Altered hepatic glucose homeostasis in AnxA6-KO mice fed a high-fat diet.
Altered hepatic glucose homeostasis in AnxA6-KO mice fed a high-fat diet.
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DOI：
10.1371/journal.pone.0201310
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Grewal T
中科院分区：
文献类型：
--
作者：
Cairns R;Fischer AW;Blanco-Munoz P;Alvarez-Guaita A;Meneses-Salas E;Egert A;Buechler C;Hoy AJ;Heeren J;Enrich C;Rentero C;Grewal T
膜联蛋白A6（AnxA 6）控制胆固醇和膜转运的内分泌和胞吐，并调节甘油三酯的积累和储存。此外，AnxA 6在许多不同的细胞类型中作为生长因子受体及其效应通路的负调节因子的支架蛋白。在这里，我们研究了AnxA 6在调节全身脂质代谢和胰岛素调节的葡萄糖稳态中的作用。因此，野生型（WT）和AnxA 6敲除（KO）小鼠喂食高脂肪饮食（HFD）17周。在HFD喂养过程中，与对照组相比，AnxA 6-KO小鼠体重增加较少，这与肥胖减少相关。喂食HFD的对照组和AnxA 6-KO小鼠的全身甘油三酯和胆固醇水平相当，AnxA 6-KO小鼠的高密度脂蛋白（HDL）水平略微升高，富含甘油三酯的脂蛋白（TRL）水平降低。AnxA 6-KO小鼠在口服葡萄糖和胰岛素耐量试验（OGTT，ITT）中显示出胰岛素敏感性改善的趋势，这与肝脏提取物中蛋白激酶B（Akt）和核糖体蛋白S6激酶（S6）的胰岛素诱导磷酸化增加相关。然而，HFD喂养的AnxA 6-KO小鼠未能下调肝再生，尽管与对照组相似的胰岛素水平和胰岛素信号传导活性，以及胰岛素敏感性转录因子的表达谱。此外，观察到HFD和普通饲料喂养的AnxA 6-KO动物的肝脏中糖原储存增加。连同在AnxA 6耗尽的HuH 7肝细胞中在胰岛素暴露后不能减少葡萄糖产生，这暗示AnxA 6有助于肝葡萄糖代谢的微调，其对健康和疾病中葡萄糖的全身控制具有潜在后果。
Annexin A6 (AnxA6) controls cholesterol and membrane transport in endo- and exocytosis, and modulates triglyceride accumulation and storage. In addition, AnxA6 acts as a scaffolding protein for negative regulators of growth factor receptors and their effector pathways in many different cell types. Here we investigated the role of AnxA6 in the regulation of whole body lipid metabolism and insulin-regulated glucose homeostasis. Therefore, wildtype (WT) and AnxA6-knockout (KO) mice were fed a high-fat diet (HFD) for 17 weeks. During the course of HFD feeding, AnxA6-KO mice gained less weight compared to controls, which correlated with reduced adiposity. Systemic triglyceride and cholesterol levels of HFD-fed control and AnxA6-KO mice were comparable, with slightly elevated high density lipoprotein (HDL) and reduced triglyceride-rich lipoprotein (TRL) levels in AnxA6-KO mice. AnxA6-KO mice displayed a trend towards improved insulin sensitivity in oral glucose and insulin tolerance tests (OGTT, ITT), which correlated with increased insulin-inducible phosphorylation of protein kinase B (Akt) and ribosomal protein S6 kinase (S6) in liver extracts. However, HFD-fed AnxA6-KO mice failed to downregulate hepatic gluconeogenesis, despite similar insulin levels and insulin signaling activity, as well as expression profiles of insulin-sensitive transcription factors to controls. In addition, increased glycogen storage in livers of HFD- and chow-fed AnxA6-KO animals was observed. Together with an inability to reduce glucose production upon insulin exposure in AnxA6-depleted HuH7 hepatocytes, this implicates AnxA6 contributing to the fine-tuning of hepatic glucose metabolism with potential consequences for the systemic control of glucose in health and disease.
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影响因子：
20.1
作者：
Drechsler M;de Jong R;Rossaint J;Viola JR;Leoni G;Wang JM;Grommes J;Hinkel R;Kupatt C;Weber C;Döring Y;Zarbock A;Soehnlein O
通讯作者：
Soehnlein O
DOI：
10.1152/ajpendo.2000.279.5.e1003
发表时间：
2000-11-01
影响因子：
5.1
作者：
Chirieac, DV;Chirieac, LR;Sparks, JD
通讯作者：
Sparks, JD
人类脂肪肝病：旧问题和新见解。
DOI：
10.1126/science.1204265
发表时间：
2011-06-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cohen JC;Horton JD;Hobbs HH
通讯作者：
Hobbs HH
DOI：
10.1016/j.bbamcr.2016.10.017
发表时间：
2017-06-01
影响因子：
5.1
作者：
Enrich, Carlos;Rentero, Carles;Grewal, Thomas
通讯作者：
Grewal, Thomas
影响因子：
7.3
作者：
Alvarez-Guaita, Anna;Vila de Muga, Sandra;Rentero, Carles
通讯作者：
Rentero, Carles