小柯机器人

FABP4-核苷激酶复合物调控胰岛功能
2021-12-11 20:37

美国哈佛大学Sabri Ülker 代谢研究中心Gökhan S. Hotamisligil研究团队的最新研究表明FABP4与核苷激酶形成的激素复合物调控胰岛功能。这一研究成果于2021年12月8日发表在国际学术期刊《自然》上。

在本研究中,研究人员发现激素FABP4与腺苷激酶(ADK)和核苷二磷酸激酶(NDPK)形成功能性激素复合物,以调节细胞外ATP和ADP水平。研究发现该激素对β细胞影响显著,并且基于β细胞在控制脂肪分解和糖尿病发展中的核心作用,研究人员假设激素FABP4是脂肪-β细胞内分泌通路的关键锑调节因子。利用抗体靶向该激素复合物可改善代谢结果,增强β细胞功能并保持β细胞完整性,以预防1型和2型糖尿病。因此,FABP4-ADK-NDPK复合物Fabkin代表了一种以前未知的激素作用机制,它将能量状态与代谢器官的功能相结合;同时,这也是潜在的对抗代谢疾病的新靶点。

研究人员表示,从脂肪细胞中释放储存的能量对于能量缺乏时维持生存至关重要;然而,与胰岛素抵抗和/或胰岛素不足相关的不受调控或慢性脂肪分解会破坏代谢稳态。最近发现的一种激素-脂肪酸结合蛋白4(FABP4)会伴随脂肪分解而释放。尽管FABP4的循环水平与临床前模型和人心脏代谢疾病密切相关,但尚未有任何作用机制对此作出解释。

附:英文原文

Title: A hormone complex of FABP4 and nucleoside kinases regulates islet function

Author: Prentice, Kacey J., Saksi, Jani, Robertson, Lauren T., Lee, Grace Y., Inouye, Karen E., Eguchi, Kosei, Lee, Alexandra, Cakici, Ozgur, Otterbeck, Emily, Cedillo, Paulina, Achenbach, Peter, Ziegler, Anette-Gabriele, Calay, Ediz S., Engin, Feyza, Hotamisligil, Gkhan S.

Issue&Volume: 2021-12-08

Abstract: The liberation of energy stores from adipocytes is critical to support survival in times of energy deficit; however, uncontrolled or chronic lipolysis associated with insulin resistance and/or insulin insufficiency disrupts metabolic homeostasis1,2. Coupled to lipolysis is the release of a recently identified hormone, fatty-acid-binding protein 4 (FABP4)3. Although circulating FABP4 levels have been strongly associated with cardiometabolic diseases in both preclinical models and humans4,5,6,7, no mechanism of action has yet been described8,9,10. Here we show that hormonal FABP4 forms a functional hormone complex with adenosine kinase (ADK) and nucleoside diphosphate kinase (NDPK) to regulate extracellular ATP and ADP levels. We identify a substantial effect of this hormone on beta cells and given the central role of beta-cell function in both the control of lipolysis and development of diabetes, postulate that hormonal FABP4 is a key regulator of an adipose–beta-cell endocrine axis. Antibody-mediated targeting of this hormone complex improves metabolic outcomes, enhances beta-cell function and preserves beta-cell integrity to prevent both type1 and type2 diabetes. Thus, the FABP4–ADK–NDPK complex, Fabkin, represents a previously unknown hormone and mechanism of action that integrates energy status with the function of metabolic organs, and represents a promising target against metabolic disease.

DOI: 10.1038/s41586-021-04137-3

Source: https://www.nature.com/articles/s41586-021-04137-3

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

分享到:

0