ESPEYB20 9. Obesity and Weight Regulation New Findings in Adipose Tissue (3 abstracts)
9.4. SUCNR1 signaling in adipocytes controls energy metabolism by modulating circadian clock and leptin expression
Villanueva-Carmona T , Cedó L , Madeira A , Ceperuelo-Mallafré V , Rodriguez-Pena M , Nunez-Roa C , Maymo-Masip E , Repolles-de-Dalman M , Badia J , Keiran N , Mirasierra M , Pimenta-Lopes C , Sabadell-Basallote J , Bosch R , Caubet L , Escola-Gil JC , Fernandez-Real JM , Vilarrasa N , Verntura F , Vallejo M , Vendrell J & Fernandez-Veledo S
Department of Endocrinology and Nutrition, Research Unit, Institut d’Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari de Tarragona Joan XXIII, Tarragona 43005, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain. sonia.fernandez@iispv.cat Cell Metabolism 2023 Apr 4;35(4):601–619.e10. Doi: 10.1016/j.cmet.2023.03.004. https://pubmed.ncbi.nlm.nih.gov/36977414/.
Brief summary: Villanueva-Carmona et al. identified succinate as a mediating metabolite in leptin secretion. Its action is mediated by the succinate receptor SUCNR in adipocytes via the circadian clock in an AMPK/JNK-C/EBPa-dependent manner.
Although the regulatory circuits of leptin action on hunger and satiety are well understood, the pathways that mediate acute leptin production in the adipose tissue are less investigated. To investigate how adipocytes react to changes in food supply, regulation of leptin expression and secretion by circulating nutrients have been investigated in the past, but without deep understanding of cellular mechanisms. Succinate as an intermediate from the Krebs cycle is a plausible candidate, as its circulating levels transiently increase in response to physiological stimuli including exercise (1), cold exposure (2), or food ingestion (3). It is an interesting finding that circadian mediators are affected by succinate, as leptin itself has a clear diurnal secretion pattern. Further research is needed to provide a complete understanding of succinate as a signal transducer of physiological function. It would be especially interesting to know whether succinate contributes to the high inter-individual differences in leptin levels independently of body mass.
References: 1. Reddy A, Bozi LHM, Yaghi OK, Mills EL, Xiao H, Nicholson HE et al. pH-Gated Succinate Secretion Regulates Muscle Remodeling in Response to Exercise. Cell 2020; 183: 62–75.e17. 2. Mills EL, Pierce KA, Jedrychowski MP, Garrity R, Winther S, Vidoni S et al. Accumulation of succinate controls activation of adipose tissue thermogenesis. Nature 2018; 560: 102–106. 3. Astiarraga B, Martínez L, Ceperuelo-Mallafré V, Llauradó G, Terrón-Puig M, Rodríguez MM et al. Impaired Succinate Response to a Mixed Meal in Obesity and Type 2 Diabetes Is Normalized After Metabolic Surgery. Diabetes Care 2020; 43: 2581–2587.
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ESPE Yearbook of Paediatric Endocrinology
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