Visfatin mRNA在PCOS患者网膜脂肪组织中的表达

目的：探讨visfatin基因在多囊卵巢综合征（PCOS）网膜脂肪组织中的表达及相关影响因素。方法：采用半定量RT-PCR方法检测PCOS组（30例）和对照组（25例）网膜脂肪组织visfatin mRNA表达,并测量体重指数、腰臀比、空腹血糖、空腹胰岛素、胰岛素抵抗指数和血清性激素水平。结果：①PCOS组网膜脂肪组织visfatin mRNA表达量高于对照组（P=0.000）。②网膜脂肪组织visfatin mRNA的表达量与BMI、WHR、FINS、HOMA-IR呈正相关（P〈0.05）。③多元逐步回归分析显示,HOMA-IR（P=0.000）和WHR（P=0.005）是影响网膜脂肪组织visfatin mRNA表达的相关因素。结论：网膜脂肪组织visfatin mRNA表达可能与PCOS胰岛素抵抗的发生和肥胖相关。     

脑梗死患者内脂素和基质金属蛋白酶-9 与颈动脉粥样硬化 斑块易损性的关系

目的：探讨血清内脂素（Visfatin）及基质金属蛋白酶-9（MMP-9）水平与脑梗死患者颈动脉粥样硬化斑块稳定性的关系和血 清visfatin 和MMP-9 的相关性。方法：选择脑梗死患者70 例,根据颈动脉粥样硬化斑块性质分为易损性斑块组(n=43)和非易损 性斑块组(n=27),选取健康体检者30 例作为对照组。测定血清Visfatin 和MMP-9 水平,并对二者间关系进行相关分析。结果：脑 梗死伴颈动脉硬化组血清Visfatin、MMP-9 水平高于正常对照组(P＜0.01);易损性斑块组血清Visfatin 和MMP-9 水平高于非易 损性斑块组,差异有统计学意义（P＜0.017）。外周血中的Visfatin水平与MMP-9 呈正相关关系（r=0.643,P=0.000）。结论：在脑梗 死患者中,血清Visfatin和MMP-9 参与了颈动脉粥样硬化的病理生理过程,Visfatin 和MMP-9升高可能与颈动脉粥样硬化斑块 不稳定性的形成相关,Visfatin 可通过调控MMP-9 的分泌和活性从而改变斑块的易损性。     

地特胰岛素联合二甲双胍治疗妊娠糖尿病的疗效及对患者血清内脂素、抵抗素、血脂水平的影响

目的:研究地特胰岛素联合二甲双胍治疗妊娠糖尿病的临床疗效及对患者血清内脂素、抵抗素、血脂水平的影响。方法:选择2016年10月至2017年10月在我院进行治疗的妊娠糖尿病患者120例,按照随机数表法分为观察组和对照组。对照组给予二甲双胍治疗,观察组以对照组为基础联合地特胰岛素治疗。治疗后,观察和两组的临床疗效及不良反应的发生情况,治疗前后血清内脂素、抵抗素水平以及血脂血糖水平的变化。结果:治疗后,观察组总有效率(96.67%)明显高于对照组(85.00%)(P0.05);观察组血清内脂素、抵抗素、总胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖及餐后2h血糖水平均显著低于对照组(P0.05),HDL-C水平明显高于对照组(P0.05);两组不良反应发生率比较差异无统计学意义(P0.05)。结论:与单用二甲双胍相比,地特胰岛素联合二甲双胍治疗妊娠糖尿病可有效调节患者血脂血糖水平,降低血清内脂素与抵抗素水平,从而显著提高临床疗效,且安全性较好。     

Muscle type-specific responses to NAD+ salvage biosynthesis promote muscle function in Caenorhabditis elegans

Salvage biosynthesis of nicotinamide adenine dinucleotide (NAD⁺) from nicotinamide (NAM) lowers NAM levels and replenishes the critical molecule NAD⁺ after it is hydrolyzed. This pathway is emerging as a regulator of multiple biological processes. Here we probe the contribution of the NAM-NAD⁺ salvage pathway to muscle development and function using Caenorhabditis elegans. C. elegans males with mutations in the nicotinamidase pnc-1, which catalyzes the first step of this NAD⁺ salvage pathway, cannot mate due to a spicule muscle defect. Multiple muscle types are impaired in the hermaphrodites, including body wall muscles, pharyngeal muscles and vulval muscles. An active NAD⁺ salvage pathway is required for optimal function of each muscle cell type. However, we found surprising muscle-cell-type specificity in terms of both the timing and relative sensitivity to perturbation of NAD⁺ production or NAM levels. Active NAD⁺ biosynthesis during development is critical for function of the male spicule protractor muscles during adulthood, but these muscles can surprisingly do without salvage biosynthesis in adulthood under the conditions examined. The body wall muscles require ongoing NAD⁺ salvage biosynthesis both during development and adulthood for maximum function. The vulval muscles do not function in the presence of elevated NAM concentrations, but NAM supplementation is only slightly deleterious to body wall muscles during development or upon acute application in adults. Thus, the pathway plays distinct roles in different tissues. As NAM-NAD⁺ biosynthesis also impacts muscle differentiation in vertebrates, we propose that similar complexities may be found among vertebrate muscle cell types.     

Liver X Receptor (LXR) activation negatively regulates visfatin expression in macrophages

Adipose tissue macrophages (ATM) are the major source of visfatin, a visceral fat adipokine upregulated during obesity. Also known to play a role in B cell differentiation (pre-B cell colony-enhancing factor (PBEF)) and NAD biosynthesis (nicotinamide phosphoribosyl transferase (NAMPT)), visfatin has been suggested to play a role in inflammation.Liver X Receptor (LXR) and Peroxisome Proliferator-Activated Receptor (PPAR)γ are nuclear receptors expressed in macrophages controlling the inflammatory response. Recently, we reported visfatin as a PPARγ target gene in human macrophages. In this study, we examined whether LXR regulates macrophage visfatin expression. Synthetic LXR ligands decreased visfatin gene expression in a LXR-dependent manner in human and murine macrophages. The decrease of visfatin mRNA was paralleled by a decrease of protein secretion. Consequently, a modest and transient decrease of NAD⁺ concentration was observed. Interestingly, LXR activation decreased the PPARγ-induced visfatin gene and protein secretion in human macrophages.Our results identify visfatin as a gene oppositely regulated by the LXR and PPARγ pathways in human macrophages.     

内脂素对转基因小鼠血糖和运动性的影响

目的建立内脂素转基因小鼠动物模型,研究内脂素在转基因表达的情况下对小鼠的影响。方法把内脂素基因插入CMV启动子下游,构建转基因表达载体,通过显微注射法建立内脂素转基因小鼠。PCR鉴定内脂素转基因小鼠的基因型,Western Blot检测基因表达,通过血糖测定、血生化检测、转轮实验以及旷场观察,检测转基因小鼠在血糖和行为等方面的改变。结果建立了2个不同表达水平的内脂素转基因小鼠品系,转入的内脂素基因在骨骼肌和内脏脂肪组织中的表达高于内源性内脂素。血糖、血生化、代谢、疲劳度、协调性和旷场检查证实：内脂素转基因小鼠机体血糖降低,谷丙转氨酶降低,尿素氮升高,高密度脂蛋白胆固醇降低,低密度脂蛋白胆固醇升高,抗疲劳性和和协调性增高。结论成功建立了内脂素转基因小鼠,并证实内脂素对小鼠血糖和运动行为具有明显的影响,为研究脂肪细胞因子的作用机制提供了有价值的动物模型。     

Visfatin、IL-6、TNF-α与2型糖尿病的相关研究

目的：探讨血浆visfatin、IL-6、TNF-α与2型糖尿病的关系。方法：2型糖尿病患者60例,正常对照组30例。根据体重指数分为肥胖组和非肥胖组。检测空腹血浆胰岛素、糖化血红蛋白、血糖、血脂、血压、visfatin、TNF-α、白介素-6等。计算体重指数、腰臀比值及稳态模型胰岛素抵抗指数（HOMA-IR）。结果：2型糖尿病组血浆visfatin、IL-6、TNF-α水平显著高于正常对照组（P〈0.05）;2型糖尿病组与正常肥胖组比较,糖尿病非肥胖组visfatin（301.60±58.07）明显升高,糖尿病肥胖组visfatin（336.68±37.61）、TNF-α（3.58±1.10）明显升高（P〈0.05）。多元线性相关分析表明,在肥胖的2型糖尿病患者中血浆TNF-α与糖化血红蛋白显著正相关,血浆IL-6与血糖（FPG）显著正相关,血浆visfatin与腰臀比值（WHR）显著正相关（P〈0.05）。结论：visfatin、IL-6、TNF-α的变化可能对2型糖尿病的发生、发展具有一定的作用。     

Visfatin 与2 型糖尿病研究新进展

Visfatin是Fukuhara等发现的一种蛋白质细胞因子,由内脏脂肪细胞分泌,受多种因素调节,有烟酰胺磷酸核糖转移酶活性,类胰岛素作用,促炎作用等多种生物学作用。2型糖尿病是一种内分泌代谢性疾病,由多基因遗传因素、环境因素综合作用引起,visfatin与其有密切的关系。Visfatin对于寻找糖尿病新的药物靶点,开发新的疾病生物标志物有非常重要临床意义。     

妊娠期糖尿病患者糖化白蛋白、内脂素、摄食抑制因子-1水平与胰岛素抵抗和妊娠结局的关系分析

摘要 目的：观察妊娠期糖尿病（GDM）患者糖化白蛋白（GA）、内脂素（Visfatin）、摄食抑制因子-1（Nesfatin-1）水平与胰岛素抵抗的关系,并分析导致妊娠结局不良的危险因素。方法：选取2018年6月~2021年1月期间我院收治的120例GDM患者作为观察组,同一时间段选择来我院行孕检的90例正常孕妇作为对照组。检测受试者血清中Visfatin、Nesfatin-1、GA、空腹胰岛素（FINS）、空腹血糖（FPG）水平,计算胰岛素抵抗指数（HOMA-IR）、胰岛β细胞功能指数（HOMA-β）。采用Pearson相关分析Visfatin、Nesfatin-1、GA与胰岛素抵抗的关系。采用多因素Logistic回归分析妊娠结局不良的影响因素。结果：观察组的GA、Visfatin、Nesfatin-1、HOMA-IR高于对照组,HOMA-β低于对照组（P<0.05）。Pearson相关分析结果显示,GA、Visfatin、Nesfatin-1与HOMA-β呈负相关,而与HOMA-IR呈正相关（P<0.05）。观察组的妊娠不良结局发生率明显高于对照组（P<0.05）。单因素分析结果显示：妊娠不良结局与分娩年龄、居住地、糖尿病家族史、产前体质量指数（BMI）、合并多囊卵巢综合征、流产史、分娩史、甲状腺功能情况、产次、FPG、FINS、GA、Visfatin、Nesfatin-1、HOMA-IR、HOMA-β有关（P<0.05）,而与文化程度、单/双胎妊娠、孕次无关（P>0.05）。Logistic回归分析结果显示：居住地为城市、产前BMI≥28 kg/m²、分娩年龄≥35岁、合并多囊卵巢综合征、GA≥13%、Visfatin≥82mmol/L、Nesfatin-1≥9 μg/L、流产史、甲状腺功能异常是导致GDM产妇妊娠结局不良的危险因素（P＜0.05）。结论：GDM患者中存在GA、Visfatin、Nesfatin-1高表达,且与胰岛素抵抗明显相关。GDM产妇的妊娠不良结局发生率较高,受分娩年龄、居住地、产前BMI、合并多囊卵巢综合征、流产史、GA、Visfatin、Nesfatin-1、甲状腺功能异常等多种因素影响,可考虑针对上述患者采取相关干预措施,以改善患者的妊娠结局。     

Visfatin in adipocytes is upregulated by hypoxia through HIF1alpha-dependent mechanism

Obesity is associated with metabolic disorders, such as insulin resistance. Visfatin is an adipose-derived secretory factor to exert insulin-mimetic effects. Plasma visfatin levels and mRNA levels of visfatin in adipose tissues are increased in obesity. However, the mechanism that mediates induction of visfatin mRNA in adipose tissue of obesity remains unknown. Recent studies have reported that fat tissue is hypoxia in obesity. In this study, we investigated the effects of hypoxia on mRNA expression of visfatin in adipocytes. Hypoxia increased visfatin mRNA expression. Desferoxamine and Cobaltous chloride, two hypoxia mimetic compounds, also increased visfatin mRNA levels. Dimethyloxallyl glycine, a stabilizer of hypoxia-inducible factor 1alpha (HIF1alpha), mimicked the hypoxia-mediated upregulation of visfatin, and YC1, an inhibitor of HIF1 cancelled the hypoxia-induced upregulation of visfatin mRNA. We identified two functional hypoxia responsive elements (HRE) in mouse visfatin promoter. Hypoxic treatment and overexpression of HIF1alpha increased the promoter activity, and mutation of the HRE blunted hypoxia-induced activation of visfatin promoter. Our results suggest that visfatin mRNA expression is upregulated in the fat tissue of obesity through the activation of HIF1alpha pathway due to hypoxia.