Cigarette smoke exposure reprograms the hypothalamic neuropeptide Y axis to promote weight loss.
BACKGROUND
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.


OBJECTIVE
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, 3 x /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 alpha, and adipose triglyceride lipase was decreased by smoke exposure, and even lower in pair-fed mice.


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.
Chen
Hui
H
Department of Physiology, CRC for Chronic Inflammatory Diseases, The University of Melbourne Hospital, Victoria, Australia.
Hansen
Michelle J
MJ
Jones
Jessica E
JE
Vlahos
Ross
R
Bozinovski
Steve
S
Anderson
Gary P
GP
Morris
Margaret J
MJ
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000855:Anorexia / Q000209:etiology; D001069:Appetite Regulation / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007473:Ion Channels; D020738:Leptin / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D024101:Mitochondrial Proteins; D009478:Neuropeptide Y / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012907:Smoking / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1; D000071247:Uncoupling Protein 3; D015431:Weight Loss / Q000187:drug effects*
D002352:Carrier Proteins; D015850:Interleukin-6; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009478:Neuropeptide Y; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000071256:Uncoupling Protein 1; D000071247:Uncoupling Protein 3