Phosphorus is one of the important factors that accelerate the progression of chronic kidney disease. Phosphorus restriction or phosphate binders have been reported to have the ability to prevent the progression of chronic kidney disease. FGF23 is a circulating factor that regulates renal phosphorus reabsorption and 1α-hydroxylase activity. We focused on the phosphaturic activity of FGF23 and investigated whether a pharmacological dose of FGF23 is beneficial to the progression of renal insufficiency in uremic rats. To this end, we administered one of the mutant FGF23 expression plasmids into irreversible Thy1 rats. Chronic renal failure rats were established by intravenous injection of anti-rat CD90 (Thy1.1) monoclonal antibody to unilaterally nephrectomized Wistar rats. The rats were then intravenously injected every 2 wk with a naked DNA solution containing 10 μg of MOCK vector or a mutant FGF23 expression plasmid for 13 wk. Renal function was assessed biochemically and histopathologically. Mutant FGF23 significantly decreased serum creatinine and serum urea nitrogen. The marked glomerular sclerosis observed in uremic rats receiving the MOCK vector was ameliorated in rats treated with mutant FGF23. However, mutant FGF23 not only significantly decreased serum 1,25(OH)₂D and calcium but also aggravated high-turnover renal osteodystrophy from extremely high levels of PTH. These results might be a result of the mechanisms of FGF23 such as phosphaturic activity and lowering the level of 1,25(OH)₂D. In conclusion, mutant FGF23 prevented the progression of chronic renal failure by regulating serum phosphorus but aggravated renal osteodystrophy from the lowered levels of 1,25(OH)₂D.

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We have previously reported the preventive effects of light resistance exercise (voluntary tower climbing exercise) after ingestion of a high-protein snack (HPS) on muscle loss in glucocorticoid-injected rats. However, such studies have not been performed in humans. In this cross-over study, we examined the effect of light resistance exercise after ingestion of HPS on plasma branched-chain amino acid (BCAA) concentrations in humans. Seven healthy young adult females (aged 22.1±1.2 y) participated in this study. They were assigned to either an exercise group or a control group. Seven days after the first experiment, they were crossed over to the opposite intervention. The subjects ingested HPS (15 g protein, 18 g sugar) 3 h after breakfast (basal meal). The plasma BCAA concentrations increased at 30 min after HPS ingestion. The subjects in the exercise group performed light resistance exercise (15 min dumbbell exercise using 300 g brown-rice-filled fabric dumbbells) when the plasma BCAA concentrations were increased (60 min after the snack ingestion). The control group maintained a resting position during the experiment. Changes in the plasma BCAA concentrations between 60 and 90 min after HPS ingestion increased continuously in the control group (+27 μmol/L) but decreased in the exercise group (−37 μmol/L). Therefore, light resistance exercise after HPS ingestion may be effective for utilization of plasma BCAA in humans.

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Genetic factors, specifically the VKORC1 and GGCX genes, have been shown to contribute to the interindividual variability in response to the vitamin K-antagonist, warfarin, which influences the dose required to achieve the desired anticoagulation response. These differences in warfarin sensitivity may be explained by differences in vitamin K status. Men and women (n=416, 60-80 y), primarily of European descent, were genotyped for common polymorphisms in VKORC1 and GGCX. Cross-sectional associations exist between polymorphisms and biochemical markers of vitamin K [plasma phylloquinone, percent undercarboxylated osteocalcin (%ucOC)]. VKORC1 rs8050894 GG homozygotes had significantly higher cross-sectional measures of plasma phylloquinone than carriers of the CG or CC genotypes (plasma phylloquinone geometric means: GG 0.874±0.092 versus CG/CC 0.598± 0.044; p=0.020), whereas carriers of VKORC1 rs7294 AA or AG had significantly lower plasma phylloquinone concentrations compared to GG homozygotes (plasma phylloquinone geometric means: 0.579±0.045 versus 0.762±0.057; p=0.035). Cross-sectional analyses also revealed that heterozygous carriers of GGCX rs10187424 and rs7568458 had significantly lower %ucOC relative to either homozygous group. Polymorphisms in genes encoding enzymes involved in vitamin K metabolism may modulate plasma concentrations of phylloquionone and percent carboxylation of osteocalcin.

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Medium-chain triacylglycerols (MCT) are known to hydrolyze readily and completely to fatty acids and to be metabolized more easily by β-oxidation than long-chain triacylglycerols (LCT). Therefore, we investigated the effect of 2 wk of ingestion of food containing a small amount (6 g) of MCT on energy metabolism during moderate-intensity exercise and high-intensity exercise in recreational athletes. For comparison, the subjects were administered food containing MCT or LCT for 14 d, and were instructed to perform cycle ergometer exercise at a workload corresponding to 60% peak O₂ uptake (VO₂) for 40 min followed by a workload corresponding to 80% peak VO₂ until exhaustion. Blood lactate concentration, VO₂, VCO₂, and rating of perceived exertion (RPE) were measured at rest and during exercise. The exercise time to exhaustion at a workload corresponding to 80% peak VO₂ was significantly (p<0.05) longer in the MCT trial (10.2±7.6 min; mean±SD) than in the LCT trial (5.8±3.3 min). Blood lactate concentration and RPE during exercise were significantly (p<0.05) lower after ingestion of MCT-containing food. Fat oxidation rate was higher and carbohydrate oxidation rate was lower during exercise in the MCT trial than in the LCT trial, but the differences were not significant. These results indicate that the ingestion of MCT-containing food may suppress utilization of carbohydrate for energy production because of increased utilization of fatty acids for generating energy. In conclusion, our data suggest that short-term ingestion of food containing a small amount of MCT suppresses the increase in blood lactate concentration and RPE during moderate-intensity exercise and extends the duration of subsequent high-intensity exercise, at levels higher than those achieved by ingestion of LCT-containing food.

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Acrolein is a highly reactive unsaturated hazardous air pollutant of human health concern, particularly as a component of cigarette smoke. In this study, the effects of acrolein on mitochondrial damage in IMR-90 (a human lung fibroblast cell line), and the reduction of this damage by R-α-lipoic acid were examined. Our results show that acute acrolein exposure exceeding 100 μM (24 h) in IMR-90 cells caused serious cytotoxicity, including decreases in cell viability, mitochondrial membrane potential, SOD activity, GSH and ATP levels, and acute exposure also increased in ROS levels. Pretreatment with R-α-lipoic acid effectively protected IMR-90 cells from acrolein toxicity. The results show that acrolein is a mitochondrial toxin in IMR-90 cells and that acrolein-induced oxidative mitochondrial dysfunction is reduced by R-α-lipoic acid. These experiments imply R-α-lipoic acid may be an effective antioxidant for reducing or preventing chronic oxidant-induced lung cells degeneration in vivo from a variety of sources, including cigarette smoke.

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Modification of histone H3 at lysine 9 from methylations to acetylation is important for transactivation of genes. In this study, we found that all methylations (mono-, di-, tri-) of histone H3 at lysine 9 on the adiponectin gene decreased by stimulating adipocyte differentiation prior to increases in adiponectin gene expression and acetylation of histone H3 at the same residue on the gene during adipocyte differentiation of 3T3-L1 cells. Additionally, we revealed that decrease of adiponectin gene expression by treatment with TNFα, an inducer of insulin resistance in adipocytes, was associated with decreased acetylation of histone H3 at lysine 9 on the gene, but not methylations. Our results suggest that induction of the adiponectin gene during adipocyte differentiation is associated with modification of histone H3 at lysine 9 from methylations to acetylation, whereas reduction of the adiponectin gene in 3T3-L1 adipocytes with insulin resistance is associated with decreased acetylation at lysine 9 of histone H3.

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It is well-known that the small intestine of rodents rapidly undergoes differentiation and maturation during the transient suckling-weaning period from postnatal days 13 to 27. In the present study, we examined the gene expression changes in the jejunum of rats during the transient suckling-weaning period by microarray analysis. In the microarray data, we found that the expressions of many genes related to digestion/absorption/excretion of nutrients/ions, such as members of the solute carrier (Slc) family and ATP-binding cassette (Abc) subfamily, were rapidly induced during this period. Furthermore, some transcriptional factors/cofactors (Thrsp, Ppargc1a, Klf15 and Vdr), which are presumably important for the induction of intestinal gene expression after weaning, were rapidly induced during this period. In contrast, genes related to transport of nutrients, such as folate, zinc, fat and phosphate, which are important for early development, were highly expressed in the suckling period and then gradually decreased during weaning. These results indicate that the jejunum matures during the suckling-weaning period accompanied by changes in the expression of many genes related to digestion/absorption/excretion and some genes for transcriptional factors/cofactors.

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Objective: To analyze folate status changes in a group of overweight/obese young women following two different weight control programs. Methods: Fifty-seven women (BMI=24-35 kg/m²) were randomly assigned to one of two slightly hypocaloric diets: diet V, in which the consumption of vegetables was increased, or diet C, in which the consumption of cereals (especially breakfast cereals) was increased. Dietetic, anthropometric and biochemical data were collected at the start of the study and again at 6 wk. Results: At the beginning of the study, the obese women (BMI≥30 kg/m²) were at greater risk of showing serum folic acid concentrations of <14.9 nmol/L, even though there were no differences in folate intake between them and the women with a lower BMI. Energy intake was reduced and folate intake increased with both the V and C diets. Weight was lost as a consequence of this lower energy intake. Serum folic acid concentration increased and the plasma homocysteine concentration diminished only in those who lost >2.5 kg; this was the case of the subjects as a whole and of those who followed the C diet. Among those who lost the most weight (>2.5 kg), the chances of having an increased serum folate concentration were higher, although no significant differences were seen in folate intake with respect to women who lost less weight. Conclusions: Following a hypocaloric diet could lead to a better folate status through increased intake, but especially among those who lose the most body weight.

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In the first study (Study 1), 4-wk-old Sprague-Dawley (SD) rats were fed high fat diets containing casein, Alaska pollack, yellowfin tuna, or chicken as the protein source for 28 d. The purpose of this study was to compare the effect of Alaska pollack protein with other animal proteins (casein, yellowfin tuna, and chicken) on the prevention of visceral fat accumulation. We found that Alaska pollack protein was a more potent inhibitor of visceral fat accumulation than the other proteins (p<0.05). In the second study (Study 2), we determined the quantity of Alaska pollack protein needed to have an effect. To test this, 4-wk-old SD rats were fed diets containing different percentages of Alaska pollack proteins (0, 3, 10, 30 or 100%) to replace casein as the protein source for 28 d. The diets with 30 or 100% Alaska pollack protein as the protein source prevented visceral fat accumulation and elevated plasma adiponectin levels. Based on these findings, an inhibitory effect on the accumulation of visceral fats can be achieved by consuming a diet in which 30% or more of the total protein content comes from Alaska pollack.

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Zinc is known to play an important role for immune-functions. However, the effects of zinc-deficiency on the immune response system from the point of view of the distribution changes of the number of total white blood cells (WBCs) are still primarily unknown. Therefore, the effects of zinc-deficiency on the number of total WBCs, neutrophil, eosinophil, basophil, monocyte and lymphocytes (T lymphocyte, B lymphocyte and NK cell) were studied in rats. The weaned male rats were randomly divided into the zinc deficient diet (ZDD: 0.7 mg zinc/kg diet) group and the control diet (CON: 34.8 mg zinc/kg diet) group, and were pair-fed for 4 wk. The number of lymphocyte subsets, visceral organ weights, serum zinc, corticosterone and IL-6 concentrations were also determined. Zinc-deficiency increased duration-dependently the number of total white blood cells, granulocytes (neutrophil, eosinophil and basophil) and monocytes in 2-4 wk without changing the number of lymphocytes, T lymphocytes, B lymphocytes or NK cells. The relative weights of thymus and adrenals were 0.63 times (p<0.01) lower and 1.60 times (p<0.001) higher in ZDD group than in CON group, respectively. Zinc-deficiency increased serum corticosterone concentration to 1.48 times (p<0.05) without changing serum IL-6 concentration, as compared with those of CON group. From these results, zinc-deficiency increases markedly the number of granulocytes and monocytes without changing the number of lymphocytes, T lymphocytes, B lymphocytes or NK cells. These results also suggest that zinc-deficiency induces stress responses and the responses may have in part participated in increased actions of the number of granulocytes and monocytes during zinc-deficiency, and induce thymus atrophy and adrenal hypertrophy.

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The rice protein prepared from alkaline extraction (AE-RP) has high digestibility compared to that obtained from starch degradation (SD-RP) in in vitro digestion experiments, and alterations in the protein body (PB) structures were observed in AE-RP in the previous study. The improvement in the digestibility of AE-RP is probably a result of the structural change of PB. The present study was carried out to elucidate the superiority of AE-RP compared to SD-RP in bioavailability in growing rats. There were no major differences between AE-RP and SD-RP in polypeptide compositions according to SDS-PAGE and their amino acid compositions. The equivalent body weight gain and similar growth curves in both AE-RP and casein (control) groups were obtained during the feeding period of 28 d, and their values were significantly higher compared to the SD-RP group (p<0.05). The protein efficiency ratio (PER) of the SD-RP (1.73) group was significantly lower than those of the AE-RP (1.87) and casein (1.84) groups (p<0.05). The plasma lysine concentrations at the last stage of the feeding period in the AE-RP and SD-RP groups were approximate levels and were appreciably lower, compared to that of the casein group (p<0.001). Portal plasma amino acid concentrations were determined after single administration (4 g/kg) of two rice proteins in non-anaesthetized rats. All the amino acid concentrations in the 2 groups reached a maximum level at 30 min or 1 h and decreased to the pre-administration levels 6 h after the start of administration. The total amounts of three amino acids, leucine, valine and arginine, which appeared in the portal blood during the 6 h period after the start of administration of AE-RP, were higher than those of SD-RP (p<0.05). Furthermore, 13 kDa prolamin was detected with Western-blot analysis only in the feces of rats fed SD-RP. Consequently, these results indicate that the bioavailability of rice protein containing prolamin was improved by alkaline extraction.

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To elucidate the mechanism by which moderate and high protein diets fail to increase plasma homocysteine concentration despite dietary methionine levels being higher, rats were fed diets with graded levels (10, 30, and 50%) of casein or low casein diets supplemented with methionine at levels of 0.5 and 1.0% together with or without glycine+serine, which corresponded to moderate and high casein diets with respect to these amino acids, for 14 d. The plasma homocysteine concentration significantly decreased with an increase in dietary casein level, whereas it significantly increased with an increase in dietary methionine level when the low casein diet was supplemented with methionine. Supplementation with glycine+serine significantly suppressed the elevation of plasma homocysteine concentration due to methionine supplementation, but it could not decrease plasma homocysteine concentration to the levels in rats fed corresponding casein diets. Increased concentrations of hepatic S-adenosylhomocysteine and homocysteine due to methionine supplementation were also significantly suppressed by glycine+serine. The activity of hepatic cystathionine β-synthase (CBS) did not increase in response to methionine supplementation, while it significantly increased with an increase in dietary casein level. In contrast, the activity of hepatic betaine-homocysteine S-methyltransferase (BHMT) significantly increased with increase in both dietary casein level and dietary methionine level. Hepatic levels of mRNA for CBS and BHMT were parallel to the enzyme activities. The results suggest that, in contrast to methionine-supplemented low casein diets, moderate and high casein diets avoid increasing plasma homocysteine concentration through dual mechanisms, greater supply of glycine+serine and an increase in CBS activity.

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Bleomycin (BLM) is a chemotherapeutic agent against different carcinomas, one dose of which causes dependent pulmonary fibrosis. The present study was taken up in order to measure the retinyl ester, α-tocopherol and cholecalciferol (vitamin D₃) level in lung tissue in the rats following BLM-induced fibrosis. Fourteen rats were randomly divided into two groups as a control and a BLM group. On the day of the experiment, the BLM group rats were instilled with BLM (7.5 mg/kg) and the control group with sterile saline intratracheally. Fourteen days after instillation, rats in each group were sacrificed and the lungs were prepared for histopathological examination and determination of the vitamin levels with a HPLC system. The levels of retinyl ester, α-tocopherol and vitamin D₃ in the lungs of the BLM group were determined to be lower than in the controls. There was statistically significant difference for the α-tocopherol and vitamin D₃ concentrations compared to the control group (p<0.01, p<0.001), respectively. According to these results in pulmonary fibrosis, vitamins were consumed by the lung tissue and their levels decreased.

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To study the effects of different types of stressors on intestinal immune function, the lymphocyte subsets and associated immunoglobulin production in stressed rats were observed. Physical (electric foot shock) or psychological (non foot-shock) stress respectively were induced using a communication box. Rats were exposed to stress for 2 h per day, and the treatment was maintained for 14 consecutive days. Lymphocytes were isolated from the mesenteric lymph node (MLN) and spleen using Lympholyte-Rat. There was no change the lymphocyte subsets in MLN or spleen in either group. Foot-shock stress increased immunoglobulin secretions in MLN lymphocytes. These results demonstrated that intestinal immune functions were adaptively regulated under conditions of moderate stress.

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We investigated the effect of wasabi rhizome extract on atopic dermatitis (AD) model mice. The wasabi extract was fed to the HR-1 hairless mice, which develop AD-like symptoms with a special diet (HR-AD diet). The extract was expected to reduce the symptoms induced. Wasabi rhizome-containing HR-AD diet (5% and 10%) reduced the scratching behavior, and the 10% wasabi rhizome HR-AD diet significantly reduced scratching behavior on days 28, 35 and 42. Plasma components (histamine, eotaxin, IgE and thymus and activation-regulated chemokine (TARC)) were decreased in the 10% wasabi rhizome HR-AD diet. In histopathological examinations (toluidine blue (T.B.), major basic protein (MBP), CD4, IL-4, IL-5, eotaxin, TARC and IgE), the wasabi rhizome-containing HR-AD diet (5% and 10%) significantly reduced the number of positive stained cells. These results suggested that the wasabi rhizome extract improved the AD-like symptoms of HR-1 hairless mice.

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