| First Author | Villanueva-Carmona T | Year | 2023 |
| Journal | Cell Metab | Volume | 35 |
| Issue | 4 | Pages | 601-619.e10 |
| PubMed ID | 36977414 | Mgi Jnum | J:334888 |
| Mgi Id | MGI:7463797 | Doi | 10.1016/j.cmet.2023.03.004 |
| Citation | Villanueva-Carmona T, et al. (2023) SUCNR1 signaling in adipocytes controls energy metabolism by modulating circadian clock and leptin expression. Cell Metab 35(4):601-619.e10 |
| abstractText | 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/EBPalpha-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. |
