Steroid hormones control circadian Elovl3 expression in mouse liver
Steroid hormones control circadian Elovl3 expression in mouse liver
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DOI：
10.1210/en.2007-1402
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发表时间：
2008-06-01
期刊：
影响因子：
4.8
通讯作者：
Jacobsson, Anders
中科院分区：
文献类型：
--
作者：
Brolinson, Annelie;Fourcade, Stephane;Jacobsson, Anders
Elovl3基因属于Elov1基因家族，编码与超长链脂肪酸延长有关的酶。公认的酶的作用是控制饱和和单不饱和脂肪酸的伸长，最长可达24个碳。Elovl3基因最初被鉴定为冷暴露时在棕色脂肪组织中高表达的基因。在这里，我们发现肝脏Elovl3mRNA的表达只在成熟的雄性小鼠中遵循明显的昼夜节律，在清晨Zeitgeber时间(ZT)20时急剧增加，在ZT2左右达到峰值，并在ZT10时恢复到基础水平。在雌性小鼠和性不成熟雄性小鼠中，Elovl3的表达一直很低。禁食和重新喂食食物或高脂饮食的小鼠不会改变Elovl3的mRNA水平。然而，白天只喂食9d的动物表现出了倒置的表达模式。此外，我们发现Elovl3的表达受合成糖皮质激素地塞米松的转录控制和显著诱导。综上所述，这些数据表明，Elovl3在小鼠肝脏的表达受到循环中的类固醇激素，如糖皮质激素和雄激素的严格控制。最后，发现Elovl3在过氧化体转运体转运体D亚家族(ALD)成员2消融小鼠中表达上调，而在ATP结合盒D亚家族(ALD)成员2过表达的小鼠中表达抑制，这表明超长链脂肪酸合成和过氧化脂肪酸氧化之间存在紧密的相互作用。
The Elovl3 gene belongs to the Elovl gene family, which encodes for enzymes involved in the elongation of very long chain fatty acids. The recognized role for the enzyme is to control the elongation of saturated and monounsaturated fatty acids up to 24 carbons in length. Elovl3 was originally identified as a highly expressed gene in brown adipose tissue on cold exposure. Here we show that hepatic Elovl3 mRNA expression follows a distinct diurnal rhythm exclusively in mature male mice, with a sharp increase early in the morning Zeitgeber time (ZT) 20, peaks around ZT2, and is back to basal level at the end of the light period at ZT10. In female mice and sexually immature male mice, the Elovl3 expression was constantly low. Fasting and refeeding mice with chow or high-fat diet did not alter the Elovl3 mRNA levels. However, animals that were exclusively fed during the day for 9 d displayed an inverted expression profile. In addition, we show that Elovl3 expression is transcriptionally controlled and significantly induced by the exposure of the synthetic glucocorticoid dexamethasone. Taken together, these data suggest that Elovl3 expression in mouse liver is under strict diurnal control by circulating steroid hormones such as glucocorticoids and androgens. Finally, Elovl3 expression was found to be elevated in peroxisomal transporter ATP-binding cassette, subfamily D(ALD), member 2 ablated mice and suppressed in ATP-binding cassette subfamily D(ALD) member 2 overexpressing mice, implying a tight cross talk between very long chain fatty acid synthesis and peroxisomal fatty acid oxidation.