TGF-β超家族受体ALK7对代谢稳态的调节,The FEBS Journal

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TGF-β超家族受体ALK7对代谢稳态的调节
The FEBS Journal ( IF 5.5 ) Pub Date : 2021-06-26 , DOI: 10.1111/febs.16090
Carlos F. Ibáñez _{1,

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Affiliation

ALK7（激活素受体样激酶 7）是 TGF-β 受体超家族的成员，主要由参与内分泌功能的细胞和组织表达，例如下丘脑和垂体的神经元、胰腺 β 细胞和脂肪细胞。最近的研究已经开始描绘这些组织中 ALK7 调节的过程，以及这些过程如何与哺乳动物代谢的稳态调节相结合。新出现的图片表明 ALK7 在代谢调节中的主要功能是限制分解代谢活动并保存能量。除了下丘脑弓状核外，ALK7 在大脑其他部位的功能，特别是在小脑中，它被大量表达，仍有待阐明。尽管我们对 ALK7 信号传导的基本分子事件的理解受益于关于 TGF-β 受体机制的大量知识，但这些与 ALK7 在不同细胞类型中调节的生理功能之间的联系仍不完全清楚。错义和无义变体的发现一些小鼠品系和人类受试者的编码 ALK7 的Acvr1c基因表明对 ALK7 功能丧失的耐受性。最近的发现表明，ALK7 的特异性抑制剂可能在肥胖和代谢综合征中具有治疗应用，而没有明显的副作用。

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Regulation of metabolic homeostasis by the TGF-β superfamily receptor ALK7

ALK7 (Activin receptor-like kinase 7) is a member of the TGF-β receptor superfamily predominantly expressed by cells and tissues involved in endocrine functions, such as neurons of the hypothalamus and pituitary, pancreatic β-cells and adipocytes. Recent studies have begun to delineate the processes regulated by ALK7 in these tissues and how these become integrated with the homeostatic regulation of mammalian metabolism. The picture emerging indicates that ALK7’s primary function in metabolic regulation is to limit catabolic activities and preserve energy. Aside of the hypothalamic arcuate nucleus, the function of ALK7 elsewhere in the brain, particularly in the cerebellum, where it is abundantly expressed, remains to be elucidated. Although our understanding of the basic molecular events underlying ALK7 signaling has benefited from the vast knowledge available on TGF-β receptor mechanisms, how these connect to the physiological functions regulated by ALK7 in different cell types is still incompletely understood. Findings of missense and nonsense variants in the Acvr1c gene, encoding ALK7, of some mouse strains and human subjects indicate a tolerance to ALK7 loss of function. Recent discoveries suggest that specific inhibitors of ALK7 may have therapeutic applications in obesity and metabolic syndrome without overt adverse effects.

更新日期：2021-06-26

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