Obesity before pregnancy is associated with impaired metabolic status of the mother and the offspring later in life. These adverse effects have been attributed to epigenetic changes in utero, but ...little is known about the role of placental metabolism and its contribution to fetal development.
We examined the impact of maternal pre-pregnancy obesity on the expression of genes involved in placental lipid metabolism in lean and obese women.
Seventy-three lean and obese women with healthy pregnancy were recruited at term elective cesarean delivery. Metabolic parameters were measured on maternal venous blood samples. Expression of 88 genes involved in lipid metabolism was measured in whole placenta tissue. Proteins of genes differently expressed in response to maternal obesity were quantified, correlated with maternal parameters and immunolocalized in placenta sections. Isolated primary trophoblasts were used for in vitro assays.
Triglyceride (TG) content was increased in placental tissue of obese (1.10, CI 1.04-1.24 mg g
, P<0.05) vs lean (0.84, CI 0.72-1.02 mg g
) women. Among target genes examined, six showed positive correlation (P<0.05) with maternal pre-pregnancy BMI, namely ATGL (PNPLA2), FATP1 (SLC27A1), FATP3 (SLC27A3), PLIN2, PPARG and CGI-58 (ABHD5). CGI-58 protein abundance was twofold higher (P<0.001) in placentas of obese vs lean women. CGI-58 protein levels correlated positively with maternal insulin levels and pre-pregnancy body mass index (R=0.63, P<0.001 and R=0.64, P<0.001, respectively). CGI-58 and PLIN2 were primarily located in the syncytiotrophoblast and, were upregulated (1.38- and 500-fold, respectively) upon oleic acid and insulin treatment of cultured trophoblast cells.
Pre-gravid obesity significantly modifies the expression of placental genes related to transport and storage of neutral lipids. We propose that the upregulation of CGI-58, a master regulator of TG hydrolysis, contributes to the turnover of intracellular lipids in placenta of obese women, and is tightly regulated by metabolic factors of the mother.
Based on animal studies, intake of probiotic bacteria was suggested to improve insulin sensitivity by reducing endotoxinemia and inflammation. The objective of this study was to determine the effects ...of supplementation with the probiotic strain Lactobacillus casei Shirota (LcS) over 12wk on insulin sensitivity, β-cell function, inflammation, and endothelial dysfunction parameters in subjects with metabolic syndrome. In a randomized-controlled study, 30 subjects with metabolic syndrome either received Lactobacillus casei Shirota 3 times daily for 12wk or served as controls with standard medical therapy. Fasting blood samples were taken and a 75-g oral glucose tolerance test was performed to derive indices for insulin sensitivity and β-cell function. In addition, parameters to assess endothelial function and inflammation markers were determined. Even though the insulin sensitivity index significantly improved after 3mo of probiotic supplementation (0.058±0.021 vs. 0.038±0.025), the change was not significantly different compared with the control group. No improvements were seen in additional indices of insulin sensitivity (quantitative insulin sensitivity check index, insulin sensitivity by oral glucose tolerance test, and homeostasis model assessment for insulin resistance) and β-cell function (first and second phase insulin secretion, and homeostasis model assessment for β-cell function). Probiotic supplementation resulted in a significant reduction in soluble vascular cell adhesion molecule-1 (sVCAM-1) level (1,614±343 vs. 1,418±265ng/mL). No significant changes in parameters used to assess low-grade inflammation or endothelial dysfunction were observed. Intake of LcS for 12wk in subjects with metabolic syndrome did not improve insulin sensitivity, β-cell function, endothelial function, or inflammation markers in this trial.
Aims
Heart failure with preserved ejection fraction (HFpEF) has a different pathophysiological background compared to heart failure with reduced ejection fraction (HFrEF). Tailored risk prediction in ...this separate heart failure group with a high mortality rate is of major importance. Inflammation may play an important role in the pathogenesis of HFpEF because of its significant contribution to myocardial fibrosis. We therefore aimed to assess the predictive value of C‐reactive protein (CRP) in patients with HFpEF.
Methods and results
Plasma levels of CRP were determined in 459 patients with HFpEF in the LUdwigshafen Risk and Cardiovascular Health (LURIC) study using a high‐sensitivity assay. During a median follow‐up of 9.7 years 40% of these patients died. CRP predicted all‐cause mortality with an adjusted hazard ratio (HR) of 1.20 95% confidence interval (CI) 1.02–1.40, P = 0.018 and cardiovascular mortality with a HR of 1.32 (95% CI 1.08–1.62, P = 0.005) per increase of one standard deviation. CRP was a significantly stronger mortality predictor in HFpEF patients than in a control group of 522 HFrEF patients (for interaction, P = 0.015). Furthermore, CRP added prognostic value to N‐terminal pro B‐type natriuretic peptide (Nt‐proBNP): the lowest 5‐year mortality rate of 6.8% was observed for patients in the lowest tertile of Nt‐proBNP as well as CRP. The mortality risk peaked in the group combining the highest values of Nt‐proBNP and CRP with a 5‐year rate of 36.5%.
Conclusion
It was found that CRP was an independent and strong predictor of mortality in HFpEF. This observation may reflect immunological processes with an adverse impact on the course of HFpEF.
Abstract
Background. Copper and its main transport protein ceruloplasmin have been suggested to promote the development of atherosclerosis. Most of the data come from experimental and animal model ...studies. Copper and mortality have not been simultaneously evaluated in patients undergoing coronary angiography. Methods and results. We examined whether serum copper and ceruloplasmin concentrations are associated with angiographic coronary artery disease (CAD) and mortality from all causes and cardiovascular causes in 3253 participants of the Ludwigshafen Risk and Cardiovascular Health Study. Age and sex-adjusted hazard ratios (HR) for death from any cause were 2.23 (95% CI, 1.85-2.68) for copper and 2.63 (95% CI, 2.17-3.20) for ceruloplasmin when we compared the highest with the lowest quartiles. Corresponding hazard ratios (HR) for death from cardiovascular causes were 2.58 (95% CI, 2.05-3.25) and 3.02 (95% CI, 2.36-3.86), respectively. Further adjustments for various risk factors and clinical variables considerably attenuated these associations, which, however, were still statistically significant and the results remained consistent across subgroups. Conclusions. The elevated concentrations of both copper and ceruloplasmin are independently associated with increased risk of mortality from all causes and from cardiovascular causes.
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