瘦素通过迷走神经激活 JAK2-STAT3/AMPK 通路限制肝脏脂质积累和炎症。

IF 4.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
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引用次数: 0

摘要

背景:非酒精性脂肪性肝病(NAFLD)始于肝脏脂质堆积,而瘦素具有抗脂肪变性的特性。本研究探讨了瘦素通过迷走神经通路对肝脏脂肪变性和炎症的影响,而不依赖于食物摄入的抑制作用:方法:雄性 Sprague-Dawley 大鼠在高脂饮食(HFD)诱导肥胖模型后进行食物摄入匹配,腹腔注射瘦素或瘦素+利多卡因,持续 6 周。对照组大鼠接受等量生理盐水。对脂肪组织质量、非酒精性脂肪肝活动评分(NAS)、肝脏炎症因子、肝脏甘油三酯含量和肝脏脂质代谢相关蛋白水平进行了评估:结果:在有匹配摄入量的情况下,瘦素能改善高脂血症诱导的肝脏脂质积累,改善NAS,并降低肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和单核细胞趋化蛋白-1(MCP-1)的水平。利多卡因降低了信号转导子和转录激活子3(p-STAT3)在脊髓束核(NTS)中的磷酸化表达,并减弱了瘦素介导的改善作用。瘦素增加了下丘脑磷酸化 Janus 激酶 2(p-JAK2)和 p-STAT3 的表达,以及线粒体呼吸链相关基因的表达。瘦素还会增加肝脏磷酸化腺苷-5'-单磷酸激活的蛋白激酶(p-AMPK)的表达及其下游靶标乙酰辅酶A羧化酶1(ACC1)的磷酸化,从而减少脂肪的新生:我们的研究结果表明,瘦素通过迷走神经通路激活JAK2-STAT3/AMPK通路,从而改善肝脏脂质积累和炎症,而不受摄入抑制作用的影响。瘦素有可能成为早期治疗非酒精性脂肪肝的药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Leptin limits hepatic lipid accumulation and inflammation via vagal activation of the JAK2-STAT3/AMPK pathway
Non-Alcoholic Fatty Liver Disease (NAFLD) begins with hepatic lipid accumulation, and leptin has antisteatosis properties. In this study, we investigated the effects of leptin on hepatic steatosis and inflammation through the vagal pathway independently of the inhibitory effect of food intake. Male Sprague-Dawley rats were matched for food intake after the high-fat diet (HFD)-induced obesity model and were injected intraperitoneally with leptin or leptin + lidocaine for 6 weeks. Control rats received equal volumes of saline. Adipose tissue mass, NAFLD activity scores (NAS), hepatic inflammatory factors, hepatic triglyceride content and hepatic lipid metabolism-related protein levels were evaluated. Leptin ameliorated HFD-induced hepatic lipid accumulation, improved NAS, and decreased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) levels in the presence of matched intake. Lidocaine decreased the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) expression in the nucleus tractus solitarius (NTS) and abrogated the leptin-mediated improvement. Leptin increased hypothalamic phosphorylated Janus kinase 2 (p-JAK2) and p-STAT3 expression, as well as the expression of mitochondrial respiratory chain-related genes. Leptin also increased hepatic phosphorylated adenosine 5′-monophosphate-activated protein kinase (p-AMPK) expression and phosphorylation of its downstream target acetyl Co A carboxylase 1 (ACC1), reducing de novo lipogenesis. Our results suggest that leptin ameliorated hepatic lipid accumulation and inflammation by activating the JAK2-STAT3/AMPK pathway through the vagal pathway independently of the inhibitory effect of ingestion. Leptin has the potential to be a drug for early NAFLD treatment.
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来源期刊
Journal of Nutritional Biochemistry
Journal of Nutritional Biochemistry 医学-生化与分子生物学
CiteScore
9.50
自引率
3.60%
发文量
237
审稿时长
68 days
期刊介绍: Devoted to advancements in nutritional sciences, The Journal of Nutritional Biochemistry presents experimental nutrition research as it relates to: biochemistry, molecular biology, toxicology, or physiology. Rigorous reviews by an international editorial board of distinguished scientists ensure publication of the most current and key research being conducted in nutrition at the cellular, animal and human level. In addition to its monthly features of critical reviews and research articles, The Journal of Nutritional Biochemistry also periodically publishes emerging issues, experimental methods, and other types of articles.
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