Abstract
Excessive intake of glucose and fructose in beverages and foods containing high-fructose corn syrup (HFCS) plays a significant role in the progression of lifestyle-related diseases (LSRD). Glyceraldehyde-derived advanced glycation end-products (AGEs), which have been designated as toxic AGEs (TAGE), are involved in LSRD progression. Understanding of the mechanisms underlying the effects of TAGE on gene expression in the kidneys remains limited. In this study, DNA microarray analysis and quantitative real-time polymerase chain reaction (PCR) were used to investigate whether HFCS-consuming Wister rats generated increased intracellular serum TAGE levels, as well as the potential role of TAGE in liver and kidney dysfunction. HFCS consumption resulted in significant accumulation of TAGE in the serum and liver of rats, and induced changes in gene expression in the kidneys without TAGE accumulation or upregulation of receptor for AGEs (RAGE) upregulation. Changes in specific gene expression profiles in the kidney were more correlated with TAGE levels in the liver tissue than in the serum. These findings suggest a direct or indirect interaction may be present between the liver and kidneys that does not involve serum TAGE or RAGE. The involvement of internal signal transduction factors such as exosomes or cytokines without IL-1β and TNF-α is suggested to contribute to the observed changes in kidney gene expression.
Highlights
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.license.Increasing evidence suggests that excessive sugar intake leads to the development of a variety of lifestyle-related diseases (LSRD) [1,2]
As receptor for AGEs (RAGE) is expressed in the kidneys, we considered the possibility that toxic AGEs (TAGE) present in the blood induced renal dysfunction via RAGE [27]
No significant differences were observed in the levels of creatinine, uric acid, low-density lipoprotein cholesterol (LDL-C), or blood glucose between the two groups (Table S3)
Summary
Increasing evidence suggests that excessive sugar intake leads to the development of a variety of lifestyle-related diseases (LSRD) [1,2]. The relationship between obesity and the intake of soft drinks with added sugars and obesity has been well established, in developed countries [3,4,5,6]. High-fructose corn syrup (HFCS), a liquid sweetener with fructose and glucose, is present in most soft drinks at an estimated concentration of 10% [8]. Fructose and glucose are necessary carbohydrates that provide energy to the human body [9], most of the ingested HFCS uses adenosine triphosphate when metabolized by the liver, resulting in the development of gout, hypertension, cardiovascular disease (CVD), and renal dysfunction [10]. This study focused on the effects of advanced glycation end-products (AGEs) on the kidneys in a rat model
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