Published ahead of print on March 10, 2006, doi:10.1164/rccm.200506-977OC
© 2006 American Thoracic Society doi: 10.1164/rccm.200506-977OC
Cigarette Smoke Exposure Reprograms the Hypothalamic Neuropeptide Y Axis to Promote Weight LossDepartment of Pharmacology, and CRC for Chronic Inflammatory Diseases; Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Victoria; and Department of Physiology and Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, Australia Correspondence and requests for reprints should be addressed to Professor Margaret J Morris, Ph.D., Department of Physiology and Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia. E-mail: m.morris{at}unsw.edu.au Rationale: Despite irrefutable epidemiologic evidence, cigarette smoking remains the major preventable cause of lung disease morbidity worldwide. The appetite-suppressing effect of tobacco is a major behavioral determinant of smoking, but the underlying molecular and neuronal mechanisms are not understood. Neuropeptide Y (NPY) is an orexigenic neuropeptide, whose activity in the hypothalamic paraventricular nucleus governs appetite. Objectives: To compare the effects of smoke exposure and equivalent food restriction on body weight, organ mass, cytokines, and brain NPY in Balb/c mice. Methods: A pair-feeding study design compared smoke exposure (4 wk; 1 cigarette, 3x/d, 5 d/wk) to equivalent food restriction (pair-fed) and sham-exposed control mice.
Results: Smoke exposure rapidly induced mild anorexia. After 4 wk, smoke-exposed and pair-fed groups were lighter than control mice (22.0 ± 0.2, 23.2 ± 0.5, 24.9 ± 0.4 g, respectively; p < 0.05). Brown and white fat masses were only reduced by smoke exposure, relative to control mice. NPY concentration in the paraventricular nucleus was significantly and paradoxically reduced by smoke exposure, despite lower plasma leptin concentrations; this was not observed in the pair-fed group experiencing 19% food restriction. Adipose mRNA expression of uncoupling proteins, inflammatory cytokines interleukin 6 and tumor necrosis factor Conclusions: In contrast to food restriction, smoke exposure caused a reduction in hypothalamic NPY and fat mass, and regulated adipose cytokines. These findings may contribute to understanding weight loss in smoking-related lung disease and in the design of more effective smoking cessation strategies.
Key Words: anorexia • interleukin 6 • leptin • tumor necrosis factor This article has been cited by other articles:
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, and adipose triglyceride lipase was decreased by smoke exposure, and even lower in pair-fed mice. 
