Daily Consumption of α-Linolenic Acid Increases Conversion Efficiency to Eicosapentaenoic Acid in Mice.

To maintain a beneficial concentration of eicosapentaenoic acid (EPA), the efficient conversion of its precursor, α-linolenic acid (α-LA), is important. Here, we studied the conversion of α-LA to EPA using ICR and C57BL/6 mice. A single dose of perilla oil rich-in α-LA or free α-LA had not been converted to EPA 18 h following administration. The α-LA was absorbed into the circulation, and its concentration peaked 6 h after administration, after which it rapidly decreased. In contrast, EPA administration was followed by an increase in circulating EPA concentration, but this did not decrease between 6 and 18 h, indicating that the clearance of EPA is slower than that of α-LA. After ≥1 week perilla oil intake, the circulating EPA concentration was >20 times higher than that of the control group which consumed olive oil, indicating that daily consumption, but not a single dose, of α-LA-rich oil might help preserve the physiologic EPA concentration. The consumption of high concentrations of perilla oil for 4 weeks also increased the hepatic expression of Elovl5, which is involved in fatty acid elongation; however, further studies are needed to characterize the relationship between the expression of this gene and the conversion of α-LA to EPA.

Active-phase Plasma Alkaline Phosphatase Isozyme Activity Is a Sensitive Biomarker for Excessive Fructose Intake.

BACKGROUND/AIM: Excessive fructose intake reportedly leads to the development of nonalcoholic fatty liver disease (NAFLD). In our previous study, we reported that plasma activities of alkaline phosphatase (ALP) isozymes were markedly changed in rats with excessive fructose intake-induced hepatomegaly. In this study, we examined ALP isozyme activity prior to the occurrence of hepatomegaly, and investigated the effect of the timing of sample collection, to explore its potential as a biomarker. MATERIALS AND METHODS: After 1-week intake of a 63% high-fructose diet (HFrD), blood samples were collected from male rats during sleep or active phases to analyze biochemical parameters. RESULTS: Body and liver weights were similar between the HFrD and control diet groups, indicating that hepatomegaly due to excessive fructose intake had not occurred. The triglyceride levels and glutamate dehydrogenase (GLDH) activity were significantly elevated to similar degrees at both time points. HFrD intake significantly increased liver-type ALP (L-ALP) activity, stimulating it by 12.7% at the sleep phase and by 124.3% at the active phase. HFrD consumption also significantly decreased intestinal-type ALP (I-ALP) at the active phase, but only showed a decreasing trend during the sleep phase. CONCLUSION: Measurements of plasma ALP isozyme and GLDH activity, and triglyceride levels are effective early biomarkers of impending NAFLD caused by excessive fructose intake. L-ALP and I-ALP activities during the active phase are particularly sensitive for detection of excessive fructose intake before the occurrence of NAFLD.

Social confrontation stress decreases hepatic fibroblast growth factor-21 expression in aged mice.

We previously showed that social stress exposure in mature adult mice increased blood corticosterone concentrations at 2 days, disrupted hepatic lipid metabolism-related pathway at 30 days, and increased the risk of overweight with hepatic hypertrophy at 90 days. To further investigate the effects of aging on the physiological responses to social stress, we conducted a study using male BALB/c mice at the ages of 2 months (mature age), 14 months (middle age) and 26 months (old age), and exposed them to confrontation stress for 2 or 7 days. Blood corticosterone concentrations were increased at 2 days of stress, and then returned to baseline concentrations. This change was observed only at 2 months of age. We further examined the effect of aging on hepatic gene expression of fibroblast growth factor-21 (Fgf21) and found that its expression was significantly decreased after 7 days of stress at 14 months of age and after 2 days of stress at 26 months of age, indicating these decreasing effects became more pronounced with age. In conclusion, our study suggests that hepatic Fgf21 expression decrease under exposure to confrontation stress at middle or more age, indicating that stress response on Fgf21 related pathway might be more pronounced with age when exposed to stress.

Novel Biomarker Establishment for Evaluation of Excessive Fructose Consumption Using a Rat Model.

BACKGROUND/AIM: The habitual consumption of excessive fructose is associated with the onset and progression of lifestyle-related diseases, such as nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the physiological changes observed when consuming a diet containing excessive fructose on the viewpoints of hepatotoxicity biological markers using a rat model and explored the biomarker candidates that could detect the effects of excessive fructose intake at an early stage. MATERIALS AND METHODS: Male rats were fed 63% high fructose diet (HFrD) ad libitum and their blood samples were collected before and at 1, 2, 3, and 4 weeks after allocation. The plasma biochemical parameters, hepatotoxic enzyme activities including alkaline phosphatase (ALP) isozymes were analyzed. RESULTS: HFrD consumption for 4-weeks created NAFLD-like symptoms, including elevated plasma lipid parameters and hepatotoxicity markers, as well as fat accumulation in the liver compared with rats consuming a control diet. Alanine aminotransferase (ALT) and glutamate dehydrogenase (GLDH) were increased from the 3rd and 2nd weeks, respectively, but no changes were observed on ALP activity. However, the daily consumption of the HFrD increased the plasma activities of liver-type ALP isozyme, and decreased plasma small intestinal-type ALP isozyme soon after the start of feeding. CONCLUSION: ALP isozyme analysis in combination with GLDH and ALT activities in the plasma samples could be a useful tool to detect the physiological changes induced by excessive fructose intake at an early stage of the development of NAFLD.

Beneficial Effects of the Consumption of Hot-Water Extracts of Thinned Immature Mangos (Mangifera indica "Irwin") on the Hypertriglyceridemia of Apolipoprotein E-Deficient Mice.

The thinned immature fruit of the mango tree (Mangifera indica "Irwin") are regarded as waste products. In this study, we evaluated the effects of daily consumption of a hot-water extract of thinned immature mango fruits (TIMEx) on the dyslipidemia of apolipoprotein E-deficient (ApoE-/-) mice. ApoE-/- mice and wild-type BALB/c mice were fed a 20% fat diet containing 0%, 0.1%, or 1.0% TIMEx for 8 weeks. Their body mass, food intake, and water consumption were unaffected by the TIMEx. The 1.0% TIMEx supplementation significantly reduced serum triglyceride, but not total cholesterol concentration. This effect was significant in ApoE-/- mice, but less marked under normal conditions in wild-type mice. In addition, the circulating concentrations of three hormones that regulate metabolism, resistin, leptin, and glucose-dependent insulinotropic polypeptide, were reduced by TIMEx consumption, which may be involved in its effect to prevent hypertriglyceridemia. However, none of the concentrations of TIMEx reduced the size of atherosclerotic plaque lesions. In conclusion, daily consumption of TIMEx ameliorates hypertriglyceridemia but not hypercholesterolemia in genetically predisposed mice.

Subchronic toxicity evaluation of leaves from rabbiteye blueberry (Vaccinium virgatum Aiton) in rats.

Blueberry leaf may contain multiple compounds with beneficial effects. We conducted a 90-day toxicity study in rats to evaluate the safety of consuming the leaves of rabbiteye blueberry (Vaccinium virgatum Aiton; RB species). Powdered leaves were administered daily by oral gavage at doses of 500, 1000, and 2500 mg/kg body weight to male and female Sprague-Dawley rats for 90 days. Treatment did not result in death or changes in the behavior and external appearance of the animals. No alterations were observed in hematological and serum chemical parameters, urinalysis, food consumption, body weight gain, or absolute and relative organ weights at the end of the treatment period, with the exception of some leukocyte percentages in male rats treated with 500 and 1000 mg/kg blueberry leaf powder. The findings indicate that rabbiteye blueberry leaf is safe for consumption and should be investigated as a candidate functional food.

Daily Consumption of Bilberry ( Vaccinium myrtillus L.) Extracts Increases the Absorption Rate of Anthocyanins in Rats.

The effects of daily consumption of anthocyanins on bioavailability has remained unclear. In this study, we evaluated whether daily consumption affects the absorption rate of anthocyanins in rats when consumed during the active and sleep phase. Eighty rats were randomly divided into two groups. The first group consumed AIN-93G control diets, and the second group consumed AIN-93G diets containing 1% bilberry extract for 2 weeks. After 12 h fast, anthocyanins were not detected in plasma of rats. Bilberry extract (500 mg/kg body weight) was then orally administered at the beginning of the diurnal light period (ZT0, sleep phase) or at the end of the diurnal light period (ZT12, active phase). Blood concentrations of anthocyanins peaked 1 h after administration in both groups. Maximum blood concentration in rats that consumed bilberry extract daily (852 nM) was higher than that in control rats (630 nM) when the extract was administered at ZT0 but not at ZT12. Daily consumption of anthocyanins increases their absorption rate, but this effect is limited to the beginning of the sleep phase.