Differential effects of excess high-fructose corn syrup on the DNA methylation of hippocampal neurotrophic factor in childhood and adolescence

Abstract

Consumption of fructose-containing beverages such as high-fructose corn syrup (HFCS) is increasing, raising concerns about the negative effects of excessive fructose intake. A recent report indicated that excess HFCS intake impairs hippocampal function. In this study, we focused on neurotrophic factors (NFs) in the hippocampus from the viewpoint of epigenetics to clarify the adverse effects of fructose. We analyzed the effects of HFCS intake on hippocampal function in three age categories: childhood and adolescence (postnatal day (PD) 21–60), young adulthood (PD60-100), and late adulthood (PD100-140). For the experiments, male Sprague-Dawley rats were divided into three age categories, the control group was received distilled water and the HFCS group was received 20% HFCS solution for 40 days in each period. We analyzed mRNA and protein levels for qPCR and western blotting, respectively, of a hippocampal NF, brain-derived neurotrophic factor (Bdnf). HFCS consumption reduced hippocampal Bdnf mRNA and protein expressions in childhood and adolescence. Moreover, pyrosequencing assays revealed increased DNA methylation at the Bdnf promoter in childhood and adolescence. This Bdnf levels reduction may be due to hypermethylation of the promoter regions. It should be noted that this phenomenon was observed only in childhood and adolescence fructose consumption. Our results indicate that the sensitivity of the hippocampus to fructose may vary with age. This study provides insight into the adverse effects of excessive HFCS consumption on the hippocampus in children.

The Impact of Free Sugar on Human Health—A Narrative Review

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Maternal High-Fructose Corn Syrup Intake Impairs Corticosterone Clearance by Reducing Renal 11β-Hsd2 Activity via miR-27a-Mediated Mechanism in Rat Offspring

“…Kidney tissues were homogenized using radio-immunoprecipitation assay buffer (Wako Pure Chemicals, Osaka, Japan). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting were performed as described previously [24]. The primary antibodies against 5α-Red1 (Abcam, Cambridge, UK), 11β-HSD2 (Proteintech, Rosemont, USA), and β-actin (Abcam, located in Cambridge, UK) were used.…”

Unravelling the Complex Relationship between Diet and Nephrolithiasis: The Role of Nutrigenomics and Nutrigenetics

“…The exact mechanisms by which fructose modifies urine composition are still not completely understood and a specific epigenetic mechanism exerted by fructose in nephrolithiasis or risk factors for kidney stone formation have not been described. However, from available data, we know that fructose acts via epigenetic mechanisms (ncRNA and DNA methylation) in other conditions [ 57 , 58 , 59 ], such as nonalcoholic fatty liver disease (NAFLD) [ 60 , 61 , 62 ]. Therefore, we can speculate that fructose might act via epigenetic mechanisms to regulate the expression of genes that encode crucial transporters of anti- and prolithogenic urinary molecules.…”