Grupo de Interacción entre órganos en las enfermedades metabólicas

Guadalupe Sabio Jefe de Grupo
T +34 917328000 (Ext )
gsabio@cnio.es

Investigadores Científicos

Alfonso Mora

Becarios Post-doctorales

Juan Ignacio Jiménez
Ayelén Melina Santamans

Becarios Pre-Doctorales

Ana Belén Alonso
Clara Yalian Bonacasa
Beatriz Cicuéndez
Nauzet Celso Deniz
Javier Pérez

Técnicos de Laboratorio

Alba Concepción
Luis Leiva
Marta León
María Elena Rodríguez

Científico Visitante

Cintia María Folgueira
Irene Ruiz

The Organ Crosstalk in Metabolic Diseases Group is dedicated to understanding how metabolic alterations and obesity trigger other secondary diseases such as cancer, diabetes, and cardiovascular diseases. Our research takes a holistic approach, aiming to comprehend how these alterations occurring in obesity disrupt the communication between organs. In this context, we have found that during obesity several stress kinases are activated in different tissues, and that this activation can affect the development of a tumour.

The Group focuses on 3 main aspects induced by obesity:

The alteration of adipose tissue and, consequently, the secretion of adipokines. We have observed that in adipose tissue, during obesity, stress kinases are activated, the mitochondria become dysfunctional, and the circadian clock is altered. Our aim is to delve into whether these factors could serve as drivers of adipose tissue dysfunction during obesity and the associated comorbidities. The primary focus of our investigation lies in unravelling the endocrine function of adipose tissue, with particular attention to the distinctive role of brown adipose tissue in thermogenesis.
The onset of chronic inflammation, which is associated with an increased risk of cancer.We want to comprehend how stress kinases and alterations in metabolism within inflammatory cells impact the development of the disease.
Cell metabolism alteration as a driver of disease.Metabolism controls the functionality of cells in our body, as it is their means of obtaining ATP to carry out their functions or, in the case of tumours, to proliferate. Therefore, disruptions in cellular metabolism can serve as drivers of diseases, but the modulation of metabolism can also offer new therapies for cardiovascular diseases and cancer. By utilising animal models to manipulate metabolism, we aim to understand how metabolism is implicated in the development of diseases.

Publicaciones

Plata-Gómez AB, de Prado-Rivas L, Sanz A, Deleyto-Seldas N, García F, de la Calle Arregui C, Silva C, Caleiras E, Graña-Castro O, Piñeiro-Yáñez E, Krebs J, Leiva-Vega L, Muñoz J, Jain A, Sabio G, Efeyan A. (2024). Hepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver. Nat Commun 15, 1878. Publicación CNIO.
Ferreira V, Folgueira C, García-Altares M, Guillén M, Ruíz-Rosario M, DiNunzio G, Garcia-Martinez I, Alen R, Bookmeyer C, Jones JG, Cigudosa JC, López-Larrubia P, Correig-Blanchar X, Davis RJ, Sabio G, Rada P, Valverde ÁM. (2024). Hypothalamic JNK1-hepatic fatty acid synthase axis mediates a metabolic rewiring that prevents hepatic steatosis in male mice treated with olanzapine via intraperitoneal: Additional effects of PTP1B inhibition. Redox Biol , 102741. Publicación en otras instituciones.
Folgueira C, Herrera-Melle L, López JA, Galvan-Alvarez V, Martin-Rincon M, Cuartero MI, García-Culebras A, Dumesic PA, Rodríguez E, Leiva-Vega L, León M, Porteiro B, Iglesias C, Torres JL, Hernández-Cosido L, Bonacasa C, Marcos M, Moro MÁ, Vázquez J, Calbet JAL, Spiegelman BM, Mora A, Sabio G. (2024). Remodeling p38 signaling in muscle controls locomotor activity via IL-15. Sci Adv 10, eadn5993. Publicación CNIO.
Rada P, Carceller-López E, Hitos AB, Gómez-Santos B, Fernández-Hernández C, Rey E, Pose-Utrilla J, García-Monzón C, González-Rodríguez Á, Sabio G, García A, Aspichueta P, Iglesias T, Valverde ÁM. (2024). Protein kinase D2 modulates hepatic insulin sensitivity in male mice. Mol Metab (in press). Publicación CNIO.
Herrera-Melle L, Cicuéndez B, López JA, Dumesic PA, Wilensky SE, Rodríguez E, Leiva-Vega L, Caballero A, León M, Vázquez J, Spiegelman BM, Folgueira C, Mora A, Sabio G. (2024). p38α kinase governs muscle strength through PGC1α in mice. Acta Physiol 240, e14234. Publicación CNIO.
Ferreira V, Folgueira C, Montes-San Lorenzo Á, Rodríguez-López A, Gonzalez-Iglesias E, Zubiaur P, Abad-Santos F, Sabio G, Rada P, Valverde ÁM. (2024). Estrogens prevent the hypothalamus-periphery crosstalk induced by olanzapine intraperitoneal treatment in female mice: Effects on brown/beige adipose tissues and liver. Bba-Mol Basis Dis 870, 167227. Publicación CNIO.
Fondevila MF, Novoa E, Gonzalez-Rellan MJ, Fernandez U, Heras V, Porteiro B, Parracho T, Dorta V, Riobello C, da Silva Lima N, Seoane S, Garcia-Vence M, Chantada-Vazquez MP, Bravo SB, Senra A, Leiva M, Marcos M, Sabio G, Perez-Fernandez R, Dieguez C, Prevot V, Schwaninger M, Woodhoo A, Martinez-Chantar ML, Schwabe R, Cubero FJ, Varela-Rey M, Crespo J, Iruzubieta P, Nogueiras R. (2024). p63 controls metabolic activation of hepatic stellate cells and fibrosis via an HER2-ACC1 pathway. Cell Rep Med 5, 101401. Publicación en otras instituciones.
Santamans AM, Cicuéndez B, Mora A, Villalba-Orero M, Rajlic S, Crespo M, Vo P, Jerome M, Macías Á, López JA, Leiva M, Rocha SF, León M, Rodríguez E, Leiva L, Pintor Chocano A, García Lunar I, García-Álvarez A, Hernansanz-Agustín P, Peinado VI, Barberá JA, Ibañez B, Vázquez J, Spinelli JB, Daiber A, Oliver E, Sabio G. (2024). MCJ: A mitochondrial target for cardiac intervention in pulmonary hypertension. Sci Adv 10, eadk6524. Publicación en otras instituciones.
Goikoetxea-Usandizaga N, Bravo M, Egia-Mendikute L, Abecia L, Serrano-Maciá M, Urdinguio RG, Clos-García M, Rodríguez-Agudo R, Araujo-Legido R, López-Bermudo L, Delgado TC, Lachiondo-Ortega S, González-Recio I, Gil-Pitarch C, Peña-Cearra A, Simón J, Benedé-Ubieto R, Ariño S, Herranz JM, Azkargorta M, Salazar-Bermeo J, Martí N, Varela-Rey M, Falcón-Pérez JM, Lorenzo Ó, Nogueiras R, Elortza F, Nevzorova YA, Cubero FJ, Saura D, Martínez-Cruz LA, Sabio G, Palazón A, Sancho-Bru P, Elguezabal N, Fraga MF, Ávila MA, Bataller R, Marín JJG, Martín F, Martínez-Chantar ML. (2023). The outcome of boosting mitochondrial activity in alcohol-associated liver disease is organ-dependent. Hepatology 78, 878-895. Publicación en otras instituciones.
Sáenz de Urturi D, Buqué X, Porteiro B, Folgueira C, Mora A, Delgado TC, Prieto-Fernández E, Olaizola P, Gómez-Santos B, Apodaka-Biguri M, González-Romero F, Nieva-Zuluaga A, Ruiz de Gauna M, Goikoetxea-Usandizaga N, García-Rodríguez JL, Gutierrez de Juan V, Aurrekoetxea I, Montalvo-Romeral V, Novoa EM, Martín-Guerrero I, Varela-Rey M, Bhanot S, Lee R, Banales JM, Syn WK, Sabio G, Martínez-Chantar ML, Nogueiras R, Aspichueta P. (2022). Methionine adenosyltransferase 1a antisense oligonucleotides activate the liver-brown adipose tissue axis preventing obesity and associated hepatosteatosis. Nat Commun 13, 1096. Publicación en otras instituciones.
Ferreira V, Folgueira C, Guillén M, Zubiaur P, Navares M, Sarsenbayeva A, López-Larrubia P, Eriksson JW, Pereira MJ, Abad-Santos F, Sabio G, Rada P, Valverde ÁM. (2022). Modulation of hypothalamic AMPK phosphorylation by olanzapine controls energy balance and body weight. Metabolism 137, . Publicación en otras instituciones.
Sahún-Español Á, Clemente C, Jiménez-Loygorri JI, Sierra-Filardi E, Herrera-Melle L, Gómez-Durán A, Sabio G, Monsalve M, Boya P, Arroyo AG. (2022). p38 MAPK priming boosts VSMC proliferation and arteriogenesis by promoting PGC1α-dependent mitochondrial dynamics. Sci Rep 12, 5938. Publicación en otras instituciones.
Loza-Valdes A, El-Merahbi R, Kassouf T, Demczuk A, Reuter S, Viera JT, Karwen T, Noh M, Löffler MC, Romero-Becerra R, Torres JL, Marcos M, Sabio G, Wojda U, Sumara G. (2022). Targeting ERK3/MK5 complex for treatment of obesity and diabetes. Biochem Bioph Res Co 612, 119-125. Publicación en otras instituciones.
Loza-Valdes A, El-Merahbi R, Kassouf T, Demczuk A, Reuter S, Viera JT, Karwen T, Noh M, Löffler MC, Romero-Becerra R, Torres JL, Marcos M, Sabio G, Wojda U, Sumara G. (2022). Targeting ERK3/MK5 complex for treatment of obesity and diabetes.. Biochem Bioph Res Co 612, 119-125. Publicación en otras instituciones.
Gallego-Durán R, Albillos A, Ampuero J, Arechederra M, Bañares R, Blas-García A, Berná G, Caparrós E, Delgado TC, Falcón-Pérez JM, Francés R, Fernández-Barrena MG, Graupera I, Iruzubieta P, Nevzorova YA, Nogueiras R, Macías RIR, Martín F, Sabio G, Soriano G, Vaquero J, Cubero FJ, Gracia-Sancho J. (2022). Metabolic-associated fatty liver disease: From simple steatosis toward liver cirrhosis and potential complications. Proceedings of the Third Translational Hepatology Meeting, organized by the Spanish Association for the Study of the Liver (AEEH). Gastroenterol Hepatol 45, 724-734. Publicación en otras instituciones.
Pena-Leon V, Folgueira C, Barja-Fernández S, Pérez-Lois R, Da Silva Lima N, Martin M, Heras V, Martinez-Martinez S, Valero P, Iglesias C, Duquenne M, Al-Massadi O, Beiroa D, Souto Y, Fidalgo M, Sowmyalakshmi R, Guallar D, Cunarro J, Castelao C, Senra A, González-Saenz P, Vázquez-Cobela R, Leis R, Sabio G, Mueller-Fielitz H, Schwaninger M, López M, Tovar S, Casanueva FF, Valjent E, Diéguez C, Prevot V, Nogueiras R, Seoane LM. (2022). Prolonged breastfeeding protects from obesity by hypothalamic action of hepatic FGF21. Nat Metabolism 4, 901-917. Publicación en otras instituciones.