分类： 生物学 >> 生物医药 提交时间： 2017-03-30
摘要： Low plasma levels of adiponectin (hypoadiponectinemia) and elevated circulating concentrations of plasminogen activator inhibitor (PAI)-1 are causally associated with obesity-related insulin resistance and cardiovascular disease. However, the mechanism that mediates the aberrant production of these two adipokines in obesity remains poorly understood. In this study, we investigated the effects of hypoxia and reactive oxygen species (ROS) on production of adiponectin and PAI-1 in 3T3-L1 adipocytes. Quantitative PCR and immunoassays showed that ambient hypoxia markedly suppressed adiponectin mRNA expression and its protein secretion, and increased PAI-1 production in mature adipocytes. Dimethyloxallyl glycine, a stabilizer of hypoxia-inducible factor 1a (HIF-1a), mimicked the hypoxiamediated modulations of these two adipokines. Hypoxia caused a modest elevation of ROS in adipocytes. However, ablation of intracellular ROS by antioxidants failed to alleviate hypoxia-induced aberrant production of adiponectin and PAI-1. On the other hand, teantioxidants could reverse hydrogen peroxide (H2O2)-induced dysregulation of adiponectin and PAI-1 production. H2O2 treatment decreased the expression levels of peroxisome proliferator-activated receptor gamma (PPARc) and CCAAT/enhancer binding protein (C/EBPa), but had no effect on HIF-1a, whereas hypoxia stabilized HIF-1a and decreased expression of C/EBPa, but not PPARc. Taken together, these data suggest that hypoxia and ROS decrease adiponectin production and augment PAI-1 expression in adipocytes via distinct signaling pathways. These effects may contribute to hypoadiponectinemia and elevated PAI-1 levels in obesity, type 2 diabetes,and cardiovascular diseases.
分类： 生物学 >> 发育生物学 提交时间： 2017-04-06
摘要： 目的 初步探索母亲喂养行为、体型认知对儿童肥胖的影响，并比较母亲是否主要喂养人的差 【摘要】 目的 初步探索母亲喂养行为、体型认知对儿童肥胖的影响，并比较母亲是否主要喂养人的差异，为今后在家庭喂养环境中干预儿童肥胖提供借鉴。方法 在北京、西安、江苏和深圳等四个城市选取8所幼儿园，对儿童母亲进行方便抽样，共收回有效问卷456份。采用母亲报告的方法。调查内容包括人口社会学特征、体型图表认知和儿童喂养问卷。结果 81.66%超重和70.15%肥胖儿童的母亲在认知其子女体重水平时存在低估现象。认知偏差分别与填鸭式喂养(r=0.11,P＜0.05)和担心(r=0.15,P＜0.01)呈显著正相关。分层回归分析发现，母亲为主要喂养人的责任认知和填鸭式喂养比为非主要喂养人的对儿童BMI更具有预测效果。结论 超重和肥胖儿童的母亲更存在认知偏差现象更可能采取不科学的喂养行为。母亲喂养行为不科学和体型认知不正确都会增加儿童肥胖风险。
分类： 生物学 >> 生物物理学 提交时间： 2016-05-05
Chen, Xiulan
Wei, Shasha
Yang, Fuquan
Chen, Xiulan
Wei, Shasha
Yang, Fuquan
Xu, Shimeng
Deng, Yaqin
Li, Yiran
Liu, Pingsheng
Xu, Shimeng
Wei, Shasha
Deng, Yaqin
Li, Yiran
摘要： Accumulated studies demonstrate that saturated fatty acids (FAs) such as palmitic acid (PA) inhibit insulin signaling in skeletal muscle cells and monounsaturated fatty acids such as oleic acid (OA) reverse the effect of PA on insulin signaling. The detailed molecular mechanism of these opposite effects remains elusive. Here we provide a comparative proteomic study of skeletal myoblast cell line C2C12 that were untreated or treated with PA, and PA plus OA. A total of 3437 proteins were quantified using SILAC in this study and 29 proteins fall into the pattern that OA reverses PA effect. Expression of some these proteins were verified using qRT-PCR and Western blot. The most significant change was cyclooxygenase-2 (Cox-2). In addition to whole cell comparative proteomic study, we also compared lipid droplet (LD)-associated proteins and identified that Cox-2 was one of three major altered proteins under the FA treatment. This finding was then confirmed using immunofluorescence. Finally, Cox-2 selective inhibitor, celecoxib protected cells from PA-reduced insulin signaling Akt phosphorylation. Together, these results not only provide a dataset of protein expression change in FA treatment but also suggest that Cox-2 and lipid droplets (LDs) are potential players in PA- and OA-mediated cellular processes.
分类： 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间： 2016-05-12
Yin, Ruiying
Fang, Li
Li, Yingjia
Wang, Nanping
Yin, Ruiying
Fang, Li
Li, Yingjia
Wang, Nanping
Xue, Peng
Li, Yazi
Chen, Chang
Guan, Youfei
Wang, Nanping
Chang, Yongsheng
Chang, Yongsheng
摘要： Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a ligand-activated nuclear receptor and plays an essential role in insulin signaling. Macrophage infiltration into adipose tissue is a character of metabolic inflammation and closely related to insulin resistance in type 2 diabetes. The mechanism by which pro-inflammatory macrophages cause insulin resistance remains to be elucidated. Here we showed that coculture with macrophages significantly suppressed the transcriptional activity of PPAR gamma on its target genes in 3T3-L1 preadipocytes and diabetic primary adipocytes, depending on inducible nitric oxide synthase (iNOS). We further showed that PPAR gamma underwent S-nitrosylation in response to nitrosative stress. Mass-spectrometry and site-directed mutagenesis revealed that S-nitrosylation at cysteine 168 was responsible for the impairment of PPAR gamma function. Extended exposure to NO instigated the proteasome-dependent degradation of PPAR gamma. Consistently, in vivo evidence revealed an association of the decreased PPAR gamma protein level with increased macrophage infiltration in visceral adipose tissue (VAT) of obese diabetic db/db mice. Together, our results demonstrated that pro-inflammatory macrophages suppressed PPAR gamma activity in adipocytes via S-nitrosylation, suggesting a novel mechanism linking metabolic inflammation with insulin resistance. (C) 2015 Elsevier Inc. All rights reserved.
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