Department of Biological Sciences, North Dakota State University, Fargo, ND 58108, USA.
Gen Comp Endocrinol. 2012 May 1;176(3):367-76. doi: 10.1016/j.ygcen.2011.12.013. Epub 2011 Dec 20.
Previous studies have shown that food deprivation, which occurs naturally in the life cycle of many species of fish, results in cessation of growth and catabolism of stored energy reserves, including lipids. In this study, we used rainbow trout (Oncorhynchus mykiss) to identify the cellular mechanisms involved with this metabolic shift. Fish were placed on one of five dietary regimes--fed continuously for 2 or 4 weeks, fasted continuously for 2 or 4 weeks, or fasted 2 weeks then refed 2 weeks--and the effects on organismal growth and lipid catabolism and on the activation state of signaling elements (e.g., Akt, ERK, JAK-STAT, PKC) in selected tissues were measured. Fasting for either 2 or 4 weeks significantly retarded growth in terms of body weight, body length, and body condition; refeeding restored growth such that body length and body condition were similar to measures seen in continuously fed fish. Fasting activated lipid catabolism by stimulating the mRNA expression and catalytic activity of hormone-sensitive lipase (HSL). Two HSL-encoding mRNAs have been characterized, and the expression of both forms of mRNA in 2- and 4-week fasted fish were significantly elevated over levels in fed fish in all tissues. In adipose tissue, liver, and white muscle, HSL activity was significantly elevated in 2- and 4-week fasted fish compared to fed animals; whereas in red muscle, HSL activity was significantly elevated compared to fed fish after 4 weeks of fasting. Refeeding reversed both fasting-associated HSL mRNA expression and HSL activity. Fasting resulted in the deactivation of Akt, JAK2, and STAT5 in adipose tissue, liver, and red and white muscle. By contrast, fasting activated ERK and PKC in all tissues measured. Refeeding reversed fasting-associated alterations in the activation state of all signal elements. These findings suggest that deactivation of Akt and JAK-STAT in conjunction with activation of ERK and PKC underlie fasting-associated growth retardation and lipolysis.
先前的研究表明，许多鱼类物种的生命周期中自然发生的食物剥夺会导致生长停止和储存能量储备（包括脂质）的分解代谢。在这项研究中，我们使用虹鳟鱼（Oncorhynchus mykiss）来确定与这种代谢转变相关的细胞机制。鱼被置于五种饮食制度之一：连续喂食 2 或 4 周，连续禁食 2 或 4 周，或禁食 2 周然后再喂食 2 周，并测量对生物体生长和脂质分解代谢的影响，以及选定组织中信号转导元件（如 Akt、ERK、JAK-STAT、PKC）的激活状态。连续禁食 2 或 4 周显著延缓了体重、体长和身体状况的生长；再喂食恢复了生长，使体长和身体状况与连续喂食的鱼类相似。禁食通过刺激激素敏感脂肪酶（HSL）的 mRNA 表达和催化活性来激活脂质分解代谢。已经描述了两种 HSL 编码 mRNA，并且在所有组织中，2 周和 4 周禁食鱼的两种形式的 mRNA 表达均显著高于喂食鱼的水平。在脂肪组织、肝脏和白肌中，与喂食动物相比，2 周和 4 周禁食鱼的 HSL 活性显著升高；而在红肌中，与喂食鱼相比，4 周禁食后 HSL 活性显著升高。再喂食逆转了禁食相关的 HSL mRNA 表达和 HSL 活性。禁食导致 Akt、JAK2 和 STAT5 在脂肪组织、肝脏和红肌和白肌中失活。相比之下，禁食在所有测量的组织中激活了 ERK 和 PKC。再喂食逆转了禁食相关的所有信号元件激活状态的改变。这些发现表明，Akt 和 JAK-STAT 的失活以及 ERK 和 PKC 的激活是禁食相关生长迟缓和脂肪分解的基础。
