Nicotine Induces Negative Energy Balance Through Hypothalamic AMP-Activated Protein Kinase
- Pablo B. Martínez de Morentin1,2,
- Andrew J. Whittle3,
- Johan Fernø4,5,
- Rubén Nogueiras1,2,
- Carlos Diéguez1,2,
- Antonio Vidal-Puig3 and
- Miguel López1,2⇓
- 1Department of Physiology, School of Medicine-CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, A Coruña, Spain
- 2CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
- 3Institute of Metabolic Science, Metabolic Research Laboratories, NIHR Cambridge Biomedical Research Centre Addenbrooke's Hospital, University of Cambridge, Cambridge, U.K.
- 4Dr. Einar Martens’ Research Group for Biological Psychiatry, Department of Clinical Medicine, University of Bergen, Bergen, Norway
- 5Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
- Corresponding author: Miguel López, .
Smokers around the world commonly report increased body weight after smoking cessation as a major factor that interferes with their attempts to quit. Numerous controlled studies in both humans and rodents have reported that nicotine exerts a marked anorectic action. The effects of nicotine on energy homeostasis have been mostly pinpointed in the central nervous system, but the molecular mechanisms controlling its action are still not fully understood. The aim of this study was to investigate the effect of nicotine on hypothalamic AMP-activated protein kinase (AMPK) and its effect on energy balance. Here we demonstrate that nicotine-induced weight loss is associated with inactivation of hypothalamic AMPK, decreased orexigenic signaling in the hypothalamus, increased energy expenditure as a result of increased locomotor activity, increased thermogenesis in brown adipose tissue (BAT), and alterations in fuel substrate utilization. Conversely, nicotine withdrawal or genetic activation of hypothalamic AMPK in the ventromedial nucleus of the hypothalamus reversed nicotine-induced negative energy balance. Overall these data demonstrate that the effects of nicotine on energy balance involve specific modulation of the hypothalamic AMPK-BAT axis. These targets may be relevant for the development of new therapies for human obesity.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-1079/-/DC1.
See accompanying commentary, p. 776.
- Received August 2, 2011.
- Accepted December 8, 2011.
- © 2012 by the American Diabetes Association.
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