COMPARISON OF EFFECTS OF SITAGLIPTIN AND A COMBINATION OF NALTREXONE AND BUPROPION IN HIGH FAT DIET-INDUCED OBESITY MODEL IN RATS

Authors

DOI:

https://doi.org/10.22159/ajpcr.2022.v15i8.45002

Keywords:

Anti-obesity drugs, High-fat diet, Weight loss agents, Naltrexone, Bupropion, Sitagliptin

Abstract

Objective: The study aimed to compare the anti-obesity effect of Sitagliptin and a combination of Naltrexone and Bupropion in high-fat diet-induced obesity model in animals.

Methods: This study was a prospective study of 17 weeks duration. Obesity was induced in rats by feeding them a high-fat diet over a period of 17 weeks. Sitagliptin and a combination of Naltrexone and Bupropion were administered to two groups for 5 weeks and various parameters such as body weight, blood glucose, food intake, and BMI were measured and analyzed over a period of 5 weeks.

Results: In this study, on administration of Sitagliptin and a combination of Naltrexone and Bupropion, there was a gradual weight loss in rats. The combination of Naltrexone and Bupropion showed a significant (p<0.05) effect on reduction in body weight, reduction in food intake, and reduction of BMI in obese rats, whereas Sitagliptin showed a significant reduction in blood glucose in rats.

Conclusion: In the present study combination of Naltrexone and Bupropion stood most effective in reducing weight, food intake, as well as BMI.

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References

World Health Organization. Obesity and Overweight. Geneva: World Health Organization. Available from: https://www.who.int/news-room/ fact-sheets/detail/obesity-and-overweight [Last accessed on 2022 May 11].

Wang YC, McPherson K, Marsh T, Gortmaker SL, Brown M. Health and economic burden of the projected obesity trends in the USA and the UK. Lancet 2011;378:815-25. doi: 10.1016/S0140-6736(11)60814-3, PMID 21872750.

Prospective Studies Collaboration. Body-mass index and cause-specific mortality in 900 000 adults: Collaborative analyses of 57 prospective studies. Lancet 2009;373:1083-96. doi: 10.1016/S0140- 6736(09)60318-4.

Ahirwar R, Mondal PR. Prevalence of obesity in India: A systematic review. Diabetes Metab Syndr 2019;13:318-21. doi: 10.1016/j. dsx.2018.08.032, PMID 30641719.

Kopelman P. Obesity. Postgrad Med J 1995;71:511. doi: 10.1136/ pgmj.71.838.511-a.

Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss. Arterioscler Thromb Vasc Biol 2006;26:968-76. doi: 10.1161/01.ATV.0000216787.85457.f3, PMID 16627822.

Rössner S, Sjöström L, Noack R, Meinders AE, Noseda G. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European orlistat Obesity Study Group. Obes Res 2000;8:49-61. doi: 10.1038/oby.2000.8, PMID 10678259.

Druce MR, Small CJ, Bloom SR. Minireview: Gut peptides regulating satiety. Endocrinology 2004;145:2660-5. doi: 10.1210/en.2004-0089, PMID 15044353.

Kim GW, Lin JE, Blomain ES, Waldman SA. New advances in models and strategies for developing anti-obesity drugs. Expert Opin Drug Discov 2013;8:655-71. doi: 10.1517/17460441.2013.792804, PMID 23621300.

Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev 1999;20:68-100. doi: 10.1210/edrv.20.1.0357, PMID 10047974.

Billes SK, Greenway FL. Combination therapy with naltrexone and bupropion for obesity. Expert Opin Pharmacother 2011;12:1813-26. doi: 10.1517/14656566.2011.591382, PMID 21689063.

Lei F, Zhang XN, Wang W, Xing DM, Xie WD, Su H, et al. Evidence of anti-obesity effects of the pomegranate leaf extract in high-fat diet induced obese mice. Int J Obes (Lond) 2007;31:1023-9. doi: 10.1038/ sj.ijo.0803502, PMID 17299386.

Novelli EL, Diniz YS, Galhardi CM, Ebaid GM, Rodrigues HG, Mani F, et al. Anthropometrical parameters and markers of obesity in rats. Lab Anim 2007;41:111-9. doi: 10.1258/002367707779399518, PMID 17234057.

Haslam DW, James WP. Obesity. Lancet 2005;366:1197-209. doi: 10.1016/S0140-6736(05)67483-1.

Shafrir E, Ziv E. A useful list of spontaneously arising animal models of obesity and diabetes. Am J Physiol Endocrinol Metab 2009;296:E1450-2. doi: 10.1152/ajpendo.00113.2009, PMID 19468077.

Srinivasan K, Ramarao P. Animal models in Type 2 diabetes research: an overview. Indian J Med Res 2007;125:451-72. PMID 17496368.

Buettner R, Schölmerich J, Bollheimer LC. High-fat diets: Modeling the metabolic disorders of human obesity in rodents. Obesity (Silver Spring) 2007;15:798-808. doi: 10.1038/oby.2007.608, PMID 17426312.

Jain AK, Kaplan RA, Gadde KM, Wadden TA, Allison DB, Brewer ER, et al. Bupropion SR vs. placebo for weight loss in obese patients with depressive symptoms. Obes Res 2002;10:1049-56. doi: 10.1038/oby.2002.142, PMID 12376586.

Greenway FL, Whitehouse MJ, Guttadauria M, Anderson JW, Atkinson RL, Fujioka K, et al. Rational design of a combination medication for the treatment of obesity. Obesity (Silver Spring) 2009;17:30-9. doi: 10.1038/oby.2008.461, PMID 18997675.

Shimasaki T, Masaki T, Mitsutomi K, Ueno D, Gotoh K, Chiba S, et al. The dipeptidyl peptidase-4 inhibitor des-fluoro-sitagliptin regulates brown adipose tissue uncoupling protein levels in mice with diet-induced obesity. PLoS One 2013;8:e63626. doi: 10.1371/journal. pone.0063626, PMID 23696840.

Mentlein R. Dipeptidyl-peptidase IV (CD26)--role in the inactivation of regulatory peptides. Regul Pept 1999;85:9-24. doi: 10.1016/s0167- 0115(99)00089-0, PMID 10588446.

Wright FL, Rodgers RJ. Acute behavioural effects of bupropion and naltrexone, alone and in combination, in non-deprived male rats presented with palatable mash. Psychopharmacol (Berl) 2013;228:291-307. doi: 10.1007/s00213-013-3036-6, PMID 23455599.

Janhunen SK, la Fleur SE, Adan RA. Blocking alpha2A adrenoceptors, but not dopamine receptors, augments bupropion-induced hypophagiain rats. Obesity (Silver Spring) 2013;21:E700-8. doi: 10.1002/ oby.20581, PMID 23894096.

Liang NC, Bello NT, Moran TH. Additive feeding inhibitory and aversive effects of naltrexone and exendin-4 combinations. Int J Obes (Lond) 2013;37:272-8. doi: 10.1038/ijo.2012.16, PMID 22310470.

Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003;112:1821-30. doi: 10.1172/ JCI19451, PMID 14679177.

Reimer RA, Grover GJ, Koetzner L, Gahler RJ, Juneja P, Lyon MR, et al. Sitagliptin reduces hyperglycemia and increases satiety hormone secretion more effectively when used with a novel polysaccharide in obese Zucker rats. J Nutr 2012;142:1812-20. doi: 10.3945/ jn.112.163204, PMID 22915295.

Ganz ML, Wintfeld N, Li Q, Alas V, Langer J, Hammer M. The association of body mass index with the risk of Type 2 diabetes: A case-control study nested in an electronic health records system in the United States. Diabetol Metab Syndr 2014;6:50. doi: 10.1186/1758-5996-6-50, PMID 24694251.

Published

07-08-2022

How to Cite

KULMI, M., and G. SAXENA. “COMPARISON OF EFFECTS OF SITAGLIPTIN AND A COMBINATION OF NALTREXONE AND BUPROPION IN HIGH FAT DIET-INDUCED OBESITY MODEL IN RATS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 15, no. 8, Aug. 2022, pp. 119-23, doi:10.22159/ajpcr.2022.v15i8.45002.

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