Effect of sleeve gastrectomy on postprandial lipoprotein metabolism in morbidly obese patients

Background: Obesity is associated with abnormal fasting and postprandial lipids, which may link obesity with atherosclerosis. We explored fasting and postprandial lipids in morbidly obese patients treated with sleeve gastrectomy and in control subjects. Methods: After fasting for 12 h 15 morbidly obese patients (BMI 51.4 +/- 6.5 kg/m(2), 43.7 +/- 12.6 years) received a standardized oral fat load before and 3 months after bariatric surgery (sleeve gastrectomy). Controls (n=9, BMI 23.1 +/- 1.4 kg/m(2)) were studied once. Plasma was obtained fasting and then postprandially every 2 h for 8 h. Triglycerides (TG), chylomicron-TG (CM-TG), VLDL/chylomicron-remnant (VLDL/CR)-TG, cholesterol, LDL-cholesterol, VLDL/CR-cholesterol and HDL-cholesterol were isolated by ultracentrifugation at each time point. Postprandial values were expressed as area under the curve (AUC) and incremental area under the curve (iAUC). In addition, fasting glucose and insulin values and HOMA-IR-Index was measured (n=14). Results: Compared to controls morbidly obese patients had elevated TG and slightly altered postprandial lipids. Following surgery (weight loss 23.4 kg +/- 6.2 kg; 150 mg/dl) a similar pattern was observed. Fasting insulin and HOMA were reduced significantly (-51.9%; p=0.004 and -47.9%; p=0.011). Conclusions: Three months after sleeve gastrectomy fasting and postprandial lipoprotein metabolism and glucose metabolism is improved in morbidly obese patients. The potential mechanisms may relate to decreased caloric intake but also to hormonal changes

A Walnut-Enriched Diet Reduces Lipids in Healthy Caucasian Subjects, Independent of Recommended Macronutrient Replacement and Time Point of Consumption: A Prospective, Randomized, Controlled Trial

Studies indicate a positive association between walnut intake and improvements in plasma lipids. We evaluated the effect of an isocaloric replacement of macronutrients with walnuts and the time point of consumption on plasma lipids. We included 194 healthy subjects (134 females, age 63 +/- 7 years, BMI 25.1 +/- 4.0 kg/m(2)) in a randomized, controlled, prospective, cross-over study. Following a nut-free run-in period, subjects were randomized to two diet phases (8 weeks each). Ninety-six subjects first followed a walnut-enriched diet (43 g walnuts/day) and then switched to a nut-free diet. Ninety-eight subjects followed the diets in reverse order. Subjects were also randomized to either reduce carbohydrates (n = 62), fat (n = 65), or both (n = 67) during the walnut diet, and instructed to consume walnuts either as a meal or as a snack. The walnut diet resulted in a significant reduction in fasting cholesterol (walnut vs. control: -8.5 +/- 37.2 vs. -1.1 +/- 35.4 mg/dL;p = 0.002), non-HDL cholesterol (-10.3 +/- 35.5 vs. -1.4 +/- 33.1 mg/dL;p 0.001), LDL-cholesterol (-7.4 +/- 32.4 vs. -1.7 +/- 29.7 mg/dL;p = 0.029), triglycerides (-5.0 +/- 47.5 vs. 3.7 +/- 48.5 mg/dL;p = 0.015) and apoB (-6.7 +/- 22.4 vs. -0.5 +/- 37.7 mg/dL;p 0.001), while HDL-cholesterol and lipoprotein (a) did not change significantly. Neither macronutrient replacement nor time point of consumption significantly affected the effect of walnuts on lipids. Thus, 43 g walnuts/day improved the lipid profile independent of the recommended macronutrient replacement and the time point of consumption

Enabling planetary science across light-years. Ariel Definition Study Report

Ariel, the Atmospheric Remote-sensing Infrared Exoplanet Large-survey, was adopted as the fourth medium-class mission in ESA's Cosmic Vision programme to be launched in 2029. During its 4-year mission, Ariel will study what exoplanets are made of, how they formed and how they evolve, by surveying a diverse sample of about 1000 extrasolar planets, simultaneously in visible and infrared wavelengths. It is the first mission dedicated to measuring the chemical composition and thermal structures of hundreds of transiting exoplanets, enabling planetary science far beyond the boundaries of the Solar System. The payload consists of an off-axis Cassegrain telescope (primary mirror 1100 mm x 730 mm ellipse) and two separate instruments (FGS and AIRS) covering simultaneously 0.5-7.8 micron spectral range. The satellite is best placed into an L2 orbit to maximise the thermal stability and the field of regard. The payload module is passively cooled via a series of V-Groove radiators; the detectors for the AIRS are the only items that require active cooling via an active Ne JT cooler. The Ariel payload is developed by a consortium of more than 50 institutes from 16 ESA countries, which include the UK, France, Italy, Belgium, Poland, Spain, Austria, Denmark, Ireland, Portugal, Czech Republic, Hungary, the Netherlands, Sweden, Norway, Estonia, and a NASA contribution

Effect of PCSK9 inhibition with evolocumab on lipoprotein subfractions in familial dysbetalipoproteinemia (type III hyperlipidemia)

Background and aimsFamilial dysbetalipoproteinemia (FDBL) is a rare inborn lipid disorder characterized by the formation of abnormal triglyceride- and cholesterol-rich lipoproteins (remnant particles). Patients with FDBL have a high risk for atherosclerotic disease. The effect of PCSK9 inhibition on lipoproteins and its subfractions has not been evaluated in FDBL. MethodsThree patients (65 +/- 7 years, 23 +/- 3 kg/m(2), 2 females) with FDBL (diagnosed by isoelectrofocusing) and atherosclerosis (coronary and/or cerebro-vascular and/or peripheral arterial disease) resistant or intolerant to statin and fibrate therapy received evolocumab (140mg every 14 days). In addition to a fasting lipid profile (preparative ultracentrifugation), apoB and cholesterol concentrations were determined in 15 lipoprotein-subfractions (density gradient ultracentrifugation;d 1.006-1.21g/ml) before and after 12 weeks of evolocumab treatment. Patients with LDL-hypercholesterolemia (n = 8, 56 +/- 8 years, 31 +/- 7 kg/m(2)) and mixed hyperlipidemia (n = 5, 68 +/- 12 years, 30 +/- 1 kg/m(2)) also receiving evolocumab for 12 weeks were used for comparison. ResultsAll patients tolerated PCSK9 inhibition well. PCSK9 inhibitors reduced cholesterol (29-37%), non-HDL-cholesterol (36-50%) and apoB (40-52%) in all patient groups including FDBL. In FDBL, PCSK9 inhibition reduced VLDL-cholesterol and the concentration of apoB containing lipoproteins throughout the whole density spectrum (VLDL, IDL, remnants, LDL). Lipoprotein(a) was decreased in all patient groups to a similar extent. ConclusionsThis indicates that the dominant fraction of apoB-containing lipoproteins is reduced with PCSK9 inhibition, i.e. LDL in hypercholesterolemia and mixed hyperlipidemia, and cholesterol-rich VLDL, remnants and LDL in FDBL. PCSK9 inhibition may be a treatment option in patients with FDBL resistant or intolerant to statin and/or fibrate therapy

Bacterial Growth Inhibition Screen (BGIS) identifies a loss-of-function mutant of the DEK oncogene, indicating DNA modulating activities of DEK in chromatin

The DEK oncoprotein regulates cellular chromatin function via a number of protein-protein interactions. However, the biological relevance of its unique pseudo-SAP/SAP-box domain, which transmits DNA modulating activities in vitro, remains largely speculative. As hypothesis-driven mutations failed to yield DNA-binding null (DBN) mutants, we combined random mutagenesis with the Bacterial Growth Inhibition Screen (BGIS) to overcome this bottleneck. Re-expression of a DEK-DBN mutant in newly established human DEK knockout cells failed to reduce the increase in nuclear size as compared to wild type, indicating roles for DEK-DNA interactions in cellular chromatin organization. Our results extend the functional roles of DEK in metazoan chromatin and highlight the predictive ability of recombinant protein toxicity in E. coli for unbiased studies of eukaryotic DNA modulating protein domains.publishe

Lipoprotein (a) and Low-density lipoprotein apolipoprotein B metabolism following apheresis in patients with elevated lipoprotein(a) and coronary artery disease

Background: Lipoprotein apheresis effectively lowers lipoprotein(a) [Lp(a)] and low‐density lipoprotein (LDL) by approximately 60%‐70%. The rebound of LDL and Lp(a) particle concentrations following lipoprotein apheresis allows the determination of fractional catabolic rate (FCR) and hence production rate (PR) during non‐steady state conditions. We aimed to investigate the kinetics of Lp(a) and LDL apolipoprotein B‐100 (apoB) particles in patients with elevated Lp(a) and coronary artery disease undergoing regular apheresis. Patients and methods: A cross‐sectional study was carried out in 13 patients with elevated Lp(a) concentration (>500 mg/L) and coronary artery disease. Lp(a) and LDL‐apoB metabolic parameters, including FCR and PR were derived by the fit of a compartment model to the Lp(a) and LDL‐apoB concentration data following lipoprotein apheresis.500 mg/L) and coronary artery disease. Lp(a) and LDL‐apoB metabolic parameters, including FCR and PR were derived by the fit of a compartment model to the Lp(a) and LDL‐apoB concentration data following lipoprotein apheresis. Results: The FCR of Lp(a) was significantly lower than that of LDL‐apoB (0.39 [0.31, 0.49] vs 0.57 [0.46, 0.71] pools/day, P = 0.03) with no significant differences in the corresponding PR (14.80 [11.34, 19.32] vs 15.73 [11.93, 20.75] mg/ kg/day, P = 0.80). No significant associations were observed between the FCR and PR of Lp(a) and LDL‐apoB. Conclusions: In patients with elevated Lp(a), the fractional catabolism of Lp(a) is slower than that of LDL‐apoB particles, implying that different metabolic pathways are involved in the catabolism of these lipoproteins. These findings have implications for new therapies for lowering apolipoprotein(a) and apoB to prevent atherosclerotic cardiovascular disease