Metabolic and oxidative stress markers in rats with monosodium glutamate-induced obesity
Keywords:
Obesity, monosodium glutamate, oxidative stress, hyperlipemia.Abstract
Introduction: Obesity, especially visceral, is a major risk factor for several diseases such as Type 2 diabetes mellitus, cardiovascular diseases, atherosclerosis, dyslipidemia, non-alcoholic fatty liver disease, and cancer. Oxidative stress may be a unifying mechanism for the development of major obesity-related comorbidities.
Objective: To evaluate the prooxidant-antioxidant balance in monosodium glutamate-induced obesity in Wistar rats (MSG- obese rats).
Material and Methods: Female Wistar rats received subcutaneous (sc) injections of monosodium glutamate solution (4 mg/g of body weight) or vehicle (NaCl 0,9 %; control) to induce obesity during the neonatal period. At 90 days of life, obesity was determined. At 180 days of life, rats were anesthetized and killed to obtain blood and liver samples for the determination of biochemical markers.
Results: MSG obese rats presented significantly higher triglycerides, uric acid and insulin levels, as well as elevated HOMA and TyG indexes. Increased concentrations of nitrate and nitrite, 2-deoxyribose oxidation products and advanced oxidation protein products levels were observed in obese rats.
Conclusions: Obesity induced by monosodium glutamate reproduces the main metabolic alterations associated with human visceral obesity, among which oxidative stress is included. This model may be useful for the evaluation of therapeutic strategies to prevent or decrease complications associated with obesity.
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References
1. Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, Lee A, et al. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N Engl J Med. 2017; 377 (1): 13-27.
2. Varona Pérez P, Gámez SD, Díaz SME. Impacto del sobrepeso y obesidad en la mortalidad por enfermedades no trasmisibles en Cuba. Revista Cubana de Medicina General Integral. 2018; 34 (3): 71-81.
3. Vibha R, Deep G, Singh RK, Palle K, Yadav U. Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies. Life Sci. 2016; 148: 183-93.
4. Tchernof A, Després JP. Pathophysiology of human visceral obesity: an update. Physiol Rev. 2013; 93 (1): 359-404.
5. Masschelin PM, Cox AR, Chernis N, Hartig SM. The Impact of Oxidative Stress on Adipose Tissue Energy Balance. Front. Physiol. 2020; 10:1638.
6. Hernández RJ, Mahmoud AM, Königsberg M, López Díaz NE. Obesity: pathophysiology, monosodium glutamate-induced model and anti-obesity medicinal plants. Biomed Pharmacother. 2019; 111: 503-16.
7. Krinke GJ. The laboratory rat: the handbook of experimental animals. London: Academic Press; 2000.
8. Bernardis LL, Patterson BD. Correlation between Lee Index and carcass fat content in weanling and adult female rats with hypotalamic lesions. J Endocrinol. 1968; 40 (4): 527-8.
9. American Veterinary Medical Association. AVMA Guidelines for the euthanasia of animals: 2020 [Internet]. Bethesda: National Institutes of Health; 2020 [Citado 20/06/2020]. Disponible en: https://olaw.nih.gov/news/avma-guidelines-euthanasia-animals-2020-edition-posted.html
10. Arranz C, González Suárez RM. Utilización de un método rápido para la separación de la hormona libre y unida en el radioinmunoensayo de insulina. Rev Cubana Invest Biomed. 1988; 7: 150-6.
11. Mathews DR, Hosker JP, Rudenki AS, Nailor BA, Treacher DF, Turner RC. Homeostasis model assessment: Insulin resistance and Beta Cell Function from fasting plasma glucose and insulin concentration in man. Diabetología. 1985; 28 (7): 412-9.
12. Cacho J, Sevillano J, De Castro J, Herrera E, Ramos MP. Validation of simple indexes to assess insulin sensitivity during pregnancy in Wistar and Sprague-Dawley rats. Am J Physiol Endocrinol Metab. 2008; 295 (5): E1269-76.
13. Unger G, Benozzi SF, Perruzza F, Pennacchiotti GL. Índice triglicéridos y glucosa: un indicador útil de insulinorresistencia. Endocrinol Nutr. 2014; 61 (10): 533-40
14. Hisakazu M. Determination of nitrate in biological fluids using nitrate reductase in a flow system. J Health Sci. 2001; 47 (1): 65-7.
15. Witko Sarsat V, Friedlander M, Capeillere Blandin C, Nguyen Khoa T, Nguyen AT, Zingraff J, et al. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int. 1996; 49 (5): 1304-13.
16. Beutler E. Improved assay of the enzymes of glutathione synthesis. Clin Chim Acta. 1986; 158 (1): 115-23.
17. Bunce M. PCR-SSP typing. En: Bidewell Jl, Navarrete C. Histocompatibility testing. England: Imperial College Press; 2000.p.149-86.
18. Bayne K, Turner Patricia V. Laboratory animal welfare. London: Academic Press; 2014.
19. Zubiría MG, Alzamendi A, Moreno G, Portales A, Castrogiovanni D, Spinedi E, et al. Relationship between the balance of hypertrophic/hyperplastic adipose tissue expansion and the metabolic profile in a high glucocorticoids model. Nutrients. 2016; 8 (7): 89-91.
20. Farraú F, Korbonits M. Metabolic comorbidities in Cushing’s Síndrome. Eur J Endocrinol. 2015; 173: M133-57.
21. John K, Marino JS, Sánchez ER, Hinds TD. The glucocorticoid receptor: cause or cure for obesity?. Am J Physiol Endocrinol Metab. 2016; 310 (4): E249-57.
22. Damiani Cavero JS, Olivera García H, Núñez López N, Dovale Borjas A, Ferrero Rodríguez LM, Cruz García MA, et al. Sistema nervioso y endocrinología básica. En su: Morfofisiología. 2 ed. La Habana: Ecimed; 2015. p.222.
23. Damasceno DC, Sinzato YK, Bueno A, Dallaqua B, Lima PH, Calderon I, et al. Metabolic Profile and Genotoxicity in Obese Rats Exposed to Cigarette Smoke. Obesity . 2013; 21(8):1596-601.
24.França LM, Freitas LN, Chagas VT, Coêlho CF, Barroso WA, Costa GC, et al. Mechanisms underlying hypertriglyceridemia in rats with monosodium L-glutamate-induced obesity: Evidence of XBP-1/PDI/MTP axis activation. Biochem Biophys Res Commun. 2014; 443 (2): 72-3.
25. França LM, Coêlho CFF, Freitas LNC, Souza ILS, Chagas VT, Debbas V, et al. Syzygium cumini leaf extract reverts hypertriglyceridemia via downregulation of the hepatic xbp-1s/pdi/mtp axis in monosodium l-glutamate-induced obese rats. Oxid Med Cell Longev [Internet]. 2019 [Citado 20/06/2020]; 219: 9417498. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446099/
26. Lubaczeuski C, Balbo SL, Ribeiro RA, Vettorazzi JF, Santos Silva JC, Carneiro EM, et al. Vagotomy ameliorates islet morphofunction and body metabolic homeostasis in MSG-obese rats. Braz J Med Biol Res. 2015; 48 (5): 447-57.
27.Sokolowska E, Blachnio Zabielska A. The Role of Ceramides in Insulin Resistance. Front Endocrinol . 2019; 10: 577.
28. Villagarcía HG, Castro MC, Arbeláez LG, Schinella G, Massa ML, Spinedi E, et al. N-Acetyl-L-Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats. Life Sci. 2018; 199: 88-95.
29. Griendling KK, Touyz RM, Zweier JL, Dikalov S, Chilian W, Chen YR, et al. Measurement of reactive oxygen species, reactive nitrogen species, and redox-dependent signaling in the cardiovascular system: a scientific statement from the american heart association. Circ Res. 2016; 119 (5): e39–e75.
30. Da Cunha NV, Pinge Filho P, Panis C, Silva BR, Pernomian L, Grando MD, et al. Decreased endotelial nitric oxide, systemic oxidative stress, and increased sympathetic modulation contribute to hypertension in obese rats. Am J Physiol Heart Circ Physiol. 2014; 306 (10): H1472-80.
31. Seiva F, Chuffa LG, Pereira C, Amorim JP, Fernandes AA. Quercetin ameliorates glucose and lipid metabolism and improves antioxidant status in postnatally monosodium glutamate-induced metabolic alterations. Food Chem Toxicol. 2012; 50 (10): 3556-61.
32. Masschelin PM, Cox AR, Chernis N, Hartig SM. The Impact of Oxidative Stress on Adipose Tissue Energy Balance. Front Physiol. 2020; 10: 1638.
33. Battelli MG, Bortolotti M, Polito L, Bolognesi A. The role of xanthine oxidoreductase and uric acid in metabolic syndrome. Biochim Biophys Acta Mol Basis Dis. 2018; 1864 (8): 2557-65.
34. Sharaf El, Din UA, Salem MM, Abdulazim DO. Uric acid in the pathogenesis of metabolic, renal, and cardiovascular diseases: a review. J Adv Res. 2017; 8 (5): 537-54