A diurnal serum lipid integrates hepatic lipogenesis and peripheral fatty acid use.
A diurnal serum lipid integrates hepatic lipogenesis and peripheral fatty acid use.
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DOI：
10.1038/nature12710
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发表时间：
2013-10-24
期刊：
影响因子：
64.8
通讯作者：
Lee, Chih-Hao
中科院分区：
文献类型：
--
作者：
Liu, Sihao;Brown, Jonathan D.;Stanya, Kristopher J.;Homan, Edwin;Leidl, Mathias;Inouye, Karen;Bhargava, Prerna;Gangl, Matthew R.;Dai, Lingling;Hatano, Ben;Hotamisligil, Goekhan S.;Saghatelian, Alan;Plutzky, Jorge;Lee, Chih-Hao
食物摄入增加了肝脏新生脂肪生成的活性，该活性介导了葡萄糖转化为脂肪以供储存或利用。在小鼠身上，这个程序遵循昼夜节律，在夜间进食时达到顶峰，并在白天被REV-ERBα/β和含有HDAC3的复合体抑制。控制暗周期中有节奏的脂质合成的转录激活物仍然没有明确的定义。肝脏脂肪生成的紊乱也与全身代谢表型有关，这表明肝脏的脂肪生成与周围组织沟通，控制能量底物的动态平衡。在这里，我们确定了肝脏中依赖于PPARδ的从头造脂途径，该途径通过循环脂质调节肌肉对脂肪的利用。核受体PPARδ控制着暗/取食周期中成脂基因的日常表达。肝脏特异性PPARδ活性增加，而肝细胞PPARD缺失减少，肌肉脂肪酸(FA)摄取。无偏代谢产物分析确定PC(18：0/18：1)或1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine(SOPC)是一种受肝脏PPARδ活性调节的血脂。PC(18：0/18：1)通过肌肉PPARα降低餐后血脂水平，增加FA利用率。在db/db小鼠中，高脂肪喂养减少了PC(18：0/18：1)的节律性产生，而PC(18：0/18：1)改善了代谢稳态。这些发现揭示了一个集成的调节电路，通过协调两个密切相关的核受体的活动，将肝脏中的脂肪合成与肌肉中的能量利用联系起来。这些数据表明，在包括肥胖在内的代谢紊乱中，肝脏PPARδ-PC(18：0/18：1)信号的昼夜变化。
Food intake increases the activity of hepatic de novo lipogenesis, which mediates the conversion of glucose to fats for storage or utilization. In mice, this program follows a circadian rhythm that peaks with nocturnal feeding and is repressed by Rev-erbα/β and an HDAC3-containing complex during the day. The transcriptional activators controlling rhythmic lipid synthesis in the dark cycle remain poorly defined. Disturbances in hepatic lipogenesis are also associated with systemic metabolic phenotypes, suggesting that lipogenesis in the liver communicates with peripheral tissues to control energy substrate homeostasis. Here we identify a PPARδ-dependent de novo lipogenic pathway in the liver that modulates fat utilization by muscle via a circulating lipid. The nuclear receptor PPARδ controls diurnal expression of lipogenic genes in the dark/feeding cycle. Liver-specific PPARδ activation increases, while hepatocyte-Ppard deletion reduces, muscle fatty acid (FA) uptake. Unbiased metabolite profiling identifies PC(18:0/18:1), or 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC), as a serum lipid regulated by diurnal hepatic PPARδ activity. PC(18:0/18:1) reduces postprandial lipid levels and increases FA utilization through muscle PPARα. High fat feeding diminishes rhythmic production of PC(18:0/18:1), whereas PC(18:0/18:1) administration in db/db mice improves metabolic homeostasis. These findings reveal an integrated regulatory circuit coupling lipid synthesis in the liver to energy utilization in muscle by coordinating the activity of two closely related nuclear receptors. These data implicate alterations in diurnal hepatic PPARδ-PC(18:0/18:1) signaling in metabolic disorders including obesity.
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影响因子：
64.5
作者：
Cao H;Gerhold K;Mayers JR;Wiest MM;Watkins SM;Hotamisligil GS
通讯作者：
Hotamisligil GS
影响因子：
29
作者：
Reilly SM;Bhargava P;Liu S;Gangl MR;Gorgun C;Nofsinger RR;Evans RM;Qi L;Hu FB;Lee CH
通讯作者：
Lee CH
影响因子：
7.7
作者：
Floegel A;Stefan N;Yu Z;Mühlenbruch K;Drogan D;Joost HG;Fritsche A;Häring HU;Hrabě de Angelis M;Peters A;Roden M;Prehn C;Wang-Sattler R;Illig T;Schulze MB;Adamski J;Boeing H;Pischon T
通讯作者：
Pischon T
DOI：
10.1093/bioinformatics/btr079
发表时间：
2011-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Brown M;Wedge DC;Goodacre R;Kell DB;Baker PN;Kenny LC;Mamas MA;Neyses L;Dunn WB
通讯作者：
Dunn WB
影响因子：
64.8
作者：
Fu, J;Gaetani, S;Piomelli, D
通讯作者：
Piomelli, D