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Noriyuki Fuku

Publications and source records attributed to Noriyuki Fuku.

14 recordsLinked to original sources
PubMed2025

Genome-Wide Association Study on Muscle Stiffness Identified Novel Locus for Predisposition to Muscle Strain Injury.

PURPOSE: We aimed to screen the entire genome for genetic variants associated with passive muscle stiffness, which has been suggested as a risk factor for muscle strain injury. METHODS: This genome-wide association study (GWAS) on passive muscle stiffness included 350 physically active young Japanese individuals. Three hamstring constituents were measured using ultrasound shear wave elastography. Skeletal muscle transcriptomes were compared across the genotypes of GWAS-identified variants in 48 healthy Japanese individuals. Association between GWAS-identified variants and history of muscle strain injury was examined in 1428 Japanese athletes. RESULTS: Two loci on chromosome 11 demonstrated a genome-wide significant association with passive muscle stiffness of the biceps femoris long head (rs12807854 T/C: P = 5.19 × 10 -10 , rs78405694 T/C: P = 2.09 × 10 -8 ; linear regression analysis adjusted for sex, age, and stretching exercise habits). Skeletal muscle RNA sequencing revealed significantly elevated expression of extracellular matrix-related genes in muscles carrying stiffness-increasing alleles of these variants. Among athletes, rs12807854 T/C was significantly associated with a history of muscle strain injury ( P = 0.0254; logistic regression analysis adjusted for age, sex, competitive level, and main sport). Carriers of the C allele, associated with increased muscle stiffness, exhibited a heightened risk of muscle strain injury (odds ratio = 1.62; 95% confidence interval = 1.06-2.47 per C allele increase). By contrast, rs78405694 did not show a significant association with muscle strain injury in this population. CONCLUSIONS: A novel locus associated with passive muscle stiffness and muscle strain injury was identified. Elucidating the detailed mechanisms linking the identified locus to passive muscle stiffness may lead to the development of new strategies to prevent muscle strain injuries.

Humans↗
PubMed2007

Effect of running training on DMH-induced aberrant crypt foci in rat colon.

PURPOSE: We examined the effects of treadmill-running training on the induction of aberrant crypt foci (ACF), which is the first step of colon cancer induction, in the colonic mucosa of rats injected with 1,2-dimethylhydrazine (DMH). METHODS: Four-week-old F344 rats (N = 38) were randomly assigned to training (19 rats) and control (19 rats) groups. After a week, all rats were given DMH (20 mg.kg(-1) body weight) once a week for 2 wk. Running training was started at age 7 wk (speed: 10 m.min(-1), 0% grade, 120 min.d(-1), 5 d.wk(-1)). After 4 wk of training, the rats were sacrificed and the colon was removed, opened, and counted for ACF with 0.2% methylene blue staining. RESULTS: Running training resulted in lower body- (P < 0.01) and adipose fat weight (P < 0.05). The numbers of ACF and total AC were significantly lower in the running training group than in the control group (P < 0.05). The occurrences of one, three, and five aberrant crypts per focus were also significantly lower in the running training group than in the control group (P < 0.05). The ratios of total AC/ACF did not significantly differ between the running training and control groups. CONCLUSIONS: The results of the present investigation suggest that low-intensity running training inhibits the DMH-induced initiation of colon ACF development.

Animals↗
PubMed2006

Mitochondrial haplogroup N9b is protective against myocardial infarction in Japanese males.

Superoxide, which mitochondria mainly produce in vascular endothelial cells, plays an important role in the pathogenesis of atherosclerosis and coronary artery disease. Accordingly, mitochondrial functional differences are thought to be one of the most important factors for the risk of myocardial infarction among various individuals. In the present study, we surveyed mitochondrial haplogroups associated with myocardial infarction in Japanese subjects. The study population comprised 2,137 unrelated Japanese individuals, including 1,181 subjects with a first myocardial infarction (920 males, 261 females) and the control subjects (522 males, 434 females). Twenty-eight mitochondrial single nucleotide polymorphisms of 12 major mitochondrial haplogroups (A, B, D4, D5, F, G1, G2, M7a, M7b, M7c, N9a, and N9b) were determined by use of 28-plex PCR and fluorescent beads combined with sequence-specific oligonucleotide probes. After adjustment for age, sex, body mass index, and prevalence of smoking, hypertension, hypercholesterolemia, and type 2 diabetes, a significantly (P = 0.0019) lower prevalence of haplogroup N9b was detected in subjects with myocardial infarction than in the controls. Especially, the prevalence of this haplogroup was significantly lower (P = 0.0007) in the male subjects with the disease than in the male controls. In contrast, there were trends towards higher prevalence of the disease in haplogroup G1 for males (P < 0.05). No significant haplogroup-related associations were detected for females. Our data suggest that haplogroup N9b confers resistance against myocardial infarction in Japanese males.

Adult↗
PubMed2006

Cooperative effects of isoflavones and exercise on bone and lipid metabolism in postmenopausal Japanese women: a randomized placebo-controlled trial.

Cooperative effects of isoflavones and exercise on bone and lipid metabolism have been exhibited in estrogen-deficient animals; however, results from clinical trials have not been published. In this study, we determined the effects of isoflavone intake and walking and their interaction on bone and lipid metabolism in postmenopausal women over 24 weeks. The bioavailability and metabolism of isoflavones (daidzein in particular) were also examined to clarify the mechanism of their bone-protective effects in humans. One hundred twenty-eight subjects were randomly assigned to 4 groups: placebo; placebo combined with walking (3 times per week); isoflavone intake (75 mg of isoflavones conjugates per day); and isoflavone combined with walking. The subjects were classified by equol status (producers or nonproducers) as identified using production of equol from daidzein in fecal culture. Bone mineral density (BMD), body composition, and serum concentrations of isoflavones were assessed. Serum high-density lipoprotein cholesterol concentration significantly increased (6.1%, P = .03), and fat mass in the whole body significantly decreased (-4.3%, P = .0003) from the baseline in the combined intervention group. There were no significant differences in BMD between baseline and postintervention in any of the treatment groups. However, the percent changes in BMD in equol producers were -0.53% and +0.13% in the sub-whole body and total hip, respectively. This was significantly different compared with -1.35 and -1.77 for the sub-whole body and total hip, respectively, in nonproducers in the isoflavone group (P = .049 and .040, respectively). The mean serum equol concentration was significantly higher in equol producers than in nonproducers in the isoflavone groups, but not in the placebo group. The combination of isoflavones and exercise exhibited favorable effects on serum lipid and body composition of postmenopausal women. The findings of this study suggest that the preventive effects of isoflavones on bone loss depend on the individual's intestinal flora for equol production.

Asian People↗
PubMed2006

Effects of isoflavone and exercise on BMD and fat mass in postmenopausal Japanese women: a 1-year randomized placebo-controlled trial.

UNLABELLED: The combined intervention of isoflavone intake and walking exercise over 1 year in postmenopausal Japanese women exhibited a trend for a greater effect on prevention of bone loss at the total hip and Ward's triangle regions. INTRODUCTION: The additive effects of isoflavones and exercise on bone and lipid metabolism have been shown in estrogen-deficient animals. In this study, we determined the effects of isoflavone intake, walking exercise, and their interaction on bone, fat mass, and lipid metabolism over 1 year in postmenopausal Japanese women. MATERIALS AND METHODS: A total of 136 postmenopausal women at <5 years after the onset of menopause were randomly assigned to four groups: (1) placebo, (2) walking (45 minutes/day, 3 days/week) with placebo, (3) isoflavone intake (75 mg of isoflavone conjugates/day), and (4) combination of isoflavone plus walking. BMD, fat mass, serum lipid, and serum and urinary isoflavone concentrations were assessed. RESULTS: A significant main effect of isoflavone on the reduction in trunk fat mass was obtained at 12 months. Significant main effects of walking on the reduction in fat mass in the whole body and the trunk were observed at 3, 6, and 12 months and that in the legs and arms at 6 and 12 months. Serum high-density lipoprotein (HDL)-cholesterol concentration significantly increased by 12 months after the walking and the combined intervention. After 12 months, a significant main effect of isoflavone on BMD was observed only at Ward's triangle. Walking prevented bone loss at the total hip and the Ward's triangle to significant degrees. The effect of the combined intervention on BMD at total hip and Ward's triangle regions was greater than that of either alone. No significant interaction was observed between isoflavone and walking in any measurements recorded during the study. CONCLUSIONS: Our study suggest that combined intervention of 75 mg/day of isoflavone intake and walking exercise 3 times/week for 1 year showed a trend for a greater effect on BMD at total hip and Ward's triangle regions than either alone. Intervention with isoflavone in postmenopausal Japanese women showed a modest effect on BMD compared with those in Westerners. Further studies over longer treatment duration that include assessment of BMD at various regions are necessary to ascertain the clinical significance of the combined intervention of isoflavone plus walking in postmenopausal women.

Adiposity↗
PubMed2005

Mitochondrial genome polymorphisms associated with type-2 diabetes or obesity.

Although a strong correlation between type-2 diabetes and obesity has been found, no comparative analysis between diabetes and obesity has been performed with respect to mitochondrial DNA (mtDNA) polymorphisms. To test the hypothesis that certain mitochondrial single nucleotide polymorphisms (mtSNPs) might be associated with obesity or type-2 diabetes, we determined the entire sequences of the mitochondrial genomes from 96 patients with type-2 diabetes and those from 96 young obese adults by direct sequencing and compared the frequencies of mtSNPs between these two groups. A mtSNP, 8684C > T (T53I) in the mitochondrial ATP synthase subunit 6 gene (ATP6), was detected in 5 of the 96 patients with type-2 diabetes, whereas this substitution was not detected in any of the 96 young obese adults. Two mtSNPs, 3497C > T (A64V) in NADH dehydrogenase subunit 1 gene (ND1) and 1119T > C (472U > C) in the 12S rRNA gene, were detected in 5 of the 96 young obese adults, whereas these substitutions were not detected in any of the 96 diabetic patients. The 8684C > T transition associated with type-2 diabetes represents haplogroup M8a, and the 3497C > T and 1119T > C transitions predisposing to obesity represent haplogroup B4c. These results suggest that distinct mtSNPs contribute to susceptibility to type-2 diabetes or obesity, pointing out the necessity of large-scale case control studies.

Adult↗
PubMed2004

Mitochondrial genome single nucleotide polymorphisms and their phenotypes in the Japanese.

Polymorphisms in the human mitochondrial genome have been used for the elucidation of phylogenetic relationships among various ethnic groups. Because analysis by mitochondrial genetics has detected pathogenic mutations causing mitochondrial encephalomyopathy or cardiomyopathy, most of the mitochondrial single nucleotide polymorphisms (mtSNPs) found in control subjects have been regarded as merely normal variants. However, we cannot exclude the possibility that the mitochondrial functional differences among individuals are ascribable at least in part to the mtSNPs of each individual. Human lifespan in ancient history was much shorter than that at the present time. Therefore, it is reasonable to speculate that certain mtSNPs that predispose one toward susceptibility to adult- or elderly-onset diseases, such as Parkinson's disease and Alzheimer's disease, have never been a target for natural selection in the past. Similarly, thrifty mtSNPs that had been advantageous for survival under severe famine or cold climate conditions might turn out to be related to satiation-related diseases, such as diabetes mellitus and obesity. To examine these hypotheses, we have constructed a mtSNP database by sequencing the entire mitochondrial genomes of 672 subjects: 96 in each of seven groups (i.e., centenarians, young obese or non-obese subjects, diabetic patients with or without major vascular involvement, patients with Parkinson's disease, and those with Alzheimer's disease).

Brain↗
PubMed2004

Mitochondrial genome variation in eastern Asia and the peopling of Japan.

To construct an East Asia mitochondrial DNA (mtDNA) phylogeny, we sequenced the complete mitochondrial genomes of 672 Japanese individuals (http://www.giib.or.jp/mtsnp/index_e.html). This allowed us to perform a phylogenetic analysis with a pool of 942 Asiatic sequences. New clades and subclades emerged from the Japanese data. On the basis of this unequivocal phylogeny, we classified 4713 Asian partial mitochondrial sequences, with <10% ambiguity. Applying population and phylogeographic methods, we used these sequences to shed light on the controversial issue of the peopling of Japan. Population-based comparisons confirmed that present-day Japanese have their closest genetic affinity to northern Asian populations, especially to Koreans, which finding is congruent with the proposed Continental gene flow to Japan after the Yayoi period. This phylogeographic approach unraveled a high degree of differentiation in Paleolithic Japanese. Ancient southern and northern migrations were detected based on the existence of basic M and N lineages in Ryukyuans and Ainu. Direct connections with Tibet, parallel to those found for the Y-chromosome, were also apparent. Furthermore, the highest diversity found in Japan for some derived clades suggests that Japan could be included in an area of migratory expansion to Continental Asia. All the theories that have been proposed up to now to explain the peopling of Japan seem insufficient to accommodate fully this complex picture.

DNA, Mitochondrial↗
PubMed2002

Golden mean to longevity: rareness of mitochondrial cytochrome b variants in centenarians but not in patients with Parkinson's disease.

To test the hypothesis that centenarians are free from deleterious mitochondrial variations, we analyzed amino acid variations in the cytochrome b molecule of 64 Japanese centenarians. Although the frequencies of some variations, such as N260D and G251S, differed significantly between centenarians and patients with Parkinson's disease, the most striking feature of centenarian cytochrome b was the rareness of amino acid variations in contrast to the variety of amino acid replacements in patients with Parkinson's disease. These results suggest that centenarians are genetically hitting the "golden mean" (less variation from the consensus cytochrome b sequence or less mismatch with other subunits). A multiplex detection system for various deleterious variations in combination with genetic tests for longevity-associated genotypes will be necessary to predict longevity or age-related diseases.

Adult↗
PubMed2002

Mitochondrial ATPase subunit 6 and cytochrome B gene polymorphisms in young obese adults.

We hypothesized that the mutational strand asymmetry is more strongly exerted upon the mitochondrial cytochrome b (Cytb) gene, which is distant from the origin of the light-strand replication (Ori(L)), than upon the ATPase subunit 6 (ATP6) gene, which is close to the Ori(L). To test this hypothesis, we determined the sequences of these two genes in 96 Japanese young obese adults. The frequency of G-->A transitions was significantly higher than that of C-->T transitions in the Cytb gene, whereas the frequencies of G-->A and C-->T transitions were not significantly different in the ATP6 gene. The marked mutational strand asymmetry in the Cytb gene can be explained by the deamination of C to uracil in the long single-stranded state of the heavy strand during replication. The ratio of the nonsynonymous substitutions at the second codon positions to those at the first codon positions was significantly lower in the Cytb gene than in the ATP6 gene. The physicochemical differences between the standard and the replaced amino acid residues were significantly smaller in the Cytb gene than in ATP6 one. The present study indicates that amino acid sequences are less variable for Cytb than for ATP6 in spite of the strong mutational strand asymmetry for the Cytb gene.

Adenosine Triphosphatases↗
PubMed2002

Gene therapy for mitochondrial disease by delivering restriction endonuclease SmaI into mitochondria.

The restriction endonuclease SmaI has been used for the diagnosis of neurogenic muscle weakness, ataxia and retinitis pigmentosa disease or Leigh's disease, caused by the Mt8993T-->G mutation which results in a Leu156Arg replacement that blocks proton translocation activity of subunit a of F(0)F(1)-ATPase. Our ultimate goal is to apply SmaI to gene therapy for this disease, because the mutant mitochondrial DNA (mtDNA) coexists with the wild-type mtDNA (heteroplasmy), and because only the mutant mtDNA, but not the wild-type mtDNA, is selectively restricted by the enzyme. For this purpose, we transiently expressed the SmaI gene fused to a mitochondrial targeting sequence in cybrids carrying the mutant mtDNA. Here, we demonstrate that mitochondria targeted by the SmaI enzyme showed specific elimination of the mutant mtDNA. This elimination was followed with repopulation by the wild-type mtDNA, resulting in restoration of both the normal intracellular ATP level and normal mitochondrial membrane potential. Furthermore, in vivo electroporation of the plasmids expressing mitochondrion-targeted EcoRI induced a decrease in cytochrome c oxidase activity in hamster skeletal muscles while causing no degenerative changes in nuclei. Delivery of restriction enzymes into mitochondria is a novel strategy for gene therapy of a special form of mitochondrial diseases.

Apoptosis↗