Curcumin restrains hepatic glucose production by blocking cAMP/PKA signaling and reducing acetyl CoA accumulation in high-fat diet (HFD)-fed mice
Curcumin restrains hepatic glucose production by blocking cAMP/PKA signaling and reducing acetyl CoA accumulation in high-fat diet (HFD)-fed mice
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姜黄素通过阻断 cAMP/PKA 信号传导并减少高脂饮食 (HFD) 喂养的小鼠中乙酰辅酶 A 的积累来抑制肝葡萄糖的产生
DOI：
10.1016/j.mce.2018.02.018
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发表时间：
2018-10
影响因子：
4.1
通讯作者：
Yuan Xie
中科院分区：
文献类型：
--
作者：
Zixia Wang;Dan Xu;Linlin She;Yirui Zhang;Qingli Wei;Jiye Aa;Guangji Wang;Baolin Liu;Yuan Xie
本研究旨在探讨姜黄素是否通过调节第二信使cAMP降低过度的肝葡萄糖生成（HGP）。方法高脂饮食（HFD）喂养的小鼠每天口服二甲双胍（200 mg/kg）或姜黄素（50 mg/kg），持续10周。同时，我们用棕榈酸酯（PA）刺激小鼠原代肝细胞。结果姜黄素通过保留PDE 4 B诱导减少肝cAMP的积累，从而通过阻断cAMP/PKA激活抑制肝细胞的形成。姜黄素通过减少游离脂肪酸摄取减少脂质沉积，并通过对抗线粒体氧化防止乙酰辅酶A积累。由于抑制乙酰辅酶A的积累，姜黄素保护丙酮酸脱氢酶（PDH）的活性和抑制丙酮酸羧化酶（PC），限制线粒体丙酮酸从氧化到代谢的转变通过carboxylation.ConclusionCurcumin保护PDE 4 B活性减少cAMP的积累，并通过减少线粒体脂肪酸氧化抑制乙酰辅酶A的生产，从而抑制丙酮酸驱动的肝葡萄糖的生产。
ObjectiveThis study is designed to investigate whether curcumin reduces excessive hepatic glucose production (HGP) via regulation of second messenger cAMP.MethodsHigh-fat diet (HFD)-fed mice were orally administrated of metformin (200 mg/kg) or curcumin (50 mg/kg) daily for 10 weeks. Meanwhile, we stimulated mouse primary hepatocytes with palmitate (PA).ResultsCurcumin reduced hepatic cAMP accumulation by preserving PDE4B induction, thereby suppressing gluconeogenesis via blocking cAMP/PKA activation. Curcumin reduced lipid deposition by reducing free fatty acid uptake and prevented acetyl CoA accumulation by combating mitochondrial oxidation. As a result from inhibiting acetyl CoA accumulation, curcumin protected pyruvate dehydrogenase (PDH) activity and inhibited pyruvate carboxylase (PC), limiting the shift of mitochondrial pyruvate from oxidation to gluconeogenesis via the carboxylation.ConclusionCurcumin reduced cAMP accumulation by preserving PDE4B activity and inhibited acetyl CoA production by reducing mitochondrial fatty acid oxidation, thereby restraining pyruvate-driven hepatic glucose production.
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影响因子：
2
作者：
R. Dmochowski
通讯作者：
R. Dmochowski
影响因子：
29
作者：
Lin HV;Accili D
通讯作者：
Accili D
影响因子：
11.4
作者：
Xu, Wu;Kasper, Lawryn H.;Brindle, Paul K.
通讯作者：
Brindle, Paul K.