Khieokhajonkhet Anurak, Kaneko Gen, Hirano Yuki, Wang Lu, Ushio Hideki
Department of Aquatic Bioscience, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi, Bunkyo, Tokyo 113-8657, Japan; Department of Agricultural Sciences, Faculty of Agriculture, Natural Resources and Environment, Naresuan University, Muang, Phitsanulok 65000, Thailand.
Department of Aquatic Bioscience, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi, Bunkyo, Tokyo 113-8657, Japan.
Gen Comp Endocrinol. 2016 Sep 15;236:121-130. doi: 10.1016/j.ygcen.2016.06.025. Epub 2016 Jun 17.
Growth hormone (GH) increases phosphorylation and mRNA levels of hormone-sensitive lipase (HSL) in the livers of some marine teleosts. The hepatic GH-HSL axis appears to play important roles in fasting-induced lipolysis. However, it is not known whether GH exerts similar effects on HSL in fish adipose tissues. Functional differentiation of two fish-specific HSL isoforms (HSL1 and HSL2) also remains unclear. The present study seeks to address two unanswered questions about fish lipolysis using red seabream (Pagrus major): (1) Does GH increase phosphorylation and mRNA levels of HSL in adipose tissue? (2) How do GH and fasting affect mRNA levels of two HSL isoform genes in the liver and adipose tissue? To this end, we first cloned HSL1 and HSL2 cDNAs and investigated their tissue distribution. Transcripts of both HSLs and HSL1 proteins were abundant in the visceral adipose tissue, gonads, and liver, suggesting the important role of HSL in adipose tissue lipolysis. HSL2 transcript levels were 20-65% those of HSL1 except in the skin, and HSL2 proteins were not detected by our in-house antisera. Ex vivo administration of GH increased HSL1 phosphorylation, non-esterified fatty acid (NEFA) release, and levels of HSL1 and HSL2 mRNA in both the liver and visceral adipose tissue. Hepatic HSL2 mRNA was particularly sensitive to GH administration and sometimes exceeded HSL1 mRNA levels with up to 13-fold induction. In contrast, fasting for 4 and 7d increased HSL1 mRNA levels, but had only marginal effects on HSL2 mRNA levels in both adipose tissue or liver. We concluded that GH would increase HSL mRNAs during adipose tissue lipolysis in red seabream; however, GH and fasting result in different induction ratio of two HSL isoform genes, suggesting that other hormone(s) also contributes to fasting-induced lipolysis.
生长激素（GH）可提高一些海洋硬骨鱼肝脏中激素敏感性脂肪酶（HSL）的磷酸化水平和mRNA水平。肝脏中的GH-HSL轴似乎在禁食诱导的脂肪分解中发挥重要作用。然而，尚不清楚GH对鱼类脂肪组织中的HSL是否有类似作用。两种鱼类特有的HSL亚型（HSL1和HSL2）的功能分化也仍不明确。本研究旨在利用真鲷（Pagrus major）解决关于鱼类脂肪分解的两个未解决问题：（1）GH是否会提高脂肪组织中HSL的磷酸化水平和mRNA水平？（2）GH和禁食如何影响肝脏和脂肪组织中两种HSL亚型基因的mRNA水平？为此，我们首先克隆了HSL1和HSL2的cDNA并研究了它们的组织分布。HSL1和HSL2的转录本以及HSL1蛋白在内脏脂肪组织、性腺和肝脏中含量丰富，表明HSL在脂肪组织脂肪分解中起重要作用。除皮肤外，HSL2的转录水平是HSL1的20%-65%，且我们自制的抗血清未检测到HSL2蛋白。离体给予GH可增加肝脏和内脏脂肪组织中HSL1的磷酸化、非酯化脂肪酸（NEFA）释放以及HSL1和HSL2的mRNA水平。肝脏中的HSL2 mRNA对给予GH特别敏感，有时诱导倍数高达13倍，超过了HSL1 mRNA水平。相比之下，禁食4天和7天会增加HSL1的mRNA水平，但对脂肪组织或肝脏中HSL2的mRNA水平影响甚微。我们得出结论，GH会在真鲷脂肪组织脂肪分解过程中增加HSL的mRNA水平；然而，GH和禁食导致两种HSL亚型基因的诱导率不同，这表明其他激素也参与了禁食诱导的脂肪分解。
