A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response.
A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response.
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DOI：
10.1016/j.celrep.2017.09.065
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发表时间：
2017-10-10
期刊：
影响因子：
8.8
通讯作者：
Postic C
中科院分区：
文献类型：
--
作者：
Iroz A;Montagner A;Benhamed F;Levavasseur F;Polizzi A;Anthony E;Régnier M;Fouché E;Lukowicz C;Cauzac M;Tournier E;Do-Cruzeiro M;Daujat-Chavanieu M;Gerbal-Chalouin S;Fauveau V;Marmier S;Burnol AF;Guilmeau S;Lippi Y;Girard J;Wahli W;Dentin R;Guillou H;Postic C
虽然成纤维细胞生长因子21（FGF 21）肝细胞因子的生理学益处记录在响应禁食，但在葡萄糖超负荷背景下FGF 21调节的信息很少。我们报道了过氧化物酶体增殖物激活受体α（peroxisome-proliferator-activated receptor α，PPARα）是一种空腹反应的核受体，与碳水化合物敏感性转录因子碳水化合物反应元件结合蛋白（carbohydrate-responsive element-binding protein，ChREBP）一起平衡FGF 21葡萄糖反应。微阵列分析表明，只有少数肝脏基因对禁食和葡萄糖的反应与Fgf 21相似。葡萄糖激发的Chrebp−/−小鼠表现出FGF 21产生的显著减少，这种减少是通过Chrebp−/−小鼠肝脏中活性ChREBP同种型的重新表达来挽救的。出乎意料的是，肝脏Pparα基因敲除小鼠的碳水化合物激发也证明了Fgf 21的PPARα依赖性葡萄糖应答，这与蔗糖偏好增加相关。这种迟钝的反应是由于在缺乏PPARα的肝细胞中Fgf 21启动子可及性降低和ChREBP与Fgf 21碳水化合物反应元件（ChoRE）结合减少所致。我们的研究报告，PPARα是必需的ChREBP诱导的FGF 21的葡萄糖反应。Fgf 21是一种独特的肝脏基因，可由分解代谢和合成代谢信号诱导。ChREBP介导的肝细胞中Fgf 21的诱导需要PPARα。Iroz等人证明Fgf 21是一种独特的肝脏基因，可由空腹和葡萄糖信号诱导，并且转录因子PPARα和ChREBP均通过肝脏FGF 21调节糖摄入的内分泌控制。
While the physiological benefits of the fibroblast growth factor 21 (FGF21) hepatokine are documented in response to fasting, little information is available on Fgf21 regulation in a glucose-overload context. We report that peroxisome-proliferator-activated receptor α (PPARα), a nuclear receptor of the fasting response, is required with the carbohydrate-sensitive transcription factor carbohydrate-responsive element-binding protein (ChREBP) to balance FGF21 glucose response. Microarray analysis indicated that only a few hepatic genes respond to fasting and glucose similarly to Fgf21. Glucose-challenged Chrebp−/− mice exhibit a marked reduction in FGF21 production, a decrease that was rescued by re-expression of an active ChREBP isoform in the liver of Chrebp−/− mice. Unexpectedly, carbohydrate challenge of hepatic Pparα knockout mice also demonstrated a PPARα-dependent glucose response for Fgf21 that was associated with an increased sucrose preference. This blunted response was due to decreased Fgf21 promoter accessibility and diminished ChREBP binding onto Fgf21 carbohydrate-responsive element (ChoRE) in hepatocytes lacking PPARα. Our study reports that PPARα is required for the ChREBP-induced glucose response of FGF21. Fgf21 is a unique hepatic gene inducible by both catabolic and anabolic signals The ChREBP-mediated induction of Fgf21 in hepatocytes requires PPARα Loss of PPARα impairs Fgf21 promoter accessibility at the ChoRE PPARα is required for the control of sucrose preference in vivo FGF21 is a hepatokine with beneficial metabolic effects, including control of sucrose preference. Iroz et al. demonstrate that Fgf21 is a unique hepatic gene inducible by both fasting and glucose signals and that the transcription factors PPARα and ChREBP both regulate the endocrine control of sugar intake by hepatic FGF21.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
4.8
作者：
Boergesen, Michael;Poulsen, Lars la Cour;Mandrup, Susanne
通讯作者：
Mandrup, Susanne
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
29
作者：
Badman, Michael K.;Pissios, Pavlos;Maratos-Flier, Eleftheria
通讯作者：
Maratos-Flier, Eleftheria
影响因子：
8.2
作者：
Iroz, Alison;Couty, Jean-Pierre;Postic, Catherine
通讯作者：
Postic, Catherine