Lian Anji, Wu Keqiang, Liu Tianqiang, Jiang Nan, Jiang Quan
Key Laboratory of Bio-Resources and Eco-Environment of Ministry of EducationCollege of Life Sciences, Sichuan University, Chengdu 610065, People's Republic ChinaHepatic SurgeryThird Affiliated Hospital of Sun Yat-sen University, Guangdong, ChinaAnimal Health Research InstituteTongwei Co., Ltd, Chengdu, China.
Key Laboratory of Bio-Resources and Eco-Environment of Ministry of EducationCollege of Life Sciences, Sichuan University, Chengdu 610065, People's Republic ChinaHepatic SurgeryThird Affiliated Hospital of Sun Yat-sen University, Guangdong, ChinaAnimal Health Research InstituteTongwei Co., Ltd, Chengdu, China Key Laboratory of Bio-Resources and Eco-Environment of Ministry of EducationCollege of Life Sciences, Sichuan University, Chengdu 610065, People's Republic ChinaHepatic SurgeryThird Affiliated Hospital of Sun Yat-sen University, Guangdong, ChinaAnimal Health Research InstituteTongwei Co., Ltd, Chengdu, China.
J Mol Endocrinol. 2016 Jan;56(1):11-22. doi: 10.1530/JME-15-0207. Epub 2015 Oct 13.
The peptide hormone adropin plays a role in energy homeostasis. However, biological actions of adropin in non-mammalian species are still lacking. Using tilapia as a model, we examined the role of adropin in lipoprotein lipase (LPL) regulation in hepatocytes. To this end, the structural identity of tilapia adropin was established by 5'/3'-rapid amplification of cDNA ends (RACE). The transcripts of tilapia adropin were ubiquitously expressed in various tissues with the highest levels in the liver and hypothalamus. The prolonged fasting could elevate tilapia hepatic adropin gene expression, whereas no effect of fasting was observed on hypothalamic adropin gene levels. In primary cultures of tilapia hepatocytes, synthetic adropin was effective in stimulating LPL release, cellular LPL content, and total LPL production. The increase in LPL production also occurred with parallel rises in LPL gene levels. In parallel experiments, adropin could elevate cAMP production and up-regulate protein kinase A (PKA) and PKC activities. Using a pharmacological approach, cAMP/PKA and PLC/inositol trisphosphate (IP3)/PKC cascades were shown to be involved in adropin-stimulated LPL gene expression. Parallel inhibition of p38MAPK and Erk1/2, however, were not effective in these regards. Our findings provide, for the first time, evidence that adropin could stimulate LPL gene expression via direct actions in tilapia hepatocytes through the activation of multiple signaling mechanisms.
肽激素阿朴脂蛋白在能量稳态中发挥作用。然而，阿朴脂蛋白在非哺乳动物物种中的生物学作用仍不明确。我们以罗非鱼为模型，研究了阿朴脂蛋白在肝细胞脂蛋白脂肪酶（LPL）调节中的作用。为此，通过5'/3'-cDNA末端快速扩增（RACE）确定了罗非鱼阿朴脂蛋白的结构特性。罗非鱼阿朴脂蛋白的转录本在各组织中广泛表达，在肝脏和下丘脑中表达水平最高。长时间禁食可提高罗非鱼肝脏阿朴脂蛋白基因的表达，而禁食对下丘脑阿朴脂蛋白基因水平无影响。在罗非鱼肝细胞原代培养中，合成的阿朴脂蛋白可有效刺激LPL释放、细胞LPL含量和LPL总产量。LPL产量的增加与LPL基因水平的平行升高同时出现。在平行实验中，阿朴脂蛋白可提高cAMP产量并上调蛋白激酶A（PKA）和蛋白激酶C（PKC）的活性。采用药理学方法研究表明，cAMP/PKA和PLC/肌醇三磷酸（IP3）/PKC信号通路参与了阿朴脂蛋白刺激的LPL基因表达。然而，p38丝裂原活化蛋白激酶（p38MAPK）和细胞外信号调节激酶1/2（Erk1/2）的平行抑制在这些方面无效。我们的研究结果首次提供了证据，表明阿朴脂蛋白可通过激活多种信号机制在罗非鱼肝细胞中直接作用，刺激LPL基因表达。
