2026-04-30T10:43:38Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/157062024-09-27T08:28:40Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Sáenz de Urturi, Diego author Buqué, Xabier author Porteiro, Begoña author Folgueira, Cintia author Mora, Alfonso author Delgado, Teresa C author Prieto-Fernández, Endika author Olaizola, Paula author Gómez-Santos, Beatriz author Apodaka-Biguri, Maider author González-Romero, Francisco author Nieva-Zuluaga, Ane author Ruiz de Gauna, Mikel author Goikoetxea-Usandizaga, Naroa author García-Rodríguez, Juan Luis author Gutierrez de Juan, Virginia author Aurrekoetxea, Igor author Montalvo-Romeral, Valle author Novoa, Eva M author Martín-Guerrero, Idoia author Varela-Rey, Marta author Bhanot, Sanjay author Lee, Richard author Banales, Jesus M author Syn, Wing-Kin author Sabio, Guadalupe author Martínez-Chantar, María L author Nogueiras, Rubén author Aspichueta, Patricia author 2022-03-01 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. Nat Commun. 2022 Mar 1;13(1):1096 10.1038/s41467-022-28749-z 2041-1723 Nature communications 35232994 http://hdl.handle.net/20.500.12105/15706 Methionine adenosyltransferase 1a antisense oligonucleotides activate the liver-brown adipose tissue axis preventing obesity and associated hepatosteatosis.