Positive natural selection of TRIB2, a novel gene that influences visceral fat accumulation, in East Asia.

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.

Investigation of Maternal Diet and FADS1 Polymorphism Associated with Long-Chain Polyunsaturated Fatty Acid Compositions in Human Milk.

Increasing the amount of long-chain polyunsaturated fatty acids (LCPUFA) in human milk is an important strategy for infant growth and development. We investigated the associations of LCPUFA compositions in human milk with maternal diet (especially fish and shellfish intake), with fatty acid Δ5 desaturase gene (FADS1) polymorphisms, and with gene-diet interactions. The present study was performed as part of an adjunct study of the Japan Environment and Children's Study. The participants were 304 lactating females, who provided human milk 6−7 months after delivery. Fatty acids in human milk were analyzed by gas chromatography, and dietary surveys were conducted using a brief self-administered diet history questionnaire. We also analyzed a single nucleotide polymorphism of FADS1 (rs174547, T/C). There was a significant difference in arachidonic acid (ARA) composition in human milk among the genotype groups, and the values were decreasing in the order of TT > TC > CC. The concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were also different between TT and CC genotype, indicating a tendency for decreasing values in the same order. The composition of ARA showed significant gene−dietary interactions in multiple regression analysis, and the positive correlation between fish and shellfish intake and ARA composition in human milk was significant only in the CC genotype. Moreover, the factor most strongly associated with EPA and DHA composition in human milk was fish and shellfish intake. Therefore, it was suggested that increasing fish and shellfish intake in mothers may increase EPA and DHA composition in human milk, while increasing fish and shellfish intake in CC genotype mothers may lead to increased ARA composition in human milk.

High prevalence of an anti-hypertriglyceridemic variant of the MLXIPL gene in Central Asia.

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.

A single nucleotide polymorphism in the FADS1/FADS2 gene is associated with plasma lipid profiles in two genetically similar Asian ethnic groups with distinctive differences in lifestyle.

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.

Associations of erythrocyte fatty acid compositions with FADS1 gene polymorphism in Japanese mothers and infants.

Long-chain polyunsaturated fatty acids (LC-PUFAs) are involved in the fetal growth in utero, and are essential for the development of visual and cognitive functions during infancy. The purpose of this study was to examine the associations of erythrocyte fatty acid compositions with FADS1 gene polymorphism in Japanese mothers and infants. The subjects were 383 mothers who participated in an adjunct birth cohort study of the Japan Environment and Children's Study (JECS). In maternal FADS1 SNP genotypes, the precursor fatty acids composition of the Δ5 desaturase in the maternal blood showed significant differences in levels among the groups, and showed increasing values in the order of TT < TC < CC genotype groups. On the other hand, many product fatty acids levels were significantly reduced in the order of TT > TC > CC genotype groups, and DHA levels were significantly lower in the CC genotype group relative to the other groups. Likewise, the relationship between fetal genotype group and fatty acid composition in cord blood was very similar to the maternal relationship. These results indicate the maternal and fetal blood fatty acid compositions are strongly influenced by the FADS1 genotypes. With respect to the cord blood DHA composition, the levels in the fetal CC genotype group showed a trend toward lower values in the maternal CC genotype group pair (p = 0.066) compared to the maternal TC genotype group pair. However, in the fetal TT and TC genotype groups (p = 0.131, p = 0.729, respectively), the maternal genotype did not have a significant effect. The DHA composition was more influenced by the maternal genotype in the fetal CC genotype group than in the fetal TT and TC genotype groups. It was shown that DHA transport via the placenta from the mother might be promoted in the fetal CC genotype compared to the other fetal genotype groups. In conclusion, differences in the FADS1 SNP genotypes of pregnant women and their children may greatly affect the supply of LC-PUFAs. Further studies on the involvement of the FADS1 polymorphisms and the fetal LC-PUFA levels in the fetal growth and development are warranted.

Vitamin C activity of dehydroascorbic acid in humans--association between changes in the blood vitamin C concentration or urinary excretion after oral loading.

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.

Genetic polymorphisms of xenobiotic enzymes affect human vitamin C excretion.

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.

Comparative study of polymorphisms on genes associated with lifestyle related diseases in Asian and Pacific populations.

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.

Diversity in genes responsible for lifestyle-related diseases in Asia-Pacific region.

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.

Polymorphism of glutathione S-transferase P1 gene affects human vitamin C metabolism.

There are large inter-individual differences in the metabolism of vitamin C (VC), which is composed of both ascorbic acid (AsA) and dehydroascorbic acid (DAsA). AsA is oxidized to DAsA in a series of xenobiotic reactions. Thus, the effects of polymorphism A313G (Ile105Val) in the gene for glutathione S-transferases P1 (GSTP1), one of the most active xenobiotic enzymes, on human VC metabolism were studied. The variant frequency of GSTP1 among the present subjects (n=210) was AA 71.0%; GA 27.0% and GG 1.9%. At 24 h after administration of 1 mmol of VC to young women (n=17; age, 21.0+/-1.1 y), total VC excretion (46.7+/-18.1mg) by AA homozygotes of GSTP1 was greater (p<0.0069) than that (28.2+/-14.0 mg) by GA heterozygotes. One hour after administration of VC, blood total VC levels were also significantly different (p<0.0036) between the homozygotes and heterozygotes. The effects of other polymorphisms in xenobiotic enzymes on VC metabolism were small.

An intronic variable number of tandem repeat polymorphisms of the cold-induced autoinflammatory syndrome 1 (CIAS1) gene modifies gene expression and is associated with essential hypertension.

Cold-induced autoinflammatory syndrome 1 (CIAS1) gene is a member of the NALP subfamily of the CATERPILLER protein family that is expressed predominantly in peripheral blood leukocytes, which is to regulate apoptosis or inflammation through the activation of NF-kappaB and caspase. Recent genetic analyses suggested an association between inflammation and oxidative stress-related genes in the development of hypertension. This is the first genetic study indicating an association between the CIAS1 gene and susceptibility to essential hypertension (EH). The frequency of subject with the homozygote of 12 repeat allele was significantly higher in patients with hypertension compared with control subjects (987 cases, 924 controls) (P=0.030; odds ratio=1.24) at a novel VNTR polymorphism of CIAS1 intron 4 loci. We also found that the mean of systolic blood pressure of homozygotes of 12 repeat allele was 6.4 mmHg higher than those of homozygotes of non-12 repeat allele in male random population (P=0.009). The frequency of six SNPs spanning of the CIAS1 gene was not significantly between patients and controls. The real-time PCR analysis showed that among healthy young adults, 12-12 subjects expressed CIAS1 mRNA in peripheral leukocytes significantly more abundantly than homozygote of non-12 repeat alleles subjects (P<0.05). Reporter gene assay of the CIAS1-VNTR in HL60 stimulated by lipopolysaccharides showed that the intronic sequence involving 12 repeat increased the expression of luciferase compared with 9, 7, and 6 repeats. Thus, we propose here the CIAS1 is associated with EH through the dominant expression of transcripts, which may depend on the CIAS1-VNTR genotype.

Functional human NAIP promoter transcription regulatory elements for the NAIP and PsiNAIP genes.

Neuronal apoptosis inhibitory protein (NAIP) has been shown to inhibit apoptosis in vitro and in vivo with an expression which is regulated in a variety of cells and tissues and may be modulated by a variety of external stimuli. To understand the molecular basis of the transcriptional regulation of the NAIP gene, we have analyzed the 5'-flanking region and transcription of the human NAIP gene. The functional promoter and silencer elements were identified by luciferase reporter constructs in transient transfection experiments using four different human cells. Although the location of the functional elements were shared among the different cells used, the activities for the NAIP promoter varied. Further, cell type-specific protein binding activities were observed by an electrophoretic mobility shift assay (EMSA). EMSA analysis with specific antibodies and DNA sequence analysis identified the POU domain transcription factor Brn-2 as a candidate transcriptional regulator of the NAIP gene. The DNA sequence of the promoter region of the PsiNAIP gene, a copy gene for NAIP, was nearly identical to that of the NAIP gene, indicating a common regulatory mechanism for transcription of the NAIP and PsiNAIP genes. Indeed, the transcript of the PsiNAIP gene was identified. These results provided the first evidence for the functional promoter and candidate transcriptional factor for the NAIP gene and transcription of the PsiNAIP gene.

A dopamine D4 receptor antagonist attenuates ischemia-induced neuronal cell damage via upregulation of neuronal apoptosis inhibitory protein.

Neuronal apoptosis inhibitory protein (NAIP/BIRC1), the inhibitor of apoptosis protein (IAP) family member, suppresses neuronal cell death induced by a variety of insults, including cell death from ischemia and stroke. The goal of the present study was to develop an efficient method for identification of compounds with the ability to upregulate endogenous NAIP and to determine the effects on these compounds on the cellular response to ischemia. A novel NAIP-enzyme-linked immunosorbent assay (ELISA)-based in vitro drug-screening system is established. Use of this system identified an antagonist of dopamine D4 receptor, termed L-745,870, with a potent NAIP upregulatory effect. L-745,870-mediated NAIP upregulation in neuronal and nonneuronal cultured cells resulted in decreased vulnerability to oxidative stress-induced apoptosis. Reducing NAIP expression via RNA interference techniques resulted in prevention of L-745,870-mediated protection from oxidative stress. Further, systemic administration of L-745,870 attenuated ischemia-induced damage of the hippocampal CA1 neurons and upregulated NAIP expression in the rescued hippocampal CA1 neurons in a gerbil model. These data suggest that the NAIP upregulating compound, L-745,870, has therapeutic potential in acute ischemic disorders and that our NAIP-ELISA-based drug screening may facilitate the discovery of novel neuroprotective compounds.

ALS2CL, the novel protein highly homologous to the carboxy-terminal half of ALS2, binds to Rab5 and modulates endosome dynamics.

ALS2, the causative gene product for juvenile recessive amyotrophic lateral sclerosis (ALS2), is a guanine-nucleotide exchange factor for the small GTPase Rab5. Here, we report a novel ALS2 homologous gene, ALS2 C-terminal like (ALS2CL), which encodes a 108-kD ALS2CL protein. ALS2CL exhibited a specific but a relatively weak Rab5-GEF activity with accompanying rather strong Rab5-binding properties. In HeLa cells, co-expression of ALS2CL and Rab5A resulted in a unique tubulation phenotype of endosome compartments with significant colocalization of ALS2CL and Rab5A. These results suggest that ALS2CL is a novel factor modulating the Rab5-mediated endosome dynamics in the cells.

Comparison of electrocardiogram findings and lifestyles between urbanized people and ger-living people in Ulaanbaatar, Mongolia.

In Ulaanbaatar, lifestyles differ between urbanized people (group A) and ger (tent)-living people (group B). Group A earn high annual incomes and live in houses or apartments. Group B (who had moved to Ulaanbaatar from nomadic areas) earn low incomes and live in narrow gers. In 2002, we investigated daily food intake, health status, and electrocardiogram (ECG) in these groups. In total, 256 subjects (group A, 142; group B, 114) were enrolled. Group A ate meat, vegetables, and fruits high enough by a Western style. Group B consumed meat but ate only small amounts of vegetables and fruits. They took a lot of fat, however, the serum lipid levels of them were not so high. The fat source as energy was plant oil for cooking rather than meat. Several abnormal ECG findings including left ventricular hypertrophy (LVH) were found in 32 (22.5%) of group A and 50 (43.9%) of group B (P < 0.001). LVH was also found more in group B than in group A. LVH in group A males was accompanied by high body weight (BW), hypertension, and high LDL-cholesterol, whereas LVH in group B males seemed to be related to an unbalanced diet, high salt intake, smoking, and some low socio-economic problems. In order to promote health condition, such risk factors should securely be eliminated from the lifestyles.

Single-nucleotide polymorphisms in uncoding regions of ALS2 gene of Japanese patients with autosomal-recessive amyotrophic lateral sclerosis.

ALS2 is an autosomal recessive form of amyotrophic lateral sclerosis (AR-ALS) with juvenile onset, and has been mostly found in North African and Middle Eastern countries. Deletion mutations in the coding exons of a new gene ALS2, encoding a protein with guanine-nucleotide exchange factor (GEF) domains, have recently been identified in ALS2 patients. These mutations are predicted to cause a loss of protein function, indicating that ALS2 is the causative gene underlying ALS2. To examine whether ALS2 is mutated in Japanese ALS patients sharing some characteristics of ALS2, we analyzed ALS2 gene from three patients with AR-ALS. While no deletion mutation was detected in the coding regions of ALS2 gene, several single-nucleotide polymorphisms (SNPs) that have been found in healthy controls as well as in Tunisian ALS2 patients were found mostly in intronic regions of the gene. These results suggest that deletion mutations in ALS2 gene detected in ALS2 patients seem to be uncommon in Japanese AR-ALS, and that SNPs in uncoding regions might possibly be relevant to predisposition to ALS.

Polymorphism, heteroplasmy, mitochondrial fusion and diabetes.

Mitochondrial DNA (mtDNA) is highly susceptible to mutations that result in polymorphisms and diseases including diabetes. We analyzed heteroplasmy, polymorphisms related to diabetes, and complementation by fusogenic proteins. Cytoplast fusion and microinjection allow, defects in mutated mtDNA inside a heteroplasmic cell to be complemented by fusing two mitochondria via human fusogenic proteins. We characterized three hfzos as well as two OPAls that prevent apoptosis. Two coiled coil domains and GTPase domains in these fusogenic proteins regulate membrane fusion. The hfzo genes were expressed mainly in the brain and in muscle that are postmitotic, but not in the pancreas. Under the influence of polymorphisms of mtDNA and nDNA, the vicious circle of reactive oxygen species and mutations in cell can be alleviated by mitochondrial fusion.

Prevalence of diego blood group Dia antigen in Mongolians: comparison with that in Japanese.

The Diego blood group is composed of Di(a) and Di(b) antigens. Prevalence of the Di(a) antigen is known to be different among races. The Di(a) antigen is generally found in Oriental people. Thus, it is called a Mongoloid factor. In Japanese, the prevalence of this antigen is 8.78%. However, the prevalence in Mongolians had not previously been examined. In September of 2002, we determined this antigen among inhabitants of Ulaanbaatar. It was found in 24 of 242 subjects (9.92%). This prevalence approximates that in Japanese. The Rh blood group phenotypes also showed patterns similar to those in Japanese. These results are not contrary to the presumption that Mongolians and Japanese may have a common racial background.

A novel acylaminoimidazole derivative, WN1316, alleviates disease progression via suppression of glial inflammation in ALS mouse model.

Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron degenerative disease. Given that oxidative stress and resulting chronic neuronal inflammation are thought to be central pathogenic, anti-oxidative agents and modulators of neuronal inflammation could be potential therapies for ALS. We report here that the novel small molecular compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) selectively suppresses oxidative stress-induced cell death and neuronal inflammation in the late-stage ALS mice. WN1316 has high blood-brain-barrier permeability and water solubility, and boosts both neuronal apoptosis inhibitory protein (NAIP) and NF-E2-related factor 2 (Nrf2) which governed glutathione (GSH)-related anti-oxidation pathway protecting motor neurons against oxidative injuries. Post-onset oral administration of low dose (1-100 µg/kg/day) WN1316 in ALS(SOD1(H46R)) and ALS(SOD1(G93A)) mice resulted in sustained improved motor function and post onset survival rate. Immunohistochemical analysis revealed less DNA oxidative damage and motor neuronal inflammation as well as repression of both microgliosis and astrocytosis, concomitant down regulation of interleukin-1ß and inducible nitric oxide synthase, and preservation of the motoneurons in anterior horn of lumbar spinal cord and skeletal muscle (quadriceps femoris). Thus, WN1316 would be a novel therapeutic agent for ALS.

[Impact of visceral fat measurements and a weight loss support web system on visceral fat loss in a workplace setting: insights from a JVALUE2 (Japanese study of visceral adiposity and lifestyle information; utilization and evaluation)].

OBJECTIVES: Providing different programs of occupational health services in the same company is difficult. We report the results of a parallel randomized trial for the employees of our company for visceral fat measurements and the effect of a weight loss support web system. MATERIALS AND METHODS: 181 healthy employees with BMI over 23 who volunteered to participate in this study. In a parallel randomized study, we divided them into 3 groups (A, health guidance by occupational health staff with visceral fat measurements and a weight loss support web system; B, health guidance by occupational health staff with a weight loss support web system; C, without health guidance (control)) by date of birth. To assess the effects of guidance and support, we compared each group's waist circumference (WC), weight, and BMI, before and after the guidance. We also conducted questionnaire surveys of eating behavior and life activities before and after the guidance to estimate the relationship between the intervention method used for each group and their behavioral modification. RESULTS: 150 employees (83%) finished this program. Within 3 months, reduction in the outcome measures was largest in group A, and showed significant differences from the other two groups. For many employees in group A, eating behavior factors improved markedly; however, in the control group, there were no changes in eating behavior or daily living activities. CONCLUSIONS: A parallel randomized trial involving the employees of our company was performed and we scientifically verified the effects of an occupational health programs. Objective study of occupational health activities and measures were enabled by devising methods and procedures, e.g., applying the waiting-list method for the control group. This approach will lead to appropriate selection and precise implementation of evidence-based measures in occupational health in the future.