Abstract
OBJECTIVE: Obesity may be associated with increased markers of inflammation that could be triggered by metabolic, physical, infectious or environmental processes. As smoking significantly increases cytokine production, we aimed to study how smoking influences the relationship between fat mass and soluble tumor necrosis factor-α (TNF-α) receptors 1 and 2 (sTNFR1 and sTNFR2).
DESIGN: Cross-sectional, clinical observational study.
SUBJECTS: A total of 133 healthy men (age: 27–53 y, body mass index (BMI): 24–30.2 kg/m2), 80 of whom were never-smokers and 53 smokers, matched for age, BMI and waist-to-hip ratio.
MEASUREMENTS: Circulating soluble fractions of the TNF-α receptors sTNFR1 and sTNFR2 were measured to study their relationship with fat mass (bioelectric impedance).
RESULTS: Smokers had significantly lower fat mass, lower fasting glucose, insulin and leptin concentrations than nonsmokers. Despite lower fat mass and insulin, smokers showed significantly increased circulating sTNFR2 levels (3.7±0.8 vs 3.4±0.7 ng/ml, P=0.03). The slopes of the relationships between sTNFR1 and fat mass, and between sTNFR2 and fat mass, were significantly steeper in smokers than in nonsmokers. In a stepwise multiple linear regression analysis, both fat mass (P<0.00001) and smoking (P=0.025) independently contributed to 13% of sTNFR1 variance and to 4% of sTNFR2 variance (P=0.03).
CONCLUSION: Both fat mass and smoking are related to increased activity of the TNF-α axis.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
Purchase on Springer Link
Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Fernández-Real JM, Ricart W . Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 2003; 24: 278–301.
Willet WC, Green A, Stampfer MJ, Speizer FE, Colditz GA, Rosner B, Monson RR, Stason W, Hennekens CH . Relative and absolute excess risk of coronary heart disease among women who smoke cigarettes. N Engl J Med 1987; 317: 1303–1307.
Hajjar DP, Pomeranz KB . Signal transduction in atherosclerosis: integration of cytokines and the eicosanoid network. FASEB J 1992; 6: 2933–2941.
Toomey D, Redmond P, Bouchier-Hayes D . Mechanisms mediating cancer cachexia. Cancer 1995; 76: 2418–2426.
Tracey KJ, Cerami A . Tumor necrosis factor and regulation of metabolism in infection: role of systemic versus tissue levels. Proc Soc Exp Biol Med 1992; 200: 233–239.
Albanes D, Jones DY, Micozzi MS, Mattson ME . Associations between smoking and body weight in the US population: analysis of NHANES II. Am J Public Health 1987; 77: 439–444.
Tappia PS, Troughton KL, Langley-Evans SC, Grimble RF . Cigarette smoking influences cytokine production and antioxidant defences. Clin Sci 1995; 88: 485–489.
Kuschner WG, D'Alessandro A, Wong H, Blanc PD . Dose-dependent cigarette smoking-related inflammatory responses in healthy adults. Eur Respir J 1996; 9: 1989–1994.
Grunfeld C, Zhao C, Fuller J, Pollack A, Moser A, Friedman J, Feingold KR . Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters. A role for leptin in the anorexia of infection. J Clin Invest 1996; 97: 2152–2157.
Kirchgessner TG, Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS . Tumor necrosis factor-α contributes to obesity-related hyperleptinemia by regulating leptin release from adipocytes. J Clin Invest 1997; 100: 2777–2782.
Qian H, Hausman GJ, Compton MM, Azain MJ, Hartzell DL, Baile CA . Leptin regulation of peroxisome proliferator-activated receptor-gamma, tumor necrosis factor, and uncoupling protein-2 expression in adipose tissues. Biochem Biophys Res Commun 1998; 246: 660–667.
Zumbach MS, Boehme MW, Wahl P, Stremmel W, Ziegler R, Nawroth PP . Tumor necrosis factor increases serum leptin levels in humans. J Clin Endocrinol Metab 1997; 82: 4080–4082.
Mantzoros CS, Moschos S, Avramopoulos I, Kaklamani V, Liolios A, Doulgerakis DE, Griveas I, Katsilambros N, Flier JS . Leptin concentrations in relation to body mass index and the tumor necrosis factor-α system in humans. J Clin Endocrinol Metab 1997; 82: 3408–3413.
Hodge AM, Westerman RA, de Courten MP, Collier GR, Zimmet PZ, Alberti KG . Is leptin sensitivity the link between smoking cessation and weight gain. Int J Obes Rel Metab Dis 1997; 21: 50–53.
Wei M, Stern MP, Haffner SM . Serum leptin levels in Mexican Americans and non-Hispanic whites: association with body mass index and cigarette smoking. Ann Epidemiol 1997; 7: 81–86.
Yoshinari M, Wakisaka M, Fujishima M . Serum leptin levels in smokers with type 2 diabetes. Diabetes Care 1998; 21: 516–517.
Niklas BJ, Tomoyasu N, Muir J, Goldberg AP . Effects of cigarette smoking and its cessation on body weight and plasma leptin levels. Metabolism 1999; 48: 804–808.
Aderka D, Engelmann H, Maor Y, Brakebusch C, Wallach D . Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors. J Exp Med 1992; 175: 323–329.
Aderka D, Sorkine P, Abu-Abid S, Lev D, Setton A, Cope AP, Wallach D, Klausner J . Shedding kinetics of soluble tumor necrosis factor (TNF) receptors after systemic TNF leaking during isolated limb perfusion. Relevance to the pathophysiology of septic shock. J Clin Invest 1998; 101: 650–659.
Schroder J, Stuber F, Gallati H, Schade FU, Kremer B . Pattern of soluble TNF receptors I and II in sepsis. Infection 1995; 23: 143–148.
Aderka D, Engelmann H, Shemer-Avni Y, Hornik V, Galil A, Sarov B, Wallach D . Variation in serum levels of the soluble TNF receptors among healthy individuals. Lymphokine Cytokine Res 1992; 11: 157–159.
Hotamisligil GS, Arner P, Atkinson RL, Spiegelman BM . Differential regulation of the p80 tumor necrosis factor receptor in human obesity and insulin resistance. Diabetes 1997; 46: 451–455.
Fernández-Real JM, Broch M, Ricart W, Gutiérrez C, Casamitjana R, Vendrell J, Richart C . Plasma levels of the soluble fraction of tumor necrosis factor receptor 2 and insulin resistance. Diabetes 1998; 47: 1757–1762.
Hauner H, Bender M, Haastert B, Hube F . Plasma concentrations of soluble TNF-alpha receptors in obese subjects. Int J Obes Relat Metab Disord 1998; 22: 1239–1243.
Corica F, Allegra A, Corsonello A, Buemi M, Calapai G, Ruello A, Nicita Mauro V, Ceruso D . Relationship between plasma leptin levels and the tumor necrosis factor-α system in obese subjects. Int J Obes Rel Metab Dis 1999; 23: 355–360.
Haack M, Hinze-Selch D, Fenzel T, Kraus T, Kuhn M, Schuld A, Pollmacher T . Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon admission: effects of confounding factors and diagnosis. J Psychiatr Res 1999; 33: 407–418.
Boström L, Linder LE, Bergström J . Smoking and crevicular fluid levels of IL-6 and TNF-α in periodontal disease. J Clin Periodontol 1999; 26: 352–357.
Hasday JD, Bascom R, Costa JJ, Fitzgerald T, Dubin W . Bacterial endotoxin is an active component of cigarette smoke. Chest 1999; 115: 829–835.
Michel OJ, Kips J, Duchateau J, Vertongen F, Robert L, Collet H, Pauwels R, Sergysels R . Severity of asthma is related to endotoxin in house dust. Am J Respir Crit Care Med 1996; 154: 1641–1646.
Spinas GA, Keller U, Brockhaus M . Release of soluble receptors for tumor necrosis factor (TNF) in relation to circulating TNF during experimental endotoxinemia. J Clin Invest 1992; 90: 533–536.
Fahmi H, Chaby R . Selective refractoriness of macrophages to endotoxin-induced production of tumor necrosis factor, elicited by an autocrine mechanism. J Leukoc Biol 1993; 53: 45–52.
Acknowledgements
This work was partly supported by a grant from the Instituto de Salud Carlos III, RGDM (G03/212), Madrid, Spain.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fernandez-Real, JM., Broch, M., Vendrell, J. et al. Smoking, fat mass and activation of the tumor necrosis factor-α pathway. Int J Obes 27, 1552–1556 (2003). https://doi.org/10.1038/sj.ijo.0802472
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijo.0802472
Keywords
This article is cited by
-
Leptin and smoking cessation: secondary analyses of a randomized controlled trial assessing physical activity as an aid for smoking cessation
BMC Public Health (2014)
-
Inflammation marker and risk of pancreatic cancer: a nested case–control study within the EPIC cohort
British Journal of Cancer (2012)
-
Effect of Short-Term Cigarette Smoke Exposure on Body Weight, Appetite and Brain Neuropeptide Y in Mice
Neuropsychopharmacology (2005)