本文選題：肥胖 + 斑馬魚(yú)�。� 參考：《生理學(xué)報(bào)》2017年01期

【摘要】：肥胖已經(jīng)成為全球性的公共衛(wèi)生問(wèn)題,嚴(yán)重影響人類的身體健康和生活品質(zhì)。本文運(yùn)用CRISPR/Cas9技術(shù),構(gòu)建了肥胖相關(guān)基因——瘦素受體(leptin receptor,lepr)和黑素皮質(zhì)素受體4(melanocortin-4 receptor,mc4r)的斑馬魚(yú)突變體,并對(duì)其進(jìn)行形態(tài)和功能分析。結(jié)果顯示,lepr~(-/-)和mc4r~(-/-)斑馬魚(yú)在胚胎和幼魚(yú)期沒(méi)有明顯異常,但在成年期,lepr~(-/-)和mc4r~(-/-)斑馬魚(yú)相比對(duì)照進(jìn)食增多、體重增加、體脂含量升高,呈現(xiàn)肥胖表型。血糖測(cè)定結(jié)果顯示,飽食喂養(yǎng)條件可以誘導(dǎo)lepr~(-/-)和mc4r~(-/-)成年斑馬魚(yú)出現(xiàn)糖耐量受損的現(xiàn)象。進(jìn)一步地,運(yùn)用real time RT-PCR對(duì)76個(gè)能量代謝相關(guān)基因在lepr~(-/-)和mc4r~(-/-)斑馬魚(yú)肝臟中轉(zhuǎn)錄表達(dá)水平進(jìn)行檢測(cè),并與Lep~(ob/ob)小鼠肝臟c DNA microarray的數(shù)據(jù)比較,發(fā)現(xiàn)胰島素/胰島素樣生長(zhǎng)因子信號(hào)轉(zhuǎn)導(dǎo)通路(insulin/IGF signaling pathway,ISS)相關(guān)的基因在lepr~(-/-)斑馬魚(yú)和Lep~(ob/ob)小鼠肝臟中表達(dá)變化具有較高的正相關(guān)性,提示肥胖調(diào)控網(wǎng)絡(luò)在進(jìn)化中維持了一定的功能保守性。
[Abstract]:Obesity has become a global public health problem, seriously affecting human health and quality of life. Using CRISPRR / Cas9 technique, the zebrafish mutants of leptin receptor and melanocortin-4 receptor 4 were constructed, and their morphology and function were analyzed. The results showed that there was no obvious abnormality in embryonic and juvenile stages of zebrafish, but in adult and adult, zebrafish fed more, gained weight, increased body fat, and showed obesity phenotype. The results showed that full feeding could induce impaired glucose tolerance in adult zebrafish. Furthermore, real time RT-PCR was used to detect the transcriptional expression of 76 energy metabolism-related genes in the liver of lepr-r ~ (- / -) and mc4r-r ~ (- / -) zebrafish, and the results were compared with those of Lep~ (ob/ob) mouse liver. It was found that the expression of insulin / insulin-like growth factor (insulin / insulin-like growth factor signal transduction pathway) genes in the liver of lepr-r ~ (-) zebrafish and Lep~ (ob/ob) mice was positively correlated with the expression of insulin / insulin-like growth factor signal transduction pathway (insulin / insulin-like growth factor signal transduction pathway). These results suggest that the obesity regulatory network maintains a certain degree of functional conservatism in evolution.
【作者單位】： 復(fù)旦大學(xué)基礎(chǔ)醫(yī)學(xué)院生物化學(xué)與分子生物學(xué)系代謝與分子醫(yī)學(xué)教育部重點(diǎn)實(shí)驗(yàn)室;
【基金】：supported by grants from the National Natural Science Foundation of China(No.81402582) the Scientific Research Foundation for Returned Scholars,Ministry of Education of China(No.48-12)
【分類號(hào)】：R589.2

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