κ-Opioid Signaling in the Lateral Hypothalamic Area Modulates Nicotine-Induced Negative Energy Balance |
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Authors: | Patricia Seoane-Collazo Amparo Romero-Pic Eva Rial-Pensado Laura Liares-Pose nxela Estvez-Salguero Johan Fern Rubn Nogueiras Carlos Diguez Miguel Lpez |
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Affiliation: | 1.Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, 15782 Santiago de Compostela, Spain; (A.R.-P.); (E.R.-P.); (L.L.-P.); (Á.E.-S.); (R.N.); (C.D.);2.CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706 Santiago de Compostela, Spain;3.Hormone Laboratory, Haukeland University Hospital, N-5021 Bergen, Norway; |
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Abstract: | 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. |
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Keywords: | nicotine kappa opioid receptor lateral hypothalamus AMPK mTOR |
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