Plasminogen activator inhibitor-1 levels in severe and morbid obesity. Effect of weight loss and influence of 4G/5G polymorphism

INTRODUCTION: An association between an increase in plasminogen activator inhibitor type 1 and obesity has been described. It has also been shown that a decrease in adiposity has beneficial effects. However, less information is available regarding morbid obesity and hypofibrinolysis. The aim of the present study was to evaluate the effect of weight loss and the influence of the plasminogen activator inhibitor type 1 promoter 4G/5G genotype on plasminogen activator inhibitor type 1 levels in severe and morbid obesity. MATERIALS AND METHODS: Sixty-seven obese patients were studied before and three months after a weight reduction program, and compared with 67 controls. We determined plasminogen activator inhibitor type 1 antigen and activity levels, tissue type plasminogen activator antigen levels, 4G/5G genotype and biochemical parameters in both groups. RESULTS: A significant increase in plasminogen activator inhibitor type 1 antigen and activity was observed in obese patients in comparison with the control group (P<0.001). No significant differences in plasminogen activator inhibitor type 1 levels among 4G/5G genotypes were obtained. After weight loss, a significant decrease in plasminogen activator inhibitor type 1 antigen and activity was observed (P<0.001). A significant and positive correlation was observed in percentage changes in plasminogen activator inhibitor type 1 and body mass index (P=0.02). CONCLUSIONS: A decrease in body mass index in severe and morbid obesity shows a favourable effect on the fibrinolytic system due to a decrease in plasminogen activator inhibitor type 1 levels. However, no influence of 4G/5G polymorphism has been observed in this setting.     

Decreased levels of ghrelin, cortisol, and fasting blood sugar, but not n-octanoylated ghrelin, in Japanese schizophrenic inpatients treated with olanzapine

The mechanism by which chronic administration of olanzapine induces a marked weight gain in patients with schizophrenia remains unknown. We examined the influence of long-term treatment with olanzapine on plasma levels of hormones regulating food intake and energy homeostasis in schizophrenia. In this study, olanzapine was administered to 28 Japanese inpatients for 16 weeks after switching from typical antipsychotic drugs or risperidone. At endpoint, no significant changes in body weight or body mass index were found. There was a significant decrease in the plasma levels of ghrelin without any accompanying change in active, n-octanoylated ghrelin. Serum levels of leptin tended to be increased and a significant reduction in plasma cortisol levels was found. In addition, the levels of fasting blood sugar as well as free fatty acid were significantly decreased. Furthermore, we did not confirm any marked weight gain induced by chronic administration of olanzapine as previously reported. The reason for this discrepancy may be due to differences in subjects and treatment settings. Based on these findings, it is unlikely that the decrease in plasma ghrelin levels by chronic administration of olanzapine affects weight gain. Further studies examining the effect of chronic olanzapine administration on weight and energy homeostasis in inpatients are required.     

Caloric restriction improves coagulation and inflammation profile in obese mice

To evaluate associations between adiposity and coagulation or inflammation profile, obese wild-type C57Bl/6 mice were subjected to drastic caloric restriction by switching from a high fat diet to restricted normal chow. After 6 weeks, total body weights as well as subcutaneous and gonadal adipose tissue mass were markedly reduced, associated with adipocyte hypotrophy (all p < 0.001). Weight reduction was associated with markedly reduced plasma levels of plasminogen activator inhibitor-1, Factor VII and Factor VIII. Reduced oxidative stress and inflammation following weight reduction is supported by significantly lower expression in adipose tissues of pro-inflammatory interleukin-6, higher expression of anti-oxidant catalase, superoxide dismutase 1 and glutathione peroxidase 1, and lower plasma levels of C-reactive protein. Furthermore, reduced levels of leptin and enhanced levels of adiponectin were observed, whereas cholesterol and triglyceride levels were reduced. The content of structurally intact collagen fibers was significantly higher in subcutaeneous and gonadal adipose tissues after caloric restriction.Thus, caloric restriction and drastic weight loss in obese mice is associated with improved plasma coagulation profile and with reduced oxidative stress and inflammation in the adipose tissues.     

Estrogen: A master regulator of bioenergetic systems in the brain and body

Estrogen is a fundamental regulator of the metabolic system of the female brain and body. Within the brain, estrogen regulates glucose transport, aerobic glycolysis, and mitochondrial function to generate ATP. In the body, estrogen protects against adiposity, insulin resistance, and type II diabetes, and regulates energy intake and expenditure. During menopause, decline in circulating estrogen is coincident with decline in brain bioenergetics and shift towards a metabolically compromised phenotype. Compensatory bioenergetic adaptations, or lack thereof, to estrogen loss could determine risk of late-onset Alzheimer’s disease. Estrogen coordinates brain and body metabolism, such that peripheral metabolic state can indicate bioenergetic status of the brain. By generating biomarker profiles that encompass peripheral metabolic changes occurring with menopause, individual risk profiles for decreased brain bioenergetics and cognitive decline can be created. Biomarker profiles could identify women at risk while also serving as indicators of efficacy of hormone therapy or other preventative interventions.