@article{5bdada9d974a462cae922d4dc842698d,
title = "Leptin coordinates efferent sympathetic outflow to the white adipose tissue through the midbrain centrally-projecting Edinger-Westphal nucleus in male rats",
abstract = "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.",
keywords = "Energy metabolism, Leptin receptor, Pseudorabies virus, STAT3, Urocortin 1",
author = "Lu Xu and N{\'o}ra F{\"u}redi and Christoph Lutter and Bram Geenen and Erika P{\'e}terv{\'a}ri and M{\'a}rta Balask{\'o} and {\'A}d{\'a}m D{\'e}nes and Kov{\'a}cs, {Krisztina J.} and Bal{\'a}zs Gaszner and Tam{\'a}s Kozicz",
note = "Funding Information: NF was supported by the research grant of Pecs University Medical School KA-2020-03, and New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund ( {\'U}NKP-20-4-II-PTE-547 ). EP was supported by the grant from the P{\'e}cs University Medical School KA-2019-44 . KJK was supported by Hungarian National Research, Development and Innovation Office ( 124424 ), and National Brain Research Program 2017-1.2.1-NKP-2017-00002 . BG was financed by the Project no. TKP2020-IKA-08 provided from the National Research, Development and Innovation Fund of Hungary , financed under the 2020-4.1.1-TKP2020 funding scheme. (FIKP II, FIKP III), EFOP-3.6.2-16-2017-00008 and NKFIH FK124188. This work was also financed by NAP 2017-1.2.1-NKP-2017-00002; GINOP-2.3.2-15-2016-00050 “PEPSYS,” and MTA-TKI14016. Funding Information: Another limitation we have to state is that we do not provide direct experimental evidence if the leptin-sensing EWcp/LepRb/Ucn1 are the same cells that EWcp/Ucn1 neurons project to the IML, although we assume, this is the case. Related to this, one may also argue that besides the EWcp other major Ucn1-containing brain areas (e.g. supraoptic nucleus, lateral superior olive; see in ref. Bittencourt et al., 1999) areas may also project to the IML. However, we could not find any published evidence that direct nerve fiber connections would exist between the supraoptic nucleus, the lateral superior olive and the IML (Tucker and Saper, 1985). Nevertheless, together with the fact that Ucn1 fibers innervate the sympathetic outflow area of the thoracic spinal cord (Korosi et al., 2007), support the view that EWcp is one of the brain regions that regulate SNS components (Cano et al., 2021).NF was supported by the research grant of Pecs University Medical School KA-2020-03, and New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund (?NKP-20-4-II-PTE-547). EP was supported by the grant from the P?cs University Medical School KA-2019-44. KJK was supported by Hungarian National Research, Development and Innovation Office (124424), and National Brain Research Program 2017-1.2.1-NKP-2017-00002. BG was financed by the Project no. TKP2020-IKA-08 provided from the National Research, Development and Innovation Fund of Hungary, financed under the 2020-4.1.1-TKP2020 funding scheme. (FIKP II, FIKP III), EFOP-3.6.2-16-2017-00008 and NKFIH FK124188. This work was also financed by NAP 2017-1.2.1-NKP-2017-00002; GINOP-2.3.2-15-2016-00050 ?PEPSYS,? and MTA-TKI14016. Publisher Copyright: {\textcopyright} 2021",
year = "2022",
month = mar,
day = "1",
doi = "10.1016/j.neuropharm.2021.108898",
language = "English (US)",
volume = "205",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Limited",
}