Cholesterol Synthesis Is Associated with Hepatic Lipid Content and Dependent on Fructose/Glucose Intake in Healthy Humans

Visceral obesity and fatty liver have been related to high synthesis and low absorption of cholesterol. This study aimed to investigate the associations of cholesterol metabolism with liver and visceral fat content in healthy humans. Another objective was to explore the effects of very-high-fructose and very-high-glucose diets on cholesterol homeostasis. We report on a cohort of 20 people (12 males, 8 females; age 30.5 ± 2.0 years; body mass index 25.9 ± 0.5 kg/m2) who completed a four-week dietary intervention study. Between the baseline and the followup examination the study participants in addition to a balanced weight-maintaining diet received 150 g of either fructose or glucose per day. Visceral and liver fat were measured with magnetic resonance (MR) imaging and 1H-MR spectroscopy, respectively. Cholesterol absorption and synthesis were estimated from the serum noncholesterol sterol concentrations. Performing cross-sectional analyses the lanosterol and desmosterol to cholesterol ratios were positively correlated with visceral and liver fat content (all P < .03). The lathosterol to cholesterol ratio decreased in response to high-fructose diet (P = .006) but not in response to high-glucose diet. To conclude, visceral and liver fat content are associated with cholesterol synthesis in healthy humans. Furthermore, cholesterol synthesis appears to be dependent on fructose/glucose intake

Nonsuppressed Glucagon After Glucose Challenge as a Potential Predictor for Glucose Tolerance

Glucagon levels are classically suppressed after glucose challenge. It is still not clear as to whether a lack of suppression contributes to hyperglycemia and thus to the development of diabetes. We investigated the association of postchallenge change in glucagon during oral glucose tolerance tests (OGTTs), hypothesizing that higher postchallenge glucagon levels are observed in subjects with impaired glucose tolerance (IGT). Glucagon levels were measured during OGTT in a total of 4,194 individuals without diabetes in three large European cohorts. Longitudinal changes in glucagon suppression were investigated in 50 participants undergoing a lifestyle intervention. Only 66-79% of participants showed suppression of glucagon at 120 min (fold change glucagon(120/0)Peer reviewe

Role of proton MR for the study of muscle lipid metabolism

1H-MR spectroscopy (MRS) of intramyocellular lipids (IMCL) became particularly important when it was recognized that IMCL levels are related to insulin sensitivity. While this relation is rather complex and depends on the training status of the subjects, various other influences such as exercise and diet also influence IMCL concentrations. This may open insight into many metabolic interactions; however, it also requires careful planning of studies in order to control all these confounding influences. This review summarizes various historical, methodological, and practical aspects of 1H-MR spectroscopy (MRS) of muscular lipids. That includes a differentiation of bulk magnetic susceptibility effects and residual dipolar coupling that can both be observed in MRS of skeletal muscle, yet affecting different metabolites in a specific way. Fitting of the intra- (IMCL) and extramyocellular (EMCL) signals with complex line shapes and the transformation into absolute concentrations is discussed. Since the determination of IMCL in muscle groups with oblique fiber orientation or in obese subjects is still difficult, potential improvement with high-resolution spectroscopic imaging or at higher field strength is considered. Fat selective imaging is presented as a possible alternative to MRS and the potential of multinuclear MRS is discussed. 1H-MRS of muscle lipids allows non-invasive and repeated studies of muscle metabolism that lead to highly relevant findings in clinics and patho-physiology

Luteal phase support in in-vitro fertilization

Objective: To compare the clinical pregnancy rate after the use of human chorionic gonadotropin (hCG) injections (Profasi, Serono Pharmaceuticals), to that after the use of oral Duphaston (Duphaston, Solvay Pharmaceuticals B.V., Weesp, The Netherlands) , or vaginal Cyclogest (Cyclogest, Cox Pharmaceuticals, Barnstaple, Ex32 8NS, England) used for luteal phase support in in-vitro fertilization-embryo transfer (IVF-ET) cycles using gonadotropin- releasing hormone agonist. Study design: A retrospective cohort study. Setting: Tawam Hospital Fertility Clinic (a tertiary referral center) in the United Arab Emirates. Materials and methods: A total of 305 consecutive IVF/ET cycles from 1st of January to 31st of May 2000 were included in the study. All women were < 40 years of age. 201 women were treated with hCG (66%) at a dose of 1,500-2,500 IU intramuscular (IM) given every second or third day for three to five doses. 44 women were treated with oral Duphaston (14.4%) given at a dose of 40mg/day and 60 were given vaginal Cyclogest pessaries (19.6%) at a dose of 400mg twice daily, until the date of the pregnancy test. Student t test was used for statistical analysis to measure significance. Main outcome measures: Clinical pregnancy rate. Results: The use of IM hCG for luteal phase support in IVF-ET cycles was associated with similar clinical pregnancy rate compared with vaginal Cyclogest pessaries and oral progesterone (Duphaston) (24.9%, 28.3% and 25% respectively), (P=1.000and P= 0.359). Conclusion: There is no significant difference in clinical pregnancy rate when different modalities of luteal phase support medications are used in IVF-ET cycles like hCG, oral Duphaston and vaginal Cyclogest. This conclusion is affected by the small number of studied cycles and the study design being retrospective

Effects of crystalloids and colloids on liver and intestine microcirculation and function in cecal ligation and puncture induced septic rodents

Background: Septic acute liver and intestinal failure is associated with a high mortality. We therefore investigated the influence of volume resuscitation with different crystalloid or colloid solutions on liver and intestine injury and microcirculation in septic rodents. Methods: Sepsis was induced by cecal ligation and puncture (CLP) in 77 male rats. Animals were treated with different crystalloids (NaCl 0.9% (NaCl), Ringer’s acetate (RA)) or colloids (Gelafundin 4% (Gel), 6% HES 130/0.4 (HES)). After 24 h animals were re-anesthetized and intestinal (n = 6/group) and liver microcirculation (n = 6/group) were obtained using intravital microscopy, as well as macrohemodynamic parameters were measured. Blood assays and organs were harvested to determine organ function and injury. Results: HES improved liver microcirculation, cardiac index and DO2-I, but significantly increased IL-1β, IL-6 and TNF-α levels and resulted in a mortality rate of 33%. Gel infused animals revealed significant reduction of liver and intestine microcirculation with severe side effects on coagulation (significantly increased PTT and INR, decreased haemoglobin and platelet count). Furthermore Gel showed severe hypoglycemia, acidosis and significantly increased ALT and IL-6 with a lethality of 29%. RA exhibited no derangements in liver microcirculation when compared to sham and HES. RA showed no intestinal microcirculation disturbance compared to sham, but significantly improved the number of intestinal capillaries with flow compared to HES. All RA treated animals survided and showed no severe side effects on coagulation, liver, macrohemodynamic or metabolic state. Conclusions: Gelatine 4% revealed devastated hepatic and intestinal microcirculation and severe side effects in CLP induced septic rats, whereas the balanced crystalloid solution showed stabilization of macro- and microhemodynamics with improved survival. HES improved liver microcirculation, but exhibited significantly increased pro-inflammatory cytokine levels. Crystalloid infusion revealed best results in mortality and microcirculation, when compared with colloid infusion

Preoperative exercise induces endothelial progenitor cell mobilisation in patients undergoing major surgery - A prospective randomised controlled clinical proof-of-concept trial

Introduction: Prehabilitation is increasingly recognised as a therapeutic option to reduce postoperative compli-cations. Investigating the beneficial effects of exercise on cellular mechanisms, we have previously shown that a single episode of exhaustive exercise effectively stimulates endothelial progenitor cells (a cell population asso-ciated with vascular maintenance, repair, angiogenesis, and neovascularization) in correlation with fewer post-operative complications, despite the ongoing debate about the appropriate cell surface marker profiles of these cells (common phenotypical definitions include CD45dim, CD133+, CD34+ and/or CD31+). In order to translate these findings into clinical application, a feasible prehabilitation programme achieving both functional and cellular benefits in a suitable timeframe to expedite surgery is necessary. Objective: The objective of this study was to test the hypothesis that a four-week prehabilitation programme of vigorous-intensity interval exercise training is feasible, increases physical capacity (primary outcome) and the circulatory number of endothelial progenitor cells within peripheral blood. Methods: In this unblinded, parallel-group, randomised controlled proof-of-concept clinical trial (German Clinical Trial Register number: DRKS00000527) conducted between 01st December 2014 and 30th November 2016, fifteen female adult patients scheduled for incontinence surgery with abdominal laparotomy at the University Hospital Cologne were allocated to either an exercise (n = 8, exclusion of 1 patient, analysed n = 7) or non -exercise group (n = 7, exclusion of 1 patient, analysed n = 6). The exercise group's intervention consisted of a vigorous-intensity interval training for four weeks preoperatively. Cardiopulmonary Exercise Testing accompa-nied by peripheral blood collection was performed before and after the (non-)training phase. Cellular in-vestigations were conducted by flow cytometry and cluster-based analyses. Results: Vigorous-intensity interval training over four weeks was feasible in the exercise group (successful completion by 8 out of 8 patients without any harms), with significant improvements in patients' functional capacity (increased oxygen uptake at anaerobic threshold [intervention group mean + 1.71 +/- 3.20 mL/min/kg vs. control group mean-1.83 +/- 2.14 mL/min/kg; p = 0.042] and peak exercise [intervention group mean + 1.71 +/- 1.60 mL/min/kg vs. control group mean-1.67 +/- 1.37 mL/min/kg; p = 0.002]) and a significant increase in the circulatory number of endothelial progenitor cells (proportionate CD45dim/CD14dim/CD133+/CD309+/ CD34+/CD31 + subpopulation within the circulating CD45-pool [p = 0.016]). Conclusions: We introduce a novel prehabilitation concept that shows effective stimulation of an endothelial progenitor cell subpopulation within four weeks of preoperative exercise, serving as a clinical cell-mediated intervention with the aim to reduce surgical complications.Funding: Institutional funding. DFG (German Research Foundation, 491454339) support for the Article Processing Charge