Regulation of energy metabolism by interleukin-1 beta, but not by interleukin-6, is mediated by nitric oxide in primary cultured rat hepatocytes
Regulation of energy metabolism by interleukin-1 beta, but not by interleukin-6, is mediated by nitric oxide in primary cultured rat hepatocytes
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DOI：
10.1016/0167-4889(95)00188-3
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发表时间：
1996-03-27
影响因子：
5.1
通讯作者：
Okumura, T
中科院分区：
文献类型：
--
作者：
Kitade, H;Kanemaki, T;Okumura, T
在原代培养的大鼠肝细胞中研究了炎性细胞因子（白细胞介素-1 β、白细胞介素-6和肿瘤坏死因子-α）对能量代谢的影响，测定了腺嘌呤核苷酸（ATP、ADP和AMP）含量、乳酸产生、反映肝线粒体氧化还原状态的酮体比率（乙酰乙酸/β-羟基丁酸）（NAD（+）/NADH）和一氧化氮形成。胰岛素可增加肝细胞ATP含量，在培养8-12 h后作用最大。白细胞介素-1 β和白细胞介素-6均能显著抑制ATP的增加，且呈时间和剂量依赖性，而肿瘤坏死因子-α则无此作用。白细胞介素-1 β和白细胞介素-6也能刺激乳酸的产生。在同一时期，白细胞介素-1 β而不是白细胞介素-6降低了酮体比率。此外，白细胞介素-1 β显著刺激肝细胞中一氧化氮的形成，并且这种增加被N-G-单甲基-L-精氨酸（一氧化氮合酶抑制剂）和白细胞介素-1受体拮抗剂阻断。N-G-单甲基-L-精氨酸逆转了白细胞介素-1 β诱导的ATP增加、酮体比率降低和乳酸产生增加的抑制。IL-1受体拮抗剂完全消除了IL-1 β诱导的所有效应。这些结果表明，白细胞介素-1 β β和白细胞介素-6通过不同的机制影响胰岛素诱导的大鼠肝细胞能量代谢。具体而言，白细胞介素-1 β通过引起线粒体功能障碍来抑制ATP合成，这一过程可能由一氧化氮介导。
The effects of inflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha) on energy metabolism were studied in primary cultured rat hepatocytes, Adenine nucleotide (ATP, ADP, and AMP) content, lactate production, the ketone body ratio (acetoacetate/beta-hydroxybutyrate) reflecting the liver mitochondrial redox state (NAD(+)/NADH), and nitric oxide formation were measured. Insulin increased ATP content in hepatocytes and had a maximal effect after 8-12 h of culture. Both interleukin-1 beta and interleukin-6, but not tumor necrosis factor-alpha, significantly inhibited the ATP increase time- and dose-dependently, Interleukin-1 beta and interleukin-6 also stimulated lactate production. During the same period, interleukin-1 beta but not interleukin-6 decreased the ketone body ratio. Furthermore, intedeukin-1 beta markedly stimulated nitric oxide formation in hepatocytes, and this increase was blocked by N-G-monomethyl-L-arginine (a nitric oxide synthase inhibitor) and by interleukin-l receptor antagonist. N-G-monomethyl-L-arginine reversed inhibition of the ATP increase, decrease in the ketone body ratio, and increase in lactate production, which were induced by interleukin-1 beta. Interleukin-1 receptor antagonist completely abolished all of the effects induced by interleukin-1 beta. These results demonstrated that interleukin-1 beta beta and interleukin-6 affect the insulin-induced energy metabolism in rat hepatocytes by different mechanisms. Specifically, interleukin-1 beta inhibits ATP synthesis by causing the mitochondrial dysfunction, a process which may be mediated by nitric oxide.