Role of adipokines in obstructive airway disease and diabetes mellitus

Authors

  • Seema Singh Department of Respiratory Medicine, King Georges Medical University, Lucknow, India
  • Sunita Singh Department of Microbiology, King Georges Medical University, Lucknow, India
  • Santosh Kumar Department of Respiratory Medicine, King Georges Medical University, Lucknow, India
  • S K Verma Department of Respiratory Medicine, King Georges Medical University, Lucknow, India
  • Surya Kant Department of Respiratory Medicine, King Georges Medical University, Lucknow, India

DOI:

https://doi.org/10.21276/IJRDPL.2278-0238.2019.8(4).13-17

Keywords:

Adipokines, adiponectin, leptin, asthma, diabetes mellitus

Abstract

This review summarizes the state of the current literature relating to the associations of lung disease and adipokines (proteins produced by adipose tissue) in humans. The mechanistic basis for these associations in humans is not established, although a possible role for adipokines has been invoked. Leptin, a pro-inflammatory adipokine, and adiponectin, an anti-inflammatory adipokine, are causally associated with asthma in mice. Although human studies are currently inconclusive, high-serum leptin and low-serum adiponectin concentrations predict asthma, independent of obesity, in select population groups, such as premenopausal women in the United States. In contradistinction, low-serum leptin and high-serum adiponectin concentrations are associated with stable COPD, although these associations are likely confounded by fat mass. Interestingly, leptin may promote systemic and airway inflammation in stable COPD patients. On the other hand, COPD may upregulate systemic and lung adiponectin expression. The precise mechanism and significance of the associations between these adipokines and lung disease at the current stage are confusing and frankly paradoxical in places. It is now known that adipose tissue is not an inert organ simply for energy storage, but regulates systemic inflammation via a variety of secreted proteins (called adipokines). While the associations of obesity and adipokines with cardiovascular, endocrine, and rheumatological diseases are well described, the respiratory effects of obesity and adipokines are less well known. This review will focus on the effect of obesity and adipokines on asthma and chronic obstructive pulmonary disease (COPD) in humans. This area of research needs additional study that may open up novel therapeutic strategies for these lung diseases.

Downloads

Download data is not yet available.

References

Masuzaki H, Ogawa Y, Sagawa N, Hosoda K, Matsumoto T, Mise H, Nishimura H, Yoshimasa Y, Tanaka I, Mori T, Nakao K. Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat Med. 1997; 3:1029–1033. [PubMed: 9288733]

Bado A, Levasseur S, Attoub S, Kermorgant S, Laigneau JP, Bortoluzzi MN, Moizo L, Lehy T, Guerre-Millo M, Le Marchand-Brustel Y, Lewin MJ. The stomach is a source of leptin. Nature. 1998; 394:790–793. [PubMed: 9723619]

Larsson H, Ahren B. Short-term dexamethasone treatment increases plasma leptin independently of changes in insulin sensitivity in healthy women. J Clin Endocrinol Metab. 1996; 81:4428–4432. [PubMed: 8954054]

Messinis IE, Papageorgiou I, Milingos S, Asprodini E, Kollios G, Seferiadis K. Oestradiol plus progesterone treatment increases serum leptin concentrations in normal women. Hum Reprod. 2001; 16:1827–1832. [PubMed: 11527883]

Holness MJ, Munns MJ, Sugden MC. Current concepts concerning the role of leptin in reproductive function. Mol Cell Endocrinol. 1999; 157:11–20. [PubMed: 10619393]

Hsu A, Aronoff DM, Phipps J, Goel D, Mancuso P. Leptin improves pulmonary bacterial clearance and survival in ob/ob mice during pneumococcal pneumonia. Clin Exp Immunol. 2007; 150:332– 339. [PubMed: 17822444]

Mancuso, P. Leptin-Deficient Mice Exhibit Impaired Host Defense in Gram-Negative

Pneumonia.pdf. 2002. 8. WA, Mastronardi CA, Yu WH, Karanth S, Parlow AF, MSM. The possible role of prolactin in the circadian rhythm of leptin secretion in male rats. Proc Soc Exp Biol Med. 2000; 224:152–158. [PubMed: 10865230]

Shin JH, Kim JH, Lee WY, Shim JY. The expression of adiponectin receptors and the effects of adiponectin and leptin on airway smooth muscle cells. Yonsei Med J. 2008; 49:804–810. [PubMed: 18972601]

Matarese G, Moschos S, Mantzoros CS. Leptin in immunology. J Immunol. 2005; 174:3137–3142. [PubMed: 15749839]

Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006; 6:772–783. [PubMed: 16998510]

La Cava A, Alviggi C, Matarese G. Unraveling the multiple roles of leptin in inflammation and autoimmunity. J Mol Med (Berl). 2004; 82:4–11. [PubMed: 14556053]

Otero M, Lago R, Gomez R, Dieguez C, Lago F, Gomez-Reino J, Gualillo O. Towards a proinflammatory and immunomodulatory emerging role of leptin. Rheumatology (Oxford). 2006; 45:944– 950. [PubMed: 16720637]

Adeghate, E. (2008). Visfatin: Structure, function and relation to diabetes mellitus and other dysfunctions. Current Medicinal Chemistry, 15(18), 1851–1862.

Agusti, A. G., Noguera, A., Sauleda, J., Sala, E., Pons, J. and Busquets, X. (2003). Systemic effects of chronic obstructive pulmonary disease. European Respiratory Journal, 21(2), 347–360.

Al Mutairi, S. S., Mojiminiyi, O. A., Shihab-Eldeen, A., Al Rammah, T. and Abdella, N. (2011).

Arita, Y., Kihara, S., Ouchi, N., Takahashi, M., Maeda, K., Miyagawa, J., Hotta, K., Shimomura, I., Nakamura, T., Miyaoka, K., Kuriyama, H., Nishida, M., Yamashita, S., Okubo, K., Matsubara, K., Muraguchi, M., Ohmoto, Y., Funahashi, T. and Matsuzawa, Y. (1999).

Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochemical & Biophysical Research Communications, 257(1), 79–83.

Arshi, M., Cardinal, J., Hill, R. J., Davies, P. S. and Wainwright, C. (2010). Asthma and insulin resistance in children. Respirology, 15(5), 779–784.

Banks, A. S., Davis, S. M., Bates, S. H. and Myers, M. G.,Jr. (2000). Activation of downstream signals by the long form of the leptin receptor. Journal of Biological Chemistry, 275(19), 14563–14572.

Barnes, P. J. (2004). Small airways in COPD. The New England Journal of Medicine, 350(26),2635–2637.

Barnes, P. J. (2005). Molecular mechanisms and cellular effects of glucocorticosteroids. Immunology & Allergy Clinics of North America, 25(3), 451–468.

Parr, D. G. (2011). Patient phenotyping and early disease detection in chronic obstructive pulmonary disease. Proceedings of the American Thoracic Society, 8(4), 338–349.

Schols, A. M., Creutzberg, E. C., Buurman, W. A., Campfield, L. A., Saris, W. H. and Wouters, E. F. (1999). Plasma leptin is related to proinflammatory status and dietary intake in patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, 160(4), 1220–1226.

Schwartz, D. R., & Lazar, M. A. (2011). Human resistin: Found in translation from mouse to man. Trends in Endocrinology and Metabolism: TEM, 22(7), 259–265.

Scotece, M., Conde, J., Abella, V., Lopez, V., Lago, F., Pino, J., Gomez-Reino, J. J. Gualillo, O. (2014). NUCB2/nesfatin-1: A new adipokine expressed in human and murine chondrocytes with pro-inflammatory properties, an in vitro study. Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society, 32(5), 653–660.

Scotece, M., Conde, J., Vuolteenaho, K., Koskinen, A., Lopez, V., Gomez-Reino, J., Lago, F., Moilanen, E. and Gualillo, O. (2014). Adipokines as drug targets in joint and bone disease. Drug Discovery Today, 19(3), 241–258.

Setta, J. H., Neder, J. A., Bagatin, E., Terra-Filho, M., Napolis, L. M., Corso, S. D., Amorin, M., Rodrigues, R. T., Fernandes, A. L. and Nery, L. E. (2008). Relationship between induced sputum cytology and inflammatory status with lung structural and functional abnormalities in asbestosis. American Journal of Industrial Medicine, 51(3), 186–194.

Shin, J. H., Kim, J. H., Lee, W. Y. and Shim, J. Y. (2008). The expression of adiponectin receptors and the effects of adiponectin and leptin on airway smooth muscle cells. Yonsei Medical Journal, 49(5), 804–810.

Shore, S. A. (2008). Obesity and asthma: Possible mechanisms. Journal of Allergy & Clinical Immunology, 121(5), 1087–1093.

Shore, S. A., & Johnston, R. A. (2006). Obesity and asthma. Pharmacology & Therapeutics, 110(1), 83–102.

Sideleva, O., Suratt, B. T., Black, K. E., Tharp, W. G., Pratley, R. E., Forgione, P., Dienz, O.,Irvin, C. G. and Dixon, A. E. (2012). Obesity and asthma: An inflammatory disease of adipose tissue not the airway. American Journal of Respiratory and Critical Care Medicine, 186(7), 598–605.

Silswal, N., Singh, A. K., Aruna, B., Mukhopadhyay, S., Ghosh, S. and Ehtesham, N. Z. (2005).

Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 inmacrophages by NF-kappaB-dependent pathway. Biochemical and Biophysical Research Communications, 334(4), 1092–1101.

Sin, D. D., & Man, S. F. (2003). Impaired lung function and serum leptin in men and women with normal body weight: A population-based study. Thorax, 58(8), 695–698.

Sinden, N. J., & Stockley, R. A. (2010). Systemic inflammation and comorbidity in COPD: A result of ‘overspill’ of inflammatory mediators from the lungs? review of the evidence. Thorax, 65(10), 930–936.

Smith, S. G., Watson, B., Clark, G. and Gauvreau, G. M. (2012). Eculizumab for treatment of asthma. Expert Opinion on Biological Therapy, 12(4), 529-537.

Sood, A. (2010). Obesity, adipokines, and lung disease. Journal of Applied Physiology, 108(3), 744–753.

Sood, A., Cui, X., Qualls, C., Beckett, W. S., Gross, M. D., Steffes, M. W., Smith, L. J. and Jacobs, D. R.,Jr. (2008). Association between asthma and serum adiponectin concentration in women. Thorax, 63(10), 877–882.

Sood, A., Dominic, E., Qualls, C., Steffes, M. W., Thyagarajan, B., Smith, L. J., Lewis, C. E. and Jacobs, D. R. Jr. (2011). Serum adiponectin is associated with adverse outcomes of asthma in men but not in women. Frontiers in Pharmacology, 2, 55.

Sood, A., Ford, E. S. and Camargo, C. A.,Jr. (2006). Association between leptin and asthma in adults. Thorax, 61(4), 300–305.

Sood, A., Qualls, C., Seagrave, J., Stidley, C., Archibeque, T., Berwick, M. and Schuyler, M. (2009). Effect of specific allergen inhalation on serum adiponectin in human asthma.Chest, 135(2), 287–294.

L., Cook, K. S. and Flier, J. S. (1989). Adrenal glucocorticoids regulate adipsin gene expression in genetically obese mice. The Journal of Biological Chemistry, 264(3), 1811–1815.

Steppan, C. M., Bailey, S. T., Bhat, S., Brown, E. J., Banerjee, R. R., Wright, C. M., Patel, H. R.,Ahima, R. S. and Lazar, M. A. (2001). The hormone resistin links obesity to diabetes.Nature, 409(6818), 307–312.

Steppan, C. M., & Lazar, M. A. (2004). The current biology of resistin. Journal of Internal Medicine, 255(4), 439–447.

Sukumaran, S., Jusko, W. J., DuBois, D. C. and Almon, R. R. (2011). Mechanistic modeling of the effects of glucocorticoids and circadian rhythms on adipokine expression. Journal of Pharmacology & Experimental Therapeutics, 337(3), 734–746.

Summer, R., Little, F. F., Ouchi, N., Takemura, Y., Aprahamian, T., Dwyer, D., Fitzsimmons, K., Suki, B., Parameswaran, H., Fine, A. and Walsh, K. (2008). Alveolar macrophage activation and an emphysema-like phenotype in adiponectin-deficient mice. American Journal of Physiology – Lung Cellular & Molecular Physiology, 294(6), 1035–1042.

Sutherland, T. J., Sears, M. R., McLachlan, C. R., Poulton, R. and Hancox, R. J. (2009). Leptin,adiponectin, and asthma: Findings from a population-based cohort study. Annals of Allergy, Asthma, & Immunology, 103(2), 101–107.

Takabatake, N., Nakamura, H., Abe, S., Hino, T., Saito, H., Yuki, H., Kato, S. and Tomoike, H. (1999). Circulating leptin in patients with chronic obstructive pulmonary disease. American Journal of Respiratory & Critical Care Medicine, 159(4 Pt 1), 1215–1219.

Takefuji, S., Yatsuya, H., Tamakoshi, K., Otsuka, R., Wada, K., Matsushita, K., Sugiura, K., Hotta, Y., Mitsuhashi, H., Oiso, Y. and Toyoshima, H. (2007). Smoking status and adiponectin in healthy Japanese men and women. Preventive Medicine, 45(6), 471–475.

Tang, C. H., Fu, X. J., Xu, X. L., Wei, X. J. and Pan, H. S. (2012). The anti-inflammatory and anti-apoptotic effects of nesfatin-1 in the traumatic rat brain. Peptides, 36(1), 39–45.

Tarkowski, A., Bjersing, J., Shestakov, A. and Bokarewa, M. I. (2010). Resistin competes with lipopolysaccharide for binding to toll-like receptor 4. Journal of Cellular & Molecular Medicine, 14(6B), 1419–1431.

Tartaglia, L. A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G. J., Campfield, L. A., Clark, F. T., Deeds, J., Muir, C., Sanker, S., Moriarty, A., Moore, K. J., Smutko, J. S., Mays, G. G., Wool, E. A., Monroe, C. A. and Tepper, R. I. (1995).

Identification and expression cloning of a leptin receptor, OB-R. Cell, 83(7), 1263– 1271.

Tian, Z., Sun, R., Wei, H. and Gao, B. (2002). Impaired natural killer (NK) cell activity in leptin receptor deficient mice: Leptin as a critical regulator in NK cell development and activation. Biochemical & Biophysical Research Communications, 298(3), 297–302.

Tilg, H., & Moschen, A. R. (2006). Adipocytokines: Mediators linking adipose tissue, inflammation and immunity. Nature Reviews. Immunology, 6(10), 772-783.

Tomoda, K., Yoshikawa, M., Itoh, T., Tamaki, S., Fukuoka, A., Komeda, K. and Kimura, H. (2007). Elevated circulating plasma adiponectin in underweight patients with COPD. Chest, 132(1), 135–140.

Tsoukias, N. M., & George, S. C. (1998). A two-compartment model of pulmonary nitric oxide exchange dynamics. Journal of Applied Physiology, 85(2), 653–666.

Uibu, T., Oksa, P., Auvinen, A., Honkanen, E., Metsarinne, K., Saha, H., Uitti, J. and Roto, P.(2004). Asbestos exposure as a risk factor for retroperitoneal fibrosis. Lancet, 363(9419), 1422–1426.

Verbraecken, J. & McNicholas, W. T. (2013). Respiratory mechanics and ventilatory control in overlap syndrome and obesity hypoventilation. Respiratory Research, 14, 132-9921- 14-132.

Vondracek, S. F., Voelkel, N. F., McDermott, M. T. and Valdez, C. (2009). The relationship between adipokines, body composition, and bone density in men with chronic obstructive pulmonary disease. International Journal of Copd, 4, 267–277.

Vuolteenaho, K., Koskinen, A., Kukkonen, M., Nieminen, R., Paivarinta, U., Moilanen, T.and Moilanen, E. (2009). Leptin enhances synthesis of proinflammatory mediators inhuman osteoarthritic cartilage--mediator role of NO in leptin-induced PGE2, IL-6, and IL-8 production. Mediators of Inflammation, 2009, 345838.

Vuolteenaho, K., Koskinen, A., Moilanen, T. and Moilanen, E. (2012). Leptin levels areincreased and its negative regulators, SOCS-3 and sOb-R are decreased in obese patients with osteoarthritis: A link between obesity and osteoarthritis. Annals of the Rheumatic Diseases, 71(11), 1912–1913.

Waki, H., Yamauchi, T., Kamon, J., Ito, Y., Uchida, S., Kita, S., Hara, K., Hada, Y., Vasseur, F., Froguel, P., Kimura, S., Nagai, R. and Kadowaki, T. (2003). Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. Journal of Biological Chemistry, 278(41), 40352– 40363.

Walkey, A. J., Rice, T. W., Konter, J., Ouchi, N., Shibata, R., Walsh, K., deBoisblanc, B. P. and Summer, R. (2010). Plasma adiponectin and mortality in critically ill subjects withacute respiratory failure. Critical Care Medicine, 38(12), 2329–2334.

Waschki, B., Kirsten, A., Holz, O., Muller, K. C., Meyer, T., Watz, H. and Magnussen, H. (2011). Physical activity is the strongest predictor of all-cause mortality in patients with COPD: A prospective cohort study. Chest, 140(2), 331–342.

Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L. and Ferrante, A. W.,Jr. (2003). Obesity is associated with macrophage accumulation in adipose tissue. The Journal of Clinical Investigation, 112(12), 1796–1808.

Wellen, K. E., & Hotamisligil, G. S. (2005). Inflammation, stress, and diabetes. Journal of Clinical Investigation, 115(5), 1111–1119.

How to cite this article:

Singh S, Singh S, Kumar S, Verma SK, and Surya Kant. Role of adipokines in obstructive airway disease and diabetes mellitus. Int. J. Res. Dev. Pharm. L. Sci. 2019; 8(4): 13-17. doi: 10.13040/IJRDPL.2278-0238.8(4).13-17

This Journal is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.

Published

2019-10-15

How to Cite

Singh, S., Singh, . S. ., Kumar, S. ., Verma, S. K. ., & Kant, S. (2019). Role of adipokines in obstructive airway disease and diabetes mellitus. International Journal of Research and Development in Pharmacy & Life Sciences, 8(4), 13-17. https://doi.org/10.21276/IJRDPL.2278-0238.2019.8(4).13-17

Most read articles by the same author(s)

1 2 > >>