Aldo-keto reductase 1B7 is a target gene of FXR and regulates lipid and glucose homeostasis
Aldo-keto reductase 1B7 is a target gene of FXR and regulates lipid and glucose homeostasis
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DOI：
10.1194/jlr.m015859
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发表时间：
2011-08-01
影响因子：
6.5
通讯作者：
Zhang, Yanqiao
中科院分区：
文献类型：
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作者：
Ge, Xuemei;Yin, Liya;Zhang, Yanqiao
醛酮还原酶 1B7 (AKR1B7) 被认为在脂质过氧化副产物的解毒中发挥作用。在本文中，我们证明核受体法尼醇 X 受体 (FXR) 的激活会诱导肝脏和肠道中的 AKR1B7 表达，并降低肠道中而非肝脏中脂质过氧化最终产物丙二醛 (MDA) 的水平。为了确定 AKR1B7 是否调节体内 MDA 水平，我们在肝脏中过表达 AKR1B7。肝脏中 AKR1B7 的过度表达对肝脏或血浆 MDA 水平没有影响。有趣的是，AKR1B7 的肝脏表达显着降低了野生型和糖尿病 db/db 小鼠的血浆葡萄糖水平，这与肝脏糖异生减少有关。 AKR1B7 的肝脏表达还显着降低 db/db 小鼠的肝脏甘油三酯和胆固醇水平。这些数据揭示了 AKR1B7 在脂质和葡萄糖代谢中的新功能，并表明 AKR1B7 可能不会在肝脏中脂质过氧化物的解毒中发挥作用。 AKR1B7 可能是治疗与糖尿病相关的脂肪肝疾病的治疗靶点。-Ge, X., L. Yin, H. Ma, T. Li, J. Y. L.Chiang, 和 Y.Zhang。醛酮还原酶 1B7 是 FXR 的靶基因，调节脂质和葡萄糖稳态。 J.脂质研究。 2011. 52: 1561-1568。
Aldo-keto reductase 1B7 (AKR1B7) is proposed to play a role in detoxification of by-products of lipid peroxidation. In this article, we show that activation of the nuclear receptor farnesoid X receptor (FXR) induces AKR1B7 expression in the liver and intestine, and reduces the levels of malondialdehyde (MDA), the end product of lipid peroxidation, in the intestine but not in the liver. To determine whether AKR1B7 regulates MDA levels in vivo, we overexpressed AKR1B7 in the liver. Overexpression of AKR1B7 in the liver had no effect on hepatic or plasma MDA levels. Interestingly, hepatic expression of AKR1B7 significantly lowered plasma glucose levels in both wild-type and diabetic db/db mice, which was associated with reduced hepatic gluconeogenesis. Hepatic expression of AKR1B7 also significantly lowered hepatic triglyceride and cholesterol levels in db/db mice. These data reveal a novel function for AKR1B7 in lipid and glucose metabolism and suggest that AKR1B7 may not play a role in detoxification of lipid peroxides in the liver. AKR1B7 may be a therapeutic target for treatment of fatty liver disease associated with diabetes mellitus.-Ge, X., L. Yin, H. Ma, T. Li, J. Y. L. Chiang, and Y. Zhang. Aldo-keto reductase 1B7 is a target gene of FXR and regulates lipid and glucose homeostasis. J. Lipid Res. 2011. 52: 1561-1568.