Cross-Sectional Inverse Association of Regular Soy Intake with Insulin Resistance in Japanese Elderly.

Levels of isoflavones, biomarkers of soy intake, in 24-hour urine (24U) were inversely related to coronary heart disease (CHD) mortality in the World Health Organization's Cardiovascular Disease and Alimentary Comparison Study. Considering 24 U isoflavone levels were highest and CHD mortality was lowest in the Japanese, who maintained the world's longest life expectancy, the association of regular soy intake with cardiometabolic risk was investigated in Japanese adults (20-49 years old) and elderly (50-79 years old). In multivariate analysis adjusted for age, sex, and drug treatments, mean 24 U isoflavone excretion was significantly inversely associated with insulin resistance in the elderly and significantly associated with blood folate and potassium in the elderly, but also positively associated with 24 U salt in the elderly. These findings indicate that low-salt soy should be recommended to improve glucose metabolism in elderly Japanese.

Association of genetic variants for susceptibility to obesity with type 2 diabetes in Japanese individuals.

AIMS/HYPOTHESIS: In populations of East Asian descent, we performed a replication study of loci previously identified in populations of European descent as being associated with obesity measures such as BMI and type 2 diabetes. METHODS: We genotyped 14 single nucleotide polymorphisms (SNPs) from 13 candidate loci that had previously been identified by genome-wide association meta-analyses for obesity measures in Europeans. Genotyping was done in 18,264 participants from two general Japanese populations. For SNPs showing an obesity association in Japanese individuals, we further examined diabetes associations in up to 6,781 cases and 7,307 controls from a subset of the original, as well as from additional populations. RESULTS: Significant obesity associations (p < 0.1 two-tailed, concordant direction with previous reports) were replicated for 11 SNPs from the following ten loci in Japanese participants: SEC16B, TMEM18, GNPDA2, BDNF, MTCH2, BCDIN3D-FAIM2, SH2B1-ATP2A1, FTO, MC4R and KCTD15. The strongest effect was observed at TMEM18 rs4854344 (p = 7.1 × 10(-7) for BMI). Among the 11 SNPs showing significant obesity association, six were also associated with diabetes (OR 1.05-1.17; p = 0.04-2.4 × 10(-7)) after adjustment for BMI in the Japanese. When meta-analysed with data from the previous reports, the BMI-adjusted diabetes association was found to be highly significant for the FTO locus in East Asians (OR 1.13; 95% CI 1.09-1.18; p = 7.8 × 10(-10)) with substantial inter-ethnic heterogeneity (p = 0.003). CONCLUSIONS/INTERPRETATION: We confirmed that ten candidate loci are associated with obesity measures in the general Japanese populations. Six (of ten) loci exert diabetogenic effects in the Japanese, although relatively modest in size, and independently of increased adiposity.

Neuronal vulnerability of stroke-prone spontaneously hypertensive rats to ischemia and its prevention with antioxidants such as vitamin E.

Stroke-prone spontaneously hypertensive rats (SHRSP/Izm) develop severe hypertension, and more than 95% of them die of cerebral stroke. Hypoxic stimulation followed by oxygen reperfusion induces neuronal damage in both normotensive Wistar Kyoto/Izm (WKY/Izm) and SHRSP/Izm rats, and the percentage of neurons that undergo apoptosis during hypoxia-reperfusion is markedly higher in SHRSP/Izm rats than in WKY/Izm rats. The biochemical characteristics of the SHRSP/Izm rats, unlike those of WKY/Izm rats, might act as a factor in the stroke proneness of SHRSP/Izm rats. In the hippocampus, the formation of hydroxyl radicals and the cerebral blood flow-independent formation of nitric oxide (NO) were strongly increased after reperfusion in SHRSP/Izm rats, and the neuronal expression of the thioredoxin and Bcl-2 genes was significantly decreased in the SHRSP/Izm rats compared with the WKY/Izm rats. On the other hand, the effects of antioxidants against neuronal death associated with cerebral ischemia-reperfusion were stronger in the SHRSP/Izm rats, in which the addition of vitamin E or ebselen almost completely inhibited neuronal death. Namely, the addition of 100 microg/ml of vitamin E under hypoxia/reoxygenation (H/R) conditions completely inhibited WKY and SHRSP/Izm neuronal death. Vitamin E exerts a marked inhibitory effect against neuronal damage via its incorporation into mitochondrial membranes, where it captures reactive oxygen and free radicals. The susceptibility of neurons to apoptosis in SHRSP/Izm rats is partly due to an insufficiency of mitochondrial redox regulation and apoptosis-inhibitory proteins. In this review, we describe the neuronal vulnerability of SHRSP/Izm rats induced by cerebral ischemia and the effects of antioxidants such as vitamin E.

Common variants at the GCK, GCKR, G6PC2-ABCB11 and MTNR1B loci are associated with fasting glucose in two Asian populations.

AIMS/HYPOTHESIS: To test fasting glucose association at four loci recently identified or verified by genome-wide association (GWA) studies of European populations, we performed a replication study in two Asian populations. METHODS: We genotyped five common variants previously reported in Europeans: rs1799884 (GCK), rs780094 (GCKR), rs560887 (G6PC2-ABCB11) and both rs1387153 and rs10830963 (MTNR1B) in the general Japanese (n = 4,813) and Sri Lankan (n = 2,319) populations. To identify novel variants, we further examined genetic associations near each locus by using GWA scan data on 776 non-diabetic Japanese samples. RESULTS: Fasting glucose association was replicated for the five single nucleotide polymorphisms (SNPs) at p < 0.05 (one-tailed test) in South Asians (Sri Lankan) as well as in East Asians (Japanese). In fine-mapping by GWA scan data, we identified in the G6PC2-ABCB11 region a novel SNP, rs3755157, with significant association in Japanese (p = 2.6 x 10(-8)) and Sri Lankan (p = 0.001) populations. The strength of association was more prominent at rs3755157 than that of the original SNP rs560887, with allelic heterogeneity detected between the SNPs. On analysing the cumulative effect of associated SNPs, we found the per-allele gradients (beta = 0.055 and 0.069 mmol/l in Japanese and Sri Lankans, respectively) to be almost equivalent to those reported in Europeans. CONCLUSIONS/INTERPRETATION: Fasting glucose association at four tested loci was proven to be replicable across ethnic groups. Despite this overall consistency, ethnic diversity in the pattern and strength of linkage disequilibrium certainly exists and can help to appreciably reduce potential causal variants after GWA studies.

Pontine hypoplasia in children with periventricular leukomalacia.

BACKGROUND AND PURPOSE: The brain stem in patients with periventricular leukomalacia (PVL) appears smaller than normal on MR imaging, but few reports have described this feature, and the number of patients has been relatively small. The present study was conducted to examine the hypothesis that the pons in patients with PVL is smaller than normal. MATERIALS AND METHODS: Using MR imaging, we examined 80 children (43 boys and 37 girls) with PVL and 80 age-matched control children (41 boys and 39 girls). The control children were diagnosed as neurologically and developmentally normal by pediatric neurologists and also showed normal MR imaging findings. MR imaging was performed at a corrected age range of 0-5 years in both groups. We measured the anteroposterior diameter of the whole pons, the tegmentum and the basis, and the corpus callosal length by using midline T1-weighted sagittal images and compared each parameter between the PVL groups and the control groups. RESULTS: Pontine diameters in all of the regions were significantly smaller in the PVL group than in the control group (mean +/- SD, whole pontine diameters, 1.66 +/- 0.21 and 1.87 +/- 0.23 cm [P < .001]; basis diameters, 0.42 +/- 0.10 and 0.51 +/- 0.14 [P < .001]; tegmentum diameters, 1.23 +/- 0.20 and 1.36 +/- 0.19 [P < .001], respectively). The respective corpus callosal lengths were 5.02 +/- 0.90 and 5.51 +/- 0.76 (P < .001). There was no significant difference in the basis/tegmentum ratio between the PVL group and the control group. When the age-related pontine diameter differences were examined, there was already a significant difference at 0 years of age between the 2 groups. There was a significant correlation between whole pontine diameter and corpus callosal length in the PVL group (correlation coefficient, 0.52; P < .001) and the control group (correlation coefficient, 0.63; P < .001). CONCLUSION: We have proven that pontine diameter in patients with PVL is significantly smaller than that in normal control subjects, including each diameter of basis and tegmentum.

Dietary habits, plasma polyunsaturated fatty acids and selected coronary disease risk factors in Tanzania.

OBJECTIVES: To compare dietary habits and percent compositions of omega (omega)-3 fatty acid (FA) in plasma phospholipids and to examine if there is any association between fish intake and selected coronary disease risk (CHD) factors in this population. DESIGN: Cross sectional population study. SETTING: Three areas in Tanzania: urban Dar es Salaam (D), rural Handeni (H) and pastoralist population of Maasai in Moduli (Mo). SUBJECTS: One hundred and five participants (Dar 36, Handeni 37 and Monduli 32) aged 47-57 years. MAIN OUTCOME MEASURES: Fatty acids composition in plasma phospholipids. RESULTS: The frequency of intake of fish, meat, coconut milk and fruits was higher in Dar than in Handeni or Monduli (all p< 0.0001). The Maasai from Monduli had the highest percentage consumption of milk in a week (p<0.0001) and lowest intake of fish (p<0.0001). Participants from Handeni had the highest prevalence of consumption of green vegetables (p<0.0001). Percent compositions of arachidonic acid (AA; C20: 4omega-6) and docosahexaenoic acid (DHA; C22: 6omega-3) in plasma phospholipids were the lowest in Monduli (p<0.0001). Selected coronary disease risk factors were higher in the urban area Dar. The frequency of intake of fish per week correlated negatively with total cholesterol (TC) and LDL-C and HBA1c percent but not with blood pressure. The percent composition of omega-3 FA in plasma phospholipids was positively correlated with the frequency of intake of fish a week. CONCLUSION: Our results indicate that, there are significant differences in dietary patterns among the three study areas, and that the intake of fish is inversely associated with selected risk factors for coronary heart disease.

Impact of diet on the cardiovascular risk profile of Japanese immigrants living in Brazil: contributions of World Health Organization CARDIAC and MONALISA studies.

1. Japanese immigrants from Okinawa living in Brazil have a higher mortality from cardiovascular diseases and have their mean life expectancy shortened compared with their counterparts living in Japan. 2. A cross-sectional study comparing Okinawans living in Okinawa (OO) and Okinawan immigrants living in Brazil (OB) was designed to characterize the dietary factors that could interfere with the profile of cardiovascular risk factors and with this reduction on the life expectancy when Okinawans emigrate to Brazil. 3. In total, 234 OO and 160 OB (aged 45-59 years) were recruited to the present study to undergo medical and dietary history, blood pressure measurement, electrocardiograph (ECG), blood tests and 24 h food/urine collection. 4. In the present study, OO subjects presented with 37% less obesity and 50% less systemic hypertension than OB. The OB subjects used threefold more antihypertensive medication than OO. Meat intake was 34% higher in OB than OO, whereas fish intake was sevenfold higher in OO than OB. Serum potassium levels were 10% higher in OO than OB. Urinary taurine (an index of seafood intake) was 43% higher in OO than OB. Urinary isoflavones (an index of the intake of soy products) were significantly lower in OB than in OO. Of acid (20:5) and docosahexaenoic acid (22:6) were two- and threefold higher in OO than OB, respectively. 5. The rate of ischaemic ECG changes in OO subjects was only 50% of that of OB subjects. 6. There were no differences in the smoking rate between OO and OB subjects. 7. The results of the present study suggest that coronary risk factors and cardiovascular health are not only regulated by genetic factors, but that the impact of lifestyle (mainly diet) can be large enough to modulate the expression of genes.

Can foods with added soya-protein or fish-oil reduce risk factors for coronary disease? A factorial randomised controlled trial.

BACKGROUND AND AIMS: To develop functional foods which are capable of reducing key risk factors for coronary heart disease in an at risk population. The specific hypothesis tested here was that providing bread, cracker biscuits and snack bars fortified with DHA (long-chain omega 3) and soya-protein would havd a positive impact on cholesterol and blood pressure. METHODS AND RESULTS: A pragmatic, double-blind, factorial placebo-controlled randomised trial recruiting 213 middle-aged men and women with untreated elevated total cholesterol or blood pressure. The factors examined were the effect of giving supplies of bread, cereal bars and cracker biscuits fortified with 2 g fish oils (DHA, 22: 6n-3), or 25 g soya-protein (containing 50 mg of isoflavonoids) for five weeks. Primary and secondary outcomes included total, low-density and high-density cholesterol (HDL-C), and systolic and diastolic blood pressure. Compliance was assessed using biomarkers and food intake histories. DHA enriched foods increased HDL-C by 6.0% (95% CI 2.5%, 9.6%) but had no effect on total or low-density cholesterol or blood pressure. Overall, soya-protein did not influence any of the outcomes assessed. However, in women only, soya-protein increased systolic blood pressure by 5.9% (95% CI 1.73, 9.9%). CONCLUSIONS: Adding DHA (fish-oils) to staple foods might supplement existing methods to help reduce CVD morbidity and mortality. However, these findings highlight the importance of ensuring that functional foods do not present any harms to particular subgroups within a general population, if they are to be made freely available to consumers. This latter point requires further attention by the research community in relation to soya-protein.

Determinants of hyperleptinaemia in an African population.

OBJECTIVE: To examine the determinants for elevated plasma leptin concentration in normal weight (NW), obese (OB), and morbidly obese (MO) individuals in Tanzania. DESIGN: Cross-sectional epidemiological study, the CARDIAC study. SETTING: Three areas in Tanzania; Dar es Salaam, urban (U), Handeni, rural (R) and Monduli, pastoralists (P), in August 1998. SUBJECTS: Five hundred and forty five participants from a random sample of 600 people aged 46-58 years. MAIN OUTCOME MEASURES: Plasma leptin concentrations, height, weight, body mass index (BMI), lipid profiles, haemoglobin A1c (HBA1c), and blood pressure (BP). RESULTS: Plasma leptin concentrations were higher in women than in men (women; 16.0 ng/mL, men; 3.1 ng/mL; p<0.0001). Women showed a higher mean body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) than men. In both genders, plasma leptin concentration, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), systolic BP (SBP) and diastolic BP (DBP) were significantly higher in OB than in NW participants. MO women had significantly higher leptin concentration, SBP and DBP compared with the other two groups. In NW men, log leptin concentrations showed a direct correlation with weight, BMI, HBA1c, TC, LDL-C, TG, SBP and DBP (all p<0.0001 except TG; p<0.001), while among NW women and OB men, weight and BMI correlated positively with log leptin (all p<0.05). OB women observed a positive correlation between log leptin and weight, BMI and LDL-C. Regression analysis indicated that among NW subjects, gender, BMI and TC explained 53.9% of the variation in log leptin. In OB subjects, gender, BMI and LDL-C explained 51.7% of the variability in leptin levels. No relationship was found between log leptin and CVD risk factors among MO subjects. CONCLUSION: The most important determinants for hyperleptinaemia in NW participants were gender, BMI, TC, while in addition to these LDL-C, was an important determinant of leptin concentration in OB individuals. In MO women, the high leptin concentrations did not reflect the amount of adipose stores.

Polyunsaturated fatty acids induce tight junctions to form in brain capillary endothelial cells.

Tight junctions create a rate-limiting barrier to the diffusion of solutes between vertebrate epithelial cells and endothelial cells. They are also controlled within individual cells by a variety of physiologically relevant signals. We investigated the effects of polyunsaturated fatty acids on the formation of tight junctions in brain capillary endothelial cells, monitoring the transepithelial electrical resistance, and analyzed the expression of occludin messenger RNA. Brain-capillary endothelial cells were grown to confluence on filters and exposed to eicosapentaenoic acids, gamma linolenic acid and linoleic acid. Transepithelial electrical resistance was determined with voltage-measuring electrodes. The messenger RNA expression of occludin was quantitated by real-time quantitative reverse transcriptase-polymerase chain reaction. The basal resistance across monolayers of porcine brain capillary endothelial cells was 83+/-8.1 Omega cm(2). Cells cultured in eicosapentaenoic acids and gamma linolenic acid, but not linolenic acid, displayed a 2.7-fold increase in transepithelial electrical resistance at 10 microM in brain capillary endothelial cells. The expression level of occludin messenger RNA increased markedly immediately after the exposure to eicosapentaenoic acids or gamma linolenic acid. Following an 8 h exposure to exogenous eicosapentaenoic acids or gamma linolenic acid, occludin messenger RNA levels were significantly increased. In addition, the rise in transepithelial electrical resistance induced by eicosapentaenoic acids and gamma linolenic acid was markedly inhibited by the tyrosine kinase inhibitors genistein and PP2 and protein kinase C inhibitor, calphostin C. In contrast, the rise in transepithelial electrical resistance induced by eicosapentaenoic acids and gamma linolenic acid was not inhibited by the PI 3-kinase inhibitor, LY294002. We conclude that eicosapentaenoic acids and gamma linolenic acid increased the transepithelial electrical resistance and the expression of occludin messenger RNA in brain capillary endothelial cells. This gamma linolenic acid and eicosapentaenoic acid induced assembly of tight junction is likely to be regulated by protein kinase C and tyrosine kinase activity.

Obesity and lipid profiles in middle aged men and women in Tanzania.

OBJECTIVE: To examine the relationship between obesity and lipid profiles and to compare the effects of total obesity and central adiposity on lipids in three locations in Tanzania. DESIGN: Cross-sectional epidemiological study. SETTING: Three areas in Tanzania: Dar es Salaam (urban), Handeni (rural) and Monduli (pastoralists), in August 1998. SUBJECTS: Five hundred and forty five men and women from a random sample of 600 people aged 46-58 years. MAIN OUTCOME MEASURES: Mean BMI, waist circumference, WHR, TC, HDL-C, LDL-C, TG and LDL/HDL ratio. Prevalence rates of overweight,obesity, central obesity and dyslipidaemia. RESULTS: As compared to men, women had higher BMI (24.7 versus 22.5 kg/m2, p<0.0001), waist circumference (92.4 versus 89.1 cm, p<0.05), TC (4.9 versus 4.2 mmol/L, p<0.0001) and LDL-C (3.3 versus 2.6 mmol/L, p<0.0001). The urban population demonstrated higher levels of lipid factors than the rural population (TC, men 4.8 mmol/L; women 5.3 mmol/L, p<0.0001; TG, men 3.6 mmol/L; women 3.7 mmol/L, p<0.0001, LDL-C, men 2.8 mmol/L, p<0.0001). BMI and waist circumference correlated positively with serum TC, TG, and LDL-C in both genders. Stepwise regression analysis showed that BMI predicted triglyceride concentration in men (p<0.05) and women (p<0.0001). Waist circumference predicted levels of TC in women only (p<0.0001) and of LDL-C in both genders (men p<0.05, women p<0.0001). The prevalence of overweight, obesity and central obesity were significantly higher in urban than in rural areas in both men and women. Compared to lean subjects, obese men and women had significantly higher mean serum TC, TG, LDL-C and a higher prevalence of dyslipidaemia. The mean levels of TC, TG and LDL cholesterol increased across successive increases in BMI and waist circumference quintiles in both genders. CONCLUSION: Subjects from the urban area had greater lipid abnormalities related to obesity than those from the rural area and that, central adiposity had a greater effect on total cholesterol and LDL cholesterol among women than was BMI.

Tissue distribution of a major mevalonate pyrophosphate decarboxylase in rats.

The 45- and 35-kDa subunits of mevalonate pyrophosphate decarboxylase (MPD) have been purified from rat liver. In this study, we examined the relationship between 45- and 35-kDa MPD and the tissue distribution of a major MPD in rat liver. When the crude extract of rat liver fed on normal chow was subjected to immunoblot analysis using anti-rat 45-kDa MPD antibody, only the 45-kDa band was detected. In a pulse-chase experiment using anti-rat 45-kDa MPD antibody, there was no precursor-product relationship between the 45- and the 35-kDa MPD. In immunoprecipitation, more than 85% of MPD activity in the rat liver was depleted from the crude extract with an excess of the above antibody. When 45-kDa MPD contents in tissues were analyzed by immunoblotting, a single protein band with an apparent molecular weight of 45 kDa was detected in all tissues. The specific protein content of 45-kDa MPD in liver was markedly higher than in other tissues. The activity/amount ratio varied among brain, liver, and testis, being significantly highest in the liver. From these data, it is suggested that 45-kDa MPD serves as a major enzyme involved in cholesterol biosynthesis in rat liver and that a tissue-specific regulator or isozyme of 45-kDa MPD is present in rat liver.

Mevalonate pyrophosphate decarboxylase is predominantly located in the cytosol of rat hepatocytes.

Mevalonate pyrophosphate decarboxylase (MPD) is found in the 100000 x g supernatant fraction of cells or tissues and is considered to be a cytosolic protein. Recently, other groups reported that MPD is mostly located in the peroxisomes. In this study, we used two different methods to determine whether MPD is predominantly located in the peroxisomes or the cytosol of rat hepatocytes. 1) In permeabilized rat hepatocytes or normal rat kidney cells treated with digitonin, which lack cytosolic enzyme, MPD was mainly present in the medium. 2) Double immunofluorescent labeling of cells with both anti-MPD antibody and anti-hexokinase antibody yielded an immunofluorescent pattern for both enzymes typical of the cytosolic protein. These results indicate that MPD is predominantly located in the cytosol of rat hepatocytes.

Implications from and for food cultures for cardiovascular diseases: Japanese food, particularly Okinawan diets.

Okinawans, who have a different ethnicity and food cultural history to other Japanese nationals, and an exceptional longevity have been studied at home and as migrant groups in Hawaii and Brazil. Biomarkers for fish and soy intake and intervention studies indicate that these foods, along with seaweed and green vegetables are candidates for chronic non-communicable disease prevention.

Okinawa: an exception to the social gradient of life expectancy in Japan.

This paper examines why the social gradient of life expectancy does not apply in Japan when Okinawa is considered. The social gradient thesis links differences in longevity to social rank, with people and populations in higher status hierarchical positions having lower mortality and longer life expectancies than those beneath them in the social scale. Japan has been cited as a major example of this thesis in that Japanese life expectancy improved dramatically as Japan rose to the top echelon of nations in economic rank in the late 20th century. Thus it follows that Japan's most affluent and leading prefectures should be the major catalysts behind the nation's rise in life expectancy as well to the number one position in the world. However, this is not the case as life expectancy in Okinawa, Japan's poorest prefecture, exceeds that of Japan as a whole. We find that the social gradient of life expectancy does not apply at the prefectural level and question its validity for geographical areas. We suggest that healthy lifestyles, especially diet and the social support of family and friends, are more important than sense of hierarchy for longevity in Okinawa.

Evaluation of selected polymorphisms of the Mendelian hypertensive disease genes in the Japanese population.

It remains to be defined whether molecular variants of the genes underlying Mendelian forms of hypertension play some etiological role in essential hypertension. To pursue this issue, we focused on the following three genes: the epithelial sodium channel (ENaC), 11beta-hydroxysteroid dehydrogenase type 2, and mineralocorticoid receptor genes. Five sequence variations of these genes, which were either previously reported to show significant association with hypertension or identified as "mild" molecular variants, were chosen for our study. Each variation was screened in 247 severe hypertensive patients with early onset (<45 years) and any detectable variations were subsequently characterized in 291 older normotensive subjects (>60 years) for the case-control comparison. We also investigated the significance of association between the tested variants and biochemical parameters reflecting sodium-water homeostasis, such as plasma aldosterone concentration (PAC) and renin activity (PRA). Only the T663A variant (alpha-subunit of ENaC) turned out to be polymorphic in the Japanese population. In disagreement with positive associations previously reported in white and black subjects, we observed no significant association between T663A and hypertension, while allele frequencies of A663 were higher in Japanese (58-64%) compared with a reported prevalence of 29% in whites and 15% in blacks. T663A showed a borderline association (p=0.02) with the PAC/PRA ratio but not with PAC or PRA in the multivariate analysis. Our data did not support the association between Mendelian disease gene variants and essential hypertension in the Japanese. However, the present study did not definitively resolve this issue and further investigation is certainly warranted.

Up-regulation of uncoupling protein 3 gene expression by fatty acids and agonists for PPARs in L6 myotubes.

Uncoupling protein 3 (UCP3), which uncouples electron transport from ATP synthesis, is expressed at high levels in the skeletal muscle, an important organ in glucose and lipid metabolism. Because several reports proposed that fatty acids induced UCP3 gene expression in skeletal muscle in vivo, in the present study we examined the regulation of UCP3 gene expression by various fatty acids using L6 myotubes. UCP3 gene expression was increased in L6 myotubes by various fatty acids or by alpha-bromopalmitate, a nonmetabolized derivative of palmitic acid. Because fatty acids are also known as agonists for PPARs, we examined the involvement of PPARs in the regulation of the UCP3 gene expression. L-165041, a PPAR delta agonist, increased UCP3 gene expression in L6 myotubes, whereas neither Wy 14,643, a PPAR alpha agonist, nor Pioglitazone, a PPAR gamma agonist, increased it. Therefore, we conclude that UCP3 gene expression is increased by the activation of PPAR delta in L6 myotubes and postulate that PPAR delta mediates at least some part of the increased UCP3 gene expression by fatty acids in skeletal muscle in vivo.

Distribution of twenty-four hour urinary taurine excretion and association with ischemic heart disease mortality in 24 populations of 16 countries: results from the WHO-CARDIAC study.

There is considerable interest in the association between taurine (2-aminoethanesufonic acid) and risk of ischemic heart disease (IHD), but little information has been made available on the distribution of taurine in populations around the world. The present study aimed to describe the differences in taurine excretion levels and their associations with IHD mortality rates in 24 populations in 16 countries worldwide. This was a multicenter cross-sectional study. In each center, 100 men and 100 women aged 48-56 years were selected randomly from the local populations. Twenty-four hour urinary taurine excretion was measured using an amino acid analyzer (Hitachi 835, Ibaragi, Japan). Age-adjusted IHD mortality rates in the relevant populations were calculated using the direct standard method. The results indicated that (a) percentiles 25%, 50% and 75% of the distributions of 24-h taurine excretion showed large variations in the study populations. Median values of taurine ranged from 191.6 micromol/day (St John, Canada) to 2,180.6 micromol/day (Beppu, Japan) in males, and from 127.5 micromol/day (Moscow, Russia) to 1,590.0 micromol/day (Beppu, Japan) in females. The highest overall median value of taurine was found in the Japanese population samples, followed by the Chinese samples (Shanghai and Taiwan). European, North American and oceanic Caucasians, however, had much lower median values of taurine, except in the cases of the samples from France and Spain. (b) Median values of taurine were significantly associated negatively with age-adjusted IHD mortality rates across the 24 study population samples in men (R2=0.42, p<0.01), and in women (R2=0.55, p<0.01). These negative associations remained significant after adjustment for serum total cholesterol, body mass index and urinary sodium to potassium ratios. In conclusion, the study provides, for the first time, a cross-sectional database on distribution of 24-h urinary taurine excretion in 24 population samples worldwide. A strong and inverse association between population levels of taurine excretion and IHD mortality was observed.