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Sanchez-Lozada LG, Tapia E, Jimenez A, Bautista P, Cristóbal M, Nepomuceno T, et al. Fructose-induced metabolic syndrome is associated with glomerular hypertension and renal microvascular damage in rats

Division of Nephrology, Hypertension & Renal Transplantation, University of Florida, Gainesville, Florida, United States
American journal of physiology. Renal physiology (Impact Factor: 3.25). 01/2007; 292(1):F423-9. DOI: 10.1152/ajprenal.00124.2006
Source: PubMed

ABSTRACT

Fructose intake has been recently linked to the epidemic of metabolic syndrome and, in turn, the metabolic syndrome has been epidemiologically linked with renal progression. The renal hemodynamic effects of fructose intake are unknown, as well as the effects of different routes of administration. Metabolic syndrome was induced in rats over 8 wk by either a high-fructose diet (60%, F60, n = 7) or by adding fructose to drinking water (10%, F10, n = 7). Body weight and food and fluid intake of each rat were measured weekly during the follow-up. At baseline and at the end of wk 8, systolic blood pressure, plasma uric acid, and triglycerides were measured. At the end of week 8 glomerular hemodynamics was evaluated by micropuncture techniques. Wall thickening in outer cortical and juxtamedullary afferent arterioles was assessed by immunohistochemistry and computer image analysis. Fructose administration either in diet or drinking water induced hypertension, hyperuricemia, and hypertriglyceridemia; however, there was a progressive increment in these parameters with higher fructose intake (C<F10<F60). In addition, the F60 rats developed kidney hypertrophy, glomerular hypertension, cortical vasoconstriction, and arteriolopathy of preglomerular vessels. In conclusion, fructose-induced metabolic syndrome is associated with renal disturbances characterized by renal hypertrophy, arteriolopathy, glomerular hypertension, and cortical vasoconstriction. These changes are best observed in rats administered high doses (60% diet) of fructose.

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Available from: Laura Gabriela Sánchez-Lozada
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    • "In terms of renal modifications, data from the National Health and Nutrition Examination Survey (NHANES) indicate a positive association between soda consumption, a major source of dietary fructose , and albuminuria in humans [5]. The administration of fructose to rats leads to renal hypertrophy, afferent arteriolar thickening, glomerular hypertension, and cortical vasoconstriction, all of them contributing to the development of chronic kidney disease [6]. Among several undesirable conditions developed in fructose fed-rats, elevated superoxide anion production seems to be a ubiquitous condition. "
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    ABSTRACT: High fructose consumption has been associated to deleterious metabolic conditions. In the kidney, high fructose causes renal alterations that contribute to the development of chronic kidney disease. Evidence suggests that dietary flavonoids have the ability to prevent/attenuate risk factors of chronic diseases. This work investigated the capacity of (‒)-epicatechin to prevent the renal damage induced by high fructose consumption in rats. Male Sprague Dawley rats received 10% (w/v) fructose in the drinking water for 8w, with or without supplementation with (‒)-epicatechin (20mg/kg body weight/d) in the rat chow diet. Results showed that, in the presence of mild proteinuria, the renal cortex from fructose-fed rats exhibited fibrosis and decreases in nephrin, synaptopodin, and WT1, all indicators of podocyte function in association with: i) increased markers of oxidative stress; ii) modifications in the determinants of NO bioavailability, i.e., NO synthase (NOS) activity and expression; and iii) development of a pro-inflammatory condition, manifested as NF-κB activation, and associated with high expression of TNFα, iNOS, and IL-6. Dietary supplementation with (‒)-epicatechin prevented or ameliorated the adverse effects of high fructose consumption. These results suggest that (‒)-epicatechin ingestion would benefit when renal alterations occur associated with inflammation or metabolic diseases.
    Preview · Article · Nov 2015 · Free Radical Biology and Medicine
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    • "In addition, fructose induced insulin resistance as evidenced by the significant increase in HOMA-IR index. Together, these alterations confirm the proper induction of MS in our study, which is in agreement with previous reports [8], [43], [44]. "
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    ABSTRACT: The metabolic syndrome (MS) is characterized by insulin resistance, dyslipidemia and hypertension. It is associated with increased risk of cardiovascular diseases and type-2 diabetes. Consumption of fructose is linked to increased prevalence of MS. Ursodeoxycholic acid (UDCA) is a steroid bile acid with antioxidant, anti-inflammatory activities and has been shown to improve insulin resistance. The current study aims to investigate the effect of UDCA (150 mg/kg) on MS induced in rats by fructose administration (10%) in drinking water for 12 weeks. The effects of UDCA were compared to fenofibrate (100 mg/kg), an agonist of PPAR-α receptors. Treatment with UDCA or fenofibrate started from the 6th week after fructose administration once daily. Fructose administration resulted in significant increase in body weight, elevations of blood glucose, serum insulin, cholesterol, triglycerides, advanced glycation end products (AGEs), uric acid levels, insulin resistance index and blood pressure compared to control rats. Moreover, fructose increased oxidative stress in aortic tissues indicated by significant increases of malondialdehyde (MDA), expression of iNOS and reduction of reduced glutathione (GSH) content. These disturbances were associated with decreased eNOS expression, increased infiltration of leukocytes and loss of aortic vascular elasticity. Treatment with UDCA successfully ameliorated the deleterious effects of fructose. The protective effect of UDCA could be attributed to its ability to decrease uric acid level, improve insulin resistance and diminish oxidative stress in vascular tissues. These results might support possible clinical application of UDCA in MS patients especially those present with liver diseases, taking into account its tolerability and safety. However, further investigations on human subjects are needed before the clinical application of UDCA for this indication.
    Full-text · Article · Sep 2014 · PLoS ONE
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    • "The fructose that was used was D-fructose >99% (Syarikat System Malaysia). Fructose drinking water was freshly prepared every alternate day [13] and was based on weight/volume formula [14]. To prepare fructose 20% drinking water, 20 g of fructose was diluted in 100 mL of tap water. "
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    ABSTRACT: Background. Metabolic syndrome can be caused by modification of diet by means of consumption of high carbohydrate and high fat diet such as fructose. Aims. To develop a metabolic syndrome rat model by induction of fructose drinking water (FDW) in male Wistar rats. Methods. Eighteen male Wistar rats were fed with FDW 20% and FDW 25% for a duration of eight weeks. The physiological changes with regard to food and fluid intake, as well as calorie intake, were measured. The metabolic changes such as obesity, dyslipidaemia, hypertension, and hyperglycaemia were determined. Data was presented in mean ± SEM subjected to one-way ANOVA. Results. Male Wistar rats fed with FDW 20% for eight weeks developed significant higher obesity parameters compared to those fed with FDW 25%. There was hypertrophy of adipocytes in F20 and F25. There were also systolic hypertension, hypertriglyceridemia, and hyperglycemia in both groups. Conclusion. We conclude that the metabolic syndrome rat model is best established with the induction of FDW 20% for eight weeks. This was evident in the form of higher obesity parameter which caused the development of the metabolic syndrome.
    Full-text · Article · Jun 2014 · BioMed Research International
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