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DOI: 10.1055/a-1023-6710
Hyperuricemia Inhibition Protects SD Rats Against Fructose-Induced Obesity Hypertension Via Modulation of Inflammation and Renin-Angiotensin System in Adipose Tissue
Funding: This work was supported by the National Natural Science Foundation of China (NSFC Number 81500654); Hubei Province health and family planning scientific research project (Number WJ2018H0062); and the Bethune-Merck Diabetes Research Foundation (Number G2018030).
Abstract
Objective The present study was aimed to reveal the relationship between uric acid and fructose-induced obesity hypertension and its mechanisms.
Methods A rat model with obesity hypertension was induced by a high-fructose diet. In the experiment I, the rats were fed with fructose for 8 wks along with allopurinol or benzbromarone at the beginning. In the experiment II, the rats were fed with fructose for 8 wks firstly. And then, these rats were treated with allopurinol or benzbromarone for additional 6 wks.
Results Fructose-fed rats showed hyperuricemia, abdominal obesity hypertension and an activation in adipose renin-angiotensin system (RAS). Also, fructose-fed rats had higher levels of proinflammatory cytokines and more macrophages infiltrating in adipose tissue. In the experiment I, allopurinol and benzbromarone significantly reduced serum uric acid at 8 wk. Adipose RAS overactivation, adipose inflammatory responses and the development of obesity hypertension were all effectively prevented by hyperuricemia inhibition. In the experiment II, 6-wk treatment with allopurinol and benzbromarone significantly decreased serum uric acid, downregulated adipose RAS, abolished adipose inflammation and improved obesity hypertension.
Conclusion In conclusion, urate-lowering therapy protects rats against fructose-induced obesity hypertension. The mechanisms appear to be via downregulated adipose RAS and reduced inflammation in adipose tissue.
Publikationsverlauf
Eingereicht: 23. Juni 2019
Eingereicht: 16. September 2019
Angenommen: 08. Oktober 2019
Artikel online veröffentlicht:
04. November 2019
© 2019. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
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References
- 1 Wilson PW, D'Agostino RB, Sullivan L. et al. Overweight and obesity as determinants of cardiovascular risk: The Framingham experience. Arch Intern Med 2002; 162: 1867-1872
- 2 Droyvold WB, Midthjell K, Nilsen Ti. et al. Change in body mass index and its impact on blood pressure: A prospective population study. Int J Obes 2005; 29: 650-655
- 3 Brown IJ, Stamler J, Van Horn L. et al. International Study of Macro/Micronutrients and Blood Pressure Research Group- Sugar-sweetened beverage, sugar intake of individuals, and their blood pressure: International study of macro/micronutrients and blood pressure. Hypertension 2011; 57: 695-701
- 4 Malik AH, Akram Y, Shetty S. et al. Impact of sugar-sweetened beverages on blood pressure. Am J Cardiol 2014; 113: 1574-1580
- 5 Zhang W, Sun K, Yang Y. et al. Plasma uric acid and hypertension in a Chinese community: Prospective study and meta-analysis. Clin Chem 2009; 55: 2026-2034
- 6 Soletsky B, Feig D.. Uric acid reduction rectifies pre-hypertension in obese adolescents. Hypertension 2012; 60: 1148-1156
- 7 Baldwin W, McRae S. et al. Hyperuricemia as a mediator of the proinflammatory endocrine imbalance in the adipose tissue in a murine model of the metabolic syndrome. Diabetes 2011; 60: 1258-1269
- 8 Cox CL, Stanhope KL, Schwarz JM. et al. Consumption of fructose- but not glucose-sweetened beverages for 10 weeks increases circulating concentrations of uric acid, retinol binding protein-4, and gamma-glutamyl transferase activity in overweight/obese humans. Nutr Metab 2012; 9: 68
- 9 Nakagawa T, Hu H, Zharikov S. et al. A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol Renal Physiol 2006; 290: F625-63
- 10 Perez-Pozo SE, Schold J, Nakagawa T. et al. Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: Role of uric acid in the hypertensive response. Int J Obes (Lond) 2010; 34: 454-461
- 11 Kanellis J, Watanabe S, Li JH. et al. Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2. Hypertension 2003; 41: 1287-1293
- 12 Dorresteijn JA, Visseren FL, Spiering W.. Mechanisms linking obesity to hypertension. Obes Rev 2012; 13: 17-26
- 13 Klein AV, Kiat H. The mechanisms underlying fructose-induced hypertension: A review. J Hypertens 2015; 33: 912-920
- 14 Ma J, McKeown NM, Hwang Sj. et al. Sugar-sweetened beverage consumption is associated with change of visceral adipose tissue over 6 years of follow-up. Circulation 2016; 133: 370-377
- 15 Stanhope KL, Schwarz JM, Keim Nl. et al. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest 2009; 119: 1322-1334
- 16 Jayalath VH, de Souza RJ, Ha V. et al. Sugar-sweetened beverage consumption and incident hypertension: A systematic review and meta-analysis of prospective cohorts. Am J Clin Nutr 2015; 102: 914-921
- 17 Vasdev S, Gill V, Parai S. et al. Dietary vitamin E and C supplementation prevents fructose induced hypertension in rats. Mol Cell Biochem 2002; 241: 107-114
- 18 Kim HY, Okubo T, Juneja LR. et al. The protective role of amla (Emblica officinalis Gaertn.) against fructose-induced metabolic syndrome in a rat model. Br J Nutr 2010; 103: 502-512
- 19 Tran LT, Yuen VG, McNeill JH.. The fructose-fed rat: A review on the mechanisms of fructose-induced insulin resistance and hypertension. Mol Cell Biochem 2009; 332: 145-159
- 20 Hannou SA, Haslam DE, McKeown NM. et al. Fructose metabolism and metabolic disease. J Clin Invest 2018; 128: 545-555
- 21 Johnson RJ, Kang DH, Feig D. et al. Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease?. Hypertension 2003; 41: 1183-1190
- 22 Schmieder RE, Hilgers KF, Schlaich MP. et al. Reninangiotensin system and cardiovascular risk. Lancet 2007; 369: 1208-1219
- 23 Massiéra F, Bloch-Faure M, Ceiler D. et al. Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. FASEB J 2001; 15: 2727-2729
- 24 Paul M, Poyan Mehr A, Kreutz R.. Physiology of local renin angiotensin systems. Physiol Rev 2006; 86: 747-803
- 25 Thatcher S, Yiannikouris F, Gupte M. et al. The adipose renin-angiotensin system: Role in cardiovascular disease. Mol Cell Endocrinol 2009; 302: 111-117
- 26 Kalupahana NS, Moustaid-Moussa N.. The renin-angiotensin system: A link between obesity, inflammation and insulin resistance. Obes Rev 2012; 13: 136-149
- 27 Boustany CM, Bharadwaj K, Daugherty A. et al. Activation of the systemic and adipose renin-angiotensin system in rats with diet-induced obesity and hypertension. Am J Physiol Regul Integr Comp Physiol 2004; 287: R943-R949
- 28 Yu MA, Sánchez-Lozada LG, Johnson RJ. et al. Oxidative stress with an activation of the renin–angiotensin system in human vascular endothelial cells as a novel mechanism of uric acid-induced endothelial dysfunction. J Hypertens 2010; 28: 1234-1242
- 29 Corry DB, Eslami P, Yamamoto K. et al. Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin–angiotensin system. J Hypertens 2008; 26: 269-275
- 30 Zhang JX, Zhang YP, Wu QN. et al. Uric acid induces oxidative stress via an activation of the renin-angiotensin system in 3T3-L1 adipocytes. Endocrine 2015; 48: 135-142
- 31 Feig DI.. Uric acid and hypertension. Semin Nephrol 2011; 31: 441-446
- 32 Takir M, Kostek O, Ozkok A. et al. Lowering uric acid with allopurinol improves insulin resistance and systemic inflammation in asymptomatic hyperuricemia. J Investig Med 2015; 63: 924-929
- 33 Tomiyama H, Shiina K, Vlachopoulos C. et al. Involvement of arterial stiffness and inflammation in hyperuricemia-related development of hypertension. Hypertension 2018; 72: 739-745
- 34 Romi MM, Arfian N, Tranggono U. et al. Uric acid causes kidney injury through inducing fibroblast expansion, Endothelin-1 expression, and inflammation. BMC Nephrol 2017; 18: 326
- 35 Liang WY, Zhu XY, Zhang JW. et al. Uric acid promotes chemokine and adhesion molecule production in vascular endothelium via nuclear factor-kappa B signaling. Nutr Metab Cardiovasc Dis 2015; 25: 187-194
- 36 Kang YS.. Obesity associated hypertension: New insights into mechanism. Electrolyte. Blood Press 2013; 11: 46-52
- 37 Bando S, Fukuda D, Soeki T. et al. Expression of NLRP3 in subcutaneous adipose tissue is associated with coronary atherosclerosis. Atherosclerosis 2015; 242: 407-414