Leptin coordinates efferent sympathetic outflow to the white adipose tissue through the midbrain centrally-projecting Edinger-Westphal nucleus in male rats
Autor: | Adam Denes, Lu Xu, Krisztina J. Kovács, Bram Geenen, Nóra Füredi, Márta Balaskó, Christoph Lutter, Balázs Gaszner, Erika Pétervári, Tamas Kozicz |
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Rok vydání: | 2022 |
Předmět: |
Leptin
Male STAT3 Transcription Factor medicine.medical_specialty Sympathetic Nervous System Adipose Tissue White Efferent Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] Adipose tissue White adipose tissue Biology Edinger-Westphal Nucleus Midbrain Cellular and Molecular Neuroscience Internal medicine medicine Animals Urocortins Pharmacology Leptin receptor Edinger–Westphal nucleus Herpesvirus 1 Suid Rats Endocrinology medicine.anatomical_structure Receptors Leptin Nucleus hormones hormone substitutes and hormone antagonists |
Zdroj: | Neuropharmacology, 205 |
ISSN: | 0028-3908 |
Popis: | Contains fulltext : 249492.pdf (Publisher’s version ) (Open Access) The centrally-projecting Edinger-Westphal nucleus (EWcp) hosts a large population of neurons expressing urocortin 1 (Ucn1) and about half of these neurons also express the leptin receptor (LepRb). Previously, we have shown that the peripheral adiposity hormone leptin signaling energy surfeit modulates EWcp neurons' activity. Here, we hypothesized that Ucn1/LepRb neurons in the EWcp would act as a crucial neuronal node in the brain-white adipose tissue (WAT) axis modulating efferent sympathetic outflow to the WAT. We showed that leptin bound to neurons of the EWcp stimulated STAT3 phosphorylation, and increased Ucn1-production in a time-dependent manner. Besides, retrograde transneuronal tract-tracing using pseudorabies virus (PRV) identified EWcp Ucn1 neurons connected to WAT. Interestingly, reducing EWcp Ucn1 contents by ablating EWcp LepRb-positive neurons with leptin-saporin, did not affect food intake and body weight gain, but substantially (+26%) increased WAT weight accompanied by a higher plasma leptin level and changed plasma lipid profile. We also found that ablation of EWcp Ucn1/LepRb neurons resulted in lower respiratory quotient and oxygen consumption one week after surgery, but was comparable to sham values after 3 and 5 weeks of surgery. Taken together, we report that EWcp/LepRb/Ucn1 neurons not only respond to leptin signaling but also control WAT size and fat metabolism without altering food intake. These data suggest the existence of a EWcp-WAT circuitry allowing an organism to recruit fuels without being able to eat in situations such as the fight-or-flight response. |
Databáze: | OpenAIRE |
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