The Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education, Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
Chongqing Key Laboratory for Oral Diseases and Biomedical Science, College of Stomatology, Chongqing Medical University, Chongqing, China.
FASEB J. 2020 May;34(5):7058-7074. doi: 10.1096/fj.201901836RR. Epub 2020 Apr 10.
The role of central juxtaposed with another zinc finger gene 1 (JAZF1) in glucose regulation remains unclear. Here, we activated mediobasal hypothalamus (MBH) JAZF1 in high-fat diet (HFD)-fed rats by an adenovirus expressing JAZF1 (Ad-JAZF1). We evaluated the changes in the hypothalamic insulin receptor (InsR)-PI3K-Akt-AMPK pathway and hepatic glucose production (HGP). To investigate the impact of MBH Ad-JAZF1 on HGP, we activated MBH JAZF1 in the presence or absence of ATP-dependent potassium (K ) channel inhibition, hepatic branch vagotomy (HVG), or an AMPK activator (AICAR). In HFD-fed rats, MBH Ad-JAZF1 decreased body weight and food intake, and inhibited HGP by increasing hepatic insulin signaling. Under insulin stimulation, MBH Ad-JAZF1 increased InsR and Akt phosphorylation, and phosphatidylinositol 3, 4, 5-trisphosphate (PIP3) formation; however, AMPK phosphorylation was decreased in the hypothalamus. The positive effect of MBH JAZF1 on hepatic insulin signaling and HGP was prevented by treatment with a K channel inhibitor or HVG. The metabolic impact of hypothalamic JAZF1 was also blocked by MBH AICAR. Ad-JAZF1 treatment in SH-SY5Y cells resulted in an elevation of InsR and Akt phosphorylation following insulin stimulation. Our findings show that hypothalamic JAZF1 regulates HGP via the InsR-PI3K-Akt-AMPK pathway and K channels.
中央与另一个锌指基因 1（JAZF1）在葡萄糖调节中的作用尚不清楚。在这里，我们通过表达 JAZF1 的腺病毒（Ad-JAZF1）激活高脂肪饮食（HFD）喂养大鼠的中基底下丘脑（MBH）JAZF1。我们评估了下丘脑胰岛素受体（InsR）-PI3K-Akt-AMPK 通路和肝葡萄糖产生（HGP）的变化。为了研究 MBH Ad-JAZF1 对 HGP 的影响，我们在存在或不存在 ATP 依赖性钾（K）通道抑制、肝分支迷走神经切断术（HVG）或 AMPK 激活剂（AICAR）的情况下激活 MBH JAZF1。在 HFD 喂养的大鼠中，MBH Ad-JAZF1 降低了体重和食物摄入量，并通过增加肝胰岛素信号来抑制 HGP。在胰岛素刺激下，MBH Ad-JAZF1 增加了 InsR 和 Akt 磷酸化，并形成了磷脂酰肌醇 3,4,5-三磷酸（PIP3）；然而，下丘脑的 AMPK 磷酸化减少。用 K 通道抑制剂或 HVG 处理可防止 MBH JAZF1 对肝胰岛素信号和 HGP 的正向作用。下丘脑 JAZF1 的代谢影响也被 MBH AICAR 阻断。Ad-JAZF1 在 SH-SY5Y 细胞中的处理导致胰岛素刺激后 InsR 和 Akt 磷酸化的升高。我们的研究结果表明，下丘脑 JAZF1 通过 InsR-PI3K-Akt-AMPK 通路和 K 通道调节 HGP。
