RT Journal Article
T1 κ-Opioid Signaling in the Lateral Hypothalamic Area Modulates Nicotine-Induced Negative Energy Balance
A1 Seoane Collazo, Patricia
A1 Romero Picó, Amparo
A1 Rial Pensado, Eva
A1 Liñares Pose, Laura
A1 Estévez Salguero, Ánxela
A1 Fernø, Johan
A1 Nogueiras Pozo, Rubén
A1 Diéguez González, Carlos
A1 López Pérez, Miguel A.
K1 Nicotine
K1 Kappa opioid receptor
K1 Lateral hypothalamus
K1 AMPK
K1 mTOR
AB 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
PB MDPI
YR 2021
FD 2021
LK http://hdl.handle.net/10347/24455
UL http://hdl.handle.net/10347/24455
LA eng
NO Int. J. Mol. Sci. 2021, 22(4), 1515; https://doi.org/10.3390/ijms22041515
NO 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
DS Minerva
RD 23 abr 2026