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Abstract

Background: The prevalence of obesity is on the rise, and with it comes the burden on healthcare systems due to the increased likelihood of complications such as diabetes, heart disease, hypertension, cancer, and many more. Obesity manifests in the body as an increase in adipose tissue and the production of harmful chemicals by fat cells. One of the pathological changes recorded in obesity is the excessive amount of reactive oxygen species and oxidative stress. An effective medication for oxidative stress and glucose metabolism regulation, including glucose variability is semaglutide. Objective: This study aims to investigate the impact of semaglutide on the hepatic oxidative stress inspired by a high-fat diet in male rats. Material and Methods: Twenty-eight Sprague Dawley rats were split into four groups; the control group, the obese control group, the obese + vehicle group, and the treatment group. The treatment group received 30 nmole of Semaglutide subcutaneous with a high-fat diet for four weeks. A blood glucose level was obtained from blood samples, oxidative stress (Malondialdehyde, Superoxide dismutase) was estimated in liver tissue and the changes in animal weight were monitored throughout the experiment. Results: the consequences of the examine demonstrated that in the obesity group, there is a considerable rise in body weight and fasting blood glucose as contrasted with the normal group. The hepatic Malondialdehyde also much improved in the obesity group, while hepatic Superoxide dismutase greatly diminished in comparison to the normal group. In the liver, the level of Superoxide dismutase considerably raised in obese rats after treatment with semaglutide. Fasting blood glucose and body weight dropped with semaglutide treatment compared with obesity group. Conclusions: Animals fed diet pellets that are high in fat caused an apparent increase in rat weight, leading to obesity. Semaglutide treatment significantly decreases both blood glucose and body weight. The outcomes of our study indicate that obese rats treated with semaglutide had a reduction in oxidative stress levels.

References

References

[1] Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet 2011;378(9793):804-14. https://doi.org/10.1016/S0140- 6736(11)60813-1.

[2] Reddy KS. Global burden of disease study 2015 provides GPS for global health 2030. Lancet 2016;388(10053):1448-9. https://doi.org/10.1016/S0140-6736(16)31743-3.

[3] Kim DD, Basu A. Estimating the medical care costs of obesity in the United States: systematic review, meta-analysis, and empirical analysis. Value Health 2016;19(5):602-13. https:// doi.org/10.1016/j.jval.2016.02.008.

[4] Kinlen D, Cody D, O'Shea D. Complications of obesity. QJM 2018;111(7):437-43. https://doi.org/10.1093/qjmed/hcx152.

[5] Thomas DM, Weedermann M, Fuemmeler BF, Martin CK, Dhurandhar NV, Bredlau C, et al. A dynamic model predicting overweight, obesity, and extreme obesity prevalence trends. Obesity (Silver Spring, Md.) 2014;22(2):590-7. https:// doi.org/10.1002/oby.20520.

[6] Mahapatra MK, Karuppasamy M, Sahoo BM. Semaglutide is a glucagon-like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes. Rev Endocr Metab Disord 2022;23(3):521-39.

[7] Tan Q, Akindehin SE, Orsso CE, Waldner RC, DiMarchi RD, Müller TD, et al. Recent advances in incretin-based pharmacotherapies for the treatment of obesity and diabetes. Front Endocrinol 2022;13:838410. https://doi.org/10.3389/ fendo.2022.838410.

[8] Knudsen LB, Lau J. The discovery and development of liraglutide and semaglutide. Front Endocrinol 2019;10:155. https://doi.org/10.3389/fendo.2019.00155.

[9] Warolin J, Coenen KR, Kantor JL, Whitaker LE, Wang L, Acra SA, et al. The relationship of oxidative stress, adiposity, and metabolic risk factors in healthy Black and White American youth. Pediatric obesity 2014;9(1):43-52.

[10] Oyebode OA, Erukainure OL, Sanni O, Islam MS. Crassocephalum rubens (Juss. Ex Jacq.) S. Moore improves pancreatic histology, insulin secretion, liver and kidney functions, and ameliorates oxidative stress in fructosestreptozotocin- induced type 2 diabetic rats. Drug Chem Toxicol 2022;45(2):481-90. https://doi.org/10.1080/01480545. 2020.1716783.

[11] Manna P, Jain SK. Obesity, oxidative stress, adipose tissue dysfunction, and the associated health risks: causes and therapeutic strategies. Metab Syndr Relat Disord 2015;13(10): 423-44. https://doi.org/10.1089/met.2015.0095.

[12] Serra D, Mera P, Malandrino MI, Mir JF, Herrero L. Mitochondrial fatty acid oxidation in obesity. Antioxidants Redox Signal 2013;19(3):269-84.

[13] Drougard A, Fournel A, Valet P, Knauf C. Impact of hypothalamic reactive oxygen species in the regulation of energy metabolism and food intake. Front Neurosci 2015;9:56. https://doi.org/10.3389/fnins.2015.00056.

[14] Higuchi M, Dusting GJ, Peshavariya H, Jiang F, Hsiao STF, Chan EC, et al. Differentiating human adipose-derived stem cells into fat involves reactive oxygen species and Forkhead box O1-mediated upregulation of antioxidant enzymes. Stem Cell Dev 2013;22(6):878-88.

[15] Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004;114: 1752-61.

[16] Festing MF, Altman DG. Guidelines for the design and statistical analysis of experiments using laboratory animals. ILAR J 2002;43(4):244-58.

[17] Chen SY, Beretta M, Olzomer EM, Alexopoulos SJ, Shah DP, Byrne FL, et al. Head-to-head comparison of BAM15, semaglutide, rosiglitazone, NEN, and calorie restriction on metabolic physiology in female db/db mice. Biochim Biophys Acta, Mol Basis Dis 2024;1870(1):166908.

[18] Li R, Ye Z, She D, Fang P, Zong G, Hu K, et al. Semaglutide may alleviate hepatic steatosis in T2DM combined with NFALD mice via miR-5120/ABHD6. Drug Des Dev Ther 2023:3557-72.

[19] Cruz Hernandez JH, Rosado Lom_an WN, G_omez- Cris_ostomo NP, De la Cruz-Hern_andez EN, Guzman Garcia LM, Gomez Gomez M, et al. High sugar but not high fat diet consumption induces hepatic metabolic disruption and up-regulation of mitochondrial fission-associated protein Drp1 in a model of moderate obesity. Arch Physiol Biochem 2023;129(1):233-40.

[20] Omachi T, Ohara M, Fujikawa T, Kohata Y, Sugita H, Irie S, et al. Comparison of effects of injectable semaglutide and dulaglutide on oxidative stress and glucose variability in patients with type 2 diabetes mellitus: a prospective preliminary study. Diabetes Therapy 2024;15(1):111-26.

[21] Rubino F, Puhl RM, Cummings DE, Eckel RH, Ryan DH, Mechanick JI, et al. Joint international consensus statement for ending the stigma of obesity. Nat Med 2020;26(4):485-97. https://doi.org/10.1038/s41591-020-0803-x.

[22] Ramasamy A, Lalibert_e F, Aktavoukian SA, Lejeune D, DerSarkissian M, Cavanaugh C, et al. Direct and indirect cost of obesity among the privately insured in the United States: a focus on the impact by type of industry. J Occup Environ Med 2019;61(11):877-86. https://doi.org/10.1097/ JOM.0000000000001693.

[23] Purnell JQ. Definitions, classification, and epidemiology of obesity. 2015.

[24] Tiba AT, Qassam H, Hadi NR. Semaglutide in renal ischemia-reperfusion injury in mice. J Med Life 2023;16(2): 317-24. https://doi.org/10.25122/jml-2022-0291.

[25] Chen NG, Reaven GM. Fatty acid inhibition of glucosestimulated insulin secretion is enhanced in pancreatic islets from insulin-resistant rats. Metabolism 1999;48(10):1314-7.

[26] Busetto L. Visceral obesity and the metabolic syndrome: effects of weight loss. Nutr Metabol Cardiovasc Dis 2001;11(3): 195-204.

[27] Ramli NS, Brown L, Ismail P, Rahmat A. Effects of red pitaya juice supplementation on cardiovascular and hepatic changes in rats with high-carbohydrate, high-fat dietinduced metabolic syndrome. BMC Compl Alternative Med 2014;14:1-10.

[28] Ghibaudi L, Cook J, Farley C, Van Heek M, Hwa JJ. Fat intake affects adiposity, comorbidity factors, and energy metabolism of Sprague-Dawley rats. Obes Res 2002;10(9): 956-63.

[29] Li Q, Tuo X, Li B, Deng Z, Qiu Y, Xie H. Semaglutide attenuates excessive exercise-induced myocardial injury by inhibiting rats' oxidative stress and inflammation. Life Sci 2020;250:117531.

[30] Liu DX, Zhao CS, Wei XN, Ma YP, Wu JK. Semaglutide protects against 6-OHDA toxicity by enhancing autophagy and inhibiting oxidative stressvol. 2022. Parkinson’s Disease; 2022.

[31] Noeman SA, Hamooda HE, Baalash AA. Biochemical study of oxidative stress markers in the liver, kidney, and heart of high fat diet-induced obesity in rats. Diabetol Metab Syndrome 2011;3(1):17. https://doi.org/10.1186/1758-5996-3-17. 32] Beltowski JGDA, Wojcicki G, Gorny D, Marciniak A. The effect of dietary-induced obesity on lipid peroxidation, antioxidant enzymes, and total plasma antioxidant capacity. J Physiol Pharmacol 2000;51(4, 2).

[33] Ighodaro OM, Akinloye OA. First-line defence antioxidantssuperoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX): their fundamental role in the entire antioxidant defence grid. Alexandria J Med 2018;54(4):287-93.

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