Hepatic FGF21 expression is induced at birth via PPARalpha in response to milk intake and contributes to thermogenic activation of neonatal brown fat.
Hepatic FGF21 expression is induced at birth via PPARalpha in response to milk intake and contributes to thermogenic activation of neonatal brown fat.
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DOI：
10.1016/j.cmet.2010.02.001
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发表时间：
2010-03-03
期刊：
影响因子：
29
通讯作者：
Villarroya F
中科院分区：
文献类型：
--
作者：
Hondares E;Rosell M;Gonzalez FJ;Giralt M;Iglesias R;Villarroya F
小鼠出生后血浆 FGF21 水平和肝脏 FGF21 基因表达急剧增加。这种诱导是由哺乳开始的，需要脂质摄入，在 PPARα 无效的新生儿中受到损害，并且通过 PPARα 激活剂 Wy14,643 的治疗来模拟。新生儿因禁食而表现出 FGF21 表达减少，而成人则表达上调。由于哺乳或营养操作而导致的 FGF21 表达变化与循环游离脂肪酸和酮体水平相关。我们通过将 FGF21 注射到禁食的新生儿中来模拟 FGF21 出生后的升高，发现这增强了棕色脂肪内参与生热作用的基因的表达，并提高了体温。用 FGF21 处理的棕色脂肪细胞表现出产热基因表达增加、总呼吸和非偶联呼吸增加以及葡萄糖氧化增强。我们认为，在胎儿到新生儿的过渡过程中，肝脏诱导 FGF21 的产生介导了棕色脂肪生热作用的直接激活。
Plasma FGF21 levels and hepatic FGF21 gene expression increase dramatically after birth in mice. This induction is initiated by suckling, requires lipid intake, is impaired in PPARα null neonates, and is mimicked by treatment with the PPARα activator, Wy14,643. Neonates exhibit reduced FGF21 expression in response to fasting, in contrast to the upregulation occurring in adults. Changes in FGF21 expression due to suckling or nutritional manipulations were associated with circulating free fatty acid and ketone body levels. We mimicked the FGF21 postnatal rise by injecting FGF21 into fasting neonates, and found that this enhanced the expression of genes involved in thermogenesis within brown fat, and increased body temperature. Brown adipocytes treated with FGF21 exhibited increased expression of thermogenic genes, higher total and uncoupled respiration, and enhanced glucose oxidation. We propose that the induction of FGF21 production by the liver mediates direct activation of brown fat thermogenesis during the fetal-to-neonatal transition.
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