小柯机器人

西班牙Tarragona Joan XXIII大学医院Sonia Fernández-Veledo团队发现，脂肪细胞中的SUCNR1信号通过调控昼夜钟和瘦素的表达控制能量代谢。2023年3月27日，《细胞—代谢》杂志在线发表了这项成果。

研究人员表明，长期以来被认为是免疫反应和脂肪分解介导者的琥珀酸，通过其受体SUCNR1控制瘦素的表达。脂肪细胞特异性删除Sucnr1会根据营养状况影响代谢健康。脂肪细胞Sucnr1的缺失会损害瘦素对进食的反应，而口服琥珀酸会通过SUCNR1模拟与营养有关的瘦素动态变化。SUCNR1的激活以AMPK/JNK-C/EBPα依赖的方式通过昼夜钟控制瘦素表达。

尽管SUCNR1的抗溶脂作用在肥胖症中占优势，但其作为瘦素信号调节器的功能有助于在标准饮食条件下脂肪细胞特异性Sucnr1敲除小鼠的代谢有利表型。人类肥胖相关的高瘦素血症与SUCNR1在脂肪细胞中的过度表达有关，它成为脂肪组织瘦素表达的主要预测因素。这项研究确立了琥珀酸/SUCNR1轴是一个代谢感应途径，介导与营养物质相关的瘦素动态，进而控制整个身体的平衡。

据悉，脂肪组织通过分泌瘦素调节能量平衡，但对支配瘦素产生的因素知之甚少。

附：英文原文

Title: SUCNR1 signaling in adipocytes controls energy metabolism by modulating circadian clock and leptin expression

Author: Teresa Villanueva-Carmona, Lídia Cedó, Ana Madeira, Victòria Ceperuelo-Mallafré, M.-Mar Rodríguez-Pea, Catalina Núez-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

Issue&Volume: 2023-03-27

Abstract: Adipose tissue modulates energy homeostasis by secreting leptin, but little is knownabout the factors governing leptin production. We show that succinate, long perceivedas a mediator of immune response and lipolysis, controls leptin expression via itsreceptor 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-relatedleptin dynamics via SUCNR1. SUCNR1 activation controls leptin expression via the circadianclock in an AMPK/JNK-C/EBPα-dependent manner. Although the anti-lipolytic role ofSUCNR1 prevails in obesity, its function as a regulator of leptin signaling contributesto the metabolically favorable phenotype in adipocyte-specific Sucnr1 knockout mice under standard dietary conditions. Obesity-associated hyperleptinemiain humans is linked to SUCNR1 overexpression in adipocytes, which emerges as the majorpredictor of adipose tissue leptin expression. Our study establishes the succinate/SUCNR1axis as a metabolite-sensing pathway mediating nutrient-related leptin dynamics tocontrol whole-body homeostasis.

DOI: 10.1016/j.cmet.2023.03.004

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00082-7

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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