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H Masuzaki

Publications and source records attributed to H Masuzaki.

At least 19 recordsLinked to original sources
PubMed2001

Decreased triglyceride-rich lipoproteins in transgenic skinny mice overexpressing leptin.

Leptin is an adipocyte-derived circulating satiety factor with a variety of biological effects. Evidence has accumulated suggesting that leptin may modulate glucose and lipid metabolism. In the present study, we examined lipid metabolism in transgenic skinny mice with elevated plasma leptin concentrations. The plasma concentrations of triglycerides and free fatty acids in transgenic skinny mice were 71.5 (P < 0.01) and 89.1% (P < 0.05) of those in their nontransgenic littermates, respectively. Separation of plasma into lipoprotein classes by ultracentrifugation revealed that very low density lipoprotein-triglyceride concentrations were markedly reduced in transgenic skinny mice relative to the controls. The clearance of triglycerides estimated by a fat-loading test was enhanced in transgenic skinny mice; the triglyceride concentration in transgenic skinny mice 3 h after fat loading was 39.7% (P < 0.05) of that of their nontransgenic littermates. Postheparin plasma lipoprotein lipase activity increased 1.4-fold (P < 0.05) in transgenic skinny mice. Our data demonstrated a significant reduction in plasma triglyceride concentrations, accompanied by increased lipoprotein lipase activity in transgenic skinny mice overexpressing leptin, suggesting that leptin plays a role in long-term triglyceride metabolism.

Animals↗
PubMed2001

Troglitazone induces GLUT4 translocation in L6 myotubes.

A number of studies have demonstrated that insulin resistance in the skeletal muscle plays a pivotal role in the insulin resistance associated with obesity and type 2 diabetes. A decrease in GLUT4 translocation from the intracellular pool to the plasma membranes in skeletal muscles has been implicated as a possible cause of insulin resistance. Herein, we examined the effects of an insulin-sensitizing drug, troglitazone (TGZ), on glucose uptake and the translocation of GLUT4 in L6 myotubes. The prolonged exposure (24 h) of L6 myotubes to TGZ (10(-5) mol/l) caused a substantial increase in the 2-deoxy-[3H]D-glucose (2-DG) uptake without changing the total amount of the glucose transporters GLUT4, GLUT1, and GLUT3. The TGZ-induced 2-DG uptake was completely abolished by cytochalasin-B (10 micromol/l). The ability of TGZ to translocate GLUT4 from light microsomes to the crude plasma membranes was greater than that of insulin. Both cycloheximide treatment (3.5 x 10(-6) mol/l) and the removal of TGZ by washing reversed the 2-DG uptake to the basal level. Moreover, insulin did not enhance the TGZ-induced 2-DG uptake additively. The TGZ-induced 2-DG uptake was only partially reversed by wortmannin to 80%, and TGZ did not change the expression and the phosphorylation of protein kinase B; the expression of protein kinase C (PKC)-lambda, PKC-beta2, and PKC-zeta; or 5'AMP-activated protein kinase activity. a-Tocopherol, which has a molecular structure similar to that of TGZ, did not increase 2-DG uptake. We conclude that the glucose transport in L6 myotubes exposed to TGZ for 24 h is the result of an increased translocation of GLUT4. The present results imply that the effects of troglitazone on GLUT4 translocation may include a new mechanism for improving glucose transport in skeletal muscle.

Animals↗
PubMed2000

Disruption of klotho gene causes an abnormal energy homeostasis in mice.

klotho mice, which genetically lack klotho gene expression, are characterized with various systemic phenotypes resembling human aging, and also with growth retardation. Here we show that klotho mice have a barely detectable amount of the white adipose tissue but their brown adipose tissue (BAT) is comparably preserved. Glucose tolerance and insulin sensitivity in klotho mice are increased compared to those in wild-type mice as revealed by intraperitoneal glucose and insulin tolerance tests. Uncoupling protein-1 gene expression of BAT and body temperature in klotho mice are lower than those in wild-type mice, suggesting that klotho mice have less energy expenditure than wild-type mice. Histological examination suggests that klotho mice possess less energy storage than wild-type mice with respect to glycogen in the liver and lipid in BAT. All these changes of parameters for energy homeostasis in klotho mice are very similar to those reported under food-restricted conditions. However, the amount of food intake is not different between klotho and wild-type mice when normalized for body weight. The present study elucidates the importance of klotho gene expression for the maintenance of normal energy homeostasis.

Adipose Tissue↗
PubMed2000

The novel gene, gamma2-COP (COPG2), in the 7q32 imprinted domain escapes genomic imprinting.

The gene MEST (or PEG1) on chromosome 7q32 is paternally expressed in human fetal tissues as a result of genomic imprinting. Since some imprinted genes are clustered, we speculated that an imprinted gene cluster might exist at 7q32. We have sought to isolate additional human genes close to MEST and to characterize their allelic expression patterns. Here, we report the biallelic expression of the gene, gamma2-COP (coatomer protein complex, subunit gamma 2, HUGO-approved symbol COPG2), and monoallelic expression of the transcript, CIT1, which is located in intron 20 of gamma2-COP. Recently, gamma2-COP was reported to be a novel imprinted gene that overlaps the 3'-untranslated region (3'-UTR) of MEST in a tail-to-tail orientation. However, our results revealed biallelic expression in all fetal tissues and adult blood lymphocytes. On the other hand, CIT1 was an antisense transcript of gamma2-COP intron 20 and was expressed from the paternal allele in all fetal tissues examined. Adult blood lymphocytes showed biallelic expression. We identified additional MEST 3'-UTR sequence, which overlaps the last four exons and introns of gamma2-COP. This additional MEST 3'-UTR may complicate analysis of gamma2-COP imprinting. Our data indicate that the region containing MEST at 7q32 is an imprinted domain, but gamma2-COP adjacent to MEST escapes genomic imprinting.

3' Untranslated Regions↗
PubMed2000

High concentrations of serum inhibin in pre-eclampsia.

OBJECTIVE: To evaluate maternal serum immunoreactive inhibin (ir-inhibin) concentrations in women with pre-eclampsia, and assess the correlation between serum ir-inhibin and HCG. METHODS: The subjects comprised 28 pregnant women with suspected intrauterine growth retardation (IUGR) during the third trimester. Serum concentrations of ir-inhibin and HCG were measured in 13 women with pre-eclampsia and 15 pregnant women as control subjects. Serum ir-inhibin was determined by a double antibody radioimmunoassay, and HCG by a solid-phase immunoradiometric assay. RESULTS: There were no significant differences in maternal characteristics between the pre-eclamptic group and control group. The pre-eclamptic group had significantly higher concentrations of serum ir-inhibin and HCG compared with the control group. The serum concentrations of ir-inhibin correlated positively with those of HCG. CONCLUSION: The pre-eclamptic patients displayed high serum levels of ir-inhibin and HCG, and this might reflect hyperplasia of trophoblastic cells.

Adult↗
PubMed2000

Downregulation of leptin by free fatty acids in rat adipocytes: effects of triacsin C, palmitate, and 2-bromopalmitate.

Free fatty acid (FFA) has been reported to decrease leptin mRNA levels in 3T3-L1 adipocytes. When using this cell line, it is difficult to determine the protein levels because a very small amount of leptin is secreted into the medium. The effect of FFA on leptin secretion from adipocytes has not yet been determined. In addition, in vivo studies have failed to demonstrate a FFA-induced decrease in plasma leptin levels. To clarify the effect of FFA on leptin production, we investigated the leptin protein level in the medium and the mRNA level in primary cultured rat adipocytes treated with triacsin C, which is a potent inhibitor of acyl-coenzyme A (CoA) synthetase, palmitate, and 2-bromopalmitate. Triacsin C (0 to 5 x 10(-5) mol/L) decreased leptin concentrations in the culture medium in a dose-dependent manner. Leptin mRNA levels were decreased to 10% of the control in the presence of triacsin C. The concentration of triacsin C needed to suppress leptin production was similar to the Ki value (approximately 10(-5) mol/L) for inhibition of acyl-CoA synthetase. Both palmitate and 2-bromopalmitate decreased leptin concentra-tions but did not affect the triacsin C-induced decrease in leptin additively. In conclusion, both protein and mRNA levels of leptin were decreased by triacsin C and FFA in primary cultured rat adipocytes. Our findings suggest that FFA is involved in the regulation of leptin production in adipocytes.

Adipocytes↗
PubMed2000

Predicting incomplete uterine rupture with vaginal sonography during the late second trimester in women with prior cesarean.

OBJECTIVE: To evaluate the usefulness of serial transvaginal ultrasonographic measurement of the thickness of the lower uterine segment in the late second trimester for predicting the risk of intrapartum incomplete uterine rupture in women with previous cesarean delivery. METHODS: Serial transvaginal ultrasonography with full bladder was performed in 374 women without previous cesarean delivery (control group) and 348 women with previous cesarean delivery (cesarean group) from 19 to 39 weeks' gestation. The thickness of the lower uterine segment was measured in the longitudinal plane of the cervical canal. RESULTS: The thickness of the lower uterine segment decreased from 6.7 +/- 2.4 mm (mean +/- standard deviation [SD]) at 19 weeks' gestation to 3.0 +/- 0.7 mm at 39 weeks' gestation in the control group, but the thickness was more than 2.0 mm throughout this period in each control subject. In the cesarean group, the thickness decreased from 6.8 +/- 2.3 mm at 19 weeks' to 2.1 +/- 0.7 mm at 39 weeks' gestation and was significantly thinner than that of the control group after 27 weeks' gestation (P <.05). Eleven of 12 women (91%) with lower uterine segment less than the mean control - 1 SD in the late second trimester had a very thin lower uterine segment at cesarean delivery with fetal hair being visible through the amniotic membrane, ie, incomplete uterine rupture. In 17 of 23 women (74%) with lower uterine segment less than 2.0 mm in thickness within 1 week (4 +/- 3 days) before repeat cesarean delivery, intrapartum incomplete uterine rupture developed. CONCLUSION: Transvaginal ultrasonography is useful for measurement of the uterine wall after previous cesarean delivery.

Adult↗
PubMed2000

Effect of epidermal growth factor on lung growth in experimental fetal pulmonary hypoplasia.

The purpose of this study was (1) to compare the expression of epithelial growth factor receptor (EGFR) in the lung tissues of human fetuses with or without pulmonary hypoplasia, and (2) to investigate the effects of EGF on lung growth in experimental pulmonary hypoplasia in rabbits. Firstly, we investigated the expression of EGFR in lung tissues of human fetuses with or without pulmonary hypoplasia by immunohistochemistry. Secondly, the amniotic fluid was shunted into the maternal abdominal cavity in a group of 12 fetal rabbits, another group (n = 12) received EGF injection (5 microg, i.p.) at day 25 of gestation. The third group (n = 12) was only treated with EGF while littermates not operated on served as the control group (n = 12). On day 29 of gestation, fetuses were delivered by Cesarean section and the lungs removed. The body weight and wet lung and liver weights were measured. As a measure of fetal lung growth, we determined the size of lung acini, the number of terminal airspaces, and diameter of alveoli (n = 6, each groups). We also measured the concentration of phosphatidylcholine (PC) and the lecithin/sphingomyelin (L/S) ratio in lung lavage fluid at birth in some fetuses (n = 6, each groups). In human fetuses with pulmonary hypoplasia, there was a significant decrease in radial alveolar count and expression of EGFR compared with fetuses without pulmonary hypoplasia. Amniotic shunt significantly decreased fetal lung/body weight ratio compared with control. Injection of EGF in the shunted group significantly increased lung/body weight ratio to the control level. The concentration of PC and L/S ratio in lung fluid lavage from rabbit fetuses with hypoplastic lungs was significantly higher than the other three groups. Histopathological examination of fetuses with hypoplastic lungs treated with EGF showed no significant change in the size of acini, number of terminal airspaces or the diameter of alveoli compared with the control group. Our results suggested that EGF was associated with lung growth and maturation of human lung and that treatment of rabbit fetuses with hypoplastic lungs with EGF facilitated lung growth and development.

Amniotic Fluid↗
PubMed2000

Pathophysiological role of leptin in obesity-related hypertension.

To explore the pathophysiological role of leptin in obesity-related hypertension, we examined cardiovascular phenotypes of transgenic skinny mice whose elevated plasma leptin concentrations are comparable to those seen in obese subjects. We also studied genetically obese KKA(y) mice with hyperleptinemia, in which hypothalamic melanocortin system is antagonized by ectopic expression of the agouti protein. Systolic blood pressure (BP) and urinary catecholamine excretion are elevated in transgenic skinny mice relative to nontransgenic littermates. The BP elevation in transgenic skinny mice is abolished by alpha(1)-adrenergic, beta-adrenergic, or ganglionic blockers at doses that do not affect BP in nontransgenic littermates. Central administration of an alpha-melanocyte-stimulating hormone antagonist causes a marked increase in cumulative food intake but no significant changes in BP. The obese KKA(y) mice develop BP elevation with increased urinary catecholamine excretion relative to control KK mice. After a 2-week caloric restriction, BP elevation is reversed in nontransgenic littermates with the A(y) allele, in parallel with a reduction in plasma leptin concentrations, but is sustained in transgenic mice overexpressing leptin with the A(y) allele, which remain hyperleptinemic. This study demonstrates BP elevation in transgenic skinny mice and obese KKA(y) mice that are both hyperleptinemic, thereby suggesting the pathophysiological role of leptin in some forms of obesity-related hypertension.

Adrenergic alpha-Antagonists↗
PubMed2000

Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin.

Excess or loss of body fat can be associated with infertility, suggesting that adequate fat mass is essential for proper reproductive function. Leptin is an adipocyte-derived hormone that is involved in the regulation of food intake and energy expenditure, and its synthesis and secretion are markedly increased in obesity. Short-term administration of leptin accelerates the onset of puberty in normal mice and corrects the sterility of leptin-deficient ob/ob mice. These findings suggest a role for leptin as an endocrine signal between fat depots and the reproductive axis, but the effect of hyperleptinemia on the initiation and maintenance of reproductive function has not been elucidated. To address this issue, we examined the reproductive phenotypes of female transgenic skinny mice with elevated plasma leptin concentrations comparable to those in obese subjects. With no apparent adipose tissue, female transgenic skinny mice exhibit accelerated puberty and intact fertility at younger ages followed by successful delivery of healthy pups. However, at older ages, they develop hypothalamic hypogonadism characterized by prolonged menstrual cycles, atrophic ovary, reduced hypothalamic gonadotropin releasing hormone contents, and poor pituitary luteinizing hormone secretion. This study has demonstrated for the first time to our knowledge that accelerated puberty and late-onset hypothalamic hypogonadism are associated with chronic hyperleptinemia, thereby leading to a better understanding of the pathophysiological and therapeutic implication of leptin.

Adipose Tissue↗
PubMed2000

Demographic and reproductive factors for high seroprevalence of Chlamydia trachomatis among pregnant women in Japan.

In order to elucidate demographic and reproductive factors associated with Chlamydia trachomatis seropositivity, serological screening and questionnaire survey were conducted on pregnant women in Nagasaki Prefecture, Japan. Serum samples were taken from 1718 pregnant women between September and December, 1996, at the cooperative obstetric hospitals and clinics, and tested for the presence of antibodies to C. trachomatis using the enzyme immunoassay. A questionnaire was administered on a sub-sample (n -409), among whom 85 (20.8%) were seropositive. A multiple logistic analysis revealed that four characteristics showed a significant association with the seropositivity: (i) experience of premarital pregnancy, (ii) non use of condoms, (iii) short duration of education, and (iv) more frequent induced abortion. The unsafe sexual behavior of young people lacking proper knowledge of how to prevent STD is the most important intervention target for control of the C. trachomatis epidemic in Japan.

Abortion, Induced↗
PubMed2000

Constitutively active mitogen-activated protein kinase kinase increases GLUT1 expression and recruits both GLUT1 and GLUT4 at the cell surface in 3T3-L1 adipocytes.

To address a role of mitogen-activated protein kinase (MAPK) in the regulation of glucose transport, we made a constitutively active mutant of MAPK kinase (MAPKK) and introduced it into 3T3-L1 preadipocytes by using a retrovirus-mediated transfection procedure. The deletion of 20 amino acids (those between and including 32 and 51) in the amino terminal region of Xenopus MAPKK and the replacement of serine residues on the 218 and 222 positions by glutamic acid (dSESE-MAPKK) let Xenopus MAPKK constitutively active. The isolated cell clones differently expressing dSESE-MAPKK (clone 219 higher expression, clone 233 lower expression) efficiently differentiated to adipocytes by a standard differentiation cocktail. Accordingly, the increased expression of dSESE-MAPKK protein during differentiation resulted in the increased basal MAPK activity in clone 219 adipocytes and, to a lesser extent, in clone 233 adipocytes. In contrast to clone 233 and parental adipocytes, basal 2-deoxyglucose uptake was enhanced fourfold in clone 219 adipocytes, in accordance with increased expression of GLUT1 mRNA and protein. Whereas GLUT4 mRNA was similarly expressed in all of the adipocytes, GLUT4 protein appeared to decrease in clone 219 adipocytes. More importantly, subcellular fractionation studies showed that the localization of both GLUT1 and GLUT4 in the plasma membranes (PMs) was markedly increased in the basal state in clone 219 adipocytes compared with that in clone 233 and parental adipocytes, in which both glucose transporters were preferentially located in intracellular compartments. Consequently, insulin-induced translocation of GLUT1 was abolished in clone 219 adipocytes, although the remaining intracellular GLUT4 was still responsive to insulin stimulation, which led to the movement to the PM. As combined effects on the situation of GLUT1 and GLUT4, the foldness of insulin stimulation of glucose transport based on the basal activity was reduced in cells expressing constitutively active MAPKK. These results imply that chronic activation of MAPK could be one of the mechanisms for insulin resistance.

3T3 Cells↗
PubMed2000

[Ob gene].

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Animals↗
PubMed1999

Changes in intra-abdominal visceral fat and serum leptin levels in patients with obstructive sleep apnea syndrome following nasal continuous positive airway pressure therapy.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a common disorder in obese subjects. Visceral fat accumulation (VFA) is a better predictor of coronary heart disease than body mass index. Leptin is a hormone involved in the control of body weight and fat distribution. The effect of nasal continuous positive airway pressure (NCPAP) treatment on VFA and serum leptin levels in OSAS patients has not been known. METHODS AND RESULTS: VFA and subcutaneous fat accumulation (SFA) were assessed by CT before and after NCPAP treatment in 22 OSAS patients (mean apnea and hypopnea index >50 episodes/h). Serum leptin levels of another 21 OSAS patients were measured before and after 3 to 4 days of NCPAP to gain insight into the mechanism by which NCPAP affects fat distribution. VFA and SFA decreased significantly after 6 months of NCPAP treatment (236+/-16 to 182+/-14cm(2), P=0.0003 and 215+/-21 to 189+/-18 cm(2), P=0.003, respectively). VFA decreased significantly in the body weight reduction group (n=9, P<0.01) and the no body weight reduction group (n=13, P<0.03). In contrast, SFA changed significantly in the body weight reduction group only (P<0.01). Leptin levels decreased significantly following 3 to 4 days of NCPAP (P<0.01), whereas body weight, fasting insulin, and cortisol levels did not change significantly. CONCLUSIONS: Correction of sleep disordered breathing by NCPAP may be used to reduce VFA in OSAS patients. OSAS may have significant effects on the serum leptin levels.

Adipose Tissue↗
PubMed1999

Repeat-directed isolation of a novel gene preferentially expressed from the maternal allele in human placenta.

Using a repetitive sequence of tandemly arrayed pentanucleotides in the human H19 3'-flanking region, we isolated a phage clone (lambda PEN11) which localized to chromosome 11p15.5. The lambda PEN11 phage encodes a 2.3-kb cDNA consisting of seven exons at least. The gene was mainly expressed in brain and pancreas (and less abundantly in testis), and demonstrated differential allele usage, with maternal expression being predominant in placenta, which indicates the gene is an atypical imprinted gene. While the pentamer repeat might contribute to this effect, it is also possible that the differential allele usage might reflect the local chromosomal structure known as the imprinting domain.

Alleles↗
PubMed1999

Diagnosis of fetal pulmonary hypoplasia by measurement of blood flow velocity waveforms of pulmonary arteries with Doppler ultrasonography.

OBJECTIVE: The aim of the study was to determine the utility of ultrasonographically recorded blood flow waveforms of the pulmonary artery in the diagnosis of pulmonary hypoplasia. STUDY DESIGN: The normal values of the pulsatility index and peak systolic flow of pulmonary arterial blood velocity waveforms were determined in 300 uncomplicated single fetus pregnancies with well-established gestational ages between 24 and 40 weeks. We also measured the same parameters in 5 fetuses at high risk for development of severe pulmonary hypoplasia. We also determined the radial alveolar count and microvessel density, representing the extent of angiogenesis, in tissue specimens collected at autopsy from normal and hypoplastic lungs and stained both with hematoxylin and eosin and immunohistochemically for factor VIII. RESULTS: In healthy fetuses the pulsatility index values of both the right and left pulmonary arteries diminished significantly with advancing gestation, whereas the peak systolic velocity increased significantly with advancing gestation. In fetuses with pulmonary hypoplasia pulsatility index values were high and the peak systolic flow was significantly lower than in healthy fetuses. Histologic examination showed a lower radial alveolar count and poorer angiogenesis in fetuses with pulmonary hypoplasia than in healthy fetuses. CONCLUSION: Doppler ultrasonographic determination of pulmonary artery blood velocity waveforms is a useful tool for the diagnosis of pulmonary hypoplasia.

Blood Flow Velocity↗