Masako Sei

Spontaneous activity, sleep, and body temperature in rats lacking the CCK-A receptor.

Because of a genetic mutation, the Otsuka-Long-Evans-Tokushima Fatty (OLETF) rat, a model for human non-insulin-dependent diabetes mellitus (NIDDM), shows no expression of the CCK-A receptor gene. We investigated the spontaneous physical activity, sleep, and body temperature in young OLETF rats that had not yet developed diabetes mellitus, and compared these data with age-matched control LETO (non-diabetic strain, Long-Evans-Tokushima-Otsuka) rats. The amount of large movements during the dark phase for the OLETF rats was significantly less than that of control rats. Thus, the amounts of total daily large movement and the ratio of dark-to-light phase movement in the OLETF rats were less than those of control rats, although the amount of small movement was similar for both groups. The diurnal rhythm of body temperature was similar for both groups. In addition, the amount of and circadian rhythm for each vigilance state and slow-wave activity were similar for the two groups. This study demonstrates that the CCK-A receptor might play a role in affecting the level of motor activity, adding hyperphagia, and the circadian rhythm of large movement in these rats prior to the manifestation of NIDDM. In contrast, a CCK-A receptor deficiency does not appear to affect sleep or body temperature in these rats.

Proteasome Subunits mRNA Expressions Correlate With Male BMI: Implications for a Role in Obesity

Obesity as well as its associated chronic diseases and adverse health consequences such as type 2 diabetes mellitus, dyslipidemia, hypertension, and coronary artery disease are afflicting middle‐aged adults and an ever greater number of children globally. We planned to investigate new obesity‐related factors using proteomics approaches in a randomly selected three high and three low BMI samples of Epstein‐Barr‐transformed B (EBV‐B) lymphoblastoid cell lines prepared from two groups of young Japanese men with different BMI. To search novel obesity‐related factors, comparisons of protein expressions between high and low BMI groups were carried out by two‐dimensional gel electrophoresis (2‐DE). Gene transcripts of proteasome subunits found out from 2‐DE were further determined by quantitative real‐time PCR. Results from proteomics approach showed that the expression of proteasome α subunit type 5 (PSMA5) was significantly lower in the high BMI male group than in those with low BMI (P < 0.05). To validate these results, we expanded the study to include 20 more men and used real‐time PCR to quantify the mRNA expression level in their EBV‐B cells. Both PSMA5 and PSMA2 of EBV‐B cells showed negative correlation with BMI. Furthermore, the mRNA levels measured in the peripheral blood B lymphocytes for many proteasome subunits in 75 healthy men and women showed significant negative correlation with BMI in healthy men. Our findings suggest that proteasome expression may play a key role in obesity.

Cardiomegaly in the juvenile visceral steatosis (JVS) mouse is reduced with acute elevation of heart short-chain acyl-carnitine level after l-carnitine injection

The long‐term administration of l‐carnitine was very effective in preventing cardiomegaly in juvenile visceral steatosis (JVS) mice, which was confirmed by heart weight as well as the lipid contents in heart tissue. After i.p. injection of l‐carnitine, the concentration of free carnitine in heart remained constant, although serum free carnitine level increased up to 80‐fold. On the other hand, a significant increase in short‐chain acyl‐carnitine level in heart was observed. These results suggest that increased levels of short‐chain acyl‐carnitine, not free carnitine, might be a key compound in the protective effect of l‐carnitine administration in JVS mice.

Proteasome activity correlates with male BMI and contributes to the differentiation of adipocyte in hADSC

We have previously reported that 26S proteasome subunit mRNA expressions correlate with male body mass index (BMI). In this study, to investigate whether proteasome activities are correlated with BMI, we recruited 61 healthy young Japanese male subjects, measured proteasome activities in their plasma, and correlated them with their BMI and various metabolic factors. We found that among three different proteasome activities, chymotrypsin-like activity in plasma was positively correlated with BMI in healthy Japanese male subjects. Furthermore, we analyzed proteasome activity in vitro during the differentiation of human adipose-derived stem cell (hADSC) into mature adipocytes. In the early stage of differentiation, proteasome activity was at its highest level, and proteasome inhibitor could inhibit hADSC adipocyte differentiation. Our findings suggest that proteasome is an important controlling factor for the development of obesity and adipogenesis.

Proteasome subunits are regulated and expressed in comparable concentrations as a functional cluster

The proteasome is the main proteolytic enzyme that functions in the ubiquitin-proteasome system. The 26S proteasome has multi-subunit protease complexes consisting of 20S subunits composed of four seven-numbered rings with two outer rings containing alpha subunits and two central rings composed of beta subunits, and 19S caps of 6 ATPase and 11 non-ATPase subunits; however, it is unclear how these subunits are regulated and the 26S proteasomes assembled. To verify whether each subunits mRNA expression is associated with the mRNA expression of other proteasome subunits, we carried out expression analysis of 34 proteasome subunits mRNA on peripheral blood from 75 subjects. The expression of proteasome subunits mRNA was comparable in each individual of the studied population and the mRNA expression has been investigated in each 20S or 19S proteasome. Our results suggest that each type of subunit is regulated by respectively common factors, and that the 20S and 19S proteasomes are regulated by different systems.

Prevalence of metabolic complications in children with severe obesity.

Background: The purpose of the present paper was to clarify the prevalence of metabolic complications in severely obese children.

Association of estrogen receptor alpha gene polymorphisms and lifestyle factors with calcaneal quantitative ultrasound and osteoporosis in postmenopausal Vietnamese women

AbtractGenetic and lifestyle factors are important in the pathogenesis of osteoporosis. We investigated the relationships of PvuII and XbaI polymorphisms of the estrogen receptor alpha (ER-α) gene, lifestyle factors with speed of sound at the calcaneus (calcaneal SOS) and osteoporosis in a population-based study of 140 healthy postmenopausal women. By an analysis of covariates, women with higher copies of P or X alleles had higher calcaneal SOS compared with others (P=0.012, PP vs. pp; P=0.045, Xx vs. xx). Women with lower copies of px or higher copies of PX haplotypes had higher calcaneal SOS compared with others (P=0.021, 0 px vs. 2 px; P=0.011, 1 PX vs. 0 PX). The px and PX haplotypes, age and years since menopause were found to be independent predictors of calcaneal SOS in multiple linear regression models. Using logistic regression, we found an increased osteoporosis risk with evidence for a px haplotype dose effect (OR=2.82, 95% CI=1.50-5.31, P=0.001) and for a PX haplotype dose effect (OR=0.42, 95% CI=0.19−0.93, P=0.033). An increased educational level was associated with a reduced risk of osteoporosis (P=0.035 in the model with px, P=0.044 in the model with PX). In conclusion, the present study suggests that PvuII and XbaI polymorphims of the ER-α gene, age, years since menopause and educational level are associated with bone density, as assessed by calcaneal SOS, and osteoporosis in postmenopausal Vietnamese women.

Climatic influence on the reproductive characteristics of Japanese males

We previously performed a survey of the sperm characteristics of the partners of pregnant women in four cities in Japan. In the present study, we analyzed the sperm characteristics of these subjects and the correlations between these sperm characteristics and climatic changes or Y chromosome haplogroups. Our results showed that more haplogroup D2a1 males than O2b1 males were born in the first half of the year (January to June), whereas more O2b1 males were born in the last half of the year (July to December) (P<0.05). This was agreed and correlated with the seasonal variations in their mean sperm concentrations. The haplogroup C, D* and D2a1 males displayed lower sperm concentrations from March to May, followed by an increase in their sperm concentrations starting in June or July, while the O2b1 males displayed higher sperm concentrations in the first half of the year followed by a sudden decrease from July to August (P<0.05). We hypothesize that the Japanese climate has different effects on the sperm characteristics and reproductive seasonality of males from different lineages; and therefore, has influenced the modern population of Japan.

Circulating leptin did not associate with the development of the hyperglycemia accompanied by insulin insensitivity in spontaneous noninsulin dependent diabetes mellitus model Otsuka–Long–Evans–Tokushima–Fatty rats

Leptin, the product of the ob gene, has been reported to regulate feeding behavior and energy metabolism. Plasma leptin concentration was strongly correlated with body fat content in humans. It is well known that increased body fat content is accompanied by insulin insensitivity. In order to study the relationship between serum leptin level and metabolic variables, we performed caloric restriction on Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats, a model of noninsulin dependent diabetes mellitus. The male OLETF rats were allocated at random to three groups: 100% group, and 85% and 70% groups (which consumed 85% and 70% of the amount of food consumed by the 100% group, respectively). A significant correlation between serum leptin level and the body fat content, body weight, triglyceride, and fasting plasma glucose was observed. Using a partial correlation analysis to control for body fat content, however, the correlation between serum leptin and these variables disappeared. No significant changes in serum leptin levels were observed before and after a 1 h hyperinsulinemic euglycemic clamp test. In conclusion, serum leptin was significantly correlated with body fat content rather than fasting plasma glucose, serum insulin and insulin sensitivity. This suggests that circulating leptin per se may not result in hyperinsulinemia and insulin insensitivity in the OLETF rat.

Impact of annual body mass index gain on obesity development in Japanese 6-year-old non-obese children

Effective timing of preventive intervention for adolescent obesity in non‐obese school‐aged children remains unclear. The aim of this study was to examine the impact of annual body mass index (BMI) gain on the development of adolescent obesity in 6‐year‐old non‐obese Japanese children.