Hepatic levels of S-adenosylmethionine regulate the adaptive response to fasting.
Hepatic levels of S-adenosylmethionine regulate the adaptive response to fasting.
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DOI：
10.1016/j.cmet.2023.07.002
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发表时间：
2023-08-08
期刊：
影响因子：
29
通讯作者：
Varela-Rey, Marta
中科院分区：
文献类型：
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作者：
Capelo-Diz, Alba;Lachiondo-Ortega, Sofia;Fernandez-Ramos, David;Canas-Martin, Jorge;Goikoetxea-Usandizaga, Naroa;Serrano-Macia, Marina;Gonzalez-Rellan, Maria J.;Mosca, Laura;Blazquez-Vicens, Joan;Tinahones-Ruano, Alberto;Fondevila, Marcos F.;Buyan, Mason;Delgado, Teresa C.;de Juan, Virginia Gutierrez;Ayuso-Garcia, Paula;Sanchez-Rueda, Alejandro;Velasco-Aviles, Sergio;Fernandez-Susavila, Hector;Riobello-Suarez, Cristina;Dziechciarz, Bartlomiej;Montiel-Duarte, Cristina;Lopitz-Otsoa, Fernando;Bizkarguenaga, Maider;Bilbao-Garcia, Jon;Bernardo-Seisdedos, Ganeko;Senra, Ana;Soriano-Navarro, Mario;Millet, Oscar;Diaz-Lagares, Angel;Crujeiras, Ana B.;Bao-Caamano, Aida;Cabrera, Diana;van Liempd, Sebastiaan;Tamayo-Caro, Miguel;Borzacchiello, Luigi;Gomez-Santos, Beatriz;Buque, Xabier;de Urturi, Diego Saenz;Gonzalez-Romero, Francisco;Simon, Jorge;Rodriguez-Agudo, Ruben;Ruiz, Asier;Matute, Carlos;Beiroa, Daniel;Falcon-Perez, Juan M.;Aspichueta, Patricia;Rodriguez-Cuesta, Juan;Porcelli, Marina;Pajares, Maria A.;Ameneiro, Cristina;Fidalgo, Miguel;Aransay, Ana M.;Lama-Diaz, Tomas;Blanco, Miguel G.;Lopez, Miguel;Villa-Bellosta, Ricardo;Mueller, Timo D.;Nogueiras, Ruben;Woodhoo, Ashwin;Martinez-Chantar, Maria Luz;Varela-Rey, Marta
人们一直在集中精力揭示禁食触发身体主要器官适应性细胞反应的分子机制。在这里，我们表明，在小鼠中，肝脏S-腺苷甲硫氨酸（SAMe）-主要的甲基供体-作为营养的代谢传感器，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-氧化和肝脏中ATP的产生，以及脂肪组织中FGF 21介导的脂解和产热来微调分解代谢-禁食反应。值得注意的是，我们发现胰高血糖素诱导肝SAMe合成酶甲硫氨酸腺苷转移酶α1（MAT 1A）的表达，该酶转位至肝相关膜。这导致在这些位点产生这种代谢物，其充当制动器以防止过度β-氧化和线粒体ATP合成，从而防止内质网应激和肝损伤。这项工作提供了重要的见解，以前未描述的功能SAMe作为一个新的手臂的代谢适应禁食。禁食期间肝脏SAMe水平的降低充当营养的代谢传感器禁食期间，肝脏SAMe微调ER-线粒体接触和β-氧化肝脏MAT 1A在MAMs中表达，以在禁食期间为PEMT活性提供燃料禁食期间SAMe合成可预防ER应激和肝损伤Capelo-Diz et al.报道，肝S-腺苷甲硫氨酸（SAMe），主要的甲基供体，作为营养的代谢传感器，通过调节肝脏中的β-氧化和ATP产生来微调对禁食的适应性细胞反应，从而防止肝损伤。
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. Decrease of hepatic SAMe levels during fasting acts as a metabolic sensor of nutrition During fasting, hepatic SAMe fine-tunes ER-mitochondria contacts and β-oxidation Hepatic MAT1A is expressed in MAMs to fuel PEMT activity during fasting SAMe synthesis during fasting prevents ER stress and liver damage Capelo-Diz et al. report that hepatic S-adenosylmethionine (SAMe), the principal methyl donor, acts as a metabolic sensor of nutrition to fine-tune the adaptive cellular responses to fasting by modulating β-oxidation and ATP production in the liver and thus preventing liver damage.
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影响因子：
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DOI：
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发表时间：
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期刊：
Methods in molecular biology (Clifton, N.J.)
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DOI：
10.1002/hep.31676
发表时间：
2021-07
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Bernardo-Seisdedos G;Bilbao J;Fernández-Ramos D;Lopitz-Otsoa F;Gutierrez de Juan V;Bizkarguenaga M;Mateos B;Fondevila MF;Abril-Fornaguera J;Diercks T;Lu SC;Nogueiras R;Mato JM;Millet O
通讯作者：
Millet O