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.
Highlights
Smoking has, for a long time, been associated with a leaner phenotype
Nicotine’s effects are mediated by nicotinic acetylcholine receptors, mainly α3β4 nAChRs [2,3,15], we found that the kappa opioid receptor is necessary for the nicotine-induced activation of brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT) [6]
We previously demonstrated that κOR is essential for the ability of nicotine to exert a negative energy balance, by inducing BAT thermogenesis and browning of WAT [6]
Summary
For a long time, been associated with a leaner phenotype. Nicotine, the main bioactive compound of tobacco, is behind this effect due to its ability to regulate both food intake and energy expenditure [1]. Nicotine exerts its anorectic effect by the modulation of the hypothalamic neuropeptide systems [2,3], and increases the energy expenditure by promoting the activation of brown adipose tissue (BAT) thermogenesis and the browning of white adipose tissue (WAT) [3,4,5,6]. The energy sensor AMP-activated protein kinase (AMPK) at the central level has emerged as a mediator of several peripheral signals and compounds associated with the regulation of energy homeostasis [7,8,9,10,11,12,13], including nicotine [3,6,14].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
