Anti-obesity effect of simvastatin and omega-3 and its combination on obese model male Wistar rats

Effect of simvastatin, omega-3 and their combination on UCP1

Authors

  • Rasha Abdullatif ALJuboury Department of technical affairs, Ministry of Health and Environment, Baghdad-Iraq
  • Nada N Al-Shawi Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad, Baghdad-Iraq.

DOI:

https://doi.org/10.31351/vol31iss2pp101-112

Keywords:

Obesity, high-fat diet, simvastatin, omega-3, brown adipocyte; beige adipocytes; thermogenesis; UCP1

Abstract

      Strategies to reduce obesity have become main priority for many health institution and health staff around the world, as the prevalence of obesity has risen and exacerbated in most of the world mainly because of the modern life style which tend to be more sedentary with an increase eating unhealthy fast western food. Many years ago, the lipid-lowering drug simvastatin; and omega-3 were considered as a traditional lipid-lowering drug that have been well-documented to possess anti-inflammatory, cardioprotective and triglyceride-lowering properties; and their co-administration may demonstrate a complementary effect in lowering patients' triglycerides and total cholesterol to treat atherosclerosis. Many previous studies have been found other beneficial effects for simvastatin, and omega-3; since, simvastatin can be used for the treatment of Alzheimer's disease; and for prevention of prostate cancer; while omega 3 can reduce the risk of sudden cardiac death in addition to preventing obesity that has been documented by recent studies. But, the effect of simvastatin alone or its combination with omega-3 as potential anti-obesity therapy and /or protection against obesity is not yet known through their effects on thermogenic factors. Aim of the study is to evaluate the effect of simvastatin on thermogenic genes including (UCP1) using quantitative real time PCR, while the expression of uncoupling protein 1 (UCP1) protein was detected in iBAT and iWAT adipocyte by immunohistochemistry. Method One hundred twenty (120) male Wistar rats (five-six week age and weighing 100-150g) were allocated into five groups: treated with two different doses of simvastatin, omega-3 and mixed treatment, in addition to high fat diet group which considered as a control group. Treatments were given for eight weeks. Three rats from each group were weekly-authenticated along the 60 days interscapular brown adipose tissue (iBAT) and inguinal white adipose tissues (iWAT) were obtained. Results; showed that simvastatin and omega-3 have an obvious activation of UCP1genes, this reflects an increase in thermogenic process in adipose tissue in obese high fat diet rats and their combination exert a synergistic increase in the thermogenic mechanism when compared to simvastatin 9mg/ kg /day alone. Conclusion this study gives a hope for the utilization of simvastatin either alone or in combination with omega-3 as anti-obesity therapy; through their enhancement of thermogenic in white and brown adipose tissues with a consequent weight loss.

References

Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. The Lancet. 2014;384(9945):766-81.

Yach D, Stuckler D, Brownell KD. Epidemiologic and economic consequences of the global epidemics of obesity and diabetes. Nature medicine. 2006;12(1):62-6.

McCloskey ML, Tarazona-Meza CE, Jones-Smith JC, Miele CH, Gilman RH, Bernabe-Ortiz A, et al. Disparities in dietary intake and physical activity patterns across the urbanization divide in the Peruvian Andes. International Journal of Behavioral Nutrition and Physical Activity. 2017;14(1):90.

Ali A. Kasim AHA. The Pathological Mechanisms of Obesity-Related Glomerulopathy: A review article. IJPS. 2021; 30 (1):22-8.

Romieu I, Dossus L, Barquera S, Blottière HM, Franks PW, Gunter M, et al. Energy balance and obesity: what are the main drivers? Cancer Causes Control. 2017;28(3):247-58.

Hruby A, Hu FB. The Epidemiology of Obesity: A Big Picture. Pharmacoeconomics. 2015;33(7):673-89.

Casteilla L, Pénicaud L, Cousin B, Calise D. Choosing an adipose tissue depot for sampling. Factors in selection and depot specificity. Methods in molecular biology (Clifton, NJ). 2001;155:1-19.

Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. American journal of physiology Endocrinology and metabolism. 2007;293(2):E444-52.

Tsubota A, Okamatsu-Ogura Y, Bariuan JV, Mae J, Matsuoka S, Nio-Kobayashi J, et al. Role of brown adipose tissue in body temperature control during the early postnatal period in Syrian hamsters and mice. J Vet Med Sci. 2019;81(10):1461-7.

Lee P, Greenfield JR. Non-pharmacological and pharmacological strategies of brown adipose tissue recruitment in humans. Mol Cell Endocrinol. 2015;418:184-90.

Bargut TCL, Souza-Mello V, Aguila MB, Mandarim-de-Lacerda CA. Browning of white adipose tissue: lessons from experimental models. Horm Mol Biol Clin Investig. 2017;31(1).

Ukropec J, Anunciado RP, Ravussin Y, Hulver MW, Kozak LP. UCP1-independent thermogenesis in white adipose tissue of cold-acclimated Ucp1-/- mice. J Biol Chem. 2006;281(42):31894-908.

Srivastava S, Veech RL. Brown and Brite: The Fat Soldiers in the Anti-obesity Fight. Front Physiol. 2019;10(38).

Kontani Y, Wang Y, Kimura K, Inokuma KI, Saito M, Suzuki-Miura T, et al. UCP1 deficiency increases susceptibility to diet-induced obesity with age. Aging Cell. 2005;4(3):147-55.

Kozak LP, Anunciado-Koza R. UCP1: its involvement and utility in obesity. Int J Obes (Lond). 2008;32 Suppl 7(Suppl 7):S32-8.

Seale P, Kajimura S, Yang W, Chin S, Rohas LM, Uldry M, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab. 2007;6(1):38-54.

Liu X, Feng X, Deng C, Liu L, Zeng Y, Hu C-H. Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin. BMC Pharmacology and Toxicology. 2020;21(1):48.

Israa A Majeed NNA-S. Effects of omega-3-co-adminstration with therapeutic dose of lornoxicam on male rats' liver. IJPS. 2019;28(2):159-64.

Buckley JD, Howe PR. Anti-obesity effects of long-chain omega-3 polyunsaturated fatty acids. Obes Rev. 2009;10(6):648-59.

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Published

2022-12-23