[Show abstract][Hide abstract] ABSTRACT: Background:
Obesity is well-known as a risk factor for heart failure, including diastolic dysfunction. However, this mechanism in high-fat diet (HFD)-induced obese rats remain controversial. The purpose of this study was to investigate whether cardiac dysfunction develops when rats are fed with a HFD for 10 weeks; additionally, we sought to investigate the association between mitochondrial abnormalities, adenosine triphosphate (ATP) levels and cardiac dysfunction.
We examined myocardia in Wistar rats after 10 weeks of HFD (45 kcal% fat, n=6) or standard diet (SD, n=6). Echocardiography, histomorphologic analysis, and electron microscopy were performed. The expression levels of mitochondrial oxidative phosphorylation (OXPHOS) subunit genes, peroxisome-proliferator-activated receptor γ co-activator-1α (PGC1α) and anti-oxidant enzymes were assessed. Markers of oxidative stress damage, mitochondrial DNA copy number and myocardial ATP level were also examined.
After 10 weeks, the body weight of the HFD group (349.6±22.7 g) was significantly higher than that of the SD group (286.8±14.9 g), and the perigonadal and epicardial fat weights of the HFD group were significantly higher than that of the SD group. Histomorphologic and electron microscopic images were similar between the two groups. However, in the myocardium of the HFD group, the expression levels of OXPHOS subunit NDUFB5 in complex I and PGC1α, and the mitochondrial DNA copy number were decreased and the oxidative stress damage marker 8-hydroxydeoxyguanosine was increased, accompanied by reduced ATP levels.
Diastolic dysfunction was accompanied by the mitochondrial abnormality and reduced ATP levels in the myocardium of 10 weeks-HFD-induced rats.
[Show abstract][Hide abstract] ABSTRACT: Growth hormone insensitivity syndrome (GHIS), a genetic disease characterized by growth retardation combined with high serum concentration of growth hormone (GH) and low insulin-like growth factor 1 (IGF-1) levels, can be caused by mutations in the GH receptor (GHR) gene. We investigated the molecular defects in the GHR gene in a patient with neurofibromatosis type 1 (NF-1). The patient, a 2-year-old boy with NF-1, was assessed on his short stature by auxological, biochemical and molecular studies. Height of the patient and his family members were measured and compared to normal control. Serum concentrations of GH, IGF-1 and IGF-binding protein 3 (IGFBP3) in the patient were measured during a GH stimulation test. We examined the GHR gene in the patient and his parents. Genomic DNA and mRNA of the GHR gene were extracted from peripheral lymphocytes. All the exons and the flanking regions of the GHR gene were amplified by PCR, and directly sequenced. The patient's height was 75 cm (-2.89 SDS) with gradually reducing growth velocity, while the heights of the other family members were within the normal range. The GH stimulation test revealed that serum GH concentrations in the patient were much higher than those in the control group, and serum IGF-1 and IGFBP3 levels were extremely low. There was no germline mutation in the exons or the flanking regions of the patient's GHR gene. Interestingly, a deletion of 166 bases of exon 7 in the GHR mRNA was found, and it was suggested that the novel mutation resulted in premature termination (M207 fs. X8). This mutation decreases GH binding affinity to the GHR, and, thus, would be responsible for growth retardation.
No preview · Article · Jun 2012 · International Journal of Molecular Medicine
[Show abstract][Hide abstract] ABSTRACT: long-term ovariectomy-induced metabolic changes such as insulin resistance and glucose intolerance might be caused directly by estrogen deficiency and may occur partly as secondary effects of obesity arising due to the orexigenic effects of estrogen deficiency. Long-term estrogen treatment prevented those by exerting anorexigenic and metabolic actions in ovariectomized mice. However, the effect of short-term estrogen treatment on glucose metabolism in mice with short-term ovariectomy, during which ovariectomy-induced obesity does not develop, is not yet clear. The aim of this study was to evaluate the effect of short-term parenteral 17beta-estradiol treatment on glucose metabolism and blood glucose levels in mice at 2 weeks after ovariectomy, a time period during which ovariectomy-induced obesity does not develop.
we examined the effect of three 17beta-estradiol injections on fasting blood glucose levels, insulin resistance, components of the insulin signaling pathway, AMPK activation, and the expression of genes related to glucose metabolism in liver, skeletal muscle, and white adipose tissues of non-obese C57BL/6N mice with short-term ovariectomy.
three 17beta-estradiol injections decreased the fasting blood glucose levels, activated AMPK, and decreased the expression of gluconeogenic genes, phosphoenolpyruvate carboxykinase, glucose-6-phosphatase and peroxisome proliferator-activated receptor-γ coactivator-1α in the liver. But three 17beta-estradiol injections did not affect insulin sensitivity and the components of the insulin signaling pathway in the liver and skeletal muscle.
short-term parenteral 17beta-estradiol treatment decreases the fasting blood glucose levels not via insulin sensitivity of the skeletal muscle in non-obese mice with short-term ovariectomy.
[Show abstract][Hide abstract] ABSTRACT: Sleep disorders are great problems in modern society. Even minimal changes of sleep can affect health. Especially, patients with pulmonary diseases complain of sleep problems such as sleep disturbance and insomnia. Recent studies have shown an association between sleep deprivation (SD) and inflammation, however, the underlying mechanisms remain unclear. In the present study, we investigated whether melatonin protects against acute lung inflammation in SD. Male ICR mice were deprived sleep using modified multiplatform water bath for 3 days. Acute lung inflammation was induced by lipopolysaccharide (LPS; 5 mg/kg). Melatonin (5 mg/kg) and LPS was administered in SD mice at day 2. Mice were divided into five groups as control, SD, LPS, LPS + SD, and LPS + SD + melatonin (each group, n = 11). Mice were killed on day 3 after treatment of melatonin and LPS for 24 hr. Lung tissues were collected for histological examination and protein analysis. The malondialdehyde (MDA) level was determined for the effect of oxidative stress. Melatonin restored weight loss in LPS + SD. Histological findings revealed alveolar damages with inflammatory cell infiltration in LPS + SD. Melatonin remarkably attenuated the alveolar damages. In western blot analysis, LPS reduced the levels of Bcl-XL and procaspase-3 in SD mice. After treatment with melatonin, the levels of Bcl-XL and procaspase-3 increased when compared with LPS + SD. LPS treatment showed an increase of TUNEL-positive cells, whereas melatonin prevented the increase of cell death in LPS + SD animals. In lipid peroxidation assay, melatonin significantly reduced the elevated MDA level in LPS + SD. Our results suggest that melatonin attenuates acute lung inflammation during SD via anti-apoptotic and anti-oxidative actions.
No preview · Article · Aug 2008 · Journal of Pineal Research
[Show abstract][Hide abstract] ABSTRACT: The present study was performed to determine expression of cytochrome P450 aromatase(Cyp19) in the efferent ductules(EDs) and the epididymis of male rat reproductive tract at different postnatal ages. Total RNAs isolated were reverse-transcribed, and cDNAs were utilized for real-time PCR analysis. In the EDs, the Cyp19 transcript was expressed at all prepubertal ages with the highest level at 14 days of age, but not at 90 days of age. Expression of Cyp19 mRNA in the epididymis was found at all age groups, except 7 days of age. Distinct expression patterns of Cyp19 transcript were shown in each segment of the epididymis. These results indicate that expression of Cyp19 gene in the excurrent duct of male reproductive tract is differentially regulated in age-dependent and segment-specific manners.