| First Author | Seoane-Collazo P | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 4 | PubMed ID | 33546289 |
| Mgi Jnum | J:313364 | Mgi Id | MGI:6705671 |
| Doi | 10.3390/ijms22041515 | Citation | Seoane-Collazo P, et al. (2021) kappa-Opioid Signaling in the Lateral Hypothalamic Area Modulates Nicotine-Induced Negative Energy Balance. Int J Mol Sci 22(4) |
| abstractText | 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 (kappaOR)/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 kappaOR endogenous ligand dynorphin precursor and with a marked reduction in kappaOR 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 kappaOR deficient mice, after central pharmacological blockade of kappaOR, and in rodents where kappaOR was genetically knocked down specifically in the LHA. Moreover, kappaOR-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. |
