title: Long-term cigarette smoke exposure increases uncoupling protein expression but reduces energy intake.
abstract: The appetite suppressing effect of tobacco is a major driver of smoking behaviour; however few studies have addressed the effects of chronic cigarette smoke exposure (SE) on appetite, body weight and metabolic markers. We compared the effects of SE to equivalent food restriction (pair-fed, PF), against sham-exposure, on body weight, adiposity, cytokines, and levels of uncoupling proteins (UCP) and brain neuropeptide Y (NPY) in male Balb/C mice. SE rapidly induced anorexia, and after 12 weeks, SE and PF groups were lighter than control animals (23.9+/-0.2, 25.5+/-0.5, 26.8+/-0.4 g respectively, P<0.05). White fat (WAT) masses were reduced by both SE and PF. Plasma leptin and insulin were reduced in SE mice; insulin was further reduced by PF. Brown fat UCP1 and 3 mRNA were increased in SE animals relative to PF animals, possibly promoting thermogenesis. WAT mRNA expression of the inflammatory cytokine, TNFalpha was doubled by SE, while IL-6 was reduced by both PF and SE. Hypothalamic NPY content was increased by SE (89.3+/-2.8 vs. 75.9+/-2.4 ng control, P<0.05), and more by PF (100.7+/-3.4 ng, P<0.05 compared to both groups), suggesting disinhibition due to reduced adipose derived leptin. In contrast to equivalent food restriction, cigarette smoke exposure reduced body weight and total hypothalamic NPY, and increased thermogenesis and markers of inflammation. The suppressed hypothalamic NPY and increased UCPs may contribute to the spontaneous hypophagia and extra weight loss in SE animals. These findings contribute to our understanding of weight loss in smoking-related lung disease, suggesting a greater impact than that due to anorexia alone.
authors.affiliation: Department of Pharmacology, School of Medical Sciences, University of New South Wales, NSW 2052, Australia.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Hansen
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Jones
authors.forename: Ross
authors.initials: R
authors.lastname: Vlahos
authors.forename: Gary P
authors.initials: GP
authors.lastname: Anderson
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Morris
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D002149:Energy Intake / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012906:Smoke / Q000009:adverse effects*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1; D014026:Nicotiana
chemical_list: D016207:Cytokines; D007328:Insulin; D015850:Interleukin-6; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; D009478:Neuropeptide Y; D012333:RNA, Messenger; D012906:Smoke; D014409:Tumor Necrosis Factor-alpha; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D003345:Corticosterone