Yasuo Kagawa

Kagawa Nutrition University, Sakado, Saitama, Japan

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Publications (174)543.6 Total impact

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    ABSTRACT: Although several studies have reported associations of depressive state with specific nutrients and foods, few have examined the associations with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese patients with depression. Subjects were 166 Japanese patients (104 men and 62 women), aged 22-74 y, who were treated at a hospital psychiatry clinic in Tokyo. Depressive symptoms were assessed using the Himorogi Self-rating Depression Scale (H-SDS) and Himorogi Self-rating Anxiety Scale (H-SAS). We categorized depressive symptoms into 3 types: physical, psychiatric, and anxiety symptoms. Dietary patterns were derived using principal component analysis of the consumption of 59 food and beverage items, which was assessed by a validated brief diet history questionnaire. Three dietary patterns were identified: 1) "plant foods and fish products," 2) "fish," and 3) "Western/meat." We calculated the correlation coefficients for the relationship between each dietary pattern score and depressive symptom score in unipolar depression vs. bipolar depression and in men vs. women. In bipolar depression, the plant foods and fish products pattern showed an inverse relationship with physical and psychiatric symptoms, and in men, this pattern showed an inverse relationship with psychiatric symptoms. The fish pattern and Western/meat pattern were not significantly associated with the 3 types of depressive symptoms. In conclusion, we identified 3 dietary patterns and found that associations between these patterns and depressive symptoms were observed only in bipolar depression and only in men.
    Journal of Nutritional Science and Vitaminology 01/2013; 59(2):115-122. · 0.99 Impact Factor
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    ABSTRACT: In this study, we administered various diets of stearidonic acid (SDA, 18:4n-3) soybean oil to rats and examined the subsequent blood and organ biochemical parameters. Male Wistar rats (seven rats/group, six groups total) were fed diets supplemented with a test oil for 4 weeks. Diets containing test oils were: FFC diet (fish-oil-free control diet), C diet (control group, assuming a Japanese diet), SDA25 diet (25% 18:4n-3 soybean oil in the C diet), SDA50 (50% 18:4n-3 soybean oil in the C diet), ALA diet (34% flaxseed oil in the C diet), and EPA+DHA diet (34% fish oil in the C diet). The intake of 18:4n-3 showed increased relative efficiency of 20:5n-3 accretions in serum and liver triacylglycerol and significantly decreased the serum triacylglycerol level in rats. The results suggested that the consumption of 18:4n-3 soybean oil may modify the lipid and fatty acid profiles of body fats, even when EPA and DHA derived from fish is consumed.
    Prostaglandins Leukotrienes and Essential Fatty Acids 12/2012; · 1.98 Impact Factor
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    ABSTRACT: Accumulation of visceral fat increases cardiovascular mortality in industrialized societies. However, during the evolution of the modern human, visceral fat may have acted as energy storage facility to survive in times of famine. Therefore, past natural selection might contribute to shaping the variation of visceral fat accumulation in present populations. Here, we report that the gene encoding tribbles homolog 2 (TRIB2) influenced visceral fat accumulation and was operated by recent positive natural selection in East Asians. Our candidate gene association analysis on 11 metabolic traits of 5,810 East Asians revealed that rs1057001, a T/A transversion polymorphism in 3'untranslated region (UTR) of TRIB2, was strongly associated with visceral fat area (VFA) and waist circumference adjusted for body mass index (P = 2.7 × 10(-6) and P = 9.0 × 10(-6), respectively). rs1057001 was in absolute linkage disequilibrium with a conserved insertion-deletion polymorphism in the 3'UTR and was associated with allelic imbalance of TRIB2 transcript levels in adipose tissues. rs1057001 showed high degree of interpopulation variation of the allele frequency; the low-VFA-associated A allele was found with high frequencies in East Asians. Haplotypes containing the rs1057001 A allele exhibited a signature of a selective sweep, which may have occurred 16,546-27,827 years ago in East Asians. Given the predominance of the thrifty gene hypothesis, it is surprising that the apparently non-thrifty allele was selectively favored in the evolution of modern humans. Environmental/physiological factors other than famine would be needed to explain the non-neutral evolution of TRIB2 in East Asians.
    Human Genetics 10/2012; · 4.52 Impact Factor
  • Yasuo Kagawa
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    ABSTRACT: Biological clocks are classified into oscillatory (clock genes) and unidirectional hourglass clocks (telomeres). Clock genes align behavioral and biochemical processes with the day/night cycle. Telomeres, the repeated series of DNA sequences that cap the ends of chromosomes, become shorter during cell division. Shortened telomeres have been documented in various pathological states associated with aging. Human activity is driven by NADH and ATP produced from nutrients, and the resulting NAD and AMP play a predominant role in energy regulation. Caloric restriction increases both AMP and NAD and is known to extend the healthspan (healthy lifespan) of animals. Silent information regulator T1 (SIRT1), the NAD-dependent deacetylase, attenuates telomere shortening, while peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a master modulator of gene expression, is phosphorylated by AMP kinase and deacetylated by SIRT1. Thus, PGC-1α is a key component of the circadian oscillator that integrates the mammalian clock and energy metabolism. Reactive oxygen species produced in clock mutants result in telomere shortening. The circadian rhythms produced by clock genes and lifestyle factors are ultimately controlled by the human brain and drive homeostatic and hedonic feeding and daily activity.
    Nutrition Reviews 08/2012; 70(8):459-71. · 4.60 Impact Factor
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    ABSTRACT: Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for type 2 diabetes mellitus. In the present study, we investigated whether pharmacologic doses of biotin have the potential to abate insulin resistance in the skeletal muscles of OLETF rats. OLETF rats (34 weeks of age) were divided into 2 groups and given distilled water (OLETF-control group) or distilled water containing 3.3 mg L(-1) of biotin (OLETF-biotin group) for 8 weeks. At the end of experimental period, the OLETF-control rats developed severe hyperglycemia and hyperinsulinemia, whereas the OLETF-biotin rats showed significantly smaller responses to oral glucose tolerance test than the OLETF-control rats. The glucose uptake in the hind limbs of the rats was significantly higher in the OLETF-biotin group than in the OLETF-control group. Biotin administration increased the glucose transporter type 4 (GLUT4) protein content in the total membrane fraction but had little effect on the GLUT4 content in the plasma membrane fraction. These results indicate that administration of a pharmacological dose of biotin prevents the development of insulin resistance in the skeletal muscles of OLETF rats presumably via an increase in GLUT4 protein expression but not via GLUT4 translocation.
    Food & function. 01/2012; 3(4):414-9.
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    ABSTRACT: MLXIPL is a transcription factor integral to the regulation of glycolysis and lipogenesis in the liver. Common variants of the MLXIPL gene (MLXIPL) are known to influence plasma triglyceride levels in people of European descent. As MLXIPL has a key role in energy storage, genetic variations of the MLXIPL may be relevant to physiological adaptations to nutritional stresses that have occurred during the evolution of modern humans. In the present study, we assessed the phenotypic consequences of the Q241H variant of MLXIPL in populations of Asian and Oceanian origin and also surveyed the prevalence of Q241H variant in populations worldwide. Multiple linear regression models based on 2373 individuals of Asian origin showed that the H allele was significantly associated with decreased concentrations of plasma triglycerides (P=0.0003). Direct genotyping of 1455 individuals from Africa, Asia and Oceania showed that the triglyceride-lowering H allele was found at quite low frequencies (0.00-0.16) in most of the populations examined. The exceptions were some Central Asian populations, including Mongolians, Tibetans and Uyghurs, which exhibited much higher frequencies of the H allele (0.21-0.26). The high prevalence of the H allele in Central Asia implies that the Q241H variant of MLXIPL might have been significant for utilization of carbohydrates and fats in the common ancestors of these populations, who successfully adapted to the environment of Central Asia by relying on nomadic livestock herding.
    Journal of Human Genetics 09/2011; 56(12):828-33. · 2.53 Impact Factor
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    ABSTRACT: Parkinson's disease and other neurological disorders are prevalent in Mongolia. Our previous studies revealed a significant correlation of these diseases with high oxidative stress due to a high body burden of harmful metals, such as manganese, iron, lead, cadmium, and aluminum. This report describes a 37-year-old male Mongolian patient with multiple sclerosis and essential micronutrient deficiency. This patient demonstrated high oxidative stress, as shown by high urinary 8-hydroxy-2'-deoxyguanosine levels of 14.7 and 14.3 ng/mg creatinine (crea), although his hair levels of these toxic metals were markedly lower than other Mongolians. In addition, this patient was deficient not only in various essential minerals, including selenium, magnesium, copper, cobalt, vanadium, and nickel, but also in micronutrients such as vitamin B6, C, E, folic acid, niacin, and β-carotene. Furthermore, after taking 2,3-dimercaptosuccinic acid, a chelating agent, urinary excretion of lead, cadmium, manganese, aluminum, iron, copper, and lithium were increased 156-, 8.4-, 7.6-, 4.3-, 3.3-, 2.1-, and 2.1-fold, respectively. These results suggest that this patient suffered from a deficiency in micronutrients such as essential minerals and vitamins, which resulted in a disturbance in the ability to excrete harmful metals into the urine and hair. It is possible that a deficiency of micronutrients and a high burden of heavy metals play a role in the pathogenesis of multiple sclerosis. Nutritional treatment may be an effective approach to this disease.
    Current Aging Science 08/2011; 5(2):112-25.
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    ABSTRACT: It was previously reported that the hair of Mongolian people showed very high accumulation of manganese (Mn), which may increase oxidative stress. This study (2(nd) report), indicated that not only Mn but other minerals had also accumulated at high levels in hair. It describes the influence of these minerals on oxidative stress, Parkinson's disease-like symptom (Parkinsonism) and arthritis, these diseases being prevalent in Mongolia. 299 subjects were enrolled (including 21; Parkinsonism and 25; arthritis) from Ulaanbaatar and 5 other areas in Mongolia. Oxidative stress was evaluated by measuring the level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). The minerals accumulated in scalp hair were measured by the inductively coupled plasma mass spectrometry method. As a control, 81 healthy Japanese subjects were enrolled. Mongolian subjects showed high accumulated levels of Mn, iron, lead, cadmium and aluminum accumulations in hair, as compared with Japanese subjects. These levels were correlated with urinary 8-OHdG levels. The subjects with Parkinsonism and arthritis demonstrated higher levels in these minerals than healthy subjects. High accumulations of these minerals may increase oxidative stress in Mongolian people, and induce Parkinsonism and arthritis through the high oxidative stress. The high accumulations of these minerals may be induced by eating large amounts of sheep meat. In addition, sandy wind pollution may also contribute to it.
    Current Aging Science 02/2011; 4(1):42-56.
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    ABSTRACT: A low-cost and simple on-site technique for genotyping single nucleotide polymorphisms (SNPs) was developed. The technique is based on allele-specific primer PCR and the recently developed bead arrays in a single tip technique. The performance of the method was verified by genotyping four SNPs that correlate with cardiovascular diseases.
    Journal of Bioscience and Bioengineering 10/2010; 110(4):505-8. · 1.74 Impact Factor
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    ABSTRACT: Recent genome-wide association studies (GWASs) showed that single nucleotide polymorphisms (SNPs) in FADS1/FADS2 were associated with plasma lipid concentrations in populations with European ancestry. We investigated the associations between the SNPs in FADS1/FADS2 and plasma concentrations of triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in two Asian groups, i.e., Japanese and Mongolians. The genotype of rs174547 (T/C), found to be associated with triglyceride and HDL-C concentrations in the GWAS, was determined in 21,004 Japanese and 1,203 Mongolian individuals. Genotype-phenotype association was assessed by using multiple linear regression models, assuming an additive model of inheritance. The copy number of the rs174547 C allele was significantly associated with increased triglyceride levels (P = 1.5 x 10(-6)) and decreased HDL-C levels (P = 0.03) in the Japanese population. On the other hand, in the Mongolian population, the rs174547 C allele copy number was strongly associated with decreased LDL-C levels (P = 2.6 x 10(-6)), but was not associated with triglyceride and HDL-C levels. The linkage disequilibrium pattern and haplotype structures of SNPs around the FADS1/FADS2 locus showed no marked dissimilarity between Japanese and Mongolian individuals. The present data indicate that the FADS1/FADS2 locus can be added to the growing list of loci involved in polygenic dyslipidemia in Asians. Furthermore, the variable effects of FADS1/FADS2 on plasma lipid profiles in Asians may result from differences in the dietary intake of polyunsaturated fatty acids, which serve as substrates for enzymes encoded by FADS1/FADS2.
    Human Genetics 04/2010; 127(6):685-90. · 4.52 Impact Factor
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    Yasuo Kagawa
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    ABSTRACT: ATP synthase (F(o)F(1)) consists of an ATP-driven motor (F(1)) and a H(+)-driven motor (F(o)), which rotate in opposite directions. F(o)F(1) reconstituted into a lipid membrane is capable of ATP synthesis driven by H(+) flux. As the basic structures of F(1) (alpha(3)beta(3)gammadeltaepsilon) and F(o) (ab(2)c(10)) are ubiquitous, stable thermophilic F(o)F(1) (TF(o)F(1)) has been used to elucidate molecular mechanisms, while human F(1)F(o) (HF(1)F(o)) has been used to study biomedical significance. Among F(1)s, only thermophilic F(1) (TF(1)) can be analyzed simultaneously by reconstitution, crystallography, mutagenesis and nanotechnology for torque-driven ATP synthesis using elastic coupling mechanisms. In contrast to the single operon of TF(o)F(1), HF(o)F(1) is encoded by both nuclear DNA with introns and mitochondrial DNA. The regulatory mechanism, tissue specificity and physiopathology of HF(o)F(1) were elucidated by proteomics, RNA interference, cytoplasts and transgenic mice. The ATP synthesized daily by HF(o)F(1) is in the order of tens of kilograms, and is primarily controlled by the brain in response to fluctuations in activity.
    Proceedings of the Japan Academy Ser B Physical and Biological Sciences 01/2010; 86(7):667-93. · 2.77 Impact Factor
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    ABSTRACT: The Republic of Palau belongs to Micronesia, and obese people and lifestyle-related diseases are prevalent there. We investigated the relationship of dietary habits and obesity to oxidative stress in Palauan people, as compared with those of Japanese and Mongolian people. A total of 126 healthy Palauan subjects were enrolled. Oxidative stress was evaluated by serum level of reactive oxygen metabolites (ROM). Antioxidant capacity was evaluated by serum level of biological antioxidant potential (BAP). In Palauan subjects, BMI> or =30 was observed in 45.0% of males and 59.1% of females (Japanese: males 1.3%, females 0.8%, Mongolian: males 6.3%, females 14.7%). Palauan subjects consumed 2553 kcal per day (Japanese 2121 kcal, Mongolians 2534 kcal). The ratios of carbohydrate energy to total energy were 59.8 % (Japanese 54.7 %, Mongolians 50.2%). The ratios of fat energy to total energy were 22.9% (Japanese 26.7%, Mongolians 34.5%). ROM levels in Palauan subjects showed higher than those in Japanese subjects, while BAP levels of Palauan subjects did not decrease compared to those of Japanese. ROM levels correlated with body fat ratio, and showed a reverse correlation with handgrip strength. Handgrip strength decreased in the subjects of more than forty years of age. These findings suggest that the obesity in Palauan people may have a connection with high intake of calories through carbohydrate eating rather than through fat eating. Their high oxidative stress may be induced by obesity, and contribute to an early decline of handgrip strength, ultimately in early aging.
    Current Aging Science 12/2009; 2(3):214-22.
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    ABSTRACT: Retinol-binding protein 4 (RBP4) is a recently identified adipokine that was involved in insulin resistance. RBP4 is predominantly expressed from the liver in normal metabolic state to transport retinoids throughout the body, but the exact physiological function and the regulatory mechanisms of adipocyte-derived RBP4 have not been revealed. We conducted the genetic analysis about metabolic parameters in Japanese and Mongolian; the minor allele carriers of regulatory single-nucleotide polymorphism (SNP -803G>A) showed significantly higher BMI in Japanese men (P = 0.009) and women (P = 0.017), and in Mongolian women (P = 0.009). Relative quantification of RBP4 transcripts in -803GA heterozygotes showed that the minor allele-linked haplotype-derived mRNA was significantly more abundant than the transcript from major allele. RBP4 promoter assay in 3T3L1 adipocytes revealed that the minor allele increased the promoter activity double to triple and the administration of 9-cis-retinoic acid (RA) and 8-bromo-cyclic adenosine monophosphate (8-Br-cAMP) enhanced the activity. Multiple alignment analysis of human, mouse, rat, and cattle RBP4 promoter suggested conserved seven transcription factor binding motifs. Electrophoretic mobility shift assay showed the -803G>A SNP modulate the affinity against unidentified DNA-binding factor, which was assumed to be a suppressive factor. These results collectively suggested that the minor allele of RBP4 regulatory SNP enhanced the expression in adipocytes, which may be associated with the adipogenesis.
    Obesity 10/2009; 18(5):1006-14. · 4.39 Impact Factor
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    ABSTRACT: Oxidative stress induces several diseases and early aging. Previously, we reported that Mongolians are exposed in high oxidative stress, which may cause their early aging. In this study, to know the reason of high oxidative stress, we measured hair metals. This investigation was performed in Murun city, in the northern area of this country, and 469 healthy subjects, ranging from 10 to 82 years of age, were randomly enrolled. Oxidative stress was evaluated by the levels of serum reactive oxygen metabolites (ROM), malondialdehyde-modified low-density lipoprotein (MDA-LDL) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). Antioxidant capacity (AOC) was estimated by the levels of biological antioxidant potential (BAP) and superoxide dismutase (SOD) activity. Scalp hair metals were measured using an inductively coupled plasma mass spectrometry method. Murun subjects showed high ROM levels of 394+/-75 Carr U (n=342), compared with Japanese healthy subjects (n=356, 326+/-51 Carr U, p<0.001). MDA-LDL and 8-OHdG levels also showed high levels. While, BAP levels of Murun subjects were 2263+/-203 micromol/L (n=210), Japanese subjects (n=356, 2087+/-215 micromol/L, p<0.001). SOD activities were also high, suggesting that the high oxidative may accelerate the state of AOC. Murun subjects demonstrated high accumulation of several metals in the hairs. In particular, Mn accumulation exhibited from 2 fold to 40 fold increases of Japanese standard. These findings are indicative that the high Mn accumulation may contribute to the high oxidative stress. The mechanism of its high accumulation was not explained by food materials or drinking water. We should further investigate another influence such as sandy wind. In order to suppress the high oxidative stress, elimination of the high Mn accumulation should be urgently studied.
    Current Aging Science 03/2009; 2(1):28-42.
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    ABSTRACT: In order to prevent Alzheimer disease (AD), relationship between single nucleotide polymorphisms (SNPs) of methylene tetrahydrofolate reductase (MTHFR) and folate-homocysteine metabolism was studied. Subjects were 10 males and 42 females (87.9 +/- 7.7 years old) in the special nursing homes for the elderly. Their average care level was 4.2 +/- 0.9, and average cognitive ability estimated by MMSE was 6.9 +/-7.3. Dietary intake was measured by weighing method. Concentrations of serum folate and total serum homocysteine (tHcy), and genetic polymorphisms were determined. The daily nutrient intake was as follows: total energy 2.7 kcal/kg; protein, 1.0 g/kg; folic acid, 7.3 microg/kg; vitamin B12, 0.11 microg/kg. Compared with control elderly persons, serum folate was very low (4.5 ng/ml, control = 10.1 ng/ml) and serum homocysteine was very high (21.4 micromol/L, control = 10.2 microg/L), despite having an adequate folate intake (342 microg/day, mainly polyglutamyl folate). The frequency of TT homozygote of MTHFR was higher (21.1%) in Alzheimer patients than that in control (15%). TT homozygotes showed the lowest serum folate (3.5 ng/ml, 35% of control), the highest serum homocysteine 25 micromol/L, 250% of control and the lowest MMSE score (5) among all the genotypes. The bioavailability of polyglutamyl folate may be impaired in the subjects, even when their total folate intake was sufficient. The early prevention of Alzheimer's disease by monoglutamyl folate intake (400 mcg per day) is recommended especially in TT homozygote of MTHFR.
    Asia-Pacific Journal of Public Health 11/2008; 20 Suppl:111-7. · 1.11 Impact Factor
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    ABSTRACT: In Asia-Pacific countries, both environmental modernization and hereditary traits of Mongoloid reported to cause rapid increase in lifestyle-related diseases (LRD). However, reproducibility of reported responsive-factors is low. To examine this, a decision-tree method of complexity-model was applied to select LRD-responsive-factors. Genomic DNA was collected from Asia-Pacific regions. Single nucleotide polymorphisms (SNPs) on genomic DNA were determined as hereditary-trait-factor. Three indices of LRD (BMI, body fat, and serum leptin levels) were classified according to published criteria. WEKA Machine-learning system was used as decision-tree software. Age was added as a factor with different dimension. Selected factors were validated by other statistical methods. In Thai-males, GLUT) (glucose-transporter 1)-SNP was most-responsive to body fat, followed by USF1-SNP (transcription-factor for lipid metabolism). Differences between genotypes were validated (P = .002 for GLUT1 by Levene's, P = .071 for USF1 by ANOVA). Responsive-factors of Thai-females, Palau-males and Palau-females, were consisted with SNPs and age, and varied by groups. Convincing responsive-factors were not selected from mixed-data. Decision-tree-analysis successfully selected the convincing results. Responsive-factors differed by ethnic group and gender.
    Asia-Pacific Journal of Public Health 11/2008; 20 Suppl:257-61. · 1.11 Impact Factor
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    ABSTRACT: An increase in prevalence of lifestyle related diseases becomes one of the main threats to human health in Asia-Pacific regions. Especially Pacific countries face the marked epidemic of obesity and related disorders. Understanding of the genetic basis for these diseases is awaited. We investigated frequencies of 106 single nucleotide polymorphisms (SNPs) in genes associated with lifestyle related diseases in 1,878 individuals from five Asia-Pacific countries including Japan, China, Mongolia, Thailand, and Palau. Population genetic analyses revealed that disease susceptible variants of SNPs in TRIB3, PTGS2, ADIPOR1, DGAT1, UCP2, FOXC2, and ESR1 were overrepresented in the Palau population in comparison with the Asian populations. These gene variants likely contribute to the high prevalence of obesity and related diseases in Pacific populations. The present results would be helpful in coping with the lifestyle related diseases and may provide a new insight into the human dispersal in Asia-Pacific regions.
    Asia-Pacific Journal of Public Health 11/2008; 20 Suppl:173-9. · 1.11 Impact Factor
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    ABSTRACT: This study describes the effect of gene polymorphisms on the metabolism of vitamin C. An oral loading of 1 mmol ascorbic acid (176 mg) or dehydroascorbic (174 mg) was given to 17 healthy females volunteers who had consumed a low vitamin C diet (vitamin C < 5 mg/day) for 3 days before loading. The urinary total vitamin C was determined. The urinary excretion of vitamin C (VC) was compared between ascorbic acid (AsA) and dehydroascorbic acid (DAsA), and the 24 hour total VC excretion was same. However gene polymorphisms of glutathione S-transferases P1 (GSTP1) showed the effect on that excretion. GSTP1 is one of xenobiotic enzymes in VC metabolism. The VC excretions in 24 hour after VC loading were greater (P < .01) in AA homozygotes of GSTP1 (46.7 +/- 18.1 mg) than GA heterozygotes (28.2 +/- 14.0 mg). On the single oral administration, the type of polymorphisms of GSTP1 has stronger effect on VC metabolism than the form of VC, DAsA and AsA. This study showed that determination of nutrient requirement needs to be considered with personal genotype.
    Asia-Pacific Journal of Public Health 10/2008; 20 Suppl:70-9. · 1.11 Impact Factor
  • Chisato Hirai, Yasuo Kagawa
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    ABSTRACT: Adiponectin (Ad) is reported to reduce insulin resistance in metabolic syndrome. The relation between the polymorphism of Ad (t45 g), biochemical indices including Ad and insulin concentrations, and food intake was examined, since the g/g homozygotes are known to be diabetes-prone. Subjects were 45 women (68.87 +/- 7.74 years old) who received preventive intervention in our nutrition clinic. Their food intake was estimated by the three day dietary record, and the blood was taken for genetic and biochemical analyses. Polymerase chain reaction and RFLP of Ad-DNA revealed the wild type (t/t = 51%), heterozygotes (t/g = 41%) and mutant homozygotes (g/g = 9%). Concentrations of total and high molecular weight Ad (12-18mers, HMW-Ad) were determined by ELISA. The project was approved by the ethics committee of our university and by the written agreement of the subject. Serum insulin concentration was negatively correlated with HMW-Ad (y = -0.802 + 11.7, P = .006), but not correlated with total Ad. HMW-Ad in the g/g homozygotes (1.18 +/- 1.28 microg/ml) was significantly (P = .024) lower than that in both wild type (t/t, 4.07 +/- 2.96 microg/ml) and heterozygotes (t/g, 2.23 +/- 1.90 microg/ml). The concentrations of fasting plasma glucose (average = 157.5 +/- 49.4 mg/dl) and HbAlc (average = 7.3 +/- 1.7%) in g/g were significantly (P < .001, in any combination) higher than those in both t/t and t/g. HMW-Ad were negatively correlated with intakes of both carbohydrate (group I food of Ministry of Health, Welfare and Labor) and sugar. The intakes of carbohydrate and sugar were not different among t/t, t/g and g/g groups. Although g/g homozygotes are diabetes prone, improvement of the insulin resistance by restricting the intakes of both carbohydrate-rich foods and cane sugar may be easier in g/g than in t/g and t/t.
    Asia-Pacific Journal of Public Health 10/2008; 20 Suppl:80-6. · 1.11 Impact Factor
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    ABSTRACT: We performed oral loading of AsA or DAsA (1 mmol) in subjects who had consumed a diet low in vitamin C (C) (C< or =5 mg/d) for 3 d before loading, and measured urinary and blood vitamin C. Since the crossover method was used, the same experiment was repeated after an interval of about 1 mo in each subject. The results of the experiment including a total of 17 subjects for 2005 and 2006, were as follows. (1) There were marked individual differences in urinary C excretion. (2) The C level in 24-h urine after C loading did not differ between the two orally administered C forms (AsA and DAsA). (3) C excretion between 0 and 3 h after C loading was significantly higher (p<0.05) for the DAsA group, while those between 3 and 6, 6 and 9, 9 and 12, and 12 and 24 h after C loading were significantly higher (p<0.05 or p<0.01) for the AsA group. (4) The blood C concentration and the increase in C 1 h after C loading were significantly higher (p<0.05 and p<0.01, respectively) in the DAsA than in the AsA group. (5) Evaluation of the association between C metabolism and the single nucleotide polymorphisms of glutathione S-transferase P (GSTP) 1-1 showed a lower urinary C excretion and a significantly lower C level in 24-h urine (p<0.05) after AsA loading, and a significantly lower urinary C excretion between 0 and 3 h after DAsA loading (p<0.05) for the GA heterozygotes than for the AA homozygotes. Considering the activity of C as DAsA in humans, based on urinary and blood C levels after a single loading of C, the utilization of DAsA is equivalent to that of AsA, although the metabolic turnover time is different. The involvement of polymorphisms in the xenobiotic metabolizing enzyme, GSTP1-1, in C metabolism, particularly urinary C excretion, was also clarified. This demonstrates the necessity of considering gene polymorphisms in determining individual C requirements. An abstract of this paper was reported by the Vitamin C Research Committee (Ochanomizu University) in 2007.
    Journal of Nutritional Science and Vitaminology 09/2008; 54(4):315-20. · 0.87 Impact Factor

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3k Citations
543.60 Total Impact Points


  • 2001–2012
    • Kagawa Nutrition University
      Sakado, Saitama, Japan
  • 1987–2012
    • Jichi Medical University
      • • Department of Human Genetics
      • • Department of Biochemistry
      • • Division of Pulmonary Medicine
      Totigi, Tochigi, Japan
  • 1996
    • Nippon Medical School
      • Nippon Medical School Hospital
      Tokyo, Tokyo-to, Japan
    • Toyota Physical and Chemical Institute
      Seto, Aichi, Japan
  • 1995
    • Osaka University
      • Institute for Protein Research
      Ōsaka-shi, Osaka-fu, Japan
  • 1993
    • University of Tsukuba
      • Institute of Basic Medical Sciences
      Tsukuba, Ibaraki-ken, Japan
  • 1992
    • Himeji Institute of Technology
      • Faculty of Science
      Himezi, Hyōgo, Japan
  • 1988–1991
    • The University of Tokyo
      • • Institute for Solid State Physics
      • • Department of Biophysics and Biochemistry
      Tokyo, Tokyo-to, Japan
  • 1989
    • Juntendo University
      • Department of Neurology
      Tokyo, Tokyo-to, Japan