Effects of supplemented isoenergetic diets varying in cereal fiber and protein content on the bile acid metabolic signature and relation to insulin resistance

Bile acids (BA) are potent metabolic regulators influenced by diet. We studied effects of isoenergetic increases in the dietary protein and cereal-fiber contents on circulating BA and insulin resistance (IR) in overweight and obese adults. Randomized controlled nutritional intervention (18 weeks) in 72 non-diabetic participants (overweight/obese: 29/43) with at least one further metabolic risk factor. Participants were group-matched and allocated to four isoenergetic supplemented diets: control; high cereal fiber (HCF); high-protein (HP); or moderately increased cereal fiber and protein (MIX). Whole-body IR and insulin-mediated suppression of hepatic endogenous glucose production were measured using euglycaemic–hyperinsulinemic clamps with [6-62H2] glucose infusion. Circulating BA, metabolic biomarkers, and IR were measured at 0, 6, and 18 weeks. Under isoenergetic conditions, HP-intake worsened IR in obese participants after 6 weeks (M-value: 3.77 ± 0.58 vs. 3.07 ± 0.44 mg/kg/min, p = 0.038), with partial improvement back to baseline levels after 18 weeks (3.25 ± 0.45 mg/kg/min, p = 0.089). No deleterious effects of HP-intake on IR were observed in overweight participants. HCF-diet improved IR in overweight participants after 6 weeks (M-value 4.25 ± 0.35 vs. 4.81 ± 0.31 mg/kg/min, p = 0.016), but did not influence IR in obese participants. Control and MIX diets did not influence IR. HP-induced, but not HCF-induced changes in IR strongly correlated with changes of BA profiles. MIX-diet significantly increased most BA at 18 weeks in obese, but not in overweight participants. BA remained unchanged in controls. Pooled BA concentrations correlated with fasting fibroblast growth factor-19 (FGF-19) plasma levels (r = 0.37; p = 0.003). Higher milk protein intake was the only significant dietary predictor for raised total and primary BA in regression analyses (total BA, p = 0.017; primary BA, p = 0.011). Combined increased intake of dietary protein and cereal fibers markedly increased serum BA concentrations in obese, but not in overweight participants. Possible mechanisms explaining this effect may include compensatory increases of the BA pool in the insulin resistant, obese state; or defective BA transport

Thirty years beyond discovery—Clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism

This review summarizes a presentation made at the retirement Symposium of Prof. Dr. Cornelis Jakobs in November of 2011, highlighting the progress toward clinical trials in succinic semialdehyde dehydrogenase (SSADH) deficiency, a disorder first recognized in 1981. Active and potential clinical interventions, including vigabatrin, L‐cycloserine, the GHB receptor antagonist NCS‐382, and the ketogenic diet, are discussed. Several biomarkers to gauge clinical efficacy have been identified, including cerebrospinal fluid metabolites, neuropsychiatric testing, MRI, EEG, and measures of GABAergic function including (11 C)flumazenil positron emission tomography (PET) and transcranial magnetic stimulation (TMS). Thirty years after its discovery, encompassing extensive studies in both patients and the corresponding murine model, we are now running an open‐label trial of taurine intervention, and are poised to undertake a phase II trial of the GABAB receptor antagonist SGS742

De novo transcriptome of the cosmopolitan dinoflagellate Amphidinium carterae to identify enzymes with biotechnological potential

Abstract Dinoflagellates are phytoplanktonic organisms found in both freshwater and marine habitats. They are often studied because related to harmful algal blooms but they are also known to produce bioactive compounds for the treatment of human pathologies. The aim of this study was to sequence the full transcriptome of the dinoflagellate Amphidinium carterae in both nitrogen-starved and -replete culturing conditions (1) to evaluate the response to nitrogen starvation at the transcriptional level, (2) to look for possible polyketide synthases (PKSs) in the studied clone (genes that may be involved in the synthesis of bioactive compounds), (3) if present, to evaluate if nutrient starvation can influence PKS expression, (4) to look for other possible enzymes of biotechnological interest and (5) to test strain cytotoxicity on human cell lines. Results showed an increase in nitrogen metabolism and stress response in nitrogen-starved cells and confirmed the presence of a type I β-ketosynthase. In addition, L-asparaginase (used for the treatment of Leukemia and for acrylamide reduction in food industries) and cellulase (useful for biofuel production and other industrial applications) have been identified for the first time in this species, giving new insights into possible biotechnological applications of dinoflagellates