Obesity and colorectal cancer:Role of adipokines in tumor initiation and progression

Obesity-associated diseases account for a large portion of public health challenges.Among obesity-related disorders,a direct and independent relationship has been ascertained for colorectal cancer(CRC).The evidence that adipocyte hypertrophy and excessive adipose tissue accumulation(mainly visceral)can promote pathogenic adipocyte and adipose tissue-related diseases,has led to formulate the concept of"adiposopathy",defined as adipocyte and adipose tissue dysfunction that contributes to metabolic syndrome.Adipose tissue can,indeed,be regarded as an important and highly active player of the innate immune response,in which cytokine/adipokine secretion is responsible for a paracrine loop between adipocytes and macrophages,thus contributing to the systemic chronic low-grade inflammation associated with visceral obesity,which represents a favorable niche for tumor development.The adipocyte itself participates as a central mediator of this inflammatory response in obese individuals by secreting hormones,growth factors and proinflammatory cytokines,which are of particular relevance for the pathogenesis of CRC.Among adipocyte-secreted hormones,the most relevant to colorectal tumorigenesis are adiponectin,leptin,resistin and ghrelin.All these molecules have been involved in cell growth and proliferation,as well as tumor angiogenesis and it has been demonstrated that their expression changes from normal colonic mucosa to adenoma and adenocarcinoma,suggesting their involvement in multistep colorectal carcinogenesis.These findings have led to the hypothesis that an unfavorable adipokine profile,with a reduction of those with an anti-inflammatory and anti-cancerous activity,might serve as a prognostic factor in CRC patients and that adipokines or their analogues/antagonists might become useful agents in the management or chemoprevention of CRC.     

川崎病患儿治疗前后血清抵抗素和内脂素的变化

目的 检测急性期川崎病（KD）患儿静脉注射丙种球蛋白（IVIG）治疗前后血清中抵抗素和内脂素含量的变化及意义。方法 选择2011年1月至2013年1月确诊的KD患儿50例为研究对象,同时选取30例健康儿童和30例急性感染性疾病患儿作为对照。酶联免疫吸附法检测KD患儿IVIG治疗前后及对照儿童血清中抵抗素和内脂素的水平。结果 KD患儿血清抵抗素和内脂素含量均明显高于健康对照组和急性感染性疾病患儿（均P<0.05）;经过48 h治疗后,IVIG治疗有效KD患儿血清抵抗素含量较治疗前明显降低（P<0.05）,内脂素含量在IVIG治疗有效KD患儿治疗前后差异无统计学意义（P >0.05）;IVIG治疗无效KD患儿（n=12）治疗前血清抵抗素水平明显高于IVIG治疗有效组（n=38,P<0.05）,而内脂素含量在两组患儿治疗前差异无统计学意义（P >0.05）;KD合并冠脉损害与非冠脉损害患儿的抵抗素和内脂素水平差异均无统计学意义（P >0.05）。结论 KD患儿血清中高表达的抵抗素和内脂素可能参与了KD的发生和发展;血清抵抗素含量可能成为临床观察IVIG治疗效果的新监测指标。     

Resistin expression in breast cancer tissue as a marker of prognosis and hormone therapy stratification

Objective

Adipocytokines are adipocyte-derived hormones and well documented to be involved in carcinogenesis. The expression of resistin, a newly discovered adipocytokine, in breast cancer tissues was determined and correlated with patient clinicopathological variables.

Methods

Resistin expression in breast cancer tissues and the normal adjacent breast tissues was analyzed by immunohistochemistry and was correlated with clinicopathological variables as well as recurrence rates by the chi-square test. The prognostic value of resistin for disease-free and overall survival was determined by Kaplan-Meier estimates, and the significance of differences between curves was evaluated by the log-rank test.

Results

High resistin expression was predominantly observed in breast cancer tissues but not the adjacent normal breast tissues. High resistin expression in breast cancer tissues was correlated significantly with tumor stage, tumor size, lymph node metastasis and estrogen receptor status. Hormone therapy, but not radiotherapy or chemotherapy, decreased the recurrence rate in patients with high resistin expression. While high resistin expression was associated with poor disease-free and overall survival, Cox regression analysis also revealed that resistin was an independent predictor of disease-free and overall survival.

Conclusions

High resistin expression in breast cancer tissue is associated with a more malignant clinicopathological status as well as poor patient survival. Resistin may therefore hold promise as an independent prognosis predictor for breast cancer, as a marker for hormone therapy stratification and as a potential therapeutic target.     

Adipokines,cytokines and body fat stores in hepatitis C virus liver steatosis

AIM: To identify patients with or without liver steatosis and its severity in treatment-na?ve patients affected by hepatitis C virus(HCV) infection.METHODS: We included 56 HCV infected patients, and assessed the amount of liver fat by histomorphometry, and its relationships with fat and lean mass at different parts of the body(by densitometry), hormones [insulin, homeostatic model assessment(HOMA)], adipokines(resistin, adiponectin, leptin), and cytokines(tumor necrosis factor α, interleukin-6).RESULTS: Although the intensity of liver steatosis is related to trunk fat mass and HOMA, 33% of patients showed no liver steatosis, and this finding was not related to body mass index or genotype. Besides trunkfat mass, no other factor was related to the presence or not of liver steatosis, or to the intensity of it, by multivariate analysis. Lean mass was not related to liver steatosis. Adiponectin levels were lower among patients. No differences were observed in leptin and resistin.CONCLUSION: Steatosis in HCV infection is common(67.2%), and closely related to trunk fat, and insulin resistance, but not with leg fat mass or adipokines.     

糖尿病肾病患者血清高敏C反应蛋白、抵抗素和糖化血红蛋白水平变化

目的：探讨血清高敏C反应蛋白（hs-CRP）、抵抗素和糖化血红蛋白（HbAlc）在2型糖尿病患者及糖尿病肾病患者中的变化。方法：选择健康体检者30例为对照组,2型糖尿病患者32例为糖尿病组（DM组）,2型糖尿病肾病患者38例为糖尿病肾病组（DN组）。采用散射比浊法、双抗体夹心法酶联免疫吸附试验（ELISA）、免疫比浊法和化学发光法分别检测各组患者空腹血清hs-CRP、抵抗素、HbAlc和胰岛素（FINS）含量,采用稳态模型评估法（HOMA）计算胰岛素抵抗指数。结果：DM组、DN组血清hs-CRP、抵抗素和HbAlc水平及HOMA-IR均明显高于对照组,差异有统计学意义（P〈0.01）;DM组和DN组以上各指标比较差异均有统计学意义（P〈0.01）。结论：hs-CRP、抵抗素和HbAlc是2型糖尿病及糖尿病肾病发生发展的高危因素。     

脂肪因子与银屑病

银屑病发病机制涉及遗传、免疫等多种因素。近年来逐渐认识到银屑病是一种系统性疾病,与肥胖、高血压、糖尿病及代谢综合征等相关。脂肪组织可以通过分泌脂肪因子介导胰岛素抵抗、炎症调控、内皮功能障碍及动脉粥样硬化等异常。脂肪因子如瘦素、抵抗素、chemerin、脂联素及内脂素等在银屑病中表达异常,可能参与银屑病发病机制中的免疫应答及表皮异常增殖。     

全身炎症反应患者血液净化时抵抗素含量变化的研究

目的研究连续性血液净化（CBP）治疗对全身炎症反应综合征（SIRS）患者血清抵抗素含量的影响。方法将120例SIRS患者在常规对症治疗的基础上,分为常规治疗组60例;以及在常规治疗的基础上进行CBP治疗组（CBP组）,CBP组患者均在常规治疗的同时行CBP治疗72h,在治疗0,24,48,72,96h时检测患者血清抵抗素含量,并进行APACHEⅡ评分。结果两组SIRS患者治疗前血清抵抗素含量均明显高于正常对照组（P〈0．01）,且常规治疗组和CBP组抵抗素含量比较无统计学意义（P〉0．05）,经过96h治疗,各组患者抵抗素水平均明显降低常规治疗组经过96h治疗,血清抵抗素水平降低缓慢（P〈0．05）;CBP治疗组经CBP治疗后SIRS患者血清抵抗素含量逐渐降低,治疗48h后已显著低于治疗前（P〈0．05）,治疗72h后降低更为明显（P〈0．01）。SIRS患者抵抗素与APACHEⅡ评分呈正相关（r=0．58,P〈0．01）。结论CBP治疗可清除血液中炎症因子抵抗素的作用,改善患者内皮细胞功能,并为临床观察CBP的治疗效果提供了新的监测指标。     

SLE患者胰岛素抵抗和血清抵抗素水平研究

目的 探讨SLE患者胰岛素抵抗与其抵抗素水平及疾病活动性的关系,以及糖皮质激素治疗的影响。方法 收集40例（共56份,其中活动期21份,非活动期35份;病程30天至22年）SLE患者及31例正常人对照血样,两组在年龄与性别构成上差异无统计学意义。分别测定空腹血糖、胰岛素水平,应用稳态模型评价方程（HOMA）计算胰岛素敏感性（HOMA-S）和胰腺β细胞功能（HOMA-B）。采用ELISA法检测血清抵抗素水平。结果 ①SLE患者空腹血清胰岛素水平（17.46 ± 15.65） IU/L高于正常人对照（8.57 ± 7.54） IU/L,胰岛素敏感性（0.42）明显低于正常人对照（0.78）,胰腺β细胞分泌功能（167.47）明显高于对照组（84.10）,差异均有统计学意义（P < 0.05）。②活动期SLE患者组血清抵抗素水平（10.90 mg/L）高于非活动期患者组（2.72 mg/L）及对照组（2.43 mg/L）,非活动期组高于对照组,差异均有统计学意义（P < 0.05）。③经糖皮质激素治疗后SLE患者血胰岛素水平、胰腺β细胞分泌功能（Homa-B）及血清抵抗素水平下降,胰岛素敏感性（Homa-S）增加。④SLE患者组SLEDAI与Homa-S（r = －0.48,P < 0.01）、Homa-B（r = 0.29,P < 0.05）及血清抵抗素水平（r = 0.42,P < 0.01）均有一定相关性,SLE患者组Homa-S与血清抵抗素水平呈负相关（r = －0.56,P < 0.01）。结论 SLE患者中存在胰岛素抵抗以及胰腺β细胞高分泌状态,与疾病活动状态以及血清抵抗素水平相关。糖皮质激素治疗控制病情后,情况得到改善。     

非酒精性脂肪性肝病合并2型糖尿病患者血清抵抗素和黄醇结合蛋白4水平及其临床意义探讨

目的 探讨非酒精性脂肪性肝病(NAFLD)合并2型糖尿病(T2DM)血清抵抗素和黄醇结合蛋白4(RBP4)水平变化及其临床意义.方法 2017年10月～2021年1月我院诊治的NAFLD合并T2DM患者106例和NAFLD患者106例,检测空腹血糖(FBG),采用化学发光法检测空腹胰岛素(FINS)水平,计算HOMA-...     

Resistin对人肾小球系膜细胞表型和功能的作用及机制研究

目的研究巨噬细胞因子抵抗素（Resistin）过度表达对高糖刺激作用下人肾小球系膜细胞p38MAPK信号通路的影响,探讨Resistin调控肾小球系膜细胞增殖及细胞外基质积聚的作用机制。方法通过转染携带野生型Resistin基因的腺病毒载体（Ad—Resistin）构建过度表达Resistin的人巨噬细胞模型,并与高糖刺激后的人肾小球系膜细胞共培养,^3H-氚标胸腺嘧啶掺入实验检测肾小球系膜细胞增殖,免疫细胞化学检测系膜细胞增殖相关基因（AP-1）的表达,免疫荧光检测细胞外基质蛋白（Laminin）的蛋白表达,Western blot检测系膜细胞内p38MAPK、TGF-β的表达并测定Smad2的磷酸化水平。结果Ad—Resistin感染后,人巨噬细胞Resistin mRNA水平及蛋白表达明显升高（P〈0．01）。同过度表达Resistin的人巨噬细胞共培养后,与对照组比较,人肾小球系膜细胞p38MAPK、TGF-β的蛋白表达明显增强,细胞内Smad2的磷酸化水平显著升高（p〈0．05）,肾小球系膜细胞出现明显的增殖,细胞外基质的合成增多（P〈0．05）。结论巨噬细胞因子Resistin的过度表达可能通过p38MAPK信号通路,调控高糖刺激作用下肾小球系膜细胞的增殖及细胞外基质的异常积聚。