Detrimental metabolic effects of combining long-term cigarette smoke exposure and high-fat diet in mice

Am J Physiol Endocrinol Metab. 2007 Dec;293(6):E1564-71. doi: 10.1152/ajpendo.00442.2007. Epub 2007 Oct 16.


Obesity and cigarette smoking are both important risk factors for insulin resistance, cardiovascular disease, and cancer. Smoking reduces appetite, which makes many people reluctant to quit. Few studies have documented the metabolic impact of combined smoke exposure (se) and high-fat-diet (HFD). Neuropeptide Y (NPY) is a powerful hypothalamic feeding stimulator that promotes obesity. We investigated how chronic se affects caloric intake, adiposity, plasma hormones, inflammatory mediators, and hypothalamic NPY peptide in animals fed a palatable HFD. Balb/c mice (5 wk old, male) were exposed to smoke (2 cigarettes, twice/day, 6 days/wk, for 7 wk) with or without HFD. Sham-exposed mice were handled similarly without se. Plasma leptin, hypothalamic NPY, and adipose triglyceride lipase (ATGL) mRNA were measured. HFD induced a 2.3-fold increase in caloric intake, increased adiposity, and glucose in both sham and se cohorts. Smoke exposure decreased caloric intake by 23%, with reduced body weight in both dietary groups. Fat mass and glucose were reduced only by se in the chow-fed animals. ATGL mRNA was reduced by HFD in se animals. Total hypothalamic NPY was reduced by HFD, but only in sham-exposed animals; se increased arcuate NPY. We conclude that although se ameliorated hyperphagia and reversed the weight gain associated with HFD, it failed to reverse fat accumulation and hyperglycemia. The reduced ATGL mRNA expression induced by combined HFD and se may contribute to fat retention. Our data support a powerful health message that smoking in the presence of an unhealthy Western diet increases metabolic disorders and fat accumulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism
  • Animals
  • Blood Glucose / metabolism
  • Body Weight / drug effects*
  • Brain / drug effects
  • Brain / metabolism
  • Carboxyhemoglobin / metabolism
  • Carboxylic Ester Hydrolases / genetics
  • Corticosterone / blood
  • Cytokines / genetics
  • Dietary Fats / administration & dosage
  • Dietary Fats / pharmacology*
  • Energy Intake / drug effects*
  • Gene Expression / drug effects
  • Insulin / blood
  • Ion Channels / genetics
  • Leptin / blood
  • Lipase
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mitochondrial Proteins / genetics
  • Neuropeptide Y / blood
  • Neuropeptide Y / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tobacco Smoke Pollution / adverse effects*
  • Triglycerides / blood
  • Uncoupling Protein 1


  • Blood Glucose
  • Cytokines
  • Dietary Fats
  • Insulin
  • Ion Channels
  • Leptin
  • Mitochondrial Proteins
  • Neuropeptide Y
  • RNA, Messenger
  • Tobacco Smoke Pollution
  • Triglycerides
  • Uncoupling Protein 1
  • Carboxyhemoglobin
  • Carboxylic Ester Hydrolases
  • Lipase
  • PNPLA2 protein, mouse
  • Corticosterone