American Journal of Pharmacological Sciences
ISSN (Print): 2327-6711 ISSN (Online): 2327-672X Website: Editor-in-chief: Srinivas NAMMI
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American Journal of Pharmacological Sciences. 2016, 4(3), 31-34
DOI: 10.12691/ajps-4-3-1
Open AccessArticle

Effect of Azilsartan, Aliskiren or Their Combination on Body Weight and Adipogenesis of High-fat Diet Induced Non-alcoholic Fatty Liver Disease in Rats

Rabab M. Utba1, Saad A. Hussain1, , Ammar A. Fadhil1 and Angham Ahmed1

1Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad, Baghdad, Iraq

Pub. Date: April 27, 2016

Cite this paper:
Rabab M. Utba, Saad A. Hussain, Ammar A. Fadhil and Angham Ahmed. Effect of Azilsartan, Aliskiren or Their Combination on Body Weight and Adipogenesis of High-fat Diet Induced Non-alcoholic Fatty Liver Disease in Rats. American Journal of Pharmacological Sciences. 2016; 4(3):31-34. doi: 10.12691/ajps-4-3-1


The renin-angiotensin system (RAS) plays an important role in the pathophysiology of many diseases including non-alcoholic fatty liver disease (NAFLD). This study aims to evaluate the effects of blocking RAS with azilsartan, aliskiren or their combination on the body weight and adipogenesis in rat’s model of NAFLD. Thirty-two rats were allocated into four groups and treated with either vehicle, azilsartan, aliskiren or their combination. All groups were maintained on high-fat diet for 60 days, and their body weights were monitored each 3 days. At the end of treatment all animals were authenticated and visceral adipose tissues obtained and weighed. Azilsartan attenuates both the increase in total body and adipose tissue weight compared with control, while azilsartan alone affects adipogenesis only. In conclusion, Administration of azilsartan attenuates adipogenesis and obesity in rat’s model of high-fat diet induced NAFLD, while aliskiren affects adipogenesis only.

high-fat diet NAFLD azilsartan aliskiren adipogenesis

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[1]  Marchesini G, Brizi M, Blanchi G, Tomassetti S, Bugianesi E, Lenzi M, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001; 50(8):1844-1850.
[2]  Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003; 37(5):1202-1219.
[3]  Wang CH, Li F, Takahashi N. The renin angiotensin system and the metabolic syndrome. Open Hypertens J 2010; 3:1-13.
[4]  Goossens GH. The renin-angiotensin system in the pathophysiology of type 2 diabetes. Obes Facts 2012; 5:611-624.
[5]  Huang Q, Xie Q, Shi C. Xiang X, Lin L, Gong B, Zhao G, Wang H, Jia N. Expression of angiotensin-converting enzyme 2 in CCl4-induced rat liver fibrosis. Int J Mol Med 2009; 23:717-723.
[6]  Matthew Morris E, Fletcher JA, Thyfault JP, Rector RS. The role of angiotensin II in nonalcoholic steatohepatitis. Mol Cell Endocrinol 2013; 378:29-40.
[7]  Jonsson JR, Clouston AD, Ando Y, Kelemen LI, Horn MJ, Adamson MD, Purdie DM, Powell EE. Angiotensin converting enzyme inhibition attenuates the progression of rat hepatic fibrosis. Gastroenterology 2001; 121:148-155.
[8]  de Macedoa SM, Guimaraesa TA, Feltenbergerc JD, Sousa Santosa SH. The role of renin-angiotensin system modulation on treatment and prevention of liver diseases. Peptides 2014; 62: 189-196.
[9]  Cholongitas E, Vibhakorn S, Lodato F, Burroughs AK. Angiotensin II antagonists in patients with recurrent hepatitis C virus infection after liver transplantation. Liver Int 2010; 30: 334-335.
[10]  Corey KE, Shah N, Misdraji J, Abu Dayyeh BK, Zheng H, Bhan AK, Chung RT. The effect of angiotensin-blocking agents on liver fibrosis in patients with hepatitis C. Liver Int 2009; 29:748-753.
[11]  Paschos P, Tziomalos K. Nonalcoholic fatty liver disease and the renin-angiotensin system: Implications for treatment. World J Hepatol 2012; 4:327-331.
[12]  Benson SC, Pershadsingh HA, Ho CI, Chittiboyina A, Desai P, Pravenec M, et al. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARg-modulating activity. Hypertension 2004; 43:993-1002.
[13]  Boustany CM, Bharadwaj K, Daugherty A, Brown DR, Randall DC, Cassis LA. Activation of the systemic and adipose rennin-angiotensin system in rats with diet-induced obesity and hypertension. Am J Physiol 2004; 287:943-949.
[14]  Takahashi N, Li F, Hua K, Deng J, Wang CH, Bowers RR, et al. Increased energy expenditure, dietary fat wasting, and resistance to diet-induced obesity in mice lacking renin. Cell Metab 2007; 6:506-512.
[15]  Zanchi A, Dulloo AG, Perregaux C, Montani JP, Burnier M. Telmisartan prevents the glitazone-induced weight gain without interfering with its insulin-sensitizing properties. Am J Physiol Endocrinol Metab 2007; 293:E91-E95.
[16]  Cassis LA, English VL, Bharadwaj K, Boustany CM. Differential effects of local versus systemic angiotensin II in the regulation of leptin release from adipocytes. Endocrinology 2004; 145:169-174.
[17]  Araki K, Masaki T, Katsuragi I, Tanaka K, Kakuma T, Yoshimatsu H. Telmisartan prevents obesity and increases the expression of uncoupling protein 1 in diet-induced obese mice. Hypertension 48:51-57.
[18]  Lastra G, Santos FR, Hooshmand P, Hooshmand P, Mugerfeld I, Aroor AR, et al. The novel angiotensin II receptor blocker azilsartan medoxomil ameliorates insulin resistance induced by chronic angiotensin II treatment. Cardiorenal Med 2013; 3:154-164.
[19]  Kusumoto K, Igata H, Ojima M, Tsuboi A, Imanishi M, Yamaguchi F, et al. Antihypertensive, insulin-sensitizing and renoprotective effects of a novel, potent and long-acting angiotensin II type 1 receptor blocker, azilsartan medoxomil, in rat and dog models. Eur J Pharmacol 2011; 669:84-93.
[20]  Zhao M, Li Y, Wang J, Ebihara K, Rong X, Hosoda K, et al. Azilsartan treatment improves insulin sensitivity in obese spontaneously hypertensive Koletsky rats. Diabetes Obes Metab 2011; 13:1123-1129.
[21]  Henriksen EJ. Improvement of insulin sensitivity by antagonism of the renin-angiotensin system. Am J Physiol Regulatory Integrative Comp Physiol 2007; 293:R974-R980.
[22]  Ogihara T, Asano T, Ando K, Chiba Y, Sakoda H, Anai M, Shojima N, Ono H, Onishi Y, Fujishiro M, et al. Angiotensin II-induced insulin resistance is associated with enhanced insulin signaling. Hypertension 2002; 40:872-879.
[23]  Marchionne EM, Diamond-Stanic MK, Prasonnarong M, Henriksen EJ. Chronic renin inhibition with aliskiren improves glucose tolerance, insulin sensitivity, and skeletal muscle glucose transport activity in obese Zucker rats. Am J Physiol Regul Integ Comp Physiol 2012; 302:R137-R142.
[24]  Henriksen EJ, Jacob S. Angiotensin converting enzyme inhibitors and modulation of insulin resistance. Diabetes Obes Metab 2003; 5:214-222.
[25]  Sloniger JA, Saengsirisuwan V, Diehl CJ, Kim JS, Henriksen EJ. Selective angiotensin II receptor antagonism enhances whole-body insulin sensitivity and muscle glucose transport in hypertensive TG(mREN2)27 rats. Metabolism 2005; 54:1659-1668.
[26]  Stucchi P, Victoria Cano V, Ruiz-Gayo M, Fernandez-Alfonso MS. Aliskiren reduces body-weight gain, adiposity and plasma leptin during diet-induced obesity. Br J Pharmacol 2009; 158:771-778.
[27]  Mohammed NS, Al-Karwi EN, Numan AT, Hussain SA. Effects of low doses of captopril or losartan in improving glycemic control by oral hypoglycemic agents in type 2 DM patients. Almustansriya J Pharm Sci 2010; 8(2):33-45.
[28]  Brucher R, Cifuentes M, Acuna MJ, Albala C, Rojas CV. Larger anti-adipogenic effect of angiotensin II on omental preadipose cells of obese humans. Obesity 2007; 15:1643-1646.
[29]  Skurk T, van Harmelen V, Hauner H. Angiotensin II stimulates the release of interleukin-6 and interleukin-8 from cultured human adipocytes by activation of NF-kappaB. Arterioscler Thromb Vasc Biol 2004; 24:1199-1203.
[30]  Iwai M, Chen R, Imura Y, Horiuchi M. TAK-536, a new AT1 receptor blocker, improves glucose intolerance and adipocyte differentiation. Am J Hypertens 2007; 20:579-586.
[31]  Zorad S, Dou JT, Benicky J, Hutanu D, Tybitanclova K, Zhou J, et al. Long-term angiotensin II AT1 receptor inhibition produces adipose tissue hypotrophy accompanied by increased expression of adiponectin and PPARgamma. Eur J Pharmacol 2006; 552:112-122.