肥胖与慢性炎症

肥胖及其相关的代谢类疾病严重影响人类的健康,而肥胖诱导的慢性炎症是胰岛素抵抗和代谢综合症发病的关键因素.脂肪组织慢性炎症发生的机制及其与代谢综合症的关系已经成为全球瞩目的研究热点.慢性炎症的特征主要包括脂肪组织中促炎细胞因子表达量增加,抗炎细胞因子表达量降低以及大量巨噬细胞浸润.鉴于肥胖及其相关代谢综合症对人类健康的巨大危害,现对慢性炎症的发生机制,肥胖和慢性炎症之间的关系,脂肪组织炎症中巨噬细胞浸润以及和信号传导通路进行综述.     

线粒体融合蛋白2的结构与功能研究进展

线粒体融合蛋白2(mitofusin 2,Mfn2)位于线粒体外膜上,是线粒体外膜融合的重要蛋白之一。研究发现,它不仅参与调控线粒体形态结构,还与细胞代谢、增殖、凋亡密切相关。近年来资料提示,Mfn2参与调控内质网应激、自噬、线粒体自噬等方面。由于Mfn2作用复杂,生理状态下细胞内必定存在精细的调控网络以使其保持在稳定水平。本文概括介绍了Mfn2结构、功能及其调控机制新进展。     

肥胖患者载脂蛋白M水平及其与炎症因子的关系研究

目的：观察肥胖患者载脂蛋白M水平并探讨其与炎症因子的关系。方法：58例体重正常者和36例肥胖患者常规测量体重、身高,计算体重指数,抽取空腹静脉血检测血脂、血浆载脂蛋白M（apoM）、白细胞介素-6（IL-6）、C反应蛋白（CRP）、肿瘤坏死因子α（TNF—α）。结果：肥胖患者血浆apoM、高密度脂蛋白胆固醇（HDL-C）降低（P〈0．05）,IL-6、TNF—α、CRP水平升高（P〈0．05）,肥胖患者血浆αpoM与HDL-C正相关,血浆αpoM与IL-6、TNF—α、CRP水平负相关。结论：肥胖患者血浆apoM显著降低,αpoM水平与CRP、TNF-α、IL-6水平密切相关,apoM可能受到这些炎症因子的调控。     

肥胖患者载脂蛋白M水平及其与炎症因子的关系研究

目的:观察肥胖患者载脂蛋白M水平并探讨其与炎症因子的关系。方法:58例体重正常者和36例肥胖患者常规测量体重、身高,计算体重指数,抽取空腹静脉血检测血脂、血浆载脂蛋白M(apoM)、白细胞介素-6(IL-6)、C反应蛋白(CRP)、肿瘤坏死因子α(TNF-α)。结果:肥胖患者血浆apoM、高密度脂蛋白胆固醇(HDL-C)降低(P<0.05),IL-6、TNF-α、CRP水平升高(P<0.05),肥胖患者血浆apoM与HDL-C正相关,血浆apoM与IL-6、TNF-α、CRP水平负相关。结论:肥胖患者血浆apoM显著降低,apoM水平与CRP、TNF-α、IL-6水平密切相关,apoM可能受到这些炎症因子的调控。     

肥胖治疗的研究进展

肥胖(obesity)为慢性代谢疾病,具有高发病率及世界流行趋势;能量摄入长期多于能量消耗,可导致机体脂肪过度蓄积,为肥胖的主要病因之一。肥胖高发于欧美发达国家。中国肥胖人口亦迅速增长,呈全国急速发展态势。肥胖并发症主要为冠心病、2型糖尿病、高血压、中风及癌症等。肥胖及其并发症不仅对健康构成严重威胁,亦对社会经济及医疗卫生体系造成沉重负担。肥胖的治疗是当前世界医学界面临的严峻挑战。因此,研究肥胖发病机理、对其实施有效预防与治疗,对提高人民健康水平具有重要意义。我们参考世界卫生组织、中国社科院及中国疾病控制中心的官方数据,并结合一系列重要医学期刊发表的研究成果,综述近五年来肥胖机制与药物应用研究进展,以期为肥胖防治及减肥药物研发提供新的参考信息。     

炎症和肥胖

近来研究表明：脂肪和巨噬细胞之间存在惊人的相似之处。这个结论引发人们猜测：炎症反应也许是连接肥胖和糖尿病的桥梁。     

抗阻运动对高脂饮食诱导的肥胖大鼠脂肪组织自噬和炎症因子的影响

为探讨运动对肥胖患者自噬活性和内脏脂肪组织炎症反应的影响,本研究将60只肥胖小鼠随机分为高脂饮食组(B)、正常饮食组(C)、正常饮食加耐力运动干预组(D)、正常饮食加耐力运动干预组(E)。D组和E组分别进行10周的耐力和抗阻运动,然后用RT-PCR检测自噬、炎症的基因和蛋白表达。结果显示,三个干预组的Lee指数和BFI均显著降低,2个运动组的Lee指数和BFI均显著降低,但差异无显著性;D组和E组Beclin 1表达较C组显著降低,p62表达明显升高;与C组相比,D组p62显著升高,E组无明显升高;与D组相比,E组Beclin 1基因表达增加,p62蛋白表达降低;与C组相比,D组和E组IL-6和IL-0蛋白表达均显著升高;10周不同运动干预对大鼠减脂效果无差异。运动后内脏脂肪组织的自噬活性受到抑制,尤其是无氧运动;肥胖患者运动干预前后内脏脂肪组织自噬和炎症的变化趋势一致,其中IL-10的变化最为明显。     

选择性内质网自噬受体研究进展

内质网自噬是一种可以清除受损内质网的选择性自噬,其主要功能是参与内质网容量和质量的控制,维持细胞稳态。选择性内质网自噬由相关的受体蛋白介导,这些蛋白在疾病发生发展中可能起到重要靶点效应。本文对选择性内质网自噬的作用及其与疾病的关系加以综述,并且归纳总结了相关受体蛋白介导内质网自噬的研究进展,以期对研究内质网自噬相关疾病的发生机制、发展过程及其防治手段提供新的思路和切入点。     

内质网应激的调节方式及其在脊髓损伤中的靶向作用

内质网是维持细胞稳态的重要细胞器之一,主要参与细胞内脂质合成、蛋白质折叠以及钙离子稳态等过程。创伤、缺血和缺氧等一系列病理变化会使内质网内蛋白质的折叠功能发生障碍,引发内质网应激(endoplasmic reticulum stress, ERS)。脊髓损伤(spinal cord injury, SCI)是一种常见的创伤性疾病,致残率极高,严重影响生活质量,临床上至今没有安全有效的方法。已有大量数据表明,ERS是导致SCI后细胞死亡和神经元功能障碍的重要病理变化之一,并与SCI后神经元的凋亡、自噬和炎症等信号通路存在密切联系,但ERS与SCI之间的分子机制尚未研究透彻,合理认识和探索ERS与SCI相关的潜在分子机制,可能是未来SCI治疗取得重大突破的前提。本文首先归纳了ERS相关基因的变化与SCI病理过程之间的关系,然后从未折叠蛋白反应(unfolded protein response, UPR)、内质网相关降解(ER-associated degradation, ERAD)和内质网自噬(endoplasmic reticulophagy, ER-phagy)等3种主要调节方式入...     

Glutamine Links Obesity to Inflammation in Human White Adipose Tissue

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Ferroptotic agent-induced endoplasmic reticulum stress response plays a pivotal role in the autophagic process outcome

Ferroptosis has been reported as a unique form of cell death. However, in recent years, researchers have increasingly challenged the uniqueness of ferroptosis compared to other types of cell death. In this study, we examined whether ferroptosis shares cell death pathways with other types of cell death, especially autophagy, via the autophagic process. Here, we observed that ferroptosis inducers (artesunate [ART] and erastin [ERA]) and autophagy inducers (bortezomib [BOR] and XIE62-1004) led to autophagosome formation via the endoplasmic reticulum (ER) stress response. Unlike XIE62-1004, ART, ERA, and BOR, which affect glutathione production or utilization, induced oxidative stress responses—an increase in the levels of heme oxygenase-1 and lipid peroxidation. Oxidative stress responses were attenuated by deletion of autophagy-related gene-5 or treatment with autophagy inhibitors (bafilomycin and chloroquine). Our studies provide an overview of common death pathways—the ER stress response-associated autophagic process in ferroptosis and autophagy. We also highlight the role played by glutathione redox system in the outcome of the autophagic process.     

内质网在纳米材料毒性效应形成中的作用及机制

随着纳米材料在食品、药物、生物医学等多领域的应用,其在生产使用过程中对人类健康的影响引起了广泛关注.内质网是蛋白质折叠与加工修饰、脂质合成以及Ca~(2+)储存的主要场所,是维护细胞内稳态的重要细胞器.内质网作为纳米材料的主要靶细胞器之一,在纳米材料引起的毒性效应中起重要作用.本文结合近年来国内外相关研究进展,阐述了纳米银(Ag-NPs)、纳米金(Au-NPs)、纳米二氧化钛(TiO_2-NPs)、纳米氧化锌(ZnO-NPs)、纳米二氧化硅(SiO_2-NPs)、富勒烯(C_(60))、单壁与多壁碳纳米管(SWCNTs/MWCNTs)以及石墨烯与氧化石墨烯(GO)等典型纳米材料对内质网结构与功能的影响,并归纳总结了内质网在不同纳米材料诱导的毒性效应中的作用及其异同点.纳米材料可通过引起内质网应激诱导细胞凋亡、炎症反应以及细胞自噬,还可通过激活IP_3信号通路诱导内质网Ca~(2+)释放激活钙依赖的细胞凋亡.纳米材料可在内质网中积累造成结构损伤及功能障碍,还可诱导内质网自噬.     

内质网应激响应在脂肪组织中的代谢调节作用

在真核细胞中,内质网是蛋白合成、加工及质量监控的关键细胞器,也是Ca2+储存及脂质合成的重要场所.细胞通过未折叠蛋白响应(unfolded protein response,UPR)感应外界不同刺激引发的内质网应激,在维持细胞功能稳态中发挥至关重要的作用.在哺乳动物中,三个位于内质网的跨膜蛋白——肌醇依赖酶la(ino...     

The NLPR3 inflammasome and obesity‐related kidney disease

Over the past decade, the prevalence of obesity has increased, accompanied by a parallel increase in the prevalence of chronic kidney disease (CKD). Mounting evidence suggests that high body mass index (BMI) and obesity are important risk factors for CKD, but little is known about the mechanisms of obesity‐related kidney disease (ORKD). The NLRP3 inflammasome is a polyprotein complex that plays a crucial role in the inflammatory process, and numerous recent studies suggest that the NLRP3 inflammasome is involved in ORKD development and may serve as a key modulator of ORKD. Moreover, inhibiting activation of the NLRP3 inflammasome has been shown to attenuate ORKD. In this review, we summarize recent progress in understanding the link between the NLRP3 inflammasome and ORKD and discuss targeting the NLRP3 inflammasome as a novel therapeutic approach for ORKD.     

Interleukin-38 alleviates hepatic steatosis through AMPK/autophagy-mediated suppression of endoplasmic reticulum stress in obesity models

Interleukin-38 (IL-38), recently recognized as a cytokine with anti-inflammatory properties that mitigate type 2 diabetes, has been associated with indicators of insulin resistance and nonalcoholic fatty liver disease (NAFLD). This study investigated the impact of IL-38 on hepatic lipid metabolism and endoplasmic reticulum (ER) stress. We assessed protein expression levels using Western blot analysis, while monodansylcadaverine staining was employed to detect autophagosomes in hepatocytes. Oil red O staining was utilized to examine lipid deposition. The study revealed elevated serum IL-38 levels in high-fat diet (HFD)-fed mice and IL-38 secretion from mouse keratinocytes. IL-38 treatment attenuated lipogenic lipid accumulation and ER stress markers in hepatocytes exposed to palmitate. Furthermore, IL-38 treatment increased AMP-activated protein kinase (AMPK) phosphorylation and autophagy. The effects of IL-38 on lipogenic lipid deposition and ER stress were nullified in cultured hepatocytes by suppressing AMPK through small interfering (si) RNA or 3-methyladenine (3MA). In animal studies, IL-38 administration mitigated hepatic steatosis by suppressing the expression of lipogenic proteins and ER stress markers while reversing AMPK phosphorylation and autophagy markers in the livers of HFD-fed mice. Additionally, AMPK siRNA, but not 3MA, mitigated IL-38-enhanced fatty acid oxidation in hepatocytes. In summary, IL-38 alleviates hepatic steatosis through AMPK/autophagy signaling-dependent attenuation of ER stress and enhancement of fatty acid oxidation via the AMPK pathway, suggesting a therapeutic strategy for treating NAFLD.     

Chikungunya-induced cell death is limited by ER and oxidative stress-induced autophagy

It has been recognized that macroautophagy constitutes an important survival mechanism that allows both the maintenance of cellular homeostasis and the regulation of programmed cell death pathways (e.g., apoptosis). Although several pathogens have been described to induce autophagy, the prosurvival function of this process in infectious models remains poorly characterized. Our recent studies on chikungunya virus (CHIKV), the causative agent of major epidemics in India, Southeast Asia and southern Europe, reveal a novel mechanism by which autophagy limits the cytopathic effects of CHIKV by impinging upon virus-induced cell death pathways.