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SUCNR1 signaling in adipocytes controls energy metabolism by modulating circadian clock and leptin expression by Teresa Villanueva-Carmona; Lídia Cedó; Ana Madeira; Victòria Ceperuelo-Mallafré; M.-Mar Rodríguez-Peña; Catalina Núñez-Roa; Elsa Maymó- Masip; Maria Repollés-de-Dalmau; Joan Badia; Noelia Keiran; Mercedes Mirasierra; Carolina Pimenta-Lopes; Joan Sabadell-Basallote; Ramón Bosch; Laura Caubet; Joan Carles Escolà- Gil; José-Manuel Fernández-Real; Nuria Vilarrasa; Francesc Ventura; Mario Vallejo; Joan Vendrell; Sonia Fernández-Veledo is a Medicine article available to read on EtoBox.
What is SUCNR1 signaling in adipocytes controls energy metabolism by modulating circadian clock and leptin expression about?
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.
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- Author
- Teresa Villanueva-Carmona; Lídia Cedó; Ana Madeira; Victòria Ceperuelo-Mallafré; M.-Mar Rodríguez-Peña; Catalina Núñez-Roa; Elsa Maymó- Masip; Maria Repollés-de-Dalmau; Joan Badia; Noelia Keiran; Mercedes Mirasierra; Carolina Pimenta-Lopes; Joan Sabadell-Basallote; Ramón Bosch; Laura Caubet; Joan Carles Escolà- Gil; José-Manuel Fernández-Real; Nuria Vilarrasa; Francesc Ventura; Mario Vallejo; Joan Vendrell; Sonia Fernández-Veledo
- Publisher
- Elsevier BV
- Published
- 2023
- Language
- EN
- Field
- Medicine (Life Sciences)