Metabolic effects of smoking cessation

Abstract

Smoking continues to be the leading cause of preventable death in the USA, despite the vast and widely publicized knowledge about the negative health effects of tobacco smoking. Data show that smoking cessation is often accompanied by weight gain and an improvement in insulin sensitivity over time. However, paradoxically, post-cessation-related obesity might contribute to insulin resistance. Furthermore, post-cessation weight gain is reportedly the number one reason why smokers, especially women, fail to initiate smoking cessation or relapse after initiating smoking cessation. In this Review, we discuss the metabolic effects of stopping smoking and highlight future considerations for smoking cessation programs and therapies to be designed with an emphasis on reducing post-cessation weight gain.

Figure 1. Mechanisms by which cigarette smoking reduces body weight

Smoking reduces body weight by increasing energy expenditure and inhibiting the expected compensatory increase in caloric intake. Nicotine increases energy expenditure both by direct effects on peripheral tissues (largely mediated by catecholamines) and by effects on neuroendocrine circuits in the central nervous system. The effects of nicotine on the brain also lead to suppression of appetite; smoking per se can serve as a behavioural alternative to eating. AgRP, agouti-related protein; CART, cocaine- and amphetamine-regulated transcript protein; DA, dopamine; Epi, adrenaline; GABA, γ-aminobutyric acid; NEpi, noradrenaline; NPY, neuropeptide Y; POMC, proopiomelanocortin. Modified with permission from Wiley © Audrain-McGovern, J. & Benowitz, N. L. Clin. Pharmacol. Ther. 90, 164–168 (2011).

Figure 2. Mechanisms by which nicotine leads to insulin resistance

Nicotine inhibits hypothalamic 5´-AMP-activated protein kinase (AMPK) activity, decreases food intake and increases thermogenesis. Nicotine also enhances lipolysis and increases the delivery of free fatty acids (FFA) to the liver and skeletal muscle. These effects of nicotine are associated with increased hepatic secretion of VLDL cholesterol and intramyocellular lipid saturation, as well as peripheral insulin resistance. Nicotine increases mammalian target of rapamycin (mTOR) and/or p70S6 kinase (p70S6K) activity in cultured L6 myotubes in association with increased phosphorylation (P) of insulin receptor substrate 1 (IRS-1) at Ser636 and reduced insulin-stimulated glucose uptake; the mTOR inhibitor rapamycin blocks these effects of nicotine. GLUT-4, glucose transporter type 4, insulin-responsive; NACHR, nicotinic acetylcholine receptor; p85, PI3K regulatory subunit-α; p110, PI3K catalytic subunit polypeptide; PI3K, phosphoinositide 3-kinase. American Diabetes Association, Bajaj, M. et al. Nicotine and insulin resistance: when the smoke clears. Diabetes 61, 3078–3080 (2012). Copyright and all rights reserved. Material from this publication has been used with the permission of American Diabetes Association.

Figure 3. Prevalence of smoking and obesity

Data shows the prevalence of smoking and obesity in individuals aged ≥18 years in California, USA, for the period 1989–2009. Modified with permission from the Legislative Analyst’s Office. 201 Cal Facts. California’s economy and budget in perspective [online], http://www.lao.ca.gov/reports/2011/calfacts/calfacts_010511.aspx (2011).

Figure 4. Weight gain within the first year of attempting to quit smoking

Point prevalence abstinence group includes individuals who were not continuously abstinent but who were abstinent over the 7 days before testing. At baseline, the average age of participants (n = 196) was 44.5 years. Modified with permission of Wiley © Audrain-McGovern, J. & Benowitz, N. L. Clin. Pharmacol. Ther. 90, 164–168 (2011).

Figure 5. Changes in BMI over 10 years with smoking status

At baseline, female participants (n = 5,639) and male participants (n = 3,365) had an average age of 47.1 years and 43.8 years, respectively. Modified with permission of Wiley © Audrain-McGovern, J. & Benowitz, N. L. Clin. Pharmacol. Ther. 90, 164–168 (2011).