Hypothalamic α7 nicotinic acetylcholine receptor (α7nAChR) is downregulated by TNFα-induced Let-7 overexpression driven by fatty acids.
Hypothalamic α7 nicotinic acetylcholine receptor (α7nAChR) is downregulated by TNFα-induced Let-7 overexpression driven by fatty acids.
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下丘脑α7 烟碱乙酰胆碱受体(α7nAChR) 被TNFα 诱导的脂肪酸驱动的Let-7 过度表达下调。
DOI：
10.1096/fj.202300439rr
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Torsoni,MarcioA
中科院分区：
文献类型：
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作者：
Simino,LaísAP;Baqueiro,MayaraN;Panzarin,Carolina;Lopes,PriscillaKF;Góis,MarianaM;Simabuco,FernandoM;Ignácio-Souza,LetíciaM;Milanski,Marciane;Ross,MichaelG;Desai,Mina;Torsoni,AdrianaS;Torsoni,MarcioA
α 7 nAChR对抗炎反射和控制食物摄入的神经肽的表达至关重要，但其表达可被环境因素降低。我们的目的是研究microRNA调节是否可能是短期暴露于致肥胖饮食后小鼠下丘脑α 7 nAchR下调的潜在机制。生物信息学分析显示Let-7 microRNA是调控Chrna 7的候选者，这一点通过荧光素酶测定得到了证实。暴露于致肥胖饮食3天的小鼠的Let-7a水平升高，α 7 nAChR水平降低，同时伴有下丘脑脂肪酸和TNFα含量。暴露于脂肪酸的下丘脑神经元细胞呈现较高的Let-7a和TNFα水平以及较低的Chrna 7表达，但当细胞用TLR 4抑制剂预处理时，Let-7a、TNFα和Chrna 7被拯救至正常水平。因此，脂肪酸过载触发下丘脑神经元细胞中TNFα诱导的Let-7过表达，其负调节α 7 nAChR，这一事件可能与小鼠的摄食过多和肥胖倾向有关。
The α7nAChR is crucial to the anti‐inflammatory reflex, and to the expression of neuropeptides that control food intake, but its expression can be decreased by environmental factors. We aimed to investigate whether microRNA modulation could be an underlying mechanism in the α7nAchR downregulation in mouse hypothalamus following a short‐term exposure to an obesogenic diet. Bioinformatic analysis revealedLet‐7microRNAs as candidates to regulateChrna7, which was confirmed by the luciferase assay. Mice exposed to an obesogenic diet for 3 days had increasedLet‐7aand decreased α7nAChR levels, accompanied by hypothalamic fatty acids and TNFα content. Hypothalamic neuronal cells exposed to fatty acids presented higherLet‐7aand TNFα levels and lowerChrna7expression, but when the cells were pre‐treated with TLR4 inhibitor,Let‐7a,TNFα, andChrna7were rescued to normal levels. Thus, the fatty acids overload trigger TNFα‐inducedLet‐7overexpression in hypothalamic neuronal cells, which negatively regulates α7nAChR, an event that can be related to hyperphagia and obesity predisposition in mice.