Published ahead of print on March 10, 2006, doi:10.1164/rccm.200506-977OC Am. J. Respir. Crit. Care Med., Volume 173, Number 11, June 2006, 1248-1254 A more recent version of this article appeared on June 1, 2006
Submitted on June 24, 2005 Cigarette Smoke Exposure Reprograms the Hypothalamic Neuropeptide Y Axis to Promote Weight LossHui Chen1,1 Department of Pharmacology, The University of Melbourne, Melbourne, Victoria, Australia, 2 Department of Pharmacology, The University of Melbourne, Melbourne, Victoria, Australia; CRC for Chronic Inflammatory Diseases, The University of Melbourne, Melbourne, Victoria, Australia, 3 Department of Pharmacology, The University of Melbourne, Melbourne, Victoria, Australia; Royal Melbourne Hospital, Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia; CRC for Chronic Inflammatory Diseases, The University of Melbourne, Melbourne, Victoria, Australia, 4 Department of Physiology and Pharmacology, University of New South Wales, Sydney, New South Wales, Australia * To whom correspondence should be addressed. E-mail: m.morris{at}unsw.edu.au.
Rationale: Despite irrefutable epidemiological 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 weeks, 1 cigarette, 3 times/day, 5 days/week) to equivalent food restriction (pair-fed), and sham-exposed controls. Results: Smoke exposure rapidly induced mild anorexia. After 4 weeks, smoke exposed and pair-fed groups were lighter than controls (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 controls. 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 IL-6 and TNF Key words: anorexia, leptin, uncoupling protein, TNF  , IL-6
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