(AT) of obese individuals and cause chronic low-level inflammation associated with IR. Macrophage infiltration is regulated by the chemokines that are released from hypertrophied adipocytes and the immune cells in AT. Saturated fatty acids are recognized by toll-like receptor 4(TLR4) and induce inflammatory responses in AT macrophages(ATMs). The inflammatory cytokines that are released from activated ATMs promote IR in peripheral organs, such as the liver, skeletal muscle and AT. Therefore, ATM activation is a therapeutic target for IR in obesity. The ubiquitin ligase Casitas b-lineage lymphoma-b(Cbl-b) appears to potently suppress macrophage migration and activation. Cbl-b is highly expressed in leukocytes and negatively regulates signals associated with migration and activation. Cbl-b deficiency enhances ATM accumulation and IR in aging- and diet-induced obese mice. Cbl-b inhibits migration-related signals and SFA-induced TLR4 signaling in ATMs. Thus, targeting Cbl-b may be a potential therapeutic strategy to reduce the IR induced by ATM activation. In this review, we summarize the regulatory functions of Cbl-b in ATMs.

Influence of catgut implantation at acupoints on leptin and insulin resistance in simple obesity rats

OBJECTIVES:To investigate the influence of catgut implantation at acupoints on leptin resistance(LR) and insulin resistance(IR) in the simple obesity rat.METHODS:Rats were made obese with high-fat diets,after which surgical catgut was implanted at Zusanli(ST 36) and Neiting(ST 44) acupoints once a week for 4 weeks(implantation group).Rats from the implantation group were compared with normal rats and unoperated obese rats(control group).Gene expression of the leptin receptor(OB-R) was evaluated using RT-PCR and northern blot.Serum and hypothalamus leptin and insulin(INS) levels were determined by radioimmunoassay.Body weight,Lee's index,body fat,serum and hypothalamus leptin and INS levels,and hypothalamic OB-R gene expression were determined before and after treatment.RESULTS:Body weights,Lee's index,body fat,and serum leptin and INS levels were significantly higher in obese than in normal rats.Hypothalamic leptin and INS levels and OB-R gene expression were significantly lower in obese rats.Catgut implantation at acupoint promoted weight loss and decreased serum leptin and INS levels.Hypothalamic leptin and INS levels and OB-R gene expression increased significantly.CONCLUSIONS:Catgut implantation at acupoint adjusts central and peripheral leptin and promotes hypothalamic OB-R gene expression.This may be an important method for regulation of LR,IR and abnormal endocrinology and metabolism.

Decrease in myostatin by ladder-climbing training is associated with insulin resistance in diet-induced obese rats

Background Suppression of myostatin （MSTN） has been associated with skeletal muscle atrophy and insulin resistance （IR）.However,few studies link MSTN suppression by ladder-climbing training （LCT） and IR.Therefore,we intended to identify the correlation with IR between LCT and to analyze the signaling pathways through which MSTN suppression by LCT regulates IR.Methods The rats were randomly assigned to two types of diet：normal pellet diet （NPD,n=8） and high-fat diet （HFD,n=16）.After 8 weeks,the HFD rats were randomly re-assigned to two groups （n=8 for each group）：HFD sedentary （HFD-S） and high-fat diet ladder-climbing training （HFD-LCT）.HFD-LCT rats were assigned to LCT for 8 weeks.Western blotting,immunohistochemistry and enzyme assays were used to measure expression levels and activities of MSTN,GLUT4,PI3K,Akt and Akt-activated targets （mTOR,FoxO1 and GSK-3β）.Results The LCT significantly improved IR and whole-body insulin sensitivity in HDF-fed rats.MSTN protein levels decreased in matching serum （42％,P=0.007） and muscle samples （25％,P=0.035） and its receptor mRNA expression also decreased （16％,P=0.041） from obese rats after LCT.But the mRNA expression of insulin receptor had no obvious changes in LCT group compared with NPD and HFD-S groups （P=0.074）.The ladder-climbing training significantly enhanced PI3K activity （1.7-fold,P=0.024） and Akt phosphorylation （83.3％,P=0.022） in HFD-fed rats,significantly increased GLUT4 protein expression （84.5％,P=-0.036）,enhanced phosphorylation of mTOR （4.8-fold,P ＜0.001） and inhibited phosphorylation of FoxO1 （57.7％,P=0.020）,but did not affect the phosphorylation of GSK-3β.Conclusions The LCT significantly reduced IR in diet-induced obese rats.MSTN may play an important role in regulating IR and fat accumulation by LCT via PI3K/Akt/mTOR and PI3K/Akt/FoxO1 signaling pathway in HFD-fed rats.

HIGH-FAT-DIET INDUCED OBESITY IN RATS AND EFFECTS OF ENDURANCE TRAINING ON THE BODY FAT CONTENT OF OBESE RATS

To study the high-fat-diet induced rat obesity and the of fect of endurance training on the body fat content of obese rats, we randomly divided 66 male weanling SD rats into control(16 rats) and high fat diet group(50 rats). After 10 weeks, we chose diet-induced obese rats(DIO, 26 rats) and divided them into endurance training group(DIO-T, 8 rats) and DIO groups(DIO, 18 rats) randomly. Aner 8 weeks, endurance training, all rats were killed. The results showed that nosignificant difference was found between groups in body weight, the feed efficiency of DIO groups was higher than control groups, tke carass fat con tent of DIO-T group was significantlylower than DIO group, and plasma insulin concentration of DIO group was higher than control and DIO-T groups. It was suggested that rats’ obesity was induced obesity by high fat diet, dietary obesity had relation to higher eding efficiency and hyperinsulinemia. Endurance training can effectively reduce the body fat content of high-fat-diet induced obese rats by improving its hyper-insulinemia. Plasma TCH and TG of all rats had no significant difference.

Peroxisome proliferator-activated receptors as targets to treat non-alcoholic fatty liver disease

Lately, the world has faced tremendous progress in the understanding of non-alcoholic fatty liver disease(NAFLD) pathogenesis due to rising obesity rates. Peroxisome proliferator-activated receptors(PPARs) are transcription factors that modulate the expression of genes involved in lipid metabolism, energy homeostasis and inflammation, being altered in diet-induced obesity. Experimental evidences show that PPAR-alpha is the master regulator of hepatic beta-oxidation(mitochondrial and peroxisomal)and microsomal omega-oxidation, being markedly decreased by high-fat(HF) intake. PPAR-beta/delta is crucial to the regulation of forkhead box-containing protein O subfamily-1 expression and, hence, the modulation of enzymes that trigger hepatic gluconeogenesis. In addition, PPAR-beta/delta can activate hepatic stellate cells aiming to the hepatic recovery from chronic insult. On the contrary, PPAR-gamma upregulation by HF diets maximizes NAFLD through the induction of lipogenic factors, which are implicated in the fatty acid synthesis. Excessive dietary sugars also upregulate PPAR-gamma, triggering de novo lipogenesis and the consequent lipid droplets deposition within hepatocytes. Targeting PPARs to treat NAFLD seems a fruitful approach as PPAR-alpha agonist elicits expressive decrease in hepatic steatosis by increasing mitochondrial beta-oxidation, besides reduced lipogenesis. PPAR-beta/delta ameliorates hepatic insulin resistance by decreasing hepatic gluconeogenesis at postprandial stage. Total PPAR-gamma activation can exert noxious effects by stimulating hepatic lipogenesis. However, partial PPAR-gamma activation leads to benefits, mainly mediated by increased adiponectin expression and decreased insulin resistance. Further studies are necessary aiming at translational approaches useful to treat NAFLD in humans worldwide by targeting PPARs.

Genetic polymorphism in CD14 gene, a co-receptor of TLR4 associated with non-alcoholic fatty liver disease

AIM To evaluate the pathogenic role of toll-like receptor(TLR) gene polymorphisms in patients with nonalcoholic fatty liver disease(NAFLD).METHODS Two hundred and fifty subjects(NAFLD = 200, healthy volunteers = 50) underwent polymerase chain reaction and restriction fragment length polymorphism to assess one polymorphism in the toll-like receptor 2(TLR2) gene(A753G), two polymorphisms in the TLR4 gene(TLR4 Asp299 Gly and Thr399 Ile allele), and two polymorphisms in the cluster of differentiation 14(CD14)(C-159 T and C-550T) gene, a co-receptor of TLR4. Association of TLR gene polymorphisms with NAFLD and its severity was evaluated by genetic models of association.RESULTS On both multiplicative and recessive models of gene polymorphism association, there was significant association of CD14 C(-159) T polymorphism with NAFLD; patients with TT genotype had a 2.6 fold increased risk of developing NAFLD in comparison to CC genotype. There was no association of TLR2 Arg753 Gln, TLR4 Asp299 Gly, Thr399 Ile, and CD14 C(-550) T polymorphisms with NAFLD. None of the TLR gene polymorphisms had an association with histological severity of NAFLD.CONCLUSION Patients with CD14 C(-159) T gene polymorphism, a co-receptor of TLR4, have an increased risk of NAFLD development.

Obesity phenotype in relation to gene polymorphism among samples of Egyptian children and their mothers

Obesity is complex heterogeneous disease controlled by genes,environmental factors,and their interaction.Genetic factors account for 40e90%of the body mass index variations.Body mass index(BMI)of children correlates more closely with maternal than paternal BMI.So,this studu was aimed to investigate the role of leptin receptor LEPR Gln223Arg,the uncoupling protein 2(UCP2 G 866 A)and insulin receptor gene(INSR exon 17)polymorphisms in the pathogenesis of obesity.A cross-sectional study executed on 130 children and their obese mothers;classified into 2 groups according to their BMI.The 2 groups were evaluated regarding the anthropometry.Restriction fragment length analysis for LEPR Gln223Arg,UCP2-866 G/A and INSR exon 17 polymorphisms were applied.It was reported that increased risk of obesity was found in LEPR AG t AA genotype and the A allele.Significant statistical difference was detected only in female children.Concerning UCP2,the AG followed by the GG genotype was the most frequent in all groups and the G allele was the mostly present in obese mothers and obese male children but with no statistical significance.There was difference in the INSR genotype and alleles between groups,but this difference was not statistically significant.This study concluded that the LEPR Gln223Arg,UCP2 G 866 A and INSR exon 17 polymorphisms are related to obesity in Egyptian population.Further researches on larger population are recommended to ascertain the implications of LEPR,UCP2 and INSR polymorphisms in obesity.

Peroxisome proliferator-activated receptors as targets to treat metabolic diseases:Focus on the adipose tissue,liver,and pancreas

The world is experiencing reflections of the intersection of two pandemics:Obesity and coronavirus disease 2019.The prevalence of obesity has tripled since 1975 worldwide,representing substantial public health costs due to its comorbidities.The adipose tissue is the initial site of obesity impairments.During excessive energy intake,it undergoes hyperplasia and hypertrophy until overt inflammation and insulin resistance turn adipocytes into dysfunctional cells that send lipotoxic signals to other organs.The pancreas is one of the organs most affected by obesity.Once lipotoxicity becomes chronic,there is an increase in insulin secretion by pancreatic beta cells,a surrogate for type 2 diabetes mellitus(T2DM).These alterations threaten the survival of the pancreatic islets,which tend to become dysfunctional,reaching exhaustion in the long term.As for the liver,lipotoxicity favors lipogenesis and impairs beta-oxidation,resulting in hepatic steatosis.This silent disease affects around 30%of the worldwide population and can evolve into end-stage liver disease.Although therapy for hepatic steatosis remains to be defined,peroxisome proliferator-activated receptors(PPARs)activation copes with T2DM management.Peroxisome PPARs are transcription factors found at the intersection of several metabolic pathways,leading to insulin resistance relief,improved thermogenesis,and expressive hepatic steatosis mitigation by increasing mitochondrial beta-oxidation.This review aimed to update the potential of PPAR agonists as targets to treat metabolic diseases,focusing on adipose tissue plasticity and hepatic and pancreatic remodeling.

Team players in the pathogenesis of metabolic dysfunctionsassociated steatotic liver disease:The basis of development of pharmacotherapy

Nutrient metabolism is regulated by several factors.Social determinants of health with or without genetics are the primary regulator of metabolism,and an unhealthy lifestyle affects all modulators and mediators,leading to the adaptation and finally to the exhaustion of cellular functions.Hepatic steatosis is defined by presence of fat in more than 5%of hepatocytes.In hepatocytes,fat is stored as triglycerides in lipid droplet.Hepatic steatosis results from a combination of multiple intracellular processes.In a healthy individual nutrient metabolism is regulated at several steps.It ranges from the selection of nutrients in a grocery store to the last step of consumption of ATP as an energy or as a building block of a cell as structural component.Several hormones,peptides,and genes have been described that participate in nutrient metabolism.Several enzymes participate in each nutrient metabolism as described above from ingestion to generation of ATP.As of now several publications have revealed very intricate regulation of nutrient metabolism,where most of the regulatory factors are tied to each other bidirectionally,making it difficult to comprehend chronological sequence of events.Insulin hormone is the primary regulator of all nutrients’metabolism both in prandial and fasting states.Insulin exerts its effects directly and indirectly on enzymes involved in the three main cellular function processes;metabolic,inflammation and repair,and cell growth and regeneration.Final regulators that control the enzymatic functions through stimulation or suppression of a cell are nuclear receptors in especially farnesoid X receptor and peroxisome proliferator-activated receptor/RXR ligands,adiponectin,leptin,and adiponutrin.Insulin hormone has direct effect on these final modulators.Whereas blood glucose level,serum lipids,incretin hormones,bile acids in conjunction with microbiota are intermediary modulators which are controlled by lifestyle.The purpose of this review is to overview the key players in the pathogenesis of metabolic dysfunction-associated steatotic liver disease(MASLD)that help us understand the disease natural course,risk stratification,role of lifestyle and pharmacotherapy in each individual patient with MASLD to achieve personalized care and target the practice of precision medicine.PubMed and Google Scholar databases were used to identify publication related to metabolism of carbohydrate and fat in states of health and disease states;MASLD,cardiovascular disease and cancer.More than 1000 publications including original research and review papers were reviewed.

不同强度训练方式对2型糖尿病超重或肥胖者体成分及糖代谢影响的Meta分析

目的:系统评价高强度间歇训练(high-intensity interval training,HIIT)与中等强度持续性训练(moderate-intensity continuous training,MICT)对2型糖尿病超重或肥胖患者体成分、糖代谢相关指标干预效果,对比两种运动方式的改善效果,为2型糖尿病超重或肥胖患者运动处方的制定提供参考依据。方法:检索The Cochrane Library、PubMed、EMbase、Web of Science、中国知网、中国生物医学文献数据库(CBM)、万方及美国临床试验注册中心数据库,搜集HIIT与MICT对2型糖尿病超重或肥胖患者体成分和糖代谢相关指标干预效果比较的随机对照试验,检索时间为各数据库建库至2022年6月。由2名研究者对所纳入的研究进行筛选、质量评价和数据提取,采用RevMan 5.4软件对结局指标进行Meta分析。结果:①共纳入13项随机对照试验,包括371例患者,所纳入研究整体质量较高。②HIIT组与MICT组对体成分改善效果无显著性差异(体质量:WMD=2.44,95%CI:-3.01-7.89,P>0.05;体质量指数:WMD=0.28,95%CI:-1.21-1.77,P>0.05;腰围:WMD=2.16,95%CI:-2.04-6.35,P>0.05;体脂百分比:WMD=0.47,95%CI:-2.11-3.05,P>0.05);③两组体质量与体质量指数指标“训练周期≥12周”亚组“训练频率≤3次/周”亚组差异有显著性意义(训练周期≥12周亚组:WMD=4.25,95%CI:0.90-7.59,P=0.01;WMD=2.71,95%CI:1.92-3.51,P<0.00001;训练频率≤3次/周亚组:WMD=5.14,95%CI:1.7-8.57,P=0.003;WMD=1.67,95%CI:0.66-2.67,P=0.001);④敏感性分析结果显示,HIIT组与MICT组体脂百分比指标差异有显著性意义(WMD=2.17,95%CI:1.20-3.14,P<0.0001),两组对糖代谢改善效果无显著性差异(空腹血糖:WMD=0.31,95%CI:-0.17-0.79,P>0.05;糖化血红蛋白:WMD=0.01,95%CI:-0.19-0.20,P>0.05;胰岛素抵抗指数:WMD=-0.14,95%CI:-0.71-0.42,P>0.05);⑤亚组分析结果显示,空腹血糖指标在“训练频率≤3次/周”亚组分析中差异有显著性意义(WMD=0.92,95%CI:0.25-1.60,P=0.007);糖化血红蛋白在“训练频率>3次/周”亚组分析中差异有显著性意义(WMD=-0.2,95%CI:-0.3至-0.1,P<0.0001)。结论:①整体而言,HIIT与MICT对改善2型糖尿病超重或肥胖患者体质量、体质量指数、腰围及体脂百分比等体成分和空腹血糖、糖化血红蛋白及胰岛素抵抗指数等糖代谢指标无显著差异;②当训练周期≥12周、训练频率≤3次/周时,MICT对体质量以及体质量指数的改善效果具有一定优势。

耐力训练对饮食性肥胖大鼠胰岛素作用的影响

为观察耐力训练对饮食性肥胖鼠胰岛素作用的影响，选用４４只雄性离乳ＳＤ大鼠，３６只饲以高脂饲料。饲养１０周后，１８只确定为饮食诱发肥胖鼠（ＤＩＯ），其中８只进行耐力训练（跑台６５－７５％Ｖｏ２ｍａｘ），所有大鼠继续饲养８周后处死。测定各组大鼠的血中胰岛素，细胞膜胰岛素受体。处死前进行葡萄糖负荷实验。实验结果如下：肥胖鼠存在高胰岛素血症，胰岛素敏感性下降及胰岛素抵抗，葡萄糖负荷实验，血胰岛素分泌峰值和分泌曲线下面积均增加，细胞膜胰岛素受体结合下降。耐力训练可通过增加肝细胞、脂肪细胞和白肌细胞膜胰岛素受体结合力，减轻胰岛素抵抗，提高胰岛素敏感性，改善高胰岛素血症。提示，高胰岛素血症，胰岛素敏感性下降及胰岛素抵抗是高脂饲料诱发肥胖大鼠的特征之一，耐力训练是通过改善肥胖鼠的代谢失常而降低其体脂的有效方法。

高强度间歇训练对肥胖女大学生体成分和血脂及空腹胰岛素水平的影响

目的观察高强度间歇训练(HIIT)对肥胖女大学生体成分、血脂和空腹胰岛素(FIN)水平的影响。方法 2015年1—6月选取浙江旅游职业学院符合纳入与排除标准的在校肥胖女大学生36例为研究对象。按研究对象体质指数(BMI)从小到大进行排序,先以4例为1层(共分为9层),采用随机数字表法将每层研究对象分为运动组和对照组,最终每组纳入18例。两组均给予自我运动锻炼宣教,运动组在此基础上给予集中的HIIT。于试验开始前1周及试验结束后1周检测研究对象体成分指标〔体质量、体质指数(BMI)、体脂肪、体脂百分比、内脏脂肪、去脂体质量、静息代谢率、腹围、臀围〕、血脂〔三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)〕水平、FIN水平。结果运动组试验后体质量、BMI、体脂肪、体脂百分比、腹围小于对照组,去脂体质量、静息代谢率大于对照组(P<0.05)。运动组试验后体质量、BMI、体脂肪、体脂百分比、腹围小于试验前,去脂体质量、静息代谢率大于试验前(P<0.05)。运动组试验后HDL-C水平高于对照组,LDL-C、FIN水平低于对照组(P<0.05)。运动组试验后HDL-C水平高于试验前,LDL-C、FIN水平低于试验前(P<0.05)。结论HIIT可以降低肥胖女大学生体脂含量,增加静息代谢率,同时改善血脂和FIN水平,对改善肥胖女大学生的健康水平有积极影响。

饮食脂肪含量和耐力运动对肥胖鼠胰岛素受体酪氨酸蛋白激酶的影响

研究利用含 2 0 %猪油的高脂饲料诱发大鼠肥胖模型 ,对胰岛素在肥胖发生中的作用 ,及胰岛素受体酪氨酸蛋白激酶活性的变化进行研究 ,并探讨耐力运动的减体脂机制 ,及饮食脂肪含量对胰岛素受体酶活性的影响。得出以下结论 :1.高脂饲料诱发肥胖鼠存在高胰岛素血症 ,胰岛素敏感性下降 ,及胰岛素抵抗。其肝细胞膜、脂肪细胞膜、肌细胞膜胰岛素受体结合容量下降 ,同时 ,肝细胞膜与肌细胞膜胰岛素受体酪氨酸激酶活性 (受体激酶自动磷酸化 )也下降 ,加重了胰岛素抵抗程度。 2 .耐力运动可减少高脂饲料诱发肥胖鼠体脂含量 ,通过增加肥胖鼠细胞膜胰岛素受体结合力 ,减轻其胰岛素抵抗。减少饮食中脂肪含量同时结合耐力运动 ,可降低肥胖鼠的体脂含量至对照水平 ,既可提高细胞膜胰岛素受体结合力 ,也可提高受体后 TPK活性 。

有氧耐力训练对高脂饮食大鼠肥胖及糖代谢的影响

为了探讨长期的有氧耐力训练对高脂饮食肥胖大鼠减肥效果及机体糖代谢的影响,雄性SD大鼠高脂喂养8周后按体重分为肥胖组大鼠(DIO)、肥胖抵抗组大鼠(DIO-R)和介于之间的中间对照组大鼠(C),再随机将每组分为两个亚组即运动组和非运动组,继续高脂饮食7周,运动组进行为期7周的游泳训练,末次训练后12h禁食,24h取样。测定体重和腹腔内脂肪含量及血糖、肌糖原、肝糖原,放射免疫法测定血清胰岛素。结果显示:肥胖组大鼠与中间对照组大鼠相比体重、脂肪量、体脂率和胰岛素均增高极显著(P<0.01),而血糖、肌糖原、肝糖原无显著差异(P>0.05);肥胖运动组大鼠与肥胖组大鼠相比,体重、脂肪量、体脂率、血糖均降低极显著(P<0.01),胰岛素降低显著(P<0.05),肌糖原、肝糖原无显著差异(P>0.05);中间对照运动组大鼠与中间对照组大鼠相比体重极显著下降(P<0.01),血糖水平显著下降(P<0.05),肌糖原、肝糖原、胰岛素、脂肪、体脂率均无显著差异(P>0.05),抵抗运动组大鼠与抵抗组大鼠相比各项指标均无显著变化(P>0.05)。结论:大鼠对高脂饮食诱导肥胖敏感程度存在很大差异,高脂饮食诱导大鼠肥胖与胰岛素抵抗有关。长期有氧耐力训练对肥胖组和中间对照组大鼠有明显的减肥作用,并且可有效降低肥胖大鼠的血清胰岛素,改善胰岛素抵抗。但对抵抗组大鼠作用不明显。

遗传对儿童肥胖及相关因子分泌影响

目的探讨遗传因素对儿童肥胖发生及肥胖儿童体内瘦素、可溶性瘦素受体和胰岛素分泌的影响。方法以204名12-14岁肥胖和正常对照儿童为研究对象,采用放射免疫方法测定其血清瘦素、胰岛素含量,用酶联免疫吸附法测定可溶性瘦素受体含量;测量儿童父母身高和体重。结果父母一方或双方肥胖者儿童肥胖发生率为66.18%,父母双方皆无肥胖者儿童肥胖发生率为39.71%（P〈0.01）;父母肥胖与儿童肥胖关系的OR值为2.971,95%CI=1.617-5.460（P〈0.01）。儿童身高、体重和体质指数（BMI）与父母身高、体重和BMI存在相关关系。肥胖组儿童血清瘦素、胰岛素水平,男童分别为（26.00±14.66）μg/L,（36.05±15.65）mU/L;女童分别为（33.59±14.63）μg/L,（36.38±15.23）mU/L,均高于正常对照组。父母肥胖与否,儿童血清瘦素、可溶性瘦素受体、胰岛素水平差异均无统计学意义（P〉0.05）。结论父母肥胖与儿童肥胖的发生高度相关;父母肥胖对儿童血清瘦素、可溶性瘦素受体和胰岛素水平无明显影响。

TLR4抑制剂TAK-242对高脂饮食诱导的小鼠胰岛素抵抗的干预作用

目的建立高脂饮食诱导的胰岛素抵抗小鼠模型,探讨干预Toll样受体4(Toll-like receptor 4,TLR4)对高脂饮食诱导的小鼠胰岛素抵抗状态的影响。方法首先建立高脂饮食诱导的胰岛素抵抗小鼠模型。选取出生21 d的雄性C57BL/6小鼠36只,随机分为2组,正常对照组12只,以普通基础饲料喂养(low fat diet,LFD),高脂饮食实验组24只,给予高脂饲料喂养(high fat diet,HFD)。待2组小鼠体质量出现显著差异时,进行葡萄糖耐量实验(glucose tolerance test,GTT)和胰岛素耐量实验(insulin tolerance test,ITT)观察小鼠胰岛素抵抗的发生。小鼠胰岛素抵抗模型建立后,观察TLR4抑制剂TAK-242对小鼠胰岛素抵抗状态的作用。LFD组小鼠继续以基础饲料喂养(即作LFD对照组);HFD组小鼠随机分为2组,每组12只小鼠,均继续以高脂饲料喂养,其中一组HFD小鼠腹腔注射TLR4抑制剂TAK-242,以0.5 mg TAK-242/kg体质量的计量给予,每周2次(即给予TAK-242的高脂饮食实验组,HFD-T组);另一组HFD小鼠作为单纯高脂饮食的胰岛素抵抗空白对照组(HFD-C组),只给予等体积的溶媒-二甲基亚砜(DMSO)。给予小鼠TLR4抑制剂5个月,进行GTT和ITT后,处死小鼠。采用EDTA-K2抗凝管收集血液标本,立即分离外周血单核细胞(peripheral blood mononuclear cell,PBMC)和血浆。应用Western blot技术检测PBMC TLR4蛋白表达水平。采用全自动生化分析仪测定血浆葡萄糖(GLU)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙氨酸氨基转移酶(ALT)的水平。结果在小鼠胰岛素抵抗模型建立期间,与对照组相比,高脂饮食组小鼠体质量增长较快,喂养至第20周体质量出现显著差异(P<0.05);持续高脂饮食7个月,GTT和ITT结果显示,高脂饮食组小鼠对糖的调节能力受损、对胰岛素的降糖作用减低,说明高脂饮食诱导小鼠胰岛素抵抗成功。出现胰岛素抵抗的小鼠,在给予TLR4抑制剂TAK-242 5个月后,对葡萄糖的调节能力和对胰岛素的敏感性均有所改善。血浆生化指标结果显示,与对照组比较,单纯高脂组和给予TAK-242的高脂饮食干预组小鼠血浆TG、TC、LDL-C浓度均显著升高(P<0.05),GLU、HDL-C、ALT水平均有升高趋势,但无统计学意义(P>0.05)。单纯高脂组和TAK-242干预组比较,血浆GLU、TG、TC、LDL-C、HDL-C、ALT水平在2组之间不存在显著性差异(P>0.05)。Western blot实验结果发现,正常对照组小鼠PBMC未见TLR4蛋白表达,单纯高脂饮食组小鼠PBMC有高水平的TLR4蛋白表达,给予TAK-242的高脂饮食小鼠PBMC TLR4蛋白虽有表达,但表达量明显低于单纯高脂饮食组小鼠,结果提示TAK-242部分抑制了高脂饮食喂养小鼠PBMC TLR4蛋白的表达。结论高脂饮食成功诱导了小鼠产生胰岛素抵抗,抑制TLR4蛋白的表达可以改善小鼠胰岛素抵抗状态。该研究结果丰富了胰岛素抵抗发生的机制,为进一步深入研究TLR4及其信号通路在胰岛素抵抗中的作用提供了实验依据。

牙周炎与牙周治疗对肥胖大鼠胰岛素抵抗作用的影响

目的:探索实验性牙周炎和基础牙周治疗,可能影响肥胖合并牙周炎大鼠胰岛素抵抗的机制。方法:采集前期建模成功的肥胖组,肥胖合并牙周炎组,牙周炎治疗组以及空白对照组大鼠的血液及器官标本,测量身体指数,与胰岛素抵抗相关数据及观察病理学改变。结果:4组比较:牙周炎合并肥胖症时,出现了较单纯肥胖更加严重的胰岛素抵抗和胰岛结构功能的破坏。经牙周治疗后,炎症状态及胰岛素抵抗出现了好转的趋势。病理学标本也提示了这一结果。结论:合并牙周炎会加重肥胖的炎症状态,加重胰岛素抵抗。通过进行基础的牙周治疗可以缓解炎症,改善胰岛素抵抗的情况。IRS-1、IRS-2介导的信号通路受阻,以及PDX-1、GK、GLUT等蛋白表达受抑制,可能与肥胖及肥胖合并牙周炎引起的胰岛素抵抗相关。

不同胰岛素水平和脂类饮食对小鼠肥胖和脂肪细胞的影响

目的:研究不同胰岛素水平和脂类饮食对小鼠肥胖的影响。方法:60只小鼠根据空腹胰岛素水平及饮食状况分为高胰岛素高脂饮食组(HH组)、高胰岛素普通饮食组(HN组)、低胰岛素高脂饮食组(LH组)、低胰岛素普通饮食组(LN组),每组15只。12周后称量小鼠体重并计算体重增加量,分离肾周及肠系膜周围脂肪组织并称量,荧光定量PCR及Western blot法测定各组脂肪组织过氧化物酶增殖物活化受体γ2(PPARγ2)mRNA及蛋白的表达水平。结果:12周末,HH组体重增加量、脂肪组织质量、PPARγ2 mRNA及蛋白表达水平均高于其他3组(P<0.05)。结论:高胰岛素水平促进高脂饮食介导的肥胖,其机制可能与PPARγ2表达有关。

长期有氧训练对高脂膳食肥胖和肥胖抵抗大鼠骨骼肌胰岛素受体mRNA表达的影响

目的:为探讨肥胖和运动减肥的机制,观察长期的有氧耐力训练对大鼠脂代谢、血清胰岛素和骨骼肌胰岛素受体mRNA表达的影响,将100只SD大鼠进行高脂膳食喂养8周,按体重分为3大组,即肥胖、中间、肥胖抵抗组,三组间的体重极显著差异(P<0.01)。将各组分为对照组和运动组,共6组。各组继续进行高脂膳食,运动组进行7周的游泳训练,观察体重、体脂、血清胰岛素和骨骼肌胰岛素受体的mRNA的表达变化。结果显示:1)肥胖组体重、脂肪量、体脂率显著高于中间组(P<0.01);抵抗组体重、脂肪量显著低于中间组(P<0.05)。肥胖运动组、中间运动组体重、脂肪量、体脂率分别显著低于自身对照组(P<0.01)。2)肥胖组胰岛素显著高于中间组与抵抗组(P<0.01)。3)肥胖运动组血清GLU和胰岛素显著低于肥胖组(P<0.01、P<0.05),而肌糖原显著升高(P<0.05)。4)肥胖组胰岛素受体mRNA表达显著低于中间组和抵抗组(P<0.05)。肥胖运动组胰岛素受体mRNA表达有下降趋势但无显著性变化。结论:1)相同品系大鼠对高脂膳食的敏感程度存在很大差异,有氧耐力运动对肥胖和中间体重大鼠有很好的减肥作用,但对肥胖抵抗组没有降体脂的作用。2)长期的高脂膳食引起肥胖大鼠骨骼肌胰岛素敏感性下降,出现了外周性胰岛素抵抗。3)有氧耐力训练能有效降低高脂膳食诱导的肥胖大鼠体脂,降低血浆胰岛素水平,增加肌糖原含量,但未出现骨骼肌胰岛素受体mRNA表达增加,推测可能与胰岛素受体mRNA表达时序性有关。