西班牙比斯卡亚科技园的Marta Varela-Reye和María Luz Martínez-Chantar研究组合作发现，肝脏S-腺苷蛋氨酸(SAMe)水平调节对禁食的适应性反应。2023年7月31日，国际知名学术期刊《细胞—代谢》发表了这一成果。
他们表明，在小鼠中，肝脏SAMe-主要的甲基供体-作为营养代谢传感器，通过调节磷脂酰乙醇胺N -甲基转移酶(PEMT)活性、内质网-线粒体接触、β-氧化和肝脏ATP产生，以及FGF21介导的脂肪分解和脂肪组织中的产热，来微调分解代谢-禁食反应。值得注意的是，他们发现胰高血糖素诱导肝脏相同合成酶甲硫氨酸腺苷转移酶α1 (MAT1A)的表达，该酶易位到线粒体相关膜。
这导致在这些部位产生这种代谢物，它起到制动作用，防止β-过度氧化和线粒体ATP合成，从而防止内质网应激和肝损伤。这项工作为先前描述的SAMe作为代谢适应禁食的新分支的功能提供了重要的见解。
据了解，有一个强烈的焦点揭示的分子机制，在身体的主要器官可通过禁食触发适应性细胞反应。
附：英文原文
Title: Hepatic levels of S-adenosylmethionine regulate the adaptive response to fasting
Author: Alba Capelo-Diz, Sofía Lachiondo-Ortega, David Fernández-Ramos, Jorge Caas-Martín, Naroa Goikoetxea-Usandizaga, Marina Serrano-Maciá, Maria J. González-Rellan, Laura Mosca, Joan Blazquez-Vicens, Alberto Tinahones-Ruano, Marcos F. Fondevila, Mason Buyan, Teresa C. Delgado, Virginia Gutierrez de Juan, Paula Ayuso-García, Alejandro Sánchez-Rueda, Sergio Velasco-Avilés, Héctor Fernández-Susavila, Cristina Riobello-Suárez, Bartlomiej Dziechciarz, Cristina Montiel-Duarte, Fernando Lopitz-Otsoa, Maider Bizkarguenaga, Jon Bilbao-García, Ganeko Bernardo-Seisdedos, Ana Senra, Mario Soriano-Navarro, Oscar Millet, ángel Díaz-Lagares, Ana B. Crujeiras, Aida Bao-Caamano, Diana Cabrera, Sebastiaan van Liempd, Miguel Tamayo-Carro, Luigi Borzacchiello, Beatriz Gomez-Santos, Xabier Buqué, Diego Sáenz de Urturi, Francisco González-Romero, Jorge Simon, Rubén Rodríguez-Agudo, Asier Ruiz, Carlos Matute, Daniel Beiroa, Juan M. Falcon-Perez, Patricia Aspichueta, Juan Rodríguez-Cuesta, Marina Porcelli, María A. Pajares, Cristina Ameneiro, Miguel Fidalgo, Ana M. Aransay, Tomas Lama-Díaz, Miguel G. Blanco, Miguel López, Ricardo Villa-Bellosta, Timo D. Müller, Rubén Nogueiras, Ashwin Woodhoo, María Luz Martínez-Chantar, Marta Varela-Rey
Issue&Volume: 2023-07-31
Abstract: There has been an intense focus to uncover the molecular mechanisms by which fasting triggers the adaptive cellular responses in the major organs of the body. Here, we show that in mice, hepatic S-adenosylmethionine (SAMe)—the principal methyl donor—acts as a metabolic sensor of nutrition to fine-tune the catabolic-fasting response by modulating phosphatidylethanolamine N-methyltransferase (PEMT) activity, endoplasmic reticulum-mitochondria contacts, β-oxidation, and ATP production in the liver, together with FGF21-mediated lipolysis and thermogenesis in adipose tissues. Notably, we show that glucagon induces the expression of the hepatic SAMe-synthesizing enzyme methionine adenosyltransferase α1 (MAT1A), which translocates to mitochondria-associated membranes. This leads to the production of this metabolite at these sites, which acts as a brake to prevent excessive β-oxidation and mitochondrial ATP synthesis and thereby endoplasmic reticulum stress and liver injury. This work provides important insights into the previously undescribed function of SAMe as a new arm of the metabolic adaptation to fasting.
DOI: 10.1016/j.cmet.2023.07.002
Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00261-9
Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
官方网址：https://www.cell.com/cell-metabolism/home
投稿链接：https://www.editorialmanager.com/cell-metabolism/default.aspx
本期文章：《细胞—代谢》：Online/在线发表
