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   1. <dc:title>κ-Opioid Signaling in the Lateral Hypothalamic Area Modulates Nicotine-Induced Negative Energy Balance</dc:title>

   2. <dc:creator>Seoane Collazo, Patricia</dc:creator>

   3. <dc:creator>Romero Picó, Amparo</dc:creator>

   4. <dc:creator>Rial Pensado, Eva</dc:creator>

   5. <dc:creator>Liñares Pose, Laura</dc:creator>

   6. <dc:creator>Estévez Salguero, María Ánxela</dc:creator>

   7. <dc:creator>Fernø, Johan</dc:creator>

   8. <dc:creator>Nogueiras Pozo, Rubén</dc:creator>

   9. <dc:creator>Diéguez González, Carlos</dc:creator>

   10. <dc:creator>López Pérez, Miguel Antonio</dc:creator>

   11. <dc:contributor>Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas</dc:contributor>

   12. <dc:contributor>Universidade de Santiago de Compostela. Departamento de Fisioloxía</dc:contributor>

   13. <dc:subject>Nicotine</dc:subject>

   14. <dc:subject>Kappa opioid receptor</dc:subject>

   15. <dc:subject>Lateral hypothalamus</dc:subject>

   16. <dc:subject>AMPK</dc:subject>

   17. <dc:subject>mTOR</dc:subject>

   18. <dc:description>Several studies have reported that nicotine, the main bioactive component of tobacco, exerts a marked negative energy balance. Apart from its anorectic action, nicotine also modulates energy expenditure, by regulating brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. These effects are mainly controlled at the central level by modulation of hypothalamic neuropeptide systems and energy sensors, such as AMP-activated protein kinase (AMPK). In this study, we aimed to investigate the kappa opioid receptor (κOR)/dynorphin signaling in the modulation of nicotine’s effects on energy balance. We found that body weight loss after nicotine treatment is associated with a down-regulation of the κOR endogenous ligand dynorphin precursor and with a marked reduction in κOR signaling and the p70 S6 kinase/ribosomal protein S6 (S6K/rpS6) pathway in the lateral hypothalamic area (LHA). The inhibition of these pathways by nicotine was completely blunted in κOR deficient mice, after central pharmacological blockade of κOR, and in rodents where κOR was genetically knocked down specifically in the LHA. Moreover, κOR-mediated nicotine effects on body weight do not depend on orexin. These data unravel a new central regulatory pathway modulating nicotine’s effects on energy balance</dc:description>

   19. <dc:description>This research was funded from the Xunta de Galicia (R.N.: 2016-PG057; ML: 2016-PG068); Ministerio de Economía y Competitividad (MINECO) co-funded by the FEDER Program of EU (R.N.: RTI2018-099413-B-I00; C.D.: BFU2017-87721-P; M.L.: RTI2018-101840-B-I00); Atresmedia Corporación (RN and ML); Fundación BBVA (RN); “la Caixa” Foundation (ID 100010434), under the agreements LCF/PR/HR19/52160016 (R.N.) and LCF/PR/HR19/52160022 (M.L.); European Foundation for the Study of Diabetes (R.N.), ERC Synergy Grant-2019-WATCH- 810331 (R.N.) and Western Norway Regional Health Authority (Helse Vest RHF) (J.F.). P.S.-C. is the recipient of a fellowship from Xunta de Galicia (ED481B 2018/050). The CiMUS is supported by the Xunta de Galicia (2016-2019, ED431G/05). CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIII</dc:description>

   20. <dc:description>SI</dc:description>

   21. <dc:date>2021-02-15T11:44:28Z</dc:date>

   22. <dc:date>2021-02-15T11:44:28Z</dc:date>

   23. <dc:date>2021</dc:date>

   24. <dc:type>journal article</dc:type>

   25. <dc:type>VoR</dc:type>

   26. <dc:identifier>Int. J. Mol. Sci. 2021, 22(4), 1515; https://doi.org/10.3390/ijms22041515</dc:identifier>

   27. <dc:identifier>http://hdl.handle.net/10347/24455</dc:identifier>

   28. <dc:identifier>10.3390/ijms22041515</dc:identifier>

   29. <dc:identifier>1422-0067</dc:identifier>

   30. <dc:language>eng</dc:language>

   31. <dc:relation>https://doi.org/10.3390/ijms22041515</dc:relation>

   32. <dc:rights>© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)</dc:rights>

   33. <dc:rights>Atribución 4.0 Internacional</dc:rights>

   34. <dc:rights>http://creativecommons.org/licenses/by/4.0/</dc:rights>

   35. <dc:rights>open access</dc:rights>

   36. <dc:publisher>MDPI</dc:publisher>

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