Production rates and metabolism of short-chain fatty acids in the colon and whole body using stable isotopes

Short-chain fatty acids (SCFA; mainly acetate, propionate and butyrate) are largely produced in non-ruminants during the colonic bacterial fermentation of non-digestible carbohydrates. These intestinal exogenous SCFA pass in part through the splanchnic bed and reach the peripheral bloodstream, mixing with the endogenous circulating SCFA. The whole-body turnover of SCFA is thus composed of an endogenous peripheral turnover and an exogenous production that depends on dietary intake of non-digestible carbohydrates. In the present work methods were developed for determining the SCFA turnover in animals and in human subjects using stable isotopes. The original studies performed to determine endogenous and exogenous metabolism of SCFA in animals and in human subjects are summarised. Using intravenous infusion of 13C-labelled SCFA the whole-body turnover of acetate, propionate and butyrate was assessed in rats in a fasted state. The endogenous turnover of acetate and its oxidation were determined in healthy human subjects in the post-absorptive state, using intravenous infusion of[l-13C]acetate. Intragastric tracer infusions were performed to evaluate the splanchnic first-pass retention of acetate in adults. Finally, an original model was developed in healthy human subjects using intravenous infusion of[l-13C]acetate to determine in vivo the true colonic acetate production after ingestion of a non-digestible disaccharide. These present studies using stable isotopes provide the basis for a novel strategy to evaluate in vivo, in human subjects, the production of SCFA in the large intestin

Cholesterol lowering effect of a soy drink enriched with plant sterols in a French population with moderate hypercholesterolemia

<p>Abstract</p> <p>Background</p> <p>Plant sterols are an established non-pharmacological means to reduce total and LDL blood cholesterol concentrations and are therefore recommended for cholesterol management by worldwide-renown health care institutions. Their efficacy has been proven in many types of foods with the majority of trials conducted in spreads or dairy products. As an alternative to dairy products, soy based foods are common throughout the world. Yet, there is little evidence supporting the efficacy of plant sterols in soy-based foods. The objective of this study was to investigate the effect of a soy drink enriched with plant sterols on blood lipid profiles in moderately hypercholesterolemic subjects.</p> <p>Methods</p> <p>In a randomized, placebo-controlled double-blind mono-centric study, 50 subjects were assigned to 200 ml of soy drink either enriched with 2.6 g plant sterol esters (1.6 g/d free plant sterol equivalents) or without plant sterols (control) for 8 weeks. Subjects were instructed to maintain stable diet pattern and physical activity. Plasma concentrations of lipids were measured at initial visit, after 4 weeks and after 8 weeks. The primary measurement was the change in LDL cholesterol (LDL-C). Secondary measurements were changes in total cholesterol (TC), non-HDL cholesterol (non-HDL-C), HDL cholesterol (HDL-C) and triglycerides.</p> <p>Results</p> <p>Regular consumption of the soy drink enriched with plant sterols for 8 weeks significantly reduced LDL- C by 0.29 mmol/l or 7% compared to baseline (p < 0.05). TC and non-HDL-C concentrations decreased by 0.26 mmol/l and 0.31 mmol/l (each p < 0.05), respectively. Mean reductions in total, LDL and non-HDL cholesterol were significantly greater than in the placebo group (p < 0.05). HDL-C and triglycerides were not affected. Compliance was very high (>96%), and products were well tolerated.</p> <p>Conclusion</p> <p>Daily consumption of a plant sterol-enriched soy drink significantly decreased total, non-HDL and LDL cholesterol and is therefore an interesting and convenient aid in managing mild to moderate hypercholesterolemia.</p

Use of advanced cluster analysis to characterize seafood consumption patterns and methyle mercury exposures among pregnant women

Because of the variability in food contamination and nutrient contents, consumers must balance the risks and benefits of fish consumption through their choice of species, meal size and frequency. The objectives of this study were to characterize the risk of MeHg exposure in French pregnant women consuming fish, and to explore the use of unsupervised statistical learning as an advanced type of cluster analysis to identify patterns of fish consumption that could predict exposure to MeHg and the coverage of the Recommended Daily Allowance for n-3 PUFA. The proportion of pregnant women exposed at levels higher than the Tolerable Weekly Intake (PTWI) for MeHg is similar to that observed amongst women of childbearing age in previous French studies. At the same time, only about 50% of the women reached the recommended intake of 500 mg/day n-3 PUFA. Cluster analysis of the fish consumption showed that they could be grouped in five major clusters that are largely predictable of the intake of both MeHg and n-3 PUFA. This study provides demonstrates that a global increase in seafood consumption could lead to MeHg exposure above the toxicological limits, thereby questioning the potential beneficial effects of n-3 PUFA intakes

Stable isotope spectrometry to study human protein and amino acid metabolism

O desenvolvimento e uso de técnicas laboratoriais, envolvendo espectrometria de massa, permitiram que os isótopos estáveis pudessem ser utilizados na avaliação do metabolismo aminoacídico e protéico, em seres biológicos. Assim, medidas precisas de enriquecimento isotópico, ao nível de 3-6% além do basal, após infusão de 13C-, 15N- ou de ²H2 -aminoácido, tornaram possível realizar a avaliação das interrelações metabólicas protéicas no organismo, in vivo. O método pode ser considerado pouco invasivo, sendo necessário, geralmente, coleta de ar expirado e sangue periférico, para determinação de substratos na concentração em torno de nanomolar. Desta maneira, períodos de infusão isotópica, de 4-6 horas, de 13C-leucina, permitem estimativa do metabolismo protéico corpóreo total, pela medida direta da oxidação, via determinação do 13CO2, no ar expirado, e da 13C-Leu ou seu metabólito, 13C-KIC, no sangue, assim como estimativa da degradação e síntese protéica. Mais recentemente, o advento de nova técnica, ou seja, a da associação de combustão da amostra à cromatografia e espectrometria, tornou o método mais sensível, sendo possível a determinação de substrato, marcado em amostras diluídas por um fator mínimo de 10. O método também permite o estudo da interrelação do metabolismo protéico com o de hidrato de carbono e lipídeo, quando aplicado a aminoácidos, essenciais ou não, associados a glicídios e a triglicerídeos.The aim of this work is to describe the gas chromatography/mass spectrometry (GC/MS) and its clinical application. GC/MS is becoming a tool for clinical diagnosis and research procedure interested in the molecular pathogenesis of diseases. The method is highly sensitive analytical that can obtain precise information on molecule weight and structure from a trace amount of sample. It has been applied to a wide range of fields from physics and chemistry, to life sciences such as biochemistry, pharmacy and medicine

Experimenting cross-disciplinary cooperation by an experimental One Health degree program around the triad Animal-Man-Food

Magras Catherine, Diguet Anne-Laure, Lepelletier Didier, Eveillard Mathieu, Couvreur Sébastien, Ruvoen-Clouet Nathalie, Krempf Michel. L’Idefi Man-Imal : une formation One-Health de la pluri- à l’interdisciplinarité. In: Bulletin de l'Académie Vétérinaire de France tome 171 n°2, 2018. pp. 100-102

Plasma ceramide, a real-time predictive marker of pulmonary and hepatic metastases response to stereotactic body radiation therapy combined with irinotecan

AbstractBackground and purposesEarly biomarkers of tumour response are needed to discriminate between responders and non-responders to radiotherapy. We evaluated the ability of ceramide, a bioactive sphingolipid, to predict tumour sensitivity in patients treated by hypofractionated stereotactic body radiation therapy (SBRT) combined with irinotecan chemotherapy.Materials and methodsPlasma levels of total ceramide and of its subspecies were measured before and during treatment in 35 patients with liver and lung oligometastases of colorectal cancer included in a phase II trial. Cer levels were quantified by LC–ESI-MS/MS and compared to tumour volume response evaluated one year later by CT-scan.ResultsPretreatment plasma ceramide levels were not indicative of tumour response. Nevertheless, the levels of total ceramide and of its 4 main subspecies were significantly higher at days 3 and 10 of treatment in objective responders than in non-responders. According to Kaplan–Meier curves, almost complete tumour control was achieved at 1year in patients with increased total ceramide levels whereas 50% of patients with decreased levels experienced an increase in tumour volume.ConclusionsTotal plasma ceramide is a promising biomarker of tumour response to SBRT combined with irinotecan that should enable to segregate patients with high risk of tumour escape

Patient and physician factors influence decision-making in hypercholesterolemia: a questionnaire-based survey

Abstract Background Goal attainment of guideline-recommended low-density lipoprotein cholesterol (LDL-C) is suboptimal. Little is known about how patient factors influence physicians’ treatment decision-making in hypercholesterolemia. We examined physicians’ treatment recommendations in high-risk patients whose LDL-C remained uncontrolled despite statin monotherapy. Methods Physicians completed a questionnaire prior to randomization into period I of a two-period randomized controlled trial evaluating LDL-C goal attainment in patients whose LDL-C remained ≥100 mg/dL after 5 weeks’ treatment with atorvastatin 10 mg/day (NCT01154036). Physicians’ treatment recommendations were surveyed for two hypothetical and one real scenario: (1) LDL-C presumed near goal (between 100–105 mg/dL), (2) LDL-C presumed far from goal (~120 mg/dL), and (3) observed baseline LDL-C of enrolled patients. Prognostic factors considered during decision-making were identified by regression analysis. Observed lipid outcomes at the end of period I (following 6 weeks’ treatment with ezetimibe 10 mg plus atorvastatin 10 mg, atorvastatin 20 mg, or rosuvastatin 10 mg) were compared with estimated LDL-C outcomes for physicians’ treatment recommendations after 6 weeks (based on individual patients’ pre-randomization LDL-C and expected incremental change). Results Questionnaires were completed for 1,534 patients. No change in therapy, or double atorvastatin dose, were frequently recommended, even when LDL-C was far from goal (6.5% and 52.2% of patients, respectively). Double atorvastatin dose was commonly recommended in all scenarios (43–52% of patients). More intensive LDL-C-lowering regimens were recommended infrequently e.g. double atorvastatin dose and add ezetimibe only <12% in all scenarios. Overall, cardiovascular risk factors and desire to achieve a more aggressive LDL-C goal were prominent factors in decision-making for treatment. Comparison of observed and estimated LDL-C levels showed that physicians tended to overestimate the effectiveness of their recommendations. Conclusions This study provides insight into physicians’ perspectives on clinical management of hypercholesterolemia and highlights a gap in knowledge translation from guidelines to clinical practice. The need for lower LDL-C and cardiovascular risk were key drivers in clinical decision-making, but physicians’ treatment choices were more conservative than guideline recommendations, potentially resulting in poorer LDL-C reduction. When compared with actual outcomes, projected LDL-C control was better if physicians used more comprehensive strategies rather than simply doubling the statin dose. Trial registration Clinicaltrials.gov: NCT0115403

Identification of novel APOB mutations by targeted next-generation sequencing for the molecular diagnosis of familial hypobetalipoproteinemia

International audienceFamilial hypobetalipoproteinemia (FHBL) is a co-dominant disorder characterized by decreased plasma levels of LDL-cholesterol and apolipoprotein B (ApoB). Currently, genetic diagnosis in FHBL relies largely on Sanger sequencing to identify APOB and PCSK9 gene mutations and on western blotting to detect truncated ApoB species

The selective peroxisome proliferator-activated receptor alpha modulator (SPPARM) paradigm : conceptual framework and therapeutic potential: A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARM) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARM agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARM agonist safely reduces residual cardiovascular risk.Peer reviewe

Residual vascular risk in diabetes – will the SPPARM alpha concept hold the key?

No abstract available