10 research outputs found

    Characterization of different fat depots in NAFLD using inflammation-associated proteome, lipidome and metabolome

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    Non-alcoholic fatty liver disease (NAFLD) is recognized as a liver manifestation of metabolic syndrome, accompanied with excessive fat accumulation in the liver and other vital organs. Ectopic fat accumulation was previously associated with negative effects at the systemic and local level in the human body. Thus, we aimed to identify and assess the predictive capability of novel potential metabolic biomarkers for ectopic fat depots in non-diabetic men with NAFLD, using the inflammation-associated proteome, lipidome and metabolome. Myocardial and hepatic triglycerides were measured with magnetic spectroscopy while function of left ventricle, pericardial and epicardial fat, subcutaneous and visceral adipose tissue were measured with magnetic resonance imaging. Measured ectopic fat depots were profiled and predicted using a Random Forest algorithm, and by estimating the Area Under the Receiver Operating Characteristic curves. We have identified distinct metabolic signatures of fat depots in the liver (TAG50:1, glutamate, diSM18:0 and CE20:3), pericardium (N-palmitoyl-sphinganine, HGF, diSM18:0, glutamate, and TNFSF14), epicardium (sphingomyelin, CE20:3, PC38:3 and TNFSF14), and myocardium (CE20:3, LAPTGF-beta 1, glutamate and glucose). Our analyses highlighted non-invasive biomarkers that accurately predict ectopic fat depots, and reflect their distinct metabolic signatures in subjects with NAFLD.Peer reviewe

    An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans

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    A carbohydrate-restricted diet is a widely recommended intervention for non-alcoholic fatty liver disease (NAFLD), but a systematic perspective on the multiple benefits of this diet is lacking. Here, we performed a short-term intervention with an isocaloric low-carbohydrate diet with increased protein content in obese subjects with NAFLD and characterized the resulting alterations in metabolism and the gut microbiota using a multi-omics approach. We observed rapid and dramatic reductions of liver fat and other cardiometabolic risk factors paralleled by (1) marked decreases in hepatic de novo lipogenesis; (2) large increases in serum beta-hydroxybutyrate concentrations, reflecting increased mitochondrial beta-oxidation; and (3) rapid increases in folate-producing Streptococcus and serum folate concentrations. Liver transcriptomic analysis on biopsy samples from a second cohort revealed downregulation of the fatty acid synthesis pathway and upregulation of folate-mediated one-carbon metabolism and fatty acid oxidation pathways. Our results highlight the potential of exploring diet-microbiota interactions for treating NAFLD.Peer reviewe

    Pulmonary embolism location is associated with the co-existence of the deep venous thrombosis

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    Multiple studies have shown that in approximately half of individuals with pulmonary embolism (PE), the deep venous thrombosis (DVT) is not evident at the moment of PE diagnosis. The underlying factors and the origin of PE in these patients are not completely understood: missed DVT, embolization of DVT in its entirety, or de-novo PE being possible explanations. The aim of this study was to evaluate the differences in PE patient with or without co-existing DVT. Sixty-three consecutive PE patients were included. Whole leg bilateral Doppler compression ultrasound was performed to all patients. The PE location and extension, C-reactive protein, platelet count, hemostatic markers FV, FVIII, FXIIIa, Fibrinogen, von Willebrand factor antigen, thrombomodulin were assessed. Thorough clinical assessment including echocardiography and pulmonary function tests were performed upon arrival and seven months later. The mean age of the patients was 57 years (SD 17.3) and 33 (52%) were women. Thirty-one patients (49.2%) had coexisting DVT. The presence of DVT was associated with the proximal location of the PE (100%), whereas none of the patients (n = 10) with exclusively peripheral PE had coexisting DVT. The PE extension, the measured hemostatic and inflammatory markers or the patient characteristics did not statistically differ between patients with isolated PE and PE with co-existing DVT. In roughly half of the PE patients no DVT could be detected. The location of the PE was associated with the presence of co-existing DVT. There were no differences in the PE extension, hemostatic markers or in the patient characteristic between patients with isolated PE or PE with coexisting DVT. Copyright (C) 2019 Wolters Kluwer Health, Inc. All rights reserved.Peer reviewe
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