High protein diet-induced metabolic changes are transcriptionally regulated via KLF15-dependent and independent pathways.
High protein diet-induced metabolic changes are transcriptionally regulated via KLF15-dependent and independent pathways.
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DOI：
10.1016/j.bbrc.2021.10.027
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发表时间：
2021-10
影响因子：
3.1
通讯作者：
Zahra Mehrazad Saber;Yoshinori Takeuchi;Yoshikazu Sawada;Yuichi Aita;Man Hei Ho;S. Karkoutly;Du Tao;Kyoka Katabami;C. Ye;Yuki Murayama;Akito Shikama;Yukari Masuda;Y. Izumida;Takafumi Miyamoto;T. Matsuzaka;T. Sugasawa;K. Takekoshi;Y. Kawakami;H. Shimano;N. Yahagi
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文献类型：
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作者：
Zahra Mehrazad Saber;Yoshinori Takeuchi;Yoshikazu Sawada;Yuichi Aita;Man Hei Ho;S. Karkoutly;Du Tao;Kyoka Katabami;C. Ye;Yuki Murayama;Akito Shikama;Yukari Masuda;Y. Izumida;Takafumi Miyamoto;T. Matsuzaka;T. Sugasawa;K. Takekoshi;Y. Kawakami;H. Shimano;N. Yahagi
高蛋白饮食（HPD）是预防和治疗许多疾病的一种经济且积极的方法。据信，转录调节负责 HPD 喂养后的适应，Kruppel 样因子 15 (KLF15) 是一种锌指转录因子，已被证明对氨基酸、脂质和葡萄糖代谢进行转录调节，已知至少部分参与这种 HPD 反应。为了更深入地了解 HPD 控制肝脏氨基酸代谢相关基因表达的分子机制，我们对短期（3 天）喂食 HPD 的小鼠进行了 RNA-seq 分析。与低蛋白饮食相比，HPD 喂养显着增加了参与所有 20 种氨基酸分解的酶的肝脏表达。此外，使用 KLF15 敲除小鼠和体内 Ad-luc 分析系统，我们能够识别出 Cth（胱硫醚伽马裂解酶）作为 KLF15 转录的新靶基因，以及 Ast（天冬氨酸转氨酶）作为 KLF15 独立基因的一个例子，尽管它对 HPD 具有显着的响应性。这些发现为我们阐明氨基酸代谢途径的整个转录调控机制提供了线索。
High protein diet (HPD) is an affordable and positive approach in prevention and treatment of many diseases. It is believed that transcriptional regulation is responsible for adaptation after HPD feeding and Kruppel-like factor 15 (KLF15), a zinc finger transcription factor that has been proved to perform transcriptional regulation over amino acid, lipid and glucose metabolism, is known to be involved at least in part in this HPD response. To gain more insight into molecular mechanisms by which HPD controls expressions of genes involved in amino acid metabolism in the liver, we performed RNA-seq analysis of mice fed HPD for a short period (3 days). Compared to a low protein diet, HPD feeding significantly increased hepatic expressions of enzymes involved in the breakdown of all the 20 amino acids. Moreover, using KLF15 knockout mice and in vivo Ad-luc analytical system, we were able to identifyCth(cystathionine gamma-lyase) as a new target gene of KLF15 transcription as well asAst(aspartate aminotransferase) as an example of KLF15-independent gene despite its remarkable responsiveness to HPD. These findings provide us with a clue to elucidate the entire transcriptional regulatory mechanisms of amino acid metabolic pathways.