Sexual dimorphic effects of igf1 deficiency on metabolism in zebrafish.
Sexual dimorphic effects of igf1 deficiency on metabolism in zebrafish.
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DOI：
10.3389/fendo.2022.879962
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发表时间：
2022
影响因子：
5.2
通讯作者：
Yin, Zhan
中科院分区：
文献类型：
--
作者：
Zeng, Ningmei;Bao, Jiankang;Shu, TingTing;Shi, Chuang;Zhai, Gang;Jin, Xia;He, Jiangyan;Lou, Qiyong;Yin, Zhan
胰岛素样生长因子1 （IGF1）是生长激素(GH)/IGF1轴对哺乳动物体细胞生长调节的重要影响因子。然而，其在斑马鱼体内的功能尚未得到充分的研究。在本研究中，利用CRISPR/Cas9技术构建了igf1缺陷斑马鱼模型。在这项研究中，所有的结果都是在雄性和雌性动物身上进行的。雄性和雌性缺乏igf1的斑马鱼的生长都减少了。igf1缺乏导致胰岛素、igf2和igf3转录表达水平显著互补上调。这表明igf2和igf3可能具有冗余功能。而gh1表达上调仅在igf1缺陷的雌性中检测到。同时，只有igf1缺陷的男性才会出现显著的生长迟缓、脂肪肝、核糖体S6 （S6）激活水平降低。另一方面，严重的高血糖，磷酸化的细胞外信号调节激酶（ERK1/2）的转录表达水平升高，肝脏乳酸/丙酮酸（L/P）比率降低，只能在igf1缺陷的女性中观察到。在原代培养的igf1缺乏的女性肝细胞中记录了葡萄糖摄取受损，但在男性中没有。有趣的是，暴露于17 - β -雌二醇（E2）可以部分改善igf1缺陷男性的脂肪肝缺陷和AKT/mTOR信号的激活。我们的研究表明，IGF1在斑马鱼的体细胞调节中具有重要功能，具有不对称性别相关的后果。因此，我们的数据表明，在雄性斑马鱼中，IGF1优先需要激活AKT/mTOR信号，但在雌性斑马鱼中则需要激活葡萄糖摄取。
Insulin-like growth factor 1 (IGF1) is an essential effector of the growth hormone (GH)/IGF1 axis for somatic growth regulation in mammals. However, its functions have not been thoroughly investigated in zebrafish in vivo. In this study, the igf1-deficient zebrafish model was developed using the CRISPR/Cas9 technique. In this study all the results were performed on both male and female animals. The growth of both male and female igf1-deficient zebrafish were reduced. The igf1 deficiency leads to significant complementary up-regulation of transcriptional expression levels of insulin, igf2 and igf3. This suggested that igf2 and igf3 may act with redundant functions. While the upregulation of gh1 expression can only be detected in igf1-deficient females. At the same time, significant growth retardation, fatty liver, reduced activated levels of ribosomal S6 (S6) are seen only in igf1-deficient males. On the other hand, significant hyperglycemia, elevated transcriptional expression levels of phosphenolpyruvate carboxykinase (pepck) and levels of phosphorylated extracellular signal-regulated kinase (ERK1/2), with additional reduced hepatic lactate/pyruvate (L/P) ratios can only observed in igf1-deficient females. Impaired glucose uptake has been recorded in the primary cultured hepatocytes from igf1-deficient females, but not males. Intriguingly, exposure to 17beta-estroadiol (E2) can partially ameliorated the defects of fatty liver and activation of AKT/mTOR signaling in igf1-deficient males. Our studies demonstrate the significant functions of IGF1 on somatic regulation in zebrafish, with asymmetric gender-related consequences. Our data thus suggest that the zebrafish IGF1 is preferentially required for the activation of AKT/mTOR signaling in male zebrafish, but glucose uptake in females.
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影响因子：
48
作者：
Mali, Prashant;Esvelt, Kevin M.;Church, George M.
通讯作者：
Church, George M.
影响因子：
4.8
作者：
Li, Dongliang;Lou, Qiyong;Yin, Zhan
通讯作者：
Yin, Zhan
影响因子：
2.7
作者：
Nornberg, Bruna Felix;Figueiredo, Marcio Azevedo;Marins, Luis Fernando
通讯作者：
Marins, Luis Fernando
影响因子：
10.5
作者：
POWELLBRAXTON, L;HOLLINGSHEAD, P;STEWART, TA
通讯作者：
STEWART, TA
影响因子：
64.5
作者：
LIU, JP;BAKER, J;EFSTRATIADIS, A
通讯作者：
EFSTRATIADIS, A