دورية أكاديمية
Methionine adenosyltransferase 1a antisense oligonucleotides activate the liver-brown adipose tissue axis preventing obesity and associated hepatosteatosis
| العنوان: | Methionine adenosyltransferase 1a antisense oligonucleotides activate the liver-brown adipose tissue axis preventing obesity and associated hepatosteatosis |
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| المؤلفون: | Saenz de Urturi Indart, Diego, Buqué García, Xabier, Porteiro, Begoña, Folgueira, Cintia, Mora, Alfonso, Delgado, Teresa C., Prieto Fernández, Endika, Olaizola Rebe, Paula, Gómez Santos, Beatriz, Apodaka Biguri, Maider, González Romero, Francisco, Nieva Zuluaga, Ane, Ruiz de Gauna Madariaga, Mikel, Goikoetxea Usandizaga, Naroa, García Rodríguez, Juan Luis, Gutiérrez de Juan, Virginia, Aurrekoetxea Galindo, Igor, Montalvo Romeral, Valle, Novoa, Eva, Martín Guerrero, Idoia, Varela Rey, Marta, Bhanot, Sanjay, Lee, Richard, Bañales Asurmendi, Jesús María, Syn, Wing-Kin, Sabio, Guadalupe, Martínez Chantar, María Luz, Nogueiras Pozo, Rubén, Aspichueta Celaá, Patricia |
| بيانات النشر: | Nature |
| سنة النشر: | 2022 |
| المجموعة: | ADDI: Repositorio Institucional de la Universidad del País Vasco / Euskal Herriko Unibertsitatea (UPV/EHU - Basque Country University) |
| مصطلحات موضوعية: | growth-factor 21, fatty-acid oxidation, s-adenosylmethionine, insulin sensitivity, hepatic steatosis, rat-liver, mice, diet, restriction, metabolism |
| الوصف: | Altered methionine metabolism is associated with weight gain in obesity. The methionine adenosyltransferase (MAT), catalyzing the first reaction of the methionine cycle, plays an important role regulating lipid metabolism. However, its role in obesity, when a plethora of metabolic diseases occurs, is still unknown. By using antisense oligonucleotides (ASO) and genetic depletion of Mat1a, here, we demonstrate that Mat1a deficiency in diet-induce obese or genetically obese mice prevented and reversed obesity and obesity-associated insulin resistance and hepatosteatosis by increasing energy expenditure in a hepatocyte FGF21 dependent fashion. The increased NRF2-mediated FGF21 secretion induced by targeting Mat1a, mobilized plasma lipids towards the BAT to be catabolized, induced thermogenesis and reduced body weight, inhibiting hepatic de novo lipogenesis. The beneficial effects of Mat1a ASO were abolished following FGF21 depletion in hepatocytes. Thus, targeting Mat1a activates the liver-BAT axis by increasing NRF2-mediated FGF21 secretion, which prevents obesity, insulin resistance and hepatosteatosis. High methionine and S-adenosylmethionine serum levels are related with obesity. Here the authors show that knockdown of methionine adenosyltransferase by using antisense oligonucleotides provides beneficial effects in obesity and comorbidities. ; This work was supported by Ayudas para apoyar grupos de investigacion del sistema Universitario Vasco (IT971-16) and MCIU/AEI/FEDER, UE (RTI2018-095134-B-100) (to P.A.), (RTI2018-099413-B-I00 and RED2018-102379-T) (to R.N.), PID2020119486RB-100 (to M.V.R.) and (RTI2018-096759-A-100) (to T.C.D). EFSD/Lilly European Diabetes Research Program, MICIU (PID2019-104399RB-I00), Fundacion AECC PROYE19047SABI, and Comunidad de Madrid IMMUNOTHERCAN-CM B2017/BMD-3733 (to G.S.). La CAIXA Foundation LCF/PR/HP17/52190004, MINECO-FEDER SAF2017-87301-R, AYUDAS FUNDACION BBVA A EQUIPOS DE INVESTIGACION CIENTIFICA UMBRELLA 2018 and AECC Scientific Foundation, grant name: Rare Cancers 2017 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| العلاقة: | info:eu-repo/grantAgreement/MICIU/RTI2018-095134-B-100; info:eu-repo/grantAgreement/MICIU/RTI2018-099413-B-I00; info:eu-repo/grantAgreement/MICIU/RED2018-102379-T; info:eu-repo/grantAgreement/MICIU/RTI2018-096759-A-100; info:eu-repo/grantAgreement/MICIU/FJC2018-035449-I; info:eu-repo/grantAgreement/MINECO/SEV-2016-0644; info:eu-repo/grantAgreement/MICINN/PID2019-104399RB-I00; info:eu-repo/grantAgreement/MICINN/PID2020119486RB-100; https://www.nature.com/articles/s41467-022-28749-zTest; Nature Communications 13(1) : (2022) // Article ID 1096; http://hdl.handle.net/10810/57907Test |
| DOI: | 10.1038/s41467-022-28749-z |
| الإتاحة: | https://doi.org/10.1038/s41467-022-28749-zTest http://hdl.handle.net/10810/57907Test |
| حقوق: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/3.0/esTest/ ; © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.orgTest/ licenses/by/4.0/. ; Atribución 3.0 España |
| رقم الانضمام: | edsbas.F4C8FFA3 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20411723 |
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| DOI: | 10.1038/s41467-022-28749-z |