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综述了近年来microRNAs,尤其是miR-33在脂质代谢调控方面的功能研究进展.脂质代谢在细胞水平进行有规律的调控,主要参与者有肝X受体(LXRs)和固醇调节元件结合蛋白(SREBPs)等.最近研究发现,非编码RNAs家族成员microRNAs在转录后水平调节脂质代谢相关基因表达,参与胆固醇、甘油三酯和脂肪酸代谢.其中miR-33可靶向沉默三磷酸脂苷结合盒(ABC)转运体家族成员ABCA1和ABCG1,抑制胆固醇流出和高密度脂蛋白(HDL)合成;通过靶向沉默脂肪酸β-氧化相关基因,如CPT1A、CROT和HADHB表达,抑制脂肪酸氧化;还可沉默AMPK和RIP140的表达,影响甘油三酯代谢.其他microRNAs如miR-122、miR-370、miR-125a-5p、miR-27、miR-320等,也参与调控胆固醇、甘油三脂、脂肪酸代谢及脂肪细胞分化. 相似文献
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脂肪肝(NAFLD)既可是一个独立的疾病,也可是一类疾病的伴发疾病,肥胖患者、脂肪营养不良症患者、糖尿病患者均伴发脂肪肝。脂肪肝时肝细胞内蓄积的脂质多为甘油三酯,因此肝细胞甘油三酯代谢紊乱是脂肪肝发生最主要原因。肝细胞甘油三酯蓄积会破坏其对胰岛素敏感性,促进肝糖异生导致高血糖,也可引起肝细胞极低密度脂蛋白分泌增加,升高血脂。本文详细阐述肝细胞甘油三酯代谢途径的重要步骤,探讨这些步骤异常与脂肪肝之间的关系,为脂肪肝药物设计提供新靶点。的每条通路的各个步骤,探讨这些步骤异常与脂肪肝之间的关系,为脂肪肝药物设计提供新靶点。 相似文献
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林桐罗文威张丽丽刘培庆李卓明 《生理科学进展》2022,53(3):229-234
血管内皮细胞功能障碍伴随着细胞内代谢紊乱,并与动脉粥样硬化、糖尿病等多种疾病密切相关。脂肪酸代谢作为细胞能量代谢的主要形式之一,在调节内皮细胞稳态、调节内皮细胞增殖和血管新生等方面发挥重要作用,具有重要的病理生理意义。本文将综述内皮细胞的脂肪酸转运、氧化、脂质合成等脂肪酸代谢的调控机制,以及内皮细胞脂肪酸代谢的病理生理意义,为内皮功能障碍相关疾病的干预和治疗提供参考。 相似文献
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乳腺癌已经成为全球第一大癌症,其发病机制及治疗方法的探索越来越受到人们重视。脂质代谢异常是癌细胞中最突出的代谢改变之一,探索乳腺癌细胞中脂质代谢的改变,以寻找新的诊断指标和治疗靶点是至关重要的。本文从脂肪酸代谢、甘油三酯代谢、胆固醇代谢和脂质代谢信号通路4个方面介绍脂质代谢异常在乳腺癌中的研究进展,为靶向脂质代谢治疗乳腺癌提供新思路和新方法。 相似文献
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MicroRNAs简称miRNAs(微小RNAs),是真核生物、原核生物以及病毒中由非编码蛋白基因转录的初级microRNAs加工成的调控因子.在转录后水平和蛋白质翻译水平,microRNAs通过降解或翻译抑制甚至激活来调控靶mRNA.实验和计算机方法已应用于microRNAs和靶基因的鉴定.大规模测序技术使得microRNAs在不同物种的多样性分析得以实现.着重介绍microRNAs、靶基因及其功能研究的实验技术和计算机方法,以及基于microRNAs的保守性,借助模式生物中已知的microRNAs,研究其在其他生物中的功能和作用. 相似文献
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microRNAs(miRNAs)是一类长度约为22nt的非编码小RNA,从单细胞到多细胞真核生物中都广泛存在,在进化过程中高度保守,对动物发育、生理功能及病理过程都具有重要调控作用。斑马鱼(Danio rerio)是现代生物学研究中广泛使用的模式动物,以斑马鱼为模型研究miRNAs可以揭示miRNAs在脊椎动物中的功能。文章就miRNAs整体缺失对斑马鱼胚胎发育的影响及一些miRNAs在斑马鱼早期发育过程中的调控机制进行了综述,从而为探索miRNAs在脊椎动物中的功能及鱼类的生产育种提供理论基础。 相似文献
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The study deals with the lipid and fatty acid compositions of the muscles, gills and liver of marine fishes inhabiting cold waters (0.5–6°C) and caught in Peter the Great Bay (3 species) and Vostok Bay (2 species), as well as with the fatty acid compositions of the main phospholipids in the muscle tissues of fish from Olyutorskii Bay (4 species). The average content of phosphatidylcholine was about 60% in muscles and in the liver and 53.8% of the sum of all phospholipids in gills. The phosphatidylethanolamine content was on the average 24.3, 25.1 and 22.3% in muscles, liver and gills, respectively. Increased contents of phosphatidylserine and sphingomyeline were recorded in the gills. The mean (S.D.) molar ratios of cholesterol/phospholipids were 0.20, 0.32, and 0.58 in the muscles, liver, and gills, respectively. It was established that phosphatidylcholine has a higher content of saturated fatty acids, whereas phosphatidylethanolamine was richer in monoenic acids and docosahexaenoic acid (DHA). It was noted that the level of polyenic fatty acids was increasing and the level of monoenic and saturated acids was decreasing in the series from gills-liver-muscles. The species with a more active mode of life were distinguished by an increased content of docosahexaenoic acid. 相似文献
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The use of Delta 6 desaturase (D6D) twice in the conversion of alpha-linolenic acid (ALA; 18:3n-3) to docosahexaenoic acid (DHA; 22:6n-3) suggests that this enzyme may play a key regulatory role in the synthesis and accumulation of DHA from ALA. We examined this using an in vitro model of fatty acid metabolism to measure the accumulation of the long-chain metabolites of ALA in HepG2 cell phospholipids. The accumulation of ALA, eicosapentaenoic acid (20:5n-3), docosapentaenoic acid (22:5n-3), and 24:5n-3 in cell phospholipids was linearly related to the concentration of supplemented ALA over the range tested (1.8-72 microM). The accumulation of the post-D6D products of 22:5n-3, 24:6n-3 and DHA, in cell phospholipids was saturated at concentrations of >18 microM ALA. Supplementation of HepG2 cells with preformed DHA revealed that, although the accumulation of DHA in cell phospholipids approached saturation, the level of DHA in cell phospholipids was significantly greater compared with the accumulation of DHA from ALA, indicating that the accumulation of DHA from ALA was not limited by incorporation. The parallel pattern of accumulation of 24:6n-3 and DHA in response to increasing concentrations of ALA suggests that the competition between 24:5n-3 and ALA for D6D may contribute to the limited accumulation of DHA in cell membranes. 相似文献
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Stephen L. Pinkosky Sergey Filippov Rai Ajit K. Srivastava Jeffrey C. Hanselman Cheryl D. Bradshaw Timothy R. Hurley Clay T. Cramer Mark A. Spahr Ashley F. Brant Jacob L. Houghton Chris Baker Mark Naples Khosrow Adeli Roger S. Newton 《Journal of lipid research》2013,54(1):134-151
ETC-1002 (8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) is a novel investigational drug being developed for the treatment of dyslipidemia and other cardio-metabolic risk factors. The hypolipidemic, anti-atherosclerotic, anti-obesity, and glucose-lowering properties of ETC-1002, characterized in preclinical disease models, are believed to be due to dual inhibition of sterol and fatty acid synthesis and enhanced mitochondrial long-chain fatty acid β-oxidation. However, the molecular mechanism(s) mediating these activities remained undefined. Studies described here show that ETC-1002 free acid activates AMP-activated protein kinase in a Ca2+/calmodulin-dependent kinase β-independent and liver kinase β 1-dependent manner, without detectable changes in adenylate energy charge. Furthermore, ETC-1002 is shown to rapidly form a CoA thioester in liver, which directly inhibits ATP-citrate lyase. These distinct molecular mechanisms are complementary in their beneficial effects on lipid and carbohydrate metabolism in vitro and in vivo. Consistent with these mechanisms, ETC-1002 treatment reduced circulating proatherogenic lipoproteins, hepatic lipids, and body weight in a hamster model of hyperlipidemia, and it reduced body weight and improved glycemic control in a mouse model of diet-induced obesity. ETC-1002 offers promise as a novel therapeutic approach to improve multiple risk factors associated with metabolic syndrome and benefit patients with cardiovascular disease. 相似文献
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《Animal : an international journal of animal bioscience》2019,13(5):992-999
Pathogenesis of pregnancy toxemia (PT) is believed to be associated with the disruption of lipid metabolism. The present study aimed to explore the underlying mechanisms of lipid metabolism disorder in the livers of ewes with PT. In total, 10 pregnant ewes were fed normally (control group) whereas another 10 were subjected to 70% level feed restriction for 15 days to establish a pathological model of PT. Results showed that, as compared with the controls, the levels of blood β-hydroxybutyrate (BHBA), non-esterified fatty acids (NEFAs) and cholesterol were greater (P<0.05) and blood glucose level was lower (P<0.05) in PT ewes. The contents of NEFAs, BHBA, cholesterol and triglyceride were higher (P<0.05) and glycerol content was lower (P<0.05) in hepatic tissues of PT ewes than those of the controls. For ewes with PT, excessive fat vacuoles were observed in liver sections stained with hematoxylin–eosin; furthermore, inner structures of hepatocytes including nuclei, mitochondria and endoplasmic reticulum were damaged seriously according to the results of transmission electron microscope. Real-time PCR data showed that compared with the controls, the expression of hepatic genes involved in fatty acid oxidation (FAO) and triglyceride synthesis (TGS) was enhanced (P<0.05) whereas that related to acetyl-CoA metabolism (ACM) was repressed (P<0.05) in PT ewes. Generally, our results showed that negative energy balance altered the expression of genes involved in FAO, ACM and TGS, further caused lipid metabolism disorder in livers, resulting in PT of ewes. Our findings may provide the molecular basis for novel therapeutic strategies against this systemic metabolic disease in sheep. 相似文献
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Liting Chen Yuchang Li Chantal Sottas Anthoula Lazaris Stephanie K. Petrillo Peter Metrakos Lu Li Yuji Ishida Takeshi Saito Samuel Garza Vassilios Papadopoulos 《The Journal of biological chemistry》2022,298(6)
Mitochondrial ATPase ATAD3A is essential for cholesterol transport, mitochondrial structure, and cell survival. However, the relationship between ATAD3A and nonalcoholic fatty liver disease (NAFLD) is largely unknown. In this study, we found that ATAD3A was upregulated in the progression of NAFLD in livers from rats with diet-induced nonalcoholic steatohepatitis and in human livers from patients diagnosed with NAFLD. We used CRISPR-Cas9 to delete ATAD3A in Huh7 human hepatocellular carcinoma cells and used RNAi to silence ATAD3A expression in human hepatocytes isolated from humanized liver-chimeric mice to assess the influence of ATAD3A deletion on liver cells with free cholesterol (FC) overload induced by treatment with cholesterol plus 58035, an inhibitor of acetyl-CoA acetyltransferase. Our results showed that ATAD3A KO exacerbated FC accumulation under FC overload in Huh7 cells and also that triglyceride levels were significantly increased in ATAD3A KO Huh7 cells following inhibition of lipolysis mediated by upregulation of lipid droplet-binding protein perilipin-2. Moreover, loss of ATAD3A upregulated autophagosome-associated light chain 3-II protein and p62 in Huh7 cells and fresh human hepatocytes through blockage of autophagosome degradation. Finally, we show the mitophagy mediator, PTEN-induced kinase 1, was downregulated in ATAD3A KO Huh7 cells, suggesting that ATAD3A KO inhibits mitophagy. These results also showed that loss of ATAD3A impaired mitochondrial basal respiration and ATP production in Huh7 cells under FC overload, accompanied by downregulation of mitochondrial ATP synthase. Taken together, we conclude that loss of ATAD3A promotes the progression of NAFLD through the accumulation of FC, triglyceride, and damaged mitochondria in hepatocytes. 相似文献