COMBINATION OF LEPTIN ANALOG AND SALBUTAMOL: TREATMENT APPROACH FOR OBESITY-INDUCED ASTHMA
Objective: The objective of the study was to investigate the effect of leptin analog and salbutamol in obese asthmatic mice.
Methods: Obese asthmatic condition was induced by administration of hypercaloric diet for 8 weeks followed by ovalbumin-aluminum hydroxide. The animals were treated with leptin analog (0.4 mg/kg, i.p. for 14 days) and salbutamol (2 mg/kg, PO for 14 days). Biochemical parameters such as serum leptin, ghrelin, and tumor necrosis factor-α and physical parameters such as tidal volume and airflow rate were estimated to confirm the state of asthma and obesity, respectively.
Results: Elevated serum leptin and ghrelin were associated with leptin resistance in obese asthmatic mice. It was found that a significant increase in serum leptin level with animal treated with leptin analog and salbutamol when compared to animals treated with leptin analog alone. The result of respiratory parameters and serum parameters also improved with the combination of leptin analog and salbutamol. From our study, we found that salbutamol potentiates the effect of leptin analog in obese asthmatic condition.
Conclusion: Leptin analog and salbutamol are an alternative treatment approach to treat the obese asthmatic condition.
2. Farooqi IS, O’Rahilly S. Genetics of obesity in humans. Endcr Rev 2006;27:710-8.
3. Palatty PL, Saldanha E. Pharmacotherapy for weight management. J Assoc Phys India 2012;60:34-40.
4. Bollapragada MK, Shantaram M, Sunil KR. Obesity: Development, epidemiology, factors affecting, quantity, health hazards, management and natural treatment-a review. Int J Pharm Pharm Sci 2015;9:12-26.
5. Yun JW. Possible anti-obesity therapeutics from nature a review. Phytochemistry 2010;71:1625-41.
6. Anitha M, Roselin EM, Monisha DM, Karthik JC. Prevalence of obesity and overweight among medicos in both male and female students. Asian J Pharm Clin Res 2016;26:289-91.
7. Wood LG, Gibson PG. Dietary factors lead to innate immune activation in asthma. Pharmacol Ther 2009;123:37-53.
8. Jeffery RW, Epstein LH, Wilson GT, Drewnowski A, Stunkard AJ, Wing RR. Long-term maintenance of weight loss: Current status. Health Psychol 2000;19:5.
9. Boulet LP. Asthma and obesity. Clin Exp Allergy 2013;43:8-21.
10. Walker BR, Colledge NR. Davidson’s principles and practice of medicine. In: With Student Consult Online Access. United Kingdom: Elsevier Health Sciences; 2013.
11. Bousquet J, Mantzouranis E, Cruz AA, Aït-Khaled N, Baena-Cagnani CE, Bleecker ER, et al. Uniform definition of asthma severity, control, and exacerbations: Document presented for the world health organization consultation on severe asthma. J Allergy Clin Immunol 2010;126:926 38.
12. Lötvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, et al. Asthma endotypes: A new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol 2011;127:355-60.
13. Agache I, Akdis C, Jutel M, Virchow JC. Untangling asthma phenotypes and endotypes. Allergy 2012;67:835-46.
14. Farzan S. The asthma phenotype in the obese: Distinct or otherwise? J Allergy 2013;2013:11-14.
15. Soni AK, Deshpande SS, Suhagia BN. Gender specific correlation between obesity and asthma. Int J Pharm Res Scholar 2018;6:46-51.
16. Bateman ED, Hurd SS, Barnes PJ, Bousquet J, Drazen JM, FitzGerald M, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Res J 2008;31:143-78.
17. Soni AK, Deshpande SS. A novel hypothesis for pathophysiology of asthma in obesity. Int J Pharm Res Scholar 2017;6:12-8.
18. Baffi CW, Winnica DE, Holguin F. Asthma and obesity: Mechanisms and clinical implications. Asthma Res Pract 2015;1:1.
19. Uchida A, Zechner JF, Mani BK, Park WM, Aguirre V, Zigman JM. Altered ghrelin secretion in mice in response to diet-induced obesity and Roux-en-Y gastric bypass. Mol Metabolism 2014;3:717-30.
20. Soni AK, Deshpande SS, Pithadia AB, Suhagia BN. Endocrinological role of leptin in obesity and asthma. Asian J Pharm Sci Clin Respir 2019; 12:160-4.
21. Varraso R, Siroux V, Maccario J, Pin I, Kauffmann F. Asthma severity is associated with body mass index and early menarche in women. Am J Res Crit Care Med 2005;171:334-9.
22. Myers MG Jr., Leibel RL, Seeley RJ, Schwartz MW. Obesity and leptin resistance: Distinguishing cause from effect. Trends Endocrinol Metab 2010;21:643-51.
23. Goodpaster BH, Krishnaswami S, Harris TB, Katsiaras A, Kritchevsky SB, Simonsick EM, et al. Obesity, regional body fat distribution, and the metabolic syndrome in older men and women. Arch Intern Med 2005;165:777-83.
24. Arteaga-Solis E, Zee T, Emala CW, Vinson C, Wess J, Karsenty G. Inhibition of leptin regulation of parasympathetic signaling as a cause of extreme body weight-associated asthma. Cell Metab 2013;17:35-48.
25. Canöz M, Erdenen F, Uzun H, Müderrisoglu C, Aydin S. The relationship of inflammatory cytokines with asthma and obesity. Clin Invest Med 2008;31:373-9.
26. Martin SS, Qasim A, Reilly MP. Leptin resistance: A possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J Am Coll Cardiol 2008;52:1201-10.
27. Harris RB, Zhou J, Redmann SM Jr., Smagin GN, Smith SR, Rodgers E, et al. A leptin dose-response study in obese (ob/ob) and lean (+/?) mice. Endocrinology 1998;139:8-19.
28. Jadhav AD, Padwal SL, Jadhav RR, Jadhav SS, Pise HN, Choure MK. Anti-inflammatory property of salbutamol on acute and chronic models of inflammation. Natl J Physiol Pharm Pharmacol 2015;5:101.
29. Van Herpen NA, Schrauwen-Hinderling VB. Lipid accumulation in non-adipose tissue and lipotoxicity. Physiol Behav 2008;94:231-41.
30. Buettner R, Newgard CB, Rhodes CJ, O’Doherty RM. Correction of diet-induced hyperglycemia, hyperinsulinemia, and skeletal muscle insulin resistance by moderate hyperleptinemia. Am J Physiol Endocrinol Metab 2000;278:E563-9.
31. Zhou X, De Schepper J, De Craemer D, Delhase M, Gys G, Smitz J, et al. Pituitary growth hormone release and gene expression in cafeteria-diet-induced obese rats. J Endocrinol 1998;159:165-72.
32. Ali Z, Ulrik CS. Obesity and asthma: A coincidence or a causal relationship? A systematic review. Respir Med 2013;107:1287-300.
33. Khan AR, Awan FR. Leptin resistance: A possible interface between obesity and pulmonary-related disorders. Int J Endocrinol Metabolism 2016;14:e32586.
34. Rosini TC, da Silva AS, de Moraes C. Diet-induced obesity: Rodent model for the study of obesity-related disorders. Rev Assoc Méd Bras 2012;58:383-7.
35. Estadella D, Oyama LM, Dâmaso AR, Ribeiro EB, Do Nascimento CM. Effect of palatable hyperlipidic diet on lipid metabolism of sedentary and exercised rats. Nutrition 2004;20:218-4.
36. Lin S, Thomas TC, Storlien LH, Huang XF. Development of high fat diet-induced obesity and leptin resistance in C57Bl/6J mice. Int J Obes 2000;24:639.
37. Milanski M, Degasperi G, Coope A, Morari J, Denis R, Cintra DE, et al. Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: Implications for the pathogenesis of obesity. J Neurosci 2009;29:359-70.
38. Robinson AM, Williamson DH. Comparison of glucose metabolism in the lactating mammary gland of the rat in vivo and in vitro. Effects of starvation, prolactin or insulin deficiency. Biochem J 1977;164:153-9.
39. Trayhurn P, Bing C. Appetite and energy balance signals from adipocytes. Philosophical transactions of the royal society. Biol Sci 2006;361:1237-49.
40. Trayhurn P, Bing C, Wood IS. Adipose tissue and adipokines energy regulation from the human perspective. J Nutr 2006;136:1935S-9.
41. Wasim M. Role of leptin in obesity. J Obes Weight Loss Ther 2015;5:2.
42. Rosicka M, Krsek M, Matoulek M, Jarkovska Z, Marek J, Justova V, et al. Serum ghrelin levels in obese patients: The relationship to serum leptin levels and soluble leptin receptors levels. Physiol Res 2003;52:61 6.
43. Afrah-Nazar AM, Mufeedjalil E, Suhayr EA. Leptin and adiponectin levels of asthmatic Iraqi children in Hilla province. Asian J Pharm Clin Res 2017;10:431-4.
44. Shoelson SE, Lee J, Yuan M. Inflammation and the IKK?/I?B/NF- ?B axis in obesity-and diet-induced insulin resistance. Int J Obes 2003;27:S49.
45. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003;112:1796-808.
46. Sarraf P, Frederich RC, Turner EM, Ma G, Jaskowiak NT, Rivet DJ, et al. Multiple cytokines and acute inflammation raise mouse leptin levels: Potential role in inflammatory anorexia. J Exp Med 1997;185:171-6.
47. Mantzoros CS, Moschos S, Avramopoulos I, Kaklamani V, Liolios A, Doulgerakis DE, et al. Leptin concentrations in relation to body mass index and the tumor necrosis factor-? system in humans. J Clin Endocrinol Metab 1997;82:3408-13.
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