Author, as appears in the article.: Villanueva-Carmona, T; Cedó, L; Madeira, A; Ceperuelo-Mallafré, V; Rodríguez-Peña, MM; Núñez-Roa, C; Maymó-Masip, E; Repollés-de-Dalmau, M; Badia, J; Keiran, N; Mirasierra, M; Pimenta-Lopes, C; Sabadell-Basallote, J; Bosch, R; Caubet, L; Escolà-Gil, JC; Fernández-Real, JM; Vilarrasa, N; Ventura, F; Vallejo, M; Vendrell, J; Fernández-Veledo, S
Department: Bioquímica i Biotecnologia Medicina i Cirurgia Ciències Mèdiques Bàsiques
URV's Author/s: Badia Aparicio, José María / Bosch Príncep, Ramon / CEDÓ GINÉ, LÍDIA / Ceperuelo Mallafré, Maria Victoria / Fernandez Veledo, Sonia / Keiran Fernandez, Noelia Elisabeth / Maymo Masip, Elsa / RODRIGUEZ PEÑA, MARIA DEL MAR / Vendrell Ortega, Juan José / Villanueva Carmona, Teresa
Keywords: Sucnr1 Succinate Obesity Metabolite Metabolism Leptin Gpcr Circadian clock Adipose tissue Adipocyte Activated protein-kinase succinate stem-cells plasma leptin ob gene glucose-uptake gene-expression food-intake bone-formation ampk activation
Abstract: Adipose tissue modulates energy homeostasis by secreting leptin, but little is known about the factors governing leptin production. We show that succinate, long perceived as a mediator of immune response and lipolysis, controls leptin expression via its receptor SUCNR1. Adipocyte-specific deletion of Sucnr1 influences metabolic health according to nutritional status. Adipocyte Sucnr1 deficiency impairs leptin response to feeding, whereas oral succinate mimics nutrient-related leptin dynamics via SUCNR1. SUCNR1 activation controls leptin expression via the circadian clock in an AMPK/JNK-C/EBPα-dependent manner. Although the anti-lipolytic role of SUCNR1 prevails in obesity, its function as a regulator of leptin signaling contributes to the metabolically favorable phenotype in adipocyte-specific Sucnr1 knockout mice under standard dietary conditions. Obesity-associated hyperleptinemia in humans is linked to SUCNR1 overexpression in adipocytes, which emerges as the major predictor of adipose tissue leptin expression. Our study establishes the succinate/SUCNR1 axis as a metabolite-sensing pathway mediating nutrient-related leptin dynamics to control whole-body homeostasis.Copyright © 2023 Elsevier Inc. All rights reserved.
Thematic Areas: Physiology Odontología Molecular biology Medicina ii Medicina i Interdisciplinar General medicine Endocrinology & metabolism Educação física Ciências biológicas ii Ciências biológicas i Cell biology
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: josepmaria.badia@urv.cat sonia.fernandez@urv.cat teresa.villanueva@urv.cat ramon.bosch@urv.cat elsa.maymo@urv.cat victoria.ceperuelo@urv.cat ramon.bosch@urv.cat josepmaria.badia@urv.cat josepmaria.badia@urv.cat teresa.villanueva@urv.cat juanjose.vendrell@urv.cat
Author identifier: 0000-0003-2906-3788 0000-0002-9133-3120 0000-0002-4460-9761 0000-0002-6994-6115
Record's date: 2024-08-31
Papper version: info:eu-repo/semantics/acceptedVersion
Link to the original source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00082-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1550413123000827%3Fshowall%3Dtrue
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Cell Metabolism. 35 (4): 601-619.e10
APA: Villanueva-Carmona, T; Cedó, L; Madeira, A; Ceperuelo-Mallafré, V; Rodríguez-Peña, MM; Núñez-Roa, C; Maymó-Masip, E; Repollés-de-Dalmau, M; Badia, J; (2023). SUCNR1 signaling in adipocytes controls energy metabolism by modulating circadian clock and leptin expression. Cell Metabolism, 35(4), 601-619.e10. DOI: 10.1016/j.cmet.2023.03.004
Article's DOI: 10.1016/j.cmet.2023.03.004
Entity: Universitat Rovira i Virgili
Journal publication year: 2023
Publication Type: Journal Publications
Repositori URV