Traditional Korean diet can alter the urine organic acid profile, which may reflect the metabolic influence of the diet / 한국영양학회지

Purpose@#To determine the metabolic influence of the traditional Korean diet (K-diet), which has been regarded as a healthy diet, we investigated the profile of urine organic acids that are intermediates of various types of metabolism including energy metabolism. @*Methods@#Ten women aged 50–60 years were recruited and randomly divided into 2 diet groups, K-diet and control diet, the latter of which is a Westernized Korean diet that is commonly consumed by Koreans nowadays. Before and after the 2-week intervention, 46 urine organic acids were determined using LC/MS/MS, along with clinical parameters. @*Results@#The average concentrations of succinate (4.14 ± 0.84 μg/mg creatinine vs. 1.49 ± 0.11, p = 0.0346) and hydroxymethylglutarate (3.67 ± 0.36 μg/mg creatinine vs. 2.97 ± 0.29, p = 0.0466), both of which are intermediates of energy metabolism, decreased in the K-diet group after the 2-week intervention, but these were not observed in the control diet group. In particular, the average concentration of succinate in the K-diet group was lower than that in the control group (3.33 ± 0.56 μg/mg creatinine vs. 1.49 ± 0.11, p = 0.0284) after 2 weeks. The concentrations of two tryptophan metabolites, 5-hydroxyindolacetate (3.72 ± 0.22 μg/mg creatinine vs. 3.14 ± 0.21, p = 0.0183) and indican (76.99 ± 8.35 μg/mg creatinine vs. 37.89 ± 10.06, p = 0.0205) also decreased only in the K-diet group. After the 2-week intervention, the concentration of kynurenate, another tryptophan metabolite, was lower in the K-diet group than that in the control diet group (3.96 ± 0.51 μg/mg creatinine vs. 2.90 ± 0.22, p = 0.0356). Interestingly, the urine level of kynurenate was positively correlated with BMI (r = 0.61424, p = 0.0003) and total cholesterol (r = 0.46979, p = 0.0088), which decreased only in the K-diet group (239.40 ± 15.14 mg/dL vs. 198.20 ± 13.25, p = 0.0163). @*Conclusion@#The K-diet alters the urinary excretion of organic acids involved in energy metabolism and tryptophan metabolism, suggesting the influence of the K-diet on these types of metabolism. Urine organic acids changed by the K-diet may serve as biomarkers in future studies.

Walnut phenolic extracts reduce telomere length and telomerase activity in a colon cancer stem cell model

BACKGROUND/OBJECTIVES: Telomeres are located at the chromosomal ends and progressively shortened during each cell cycle. Telomerase, which is regulated by hTERT and c-MYC, maintains telomeric DNA sequences. Especially, telomerase is active in cancer and stem cells to maintain telomere length for replicative immortality. Recently we reported that walnut phenolic extract (WPE) can reduce cell viability in a colon cancer stem cell (CSC) model. We, therefore, investigated the effect of WPE on telomere maintenance in the same model. MATERIALS/METHODS: CD133+CD44+ cells from HCT116, a human colon cancer cell line, were sorted by Fluorescence-activated cell sorting (FACS) and treated with WPE at the concentrations of 0, 10, 20, and 40 µg/mL for 6 days. Telomere lengths were assessed by quantitative real-time PCR (qRT-PCR) using telomere specific primers and DNA extracted from the cells, which was further adjusted with single-copy gene and reference DNA (ddCt ). Telomerase activity was also measured by qRT-PCR after incubating the PCR mixture with cell protein extracts, which was adjusted with reference DNA (dCt ). Transcriptions of hTERT and c-MYC were determined using conventional RT-PCR. RESULTS: Telomere length of WPE-treated cells was significantly decreased in a dose-dependent manner (5.16 ± 0.13 at 0 µg/mL, 4.79 ± 0.12 at 10 µg/mL, 3.24 ± 0.08 at 20 µg/mL and 3.99 ± 0.09 at 40 µg/mL; P = 0.0276). Telomerase activities concurrently decreased with telomere length (1.47 ± 0.04, 1.09 ± 0.01, 0.76 ± 0.08, and 0.88 ± 0.06; P = 0.0067). There was a positive correlation between telomere length and telomerase activity (r = 0.9090; P < 0.0001). Transcriptions of both hTERT and c-MYC were also significantly decreased in the same manner. CONCLUSIONS: In the present cell culture model, WPE reduced telomere maintenance, which may provide a mechanistic link to the effect of walnuts on the viability of colon CSCs.

Iron Supplementation Reverses the Reduction of Hydroxymethylcytosine in Hepatic DNA Associated With Chronic Alcohol Consumption in Rats

BACKGROUND: Alcohol is known to affect two epigenetic phenomena, DNA methylation and DNA hydroxymethylation, and iron is a cofactor of ten-eleven translocation (TET) enzymes that catalyze the conversion from methylcytosine to hydroxymethylcytosine. In the present study we aimed to determine the effects of alcohol on DNA hydroxymethylation and further effects of iron on alcohol associated epigenetic changes. METHODS: Twenty-four male Sprague-Dawley rats were fed either Lieber-DeCarli alcohol diet (36% calories from ethanol) or Lieber-DeCarli control diet along with or without iron supplementation (0.6% carbonyl iron) for 8 weeks. Hepatic non-heme iron concentrations were measured by colorimetric assays. Protein levels of hepatic ferritin and transferrin receptor were determined by Western blotting. Methylcytosine, hydroxymethylcytosine and unmodified cytosine in DNA were simultaneously measured by liquid chromatography/mass spectrometry method. RESULTS: Iron supplementation significantly increased hepatic non-heme iron contents (P < 0.05) but alcohol alone did not. However, both alcohol and iron significantly increased hepatic ferritin levels and decreased hepatic transferrin receptor levels (P < 0.05). Alcohol reduced hepatic DNA hydroxymethylation (0.21% ± 0.04% vs. 0.33% ± 0.04%, P = 0.01) compared to control, while iron supplementation to alcohol diet did not change DNA hydroxymethylation. There was no significant difference in methylcytosine levels, while unmodified cytosine levels were significantly increased in alcohol-fed groups compared to control (95.61% ± 0.08% vs. 95.26% ± 0.12%, P = 0.03), suggesting that alcohol further increases the conversion from hydroxymethylcytosine to unmodified cytosine. CONCLUSIONS: Chronic alcohol consumption alters global DNA hydroxymethylation in the liver but iron supplementation reverses the epigenetic effect of alcohol.