Smoking and adipose tissue inflammation suppress leptin expression in Japanese obese males: potential mechanism of resistance to weight loss among Japanese obese smokers
More details
Hide details
Department of Dental Science for Health Promotion, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, 734-8553 Hiroshima, Japan
Division of Diabetes and Endocrinology, Kyoto Preventive Medical Center, 28 Nishinokyo, Samaryocho, Nakagyo-ku, Kyoto 604-8091, Japan
Division of Clinical Nutrition and Internal Medicine, Okayama Prefectural University, 111 Kuboki, Soja-city, Okayama 719-1197, Japan
Kyoto Institute of Health Science, Karasumaoike-Higashi, Nakagyo-ku, Kyoto 604-0845, Japan
Human health Sciences, Graduate School of medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
Health Care and Promotion Center, Yodogawa Christian Hospital, 2-9-26 Awaji, Higashiyodogawa-ku, Osaka 533-0032, Japan
Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-city 329-0498, Japan
Division of Diabetes, Clinical Nutrition and Endocrinology, Kansai Electric Power Hospital, 2-1-7 Fukushima, Fukushima-ku, Osaka 553-0003, Japan
Fusanori Nishimura   

Department of Dental Science for Health Promotion, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, 734-8553 Hiroshima, Japan
Publish date: 2012-02-28
Tobacco Induced Diseases 2012;10(February):3
The effect of smoking on leptin regulation is controversial. Smoking may induce low-grade inflammation. Recent series of studies indicated the critical role of macrophage migration in the establishment of adipose tissue inflammation. In this study, we aimed to see the effects of smoking and inflammation on leptin regulation both at cellular and epidemiological levels.

We compared the concentration of inflammatory markers and serum leptin levels among Japanese male subjects. Additionally, leptin and intercellular adhesion molecule (ICAM) -1 gene expression was assessed in adipocytes co-cultured with or without macrophages in the presence or absence of nicotine and/or lipopolysaccharide (LPS).

In subjects with BMI below 25 kg/m2 , both WBC counts and soluble-ICAM-1 levels are significantly higher in smokers than in non-smokers. However, leptin concentration did not differ according to smoking status. However, in subjects with BMI over 25 kg/m2 , smokers exhibited significantly lower serum leptin level as well as higher WBC counts and s-ICAM-1 concentration as compared with non-smokers. Leptin gene expression was markedly suppressed in adipocytes co-cultured with macrophages than in adipocyte culture alone. Furthermore, nicotine further suppressed leptin gene expression. ICAM-1 gene expression was markedly up-regulated in adipocytes co-cultured with macrophages when stimulated with LPS.

Adipose tissue inflammation appears to down-regulate leptin expression in adipose tissues. Nicotine further suppresses leptin expression. Thus, both smoking and inflammation may diminish leptin effect in obese subjects. Therefore, obese, but not normal weight, smokers might be more resistant to weight loss than nonsmokers.

Considine RV, Sinha MK, Heiman ML, et al: Serum immunoreactibe-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996, 334: 292-295. 10.1056/NEJM199602013340503.
Rabkin S: Relationship between weight change and the reduction or cessation of cigarette smoking. Int J Obese. 1984, 8: 665-673.
Eliasson B, Smith U: Leptin levels in smokers and long-term users of nicotine gum. Eur J Clin Invest. 1999, 29: 145-152. 10.1046/j.1365-2362.1999.00420.x.
Reseland JE, Mundal HH, Hollung K, et al: Cigarette smoking may reduce plasma leptin concentration via catecholamines. Prostaglandins Leukot Essent Fatty Acids. 2005, 73: 43-49. 10.1016/j.plefa.2005.04.006.
Xu H, Barnes GT, Yang Q, et al: Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003, 112: 1821-1830.
Weisberg SP, McCann D, Desai M, et al: Obesiy is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003, 112: 1796-1808.
Park E, Shin M-J, Chung N: The associations between serum leptin, adiponectin and intercellular adhesion molecule-1 in hypercholesterolemic patients. Nutr Res Prac. 2007, 1: 65-69. 10.4162/nrp.2007.1.1.65.
Yamashita A, Soga Y, Iwamoto Y, et al: Macrophage-adipocyte interaction: Marked IL-6 production by co-cultures stimulated with LPS. Obesity. 2007, 15: 2549-2552. 10.1038/oby.2007.305.
Yamashita A, Soga Y, Iwamoto Y, et al: DNA microarray analyses of genes expressed differentially in 3T3-L1 adipocytes co-cultured with murine macrophage cell line RAW 264.7 in the presence of the toll-like receptor 4 ligand bacterial endotoxin. Int J Obese. 2008, 32: 1725-1729. 10.1038/ijo.2008.153.
Kawakami M, Murase T, Ogawa H, et al: Human recombinant TNF suppresses lipoprotein lipase activity and stimulates lipolysis in 3T3-L1 cells. J Biochem. 1987, 101: 331-338.
Nakarai H, Yamashita A, Takagi M, et al: Periodontal disease and hyper-triglyceridemia in Japanese subjects: potential association with enhanced lipolysis. Metabolism. 2011, 60: 823-829. 10.1016/j.metabol.2010.07.034.
Kadowaki T, Sekikawa A, Murata K, et al: Japanese men have larger areas of visceral adipose tissue than Caucasian men in the same levels of waist circumstances in a population-based study. Int J Obese. 2006, 30: 1163-1165. 10.1038/sj.ijo.0803248.
Lazar MA: The humoral side of insulin resistance. Nat Med. 2006, 12: 43-44. 10.1038/nm0106-43.
Lau PP, Merched AJ, Zhang AL, et al: Nicotine induces proinflammatory responses in macrophages and the aorta leading to acceleration of atherosclerosis in low-density lipoprotein receptor (-/-) mice. Arterioscler Thromb Vasc Biol. 2006, 26: 143-149. 10.1161/01.ATV.0000193510.19000.10.
Massadeh AM, Gharaibeh AA, Omari KW: A single-step extraction method for the determination of nicotine and cotinine in Jordanian smokers' blood and urine samples by RP-HPLC and GC-MS. J Chromatogr Sci. 2009, 47: 170-177.
Yamaguchi M, Murakami T, Tomimatsu T, et al: Autocrine inhibition of leptin production by tumor necrosis factor-alpha (TNF-alpha) through TNF-alpha type-I receptor in vitro. Biochem Biophys Res Commun. 1998, 244: 30-34. 10.1006/bbrc.1998.8199.
Rahmouni K: Leptin-induced sympathetic nerve activation: Signaling mechanisms and cardiovascular consequences in obesity. Curr Hypertens Rev. 2010, 6: 104-209. 10.2174/157340210791170994.
Zimmet P, Boyko EJ, Collier GR, et al: Etiology of the metabolic syndrome: potential role of insulin resistance, leptin resistance, and other players. Ann NY Acad Sci. 1999, 892: 25-44. 10.1111/j.1749-6632.1999.tb07783.x.
Ozcan L, Ergin AS, Lu A, et al: Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab. 2009, 9: 35-51. 10.1016/j.cmet.2008.12.004.
Ozcan U, Cao Q, Yilmaz E, et al: Endoplasmic reticulum steress links obesity, insulinn action, and type 2 diabetes. Science. 2004, 306: 457-461. 10.1126/science.1103160.
Jorgensen E, Stinson A, Shan L, et al: Cigarette smoke induces endoplasmic reticulum stress and the unfolded protein response in normal and malignant human lung cells. BMC Cancer. 2008, 8: 229-10.1186/1471-2407-8-229.
Csordas A, Kreutmayer S, Ploner C, et al: Cigarette smoke extract induce prolonged endoplasmic reticulum stress and autophagic cell death in human umbilical vein endothelial cells. Cardiovasc Res. 2011, 92: 141-148. 10.1093/cvr/cvr165.
Miyatake N, Wada J, Kawasaki Y, et al: Relationship between metabolic syndrome and cigarette smoking in the Japanese population. Intern Med. 2006, 45: 1039-1043. 10.2169/internalmedicine.45.1850.
Nicotine may affect the secretion of adipokines leptin, resistin, and visfatin through activation of KATP channel
Xiao-Jun Bai, Li-Hong Fan, Ying He, Jie Ren, Wei Xu, Qi Liang, Hong-Bing Li, Jian-Hua Huo, Ling Bai, Hong-Yan Tian, Fen-Ling Fan, Ai-Qun Ma
A Consideration of Biomarkers to be Used for Evaluation of Inflammation in Human Nutritional Studies
P.C. Calder, N. Ahluwalia, R. Albers, N. Bosco, R. Bourdet-Sicard, D. Haller, S.T. Holgate, L.S. Jönsson, M.E. Latulippe, A. Marcos, J. Moreines, C. M'Rini, M. Müller, G. Pawelec, R.J.J. van Neerven, B. Watzl, J. Zhao
British Journal of Nutrition
Outcome Analysis of Single Incision vs Traditional Multiport Sleeve Gastrectomy: A Matched Cohort Study
Ameer Gomberawalla, Arsalan Salamat, Rami Lutfi
Obesity Surgery
Are leptin levels a cause or an indicator of cardiovascular risk?
Sait Demirkol, Mustafa Cakar, Sevket Balta, Murat Unlu
Revista Portuguesa de Cardiologia
Correlation between epicardial fat and cigarette smoking: CT imaging in patients with metabolic syndrome
Manuel Monti, Alessio Monti, Giuseppe Murdolo, Paolo Di Renzi, Maria Rosaria Pirro, Francesco Borgognoni, Giovanni Maria Vincentelli
Scandinavian Cardiovascular Journal
Visceral adiposity is a predictor of parathyroid hormone levels in healthy adults
J. A. George, S. A. Norris, M. Toman, T. Snyman, N. J. Crowther
Journal of Endocrinological Investigation
Smoking and Diabetes: Is the Association Mediated by Adiponectin, Leptin, or C-reactive Protein?
Esayas Haregot Hilawe, Hiroshi Yatsuya, Yuanying Li, Mayu Uemura, Chaochen Wang, Chifa Chiang, Hideaki Toyoshima, Koji Tamakoshi, Yan Zhang, Nobuo Kawazoe, Atsuko Aoyama
Journal of Epidemiology
Leptin and Thyrotropin Relationship Is Modulated by Smoking Status in Euthyroid Subjects
Anna Lucas, María Luisa Granada, Izaskun Olaizola, Conxa Castell, María Teresa Julián, Silvia Pellitero, Josep Roca, Manuel Puig-Domingo
Predictors of Success after Laparoscopic Sleeve Gastrectomy
Ameer Gomberawalla, Thomas D. Willson, Rami Lutfi
Bariatric Surgical Practice and Patient Care
Are leptin levels a cause or an indicator of cardiovascular risk?
Sait Demirkol, Mustafa Cakar, Sevket Balta, Murat Unlu
Revista Portuguesa de Cardiologia (English Edition)
Smoking is Associated with Reduced Leptin and Neuropeptide Y Levels and Higher Pain Experience in Patients with Fibromyalgia
Maria I. Bokarewa, Malin C. Erlandsson, Jan Bjersing, Mats Dehlin, Kaisa Mannerkorpi
Mediators of Inflammation