Sheridan Mark A
Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409, USA.
Gen Comp Endocrinol. 2021 Oct 1;312:113873. doi: 10.1016/j.ygcen.2021.113873. Epub 2021 Jul 28.
This paper develops a model for coordinate regulation of feeding, metabolism, and growth based on studies in fish. Many factors involved with the control of feeding [e.g., cholecystokinin (CCK) and ghrelin (GRLN)], energy metabolism [e.g., insulin (INS), glucagon (GLU), glucagon-like peptide (GLP), and somatostatins (SS), produced in the endocrine pancreas; and leptin (LEP) produced broadly], and growth [e.g., GRLN, growth hormone (GH), insulin-like growth factors (IGFs), GH receptors (GHR), IGF receptors (IGFR)] interact at various levels. Many such interactions serve to coordinate these systems to favor anabolic processes (i.e., lipid and protein synthesis, glycogenesis) and growth, including GH promotion of feeding and stimulation of INS production/secretion and the upregulation of GHR and IGFR by GRLN. As nutrient and stored energy status change, various feedbacks serve to curtail feeding and transition the animal from an anabolic/growth state to a catabolic state. Many factors, including LEP and IGF, promote satiety, whereas SS downregulates INS signaling as well as IGF production and GHR and IGFR abundance. As INS and IGF levels fall, GH becomes disconnected from growth as a result of altered linkage of GHR to cell signaling pathways. As a result, the catabolic actions of GH, GLU, GLP, LEP, and SS prevail, mobilizing stored energy reserves. Coordinate regulation involves relative abundances of blood-borne hormones as well as the ability to adjust responsiveness to hormones (via receptor and post-receptor events) in a cell-/tissue-specific manner that results from genetic and epigenetic programming and modulation by the local milieu of hormones, nutrients, and autocrine/paracrine interactions. The proposed model of coordinate regulation demonstrates how feeding, metabolism, and growth are integrated with each other and with other processes, such as reproduction, and how adaptive adjustments can be made to energy allocation during an animal's life history and/or in response to changes in environmental conditions.
本文基于对鱼类的研究，开发了一种进食、新陈代谢和生长的协调调节模型。许多参与进食控制的因素[如胆囊收缩素（CCK）和胃饥饿素（GRLN）]、能量代谢[如内分泌胰腺产生的胰岛素（INS）、胰高血糖素（GLU）、胰高血糖素样肽（GLP）和生长抑素（SS）；以及广泛产生的瘦素（LEP）]和生长[如GRLN、生长激素（GH）、胰岛素样生长因子（IGF）、GH受体（GHR）、IGF受体（IGFR）]在不同水平相互作用。许多这样的相互作用有助于协调这些系统，以促进合成代谢过程（即脂质和蛋白质合成、糖原生成）和生长，包括GH促进进食以及刺激INS产生/分泌，以及GRLN上调GHR和IGFR。随着营养物质和储存能量状态的变化，各种反馈会减少进食，并使动物从合成代谢/生长状态转变为分解代谢状态。许多因素，包括LEP和IGF，会促进饱腹感，而SS会下调INS信号传导以及IGF产生、GHR和IGFR丰度。随着INS和IGF水平下降，由于GHR与细胞信号通路的连接改变，GH与生长脱节。结果，GH、GLU、GLP、LEP和SS的分解代谢作用占主导，动员储存的能量储备。协调调节涉及血液中激素的相对丰度，以及以细胞/组织特异性方式调节对激素的反应性（通过受体和受体后事件）的能力，这是由遗传和表观遗传编程以及激素、营养物质的局部环境和自分泌/旁分泌相互作用的调节所导致的。所提出的协调调节模型展示了进食、新陈代谢和生长如何相互整合以及与其他过程（如繁殖）如何整合，以及在动物的生命历程中以及/或者响应环境条件变化时如何对能量分配进行适应性调整。
