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首页> 外文期刊>EBioMedicine >Role of Inflammatory Signaling in the Differential Effects of Saturated and Poly-unsaturated Fatty Acids on Peripheral Circadian Clocks
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Role of Inflammatory Signaling in the Differential Effects of Saturated and Poly-unsaturated Fatty Acids on Peripheral Circadian Clocks

机译：炎症信号在饱和和多不饱和脂肪酸对周围生物钟的差异作用中的作用

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Inflammatory signaling may play a role in high-fat diet (HFD)-related circadian clock disturbances that contribute to systemic metabolic dysregulation. Therefore, palmitate, the prevalent proinflammatory saturated fatty acid (SFA) in HFD and the anti-inflammatory, poly-unsaturated fatty acid (PUFA), docosahexaenoic acid (DHA), were analyzed for effects on circadian timekeeping and inflammatory responses in peripheral clocks. Prolonged palmitate, but not DHA, exposure increased the period of fibroblast Bmal1-dLuc rhythms. Acute palmitate treatment produced phase shifts of the Bmal1-dLuc rhythm that were larger in amplitude as compared to DHA. These phase-shifting effects were time-dependent and contemporaneous with rhythmic changes in palmitate-induced inflammatory responses. Fibroblast and differentiated adipocyte clocks exhibited cell-specific differences in the time-dependent nature of palmitate-induced shifts and inflammation. DHA and other inhibitors of inflammatory signaling (AICAR, cardamonin) repressed palmitate-induced proinflammatory responses and phase shifts of the fibroblast clock, suggesting that SFA-mediated inflammatory signaling may feed back to modulate circadian timekeeping in peripheral clocks.
机译：炎性信号可能在高脂饮食（HFD）相关的昼夜节律紊乱中起作用，而昼夜节律紊乱有助于系统性代谢异常。因此，分析了棕榈酸酯，HFD中常见的促炎性饱和脂肪酸（SFA）和抗炎，多不饱和脂肪酸（PUFA），二十二碳六烯酸（DHA）对昼夜节律和周围时钟中炎症反应的影响。长时间的棕榈酸酯暴露而不是DHA暴露增加了成纤维细胞Bmal1-dLuc节律的周期。与DHA相比，急性棕榈酸酯治疗产生的Bmal1-dLuc节律相移幅度更大。这些相移效应是时间依赖性的，并且与棕榈酸酯诱导的炎症反应的节律变化同时发生。成纤维细胞和分化的脂肪细胞时钟在棕榈酸酯诱导的转变和炎症的时间依赖性上表现出细胞特异性差异。 DHA和其他炎症信号抑制剂（AICAR，豆蔻素）可抑制棕榈酸酯诱导的促炎反应和成纤维细胞时钟的相移，表明SFA介导的炎症信号可能会反馈以调节外周时钟的生物钟。

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