Chronic consumption of the dietary polyphenol chrysin attenuates metabolic disease in fructose-fed rats
- 191 Downloads
Metabolic syndrome (MS) is a major public health issue worldwide and fructose consumption has been associated with MS development. Recently, we showed that the dietary polyphenol chrysin is an effective inhibitor of fructose uptake by human intestinal epithelial cells. Therefore, our aim was to investigate if chrysin interferes with the development of MS induced by fructose in an animal model.
Adult male Sprague–Dawley rats (220–310 g) were randomly divided into four groups: (A) tap water (control), (B) tap water and a daily dose of chrysin (100 mg/kg) by oral administration (chrysin) (C) 10% fructose in tap water (fructose), and (D) 10% fructose in tap water and a daily dose of chrysin (100 mg/kg) by oral administration (fructose + chrysin). All groups were fed ad libitum with standard laboratory chow diet and dietary manipulation lasted 18 weeks.
Fructose-feeding for 18 weeks induced an increase in serum triacylglycerols, insulin and angiotensin II levels and in hepatic fibrosis and these changes did not occur in fructose + chrysin rats. Moreover, the increase in both systolic and diastolic blood pressure which was found in fructose-fed animals from week 14th onwards was not observed in fructose + chrysin animals. In contrast, the increase in energy consumption, liver/body, heart/body and right kidney/body weight ratios, serum proteins, serum leptin and liver triacylglycerols observed in fructose-fed rats was not affected by chrysin.
Chrysin was able to protect against some of the MS features induced by fructose-feeding.
KeywordsMetabolic syndrome Chrysin Fructose Hypertension Triacylglycerol
Oral glucose tolerance test
Systolic blood pressure
Diastolic blood pressure
Mean arterial pressure
Very low-density lipoproteins
Homeostatic model assessment for insulin resistance
Messenger ribonucleic acid
Non-esterified fatty acids
Sterol regulatory binding protein 1c
Carbohydrate response element binding protein
Angiotensin type 1
Reactive oxygen species
Nicotinamide adenine dinucleotide phosphate reductase
We thank animal facility crew from Faculty of Medicine of the University of Porto for all technical support.
Conception and design: NA and FM. Acquisition of data: NA. Technical support: JTG, IR, LG. Analysis and interpretation of data: NA, FM, EK, SA, CS. Drafting the article and revising it for intellectual content: NA, FM. Study Supervision: FM. Final approval of the completed article: NA, FM, EK, SA, CS, JTG, IR, LG.
This work was financed by CAPES—Brazilian Federal Agency for Support and Evaluation of Graduate Education within the Ministry of Education of Brazil, for financing this project—PN: 10103/13-9.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
- 9.Ramirez-Espinosa JJ, Saldana-Rios J, Garcia-Jimenez S, Villalobos-Molina R, Avila-Villarreal G, Rodriguez-Ocampo AN, Bernal-Fernandez G, Estrada-Soto S (2017) Chrysin induces antidiabetic, antidyslipidemic and anti-inflammatory effects in athymic nude diabetic mice. Molecules 23(1):E67. https://doi.org/10.3390/molecules23010067 CrossRefGoogle Scholar
- 13.Pereira CD, Severo M, Araujo JR, Guimaraes JT, Pestana D, Santos A, Ferreira R, Ascensao A, Magalhaes J, Azevedo I, Monteiro R, Martins MJ (2014) Relevance of a hypersaline sodium-rich naturally sparkling mineral water to the protection against metabolic syndrome induction in fructose-fed Sprague–Dawley rats: a biochemical, metabolic, and redox approach. Int J Endocrinol 2014:384583. https://doi.org/10.1155/2014/384583 CrossRefGoogle Scholar
- 19.Singh J, Chaudhari BP, Kakkar P (2017) Baicalin and chrysin mixture imparts cyto-protection against methylglyoxal induced cytotoxicity and diabetic tubular injury by modulating RAGE, oxidative stress and inflammation. Environ Toxicol Pharmacol 50:67–75. https://doi.org/10.1016/j.etap.2017.01.013 CrossRefGoogle Scholar
- 20.Kang MK, Lee EJ, Kim YH, Kim DY, Oh H, Kim SI, Kang YH (2018) Chrysin ameliorates malfunction of retinoid visual cycle through blocking activation of AGE-RAGE-ER stress in glucose-stimulated retinal pigment epithelial cells and diabetic eyes. Nutrients 10(8):E1046. https://doi.org/10.3390/nu10081046 CrossRefGoogle Scholar
- 23.Kang MK, Park SH, Kim YH, Lee EJ, Antika LD, Kim DY, Choi YJ, Kang YH (2017) Chrysin ameliorates podocyte injury and slit diaphragm protein loss via inhibition of the PERK-eIF2alpha-ATF-CHOP pathway in diabetic mice. Acta Pharmacol Sin 38(8):1129–1140. https://doi.org/10.1038/aps.2017.30 CrossRefGoogle Scholar
- 28.Litterio MC, Vazquez Prieto MA, Adamo AM, Elesgaray R, Oteiza PI, Galleano M, Fraga CG (2015) (−)-Epicatechin reduces blood pressure increase in high-fructose-fed rats: effects on the determinants of nitric oxide bioavailability. J Nutr Biochem 26(7):745–751. https://doi.org/10.1016/j.jnutbio.2015.02.004 CrossRefGoogle Scholar
- 31.Kamide K, Rakugi H, Higaki J, Okamura A, Nagai M, Moriguchi K, Ohishi M, Satoh N, Tuck ML, Ogihara T (2002) The renin–angiotensin and adrenergic nervous system in cardiac hypertrophy in fructose-fed rats. Am J Hypert 15(1 Pt 1):66–71. https://doi.org/10.1016/s0895-7061(01)02232-4 CrossRefGoogle Scholar
- 33.Abdelmalek MF, Suzuki A, Guy C, Unalp-Arida A, Colvin R, Johnson RJ, Diehl AM, Nonalcoholic Steatohepatitis Clinical Research N (2010) Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. Hepatology 51(6):1961–1971. https://doi.org/10.1002/hep.23535 CrossRefGoogle Scholar
- 34.Vila L, Rebollo A, Adalsteisson GS, Alegret M, Merlos M, Roglans N, Laguna JC (2011) Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment. Toxicol Appl Pharmacol 251(1):32–40. https://doi.org/10.1016/j.taap.2010.11.011 CrossRefGoogle Scholar
- 36.Le KA, Tappy L (2006) Metabolic effects of fructose. Curr Opin Clin Nutr Metab Care 9(4):469–475. https://doi.org/10.1097/01.mco.0000232910.61612.4d CrossRefGoogle Scholar
- 40.Buettner C, Muse ED, Cheng A, Chen L, Scherer T, Pocai A, Su K, Cheng B, Li X, Harvey-White J, Schwartz GJ, Kunos G, Rossetti L, Buettner C (2008) Leptin controls adipose tissue lipogenesis via central, STAT3-independent mechanisms. Nat Med 14(6):667–675. https://doi.org/10.1038/nm1775 CrossRefGoogle Scholar
- 42.Ackerman Z, Oron-Herman M, Grozovski M, Rosenthal T, Pappo O, Link G, Sela BA (2005) Fructose-induced fatty liver disease: hepatic effects of blood pressure and plasma triglyceride reduction. Hypertension 45(5):1012–1018. https://doi.org/10.1161/01.HYP.0000164570.20420.67 CrossRefGoogle Scholar
- 44.Koo HY, Wallig MA, Chung BH, Nara TY, Cho BH, Nakamura MT (2008) Dietary fructose induces a wide range of genes with distinct shift in carbohydrate and lipid metabolism in fed and fasted rat liver. Biochim Biophys Acta 1782(5):341–348. https://doi.org/10.1016/j.bbadis.2008.02.007 CrossRefGoogle Scholar
- 46.Prince PD, Lanzi CR, Toblli JE, Elesgaray R, Oteiza PI, Fraga CG, Galleano M (2016) Dietary (−)-epicatechin mitigates oxidative stress, NO metabolism alterations, and inflammation in renal cortex from fructose-fed rats. Free Radic Biol Med 90:35–46. https://doi.org/10.1016/j.freeradbiomed.2015.11.009 CrossRefGoogle Scholar
- 49.Ichimura M, Masuzumi M, Kawase M, Sakaki M, Tamaru S, Nagata Y, Tanaka K, Suruga K, Tsuneyama K, Matsuda S, Omagari K (2017) A diet-induced Sprague–Dawley rat model of nonalcoholic steatohepatitis-related cirrhosis. J Nutr Biochem 40:62–69. https://doi.org/10.1016/j.jnutbio.2016.10.007 CrossRefGoogle Scholar
- 50.Jeyapal S, Putcha UK, Mullapudi VS, Ghosh S, Sakamuri A, Kona SR, Vadakattu SS, Madakasira C, Ibrahim A (2018) Chronic consumption of fructose in combination with trans fatty acids but not with saturated fatty acids induces nonalcoholic steatohepatitis with fibrosis in rats. Eur J Nutr 57(6):2171–2187. https://doi.org/10.1007/s00394-017-1492-1 CrossRefGoogle Scholar
- 53.Hermenean A, Mariasiu T, Navarro-Gonzalez I, Vegara-Meseguer J, Miutescu E, Chakraborty S, Perez-Sanchez H (2017) Hepatoprotective activity of chrysin is mediated through TNF-alpha in chemically-induced acute liver damage: an in vivo study and molecular modeling. Exp Ther Med 13(5):1671–1680. https://doi.org/10.3892/etm.2017.4181 CrossRefGoogle Scholar
- 58.Shinozaki K, Ayajiki K, Nishio Y, Sugaya T, Kashiwagi A, Okamura T (2004) Evidence for a causal role of the renin–angiotensin system in vascular dysfunction associated with insulin resistance. Hypertension 43(2):255–262. https://doi.org/10.1161/01.HYP.0000111136.86976.26 CrossRefGoogle Scholar
- 60.Cai H (2005) NAD(P)H oxidase-dependent self-propagation of hydrogen peroxide and vascular disease. Circ Res 96(8):818–822. https://doi.org/10.1161/01.RES.0000163631.07205.fb CrossRefGoogle Scholar
- 62.Bundalo MM, Zivkovic MD, Romic SD, Tepavcevic SN, Koricanac GB, Djuric TM, Stankovic AD (2016) Fructose-rich diet induces gender-specific changes in expression of the renin–angiotensin system in rat heart and upregulates the ACE/AT1R axis in the male rat aorta. J Renin Angiotensin Aldosterone Syst 17(2):1470320316642915. https://doi.org/10.1177/1470320316642915 CrossRefGoogle Scholar
- 67.Zamami Y, Takatori S, Hobara N, Yabumae N, Tangsucharit P, Jin X, Hashikawa N, Kitamura Y, Sasaki K, Kawasaki H (2011) Hyperinsulinemia induces hypertension associated with neurogenic vascular dysfunction resulting from abnormal perivascular innervations in rat mesenteric resistance arteries. Hypertens Res 34(11):1190–1196. https://doi.org/10.1038/hr.2011.97 CrossRefGoogle Scholar