Positive Regulatory Control Loop between Gut Leptin and Intestinal GLUT2/GLUT5 Transporters Links to Hepatic Metabolic Functions in Rodents

International audienceBACKGROUND AND AIMS: The small intestine is the major site of absorption of dietary sugars. The rate at which they enter and exit the intestine has a major effect on blood glucose homeostasis. In this study, we determine the effects of luminal leptin on activity/expression of GLUT2 and GLUT5 transporters in response to sugars intake and analyse their physiological consequences. METHODOLOGY: Wistar rats, wild type and AMPKalpha(2) (-/-) mice were used. In vitro and in vivo isolated jejunal loops were used to quantify transport of fructose and galactose in the absence and the presence of leptin. The effects of fructose and galactose on gastric leptin release were determined. The effects of leptin given orally without or with fructose were determined on the expression of GLUT2/5, on some gluconeogenesis and lipogenic enzymes in the intestine and the liver. PRINCIPAL FINDINGS: First, in vitro luminal leptin activating its receptors coupled to PKCbetaII and AMPKalpha, increased insertion of GLUT2/5 into the brush-border membrane leading to enhanced galactose and fructose transport. Second in vivo, oral fructose but not galactose induced in mice a rapid and potent release of gastric leptin in gastric juice without significant changes in plasma leptin levels. Moreover, leptin given orally at a dose reproducing comparable levels to those induced by fructose, stimulated GLUT5-fructose transport, and potentiated fructose-induced: i) increase in blood glucose and mRNA levels of key gluconeogenesis enzymes; ii) increase in blood triglycerides and reduction of mRNA levels of intestinal and hepatic Fasting-induced adipocyte factor (Fiaf) and iii) increase in SREBP-1c, ACC-1, FAS mRNA levels and dephosphorylation/activation of ACC-1 in liver. CONCLUSION/SIGNIFICANCE: These data identify for the first time a positive regulatory control loop between gut leptin and fructose in which fructose triggers release of gastric leptin which, in turn, up-regulates GLUT5 and concurrently modulates metabolic functions in the liver. This loop appears to be a new mechanism (possibly pathogenic) by which fructose consumption rapidly becomes highly lipogenic and deleterious

Nanoindentation and birefringence measurements on fused silica specimen exposed to low-energy femtosecond pulses,” Opt.

Abstract: Femtosecond laser pulses used in a regime below the ablation threshold have two noticeable effects on Fused Silica (a-SiO2): they locally increase the material refractive index and modify its HF etching selectivity. The nature of the structural changes induced by femtosecond laser pulses in fused silica is not fully understood. In this paper, we report on nanoindentation and birefringence measurements on fused silica exposed to low-energy femtosecond laser pulses. Our findings further back the hypothesis of localized densification effect even at low energy regime

Micro-manufacturing : research, technology outcomes and development issues

Besides continuing effort in developing MEMS-based manufacturing techniques, latest effort in Micro-manufacturing is also in Non-MEMS-based manufacturing. Research and technological development (RTD) in this field is encouraged by the increased demand on micro-components as well as promised development in the scaling down of the traditional macro-manufacturing processes for micro-length-scale manufacturing. This paper highlights some EU funded research activities in micro/nano-manufacturing, and gives examples of the latest development in micro-manufacturing methods/techniques, process chains, hybrid-processes, manufacturing equipment and supporting technologies/device, etc., which is followed by a summary of the achievements of the EU MASMICRO project. Finally, concluding remarks are given, which raise several issues concerning further development in micro-manufacturing

Saccharomyces boulardii CNCM I-745 Modulates the Fecal Bile Acids Metabolism During Antimicrobial Therapy in Healthy Volunteers

Saccharomyces boulardii CNCM I-745 (SB) is a probiotic yeast used to lower the incidence of antibiotic-associated Clostridium difficile (C. difficile) infection, though its mechanism of action remains unclear. Cholic acid is a primary bile acid, which triggers the germination and promotes the growth of C. difficile. The intestinal microbiota transforms primary into secondary bile acids. This study examined (1) the antimicrobial-induced alteration of fecal bile acid content, and (2) whether the concomitant administration of SB influences this transformation. This is an ancillary work from a randomized study, which revealed that SB modulates fecal microbiota dysbiosis during antibiotic treatment. Healthy subjects were randomly assigned to (1) SB only, (2) amoxicillin-clavulanate (AC), (3) SB plus AC, or (4) no treatment. We analyzed fecal concentrations of BA by high performance liquid chromatography/tandem mass spectrometry. Compared to the untreated or the SB-treated groups, AC decreased the percentage of fecal secondary BA significantly (days 3 and 7). When SB and AC were administered concomitantly, this decrease in secondary BA was no longer significant. Following treatment with AC, a significant peak of fecal CA was measured on days 3 and 7, which was prevented by the concomitant administration of SB. AC administered to healthy volunteers altered the microbial transformation of primary BA, decreased secondary BA, and increased CA. The latter was prevented by the concomitant administration of SB and AC, suggesting a potent mechanism protection conferred by SB against post-antimicrobial C. difficile infection.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT01473368

Generation of high-quality petawatt pulses

CPA sources need a front-end capable of generating very short seed pulses. To meet this requirement, present CPA sources rely on actively modelocked solid-state oscillators used in conjunction with non-linear fiber stages. This approach generates pulses with a residual frequency chirp, resulting in a limited peak-to-background intensity contrast ratio. The availability of an oscillator capable of producing directly (i.e. without fiber stage) picosecond or sub-picosecond pulses would significantly improve the quality of CPA sources. We have pursued different approaches to replace the standard modelocked oscillator front-end. In an initial phase, we investigated the possible use of Additive Pulse Modelocking (APM) color-center lasers as oscillators for CPA Nd:glass sources. Lately we have developed a Ti:Sapphire modelocked oscillator operating in the one-micron range. In order to generate pulses with very high peak to background contrast ratio, we have built a non-linear coupled-cavity oscillator generating 200-fs pulses. This color-center laser operates in the 1.5--1.6 micron range. A diagram of the oscillator is shown in Fig. 1. The laser is pumped with a modelocked Nd:YAG source. Both KCl and NaCl crystals were tested as gain media. NaCl was found to have a larger tuning range and to generate a higher average power (up to 150 mW). When synchronously mode-locked, the color-center generates pulses in the 10--20 ps range. Once interferometrically coupled to non-linear external-cavity, this oscillator produces very short pulses (85 to 260 fs). This oscillator was first operated with a 2 mm birefringent plate. 85 fs, near transform-limited pulses were generated at 1.54 micron. As the laser was tuned to longer wavelength, the pulse duration increased, as well as the bandwidth-duration product. With a 4 mm birefringent plate, 125 fs, transform-limited pulses were generated over the full tuning range

Thermal conductivity contrast measurement of Fused Silica exposed to low-energy femtosecond laser pulses

Femtosecond laser irradiation has various noticeable effects on fused silica. Of particular interest, pulses with energy levels below the ablation threshold can locally increase the refractive index and the material etching selectivity to hydrofluoric acid. The mechanism responsible for these effects is not yet fully understood. In this paper, we report on local thermal conductivity mapping of laser-affected zones. It is found that these zones exhibit a lower thermal conductivity at room temperature

Integrating optics and micro-mechanics in a single substrate: a step toward monolithic integration in fused silica

We present a novel optical sensor concept that merges integrated optics and micro-mechanics in a monolithic substrate. This concept pushes microsystems integration and defines a new class of monolithic optical microsystems where only optical signals are processed. As an illustration, we present a high-precision, monolithic, glass-based, micro-displacement sensor. Our displacement sensor is made out of a single piece of glass through a two-step process based on femtosecond laser illumination followed by chemical etching

Fabrication of high-aspect ratio, micro-fluidic channels and tunnels using femtosecond laser pulses and chemical etching

We present novel results obtained in the fabrication of high-aspect ratio micro-fluidic microstructures chemically etched from fused silica substrates locally exposed to femtosecond laser radiation. A volume sampling method to generate three-dimensional patterns is proposed and a systematic SEM-based analysis of the microstructure is presented. The results obtained gives new insights toward a better understanding of the femtosecond laser interaction with fused silica glass (a-SiO2)