Time sequence of the intensification of the liver glucose production induced by high-fat diet in mice

It is well established that the development of insulin resistance shows a temporal sequence in different organs and tissues. Moreover, considering that the main aspect of insulin resistance in liver is a process of glucose overproduction from gluconeogenesis, we investigated if this metabolic change also shows temporal sequence. For this purpose, a well-established experimental model of insulin resistance induced by high-fat diet (HFD) was used. The mice received HFD (HFD group) or standard diet (COG group) for 1, 7, 14 or 56?days. The HFD group showed increased (P?<?0.05 versus COG) epididymal, retroperitoneal and inguinal fat weight from days 1 to 56. In agreement with these results, the HFD group also showed higher body weight (P?<?0.05 versus COG) from days 7 to 56. Moreover, the changes induced by HFD on liver gluconeogenesis were progressive because the increment (P?<?0.05 versus COG) in glucose production from l-lactate, glycerol, l-alanine and l-glutamine occurred 7, 14, 56 and 56 days after the introduction of the HFD schedule, respectively. Furthermore, glycaemia and cholesterolemia increased (P?<?0.05 versus COG) 14?days after starting the HFD schedule. Taken together, the results suggest that the intensification of liver gluconeogenesis induced by an HFD is not a synchronous all-or-nothing process but is specific for each gluconeogenic substrate and is integrated in a temporal manner with the progressive augmentation of fasting glycaemia. Copyright (c) 2012 John Wiley & Sons, Ltd.

A Low-Protein, High-Carbohydrate Diet Increases Fatty Acid Uptake and Reduces Norepinephrine-Induced Lipolysis in Rat Retroperitoneal White Adipose Tissue

A low-protein, high-carbohydrate (LPHC) diet for 15 days increased the lipid content in the carcass and adipose tissues of rats. The aim of this work was to investigate the mechanisms of this lipid increase in the retroperitoneal white adipose tissue (RWAT) of these animals. The LPHC diet induced an approximately two- and tenfold increase in serum corticosterone and TNF-alpha, respectively. The rate of de novo fatty acid (FA) synthesis in vivo was reduced (50%) in LPHC rats, and the lipoprotein lipase activity increased (100%). In addition, glycerokinase activity increased (60%), and the phosphoenolpyruvate carboxykinase content decreased (27%). Basal [U-C-14]-glucose incorporation into glycerol-triacylglycerol did not differ between the groups; however, in the presence of insulin, [U-C-14]-glucose incorporation increased by 124% in adipocytes from only control rats. The reductions in IRS1 and AKT content as well as AKT phosphorylation in the RWAT from LPHC rats and the absence of an insulin response suggest that these adipocytes have reduced insulin sensitivity. The increase in NE turnover by 45% and the lack of a lipolytic response to NE in adipocytes from LPHC rats imply catecholamine resistance. The data reveal that the increase in fat storage in the RWAT of LPHC rats results from an increase in FA uptake from circulating lipoproteins and glycerol phosphorylation, which is accompanied by an impaired lipolysis that is activated by NE.

The spectrum of high-energy cosmic rays measured with KASCADE-Grande

The energy spectrum of cosmic rays between 10(16) eV and 10(18) eV, derived from measurements of the shower size (total number of charged particles) and the total muon number of extensive air showers by the KASCADE-Grande experiment, is described. The resulting all-particle energy spectrum exhibits strong hints for a hardening of the spectrum at approximately 2 . 10(16) eV and a significant steepening at approximate to 8 . 10(16) eV. These observations challenge the view that the spectrum is a single power law between knee and ankle. Possible scenarios generating such features are discussed in terms of astrophysical processes that may explain the transition region from galactic to extragalactic origin of cosmic rays. (C) 2012 Elsevier B.V. All rights reserved.

Effects of high-energy astrophysical events on habitable planets

With the possible exception of meteor impacts, high-energy astrophysical events such as supernovae, gamma-ray bursts (GRB) and flares are usually not taken into account for biological and evolutionary studies due to their low rates of occurrence. We show that a class of these events may occur at distances and time scales in which their biological effects are non-negligible, maybe more frequent than the impacts of large asteroids. We review the effects of four transient astrophysical sources of ionizing radiation on biospheres - stellar flares, giant flares from soft gamma repeaters (SGR), supernovae and GRB. The main damaging features of them are briefly discussed and illustrated. We point out some open problems and ongoing work. Received 28 February 2012, accepted 6 July 2012, first published online 10 August 2012

SEARCH FOR POINT-LIKE SOURCES OF ULTRA-HIGH ENERGY NEUTRINOS AT THE PIERRE AUGER OBSERVATORY AND IMPROVED LIMIT ON THE DIFFUSE FLUX OF TAU NEUTRINOS

The surface detector array of the Pierre Auger Observatory can detect neutrinos with energy E-nu between 10(17) eV and 10(20) eV from point-like sources across the sky south of +55 degrees and north of -65 degrees declinations. A search has been performed for highly inclined extensive air showers produced by the interaction of neutrinos of all flavors in the atmosphere (downward-going neutrinos), and by the decay of tau leptons originating from tau neutrino interactions in Earth's crust (Earth-skimming neutrinos). No candidate neutrinos have been found in data up to 2010 May 31. This corresponds to an equivalent exposure of similar to 3.5 years of a full surface detector array for the Earth-skimming channel and similar to 2 years for the downward-going channel. An improved upper limit on the diffuse flux of tau neutrinos has been derived. Upper limits on the neutrino flux from point-like sources have been derived as a function of the source declination. Assuming a differential neutrino flux k(PS) . E-nu(-2). from a point-like source, 90% confidence level upper limits for k(PS) at the level of approximate to 5x10(-7) and 2.5x10(-6) GeV cm(-2) s(-1) have been obtained over a broad range of declinations from the searches for Earth-skimming and downward-going neutrinos, respectively.

Caffeic acid phenethyl ester reduces the activation of the nuclear factor kappa B pathway by high-fat diet-induced obesity in mice

Objective. The aim of this study was to investigate the effect of CAPE on the insulin signaling and inflammatory pathway in the liver of mice with high fat diet induced obesity. Material/Methods. Swiss mice were fed with standard chow or high-fat diet for 12-week. After the eighth week, animals in the HFD group with serum glucose levels higher than 200 mg/dL were divided into two groups, HFD and HFD receiving 30 mg/kg of CAPE for 4 weeks. After 12 weeks, the blood samples could be collected and liver tissue extracted for hormonal and biochemical measurements, and insulin signaling and inflammatory pathway analyzes. Results. The high-fat diet group exhibited more weight gain, glucose intolerance, and hepatic steatosis compared with standard diet group. The CAPE treatment showed improvement in glucose sensitivity characterized by an area under glucose curve similar to the control group in an oral glucose tolerance test Furthermore, CAPE treatment promoted amelioration in hepatic steatosis compared with the high-fat diet group. The increase in glucose sensitivity was associated with the improvement in insulin-stimulated phosphorylation of the insulin receptor substrate-2, followed by an increase in Akt phosphorylation. In addition, it was observed that CAPE reduced the induction of the inflammatory pathway, c-jun-N- terminal kinase, the nuclear factor kappa B, and cyclooxygenase-2 expression, respectively. Conclusions. Overall, these findings indicate that CAPE exhibited anti-inflammatory activity that partly restores normal metabolism, reduces the molecular changes observed in obesity and insulin resistance, and therefore has a potential as a therapeutic agent in obesity. (C) 2012 Elsevier Inc. All rights reserved.

Exercise training improves relaxation response and SOD-1 expression in aortic and mesenteric rings from high caloric diet-fed rats

Abstract Background Obesity has been associated with a variety of disease such as type II diabetes mellitus, arterial hypertension and atherosclerosis. Evidences have shown that exercise training promotes beneficial effects on these disorders, but the underlying mechanisms are not fully understood. The aim of this study was to investigate whether physical preconditioning prevents the deleterious effect of high caloric diet in vascular reactivity of rat aortic and mesenteric rings. Methods Male Wistar rats were divided into sedentary (SD); trained (TR); sedentary diet (SDD) and trained diet (TRD) groups. Run training (RT) was performed in sessions of 60 min, 5 days/week for 12 weeks (70–80% VO2max). Triglycerides, glucose, insulin and nitrite/nitrate concentrations (NOx-) were measured. Concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained. Expression of Cu/Zn superoxide dismutase (SOD-1) was assessed by Western blotting. Results High caloric diet increased triglycerides concentration (SDD: 216 ± 25 mg/dl) and exercise training restored to the baseline value (TRD: 89 ± 9 mg/dl). Physical preconditioning significantly reduced insulin levels in both groups (TR: 0.54 ± 0.1 and TRD: 1.24 ± 0.3 ng/ml) as compared to sedentary animals (SD: 0.87 ± 0.1 and SDD: 2.57 ± 0.3 ng/ml). On the other hand, glucose concentration was slightly increased by high caloric diet, and RT did not modify this parameter (SD: 126 ± 6; TR: 140 ± 8; SDD: 156 ± 8 and TRD 153 ± 9 mg/dl). Neither high caloric diet nor RT modified NOx- levels (SD: 27 ± 4; TR: 28 ± 6; SDD: 27 ± 3 and TRD: 30 ± 2 μM). Functional assays showed that high caloric diet impaired the relaxing response to ACh in mesenteric (about 13%), but not in aortic rings. RT improved the relaxing responses to ACh either in aortic (28%, for TR and 16%, to TRD groups) or mesenteric rings (10%, for TR and 17%, to TRD groups) that was accompanied by up-regulation of SOD-1 expression and reduction in triglycerides levels. Conclusion The improvement in endothelial function by physical preconditioning in mesenteric and aortic arteries from high caloric fed-rats was directly related to an increase in NO bioavailability to the smooth muscle mostly due to SOD-1 up regulation.

Does long-term creatine supplementation impair kidney function in resistance-trained individuals consuming a high-protein diet?

Abstract Background The aim of this study was to determine the effects of creatine supplementation on kidney function in resistance-trained individuals ingesting a high-protein diet. Methods A randomized, double-blind, placebo-controlled trial was performed. The participants were randomly allocated to receive either creatine (20 g/d for 5 d followed by 5 g/d throughout the trial) or placebo for 12 weeks. All of the participants were engaged in resistance training and consumed a high-protein diet (i.e., ≥ 1.2 g/Kg/d). Subjects were assessed at baseline (Pre) and after 12 weeks (Post). Glomerular filtration rate was measured by 51Cr-EDTA clearance. Additionally, blood samples and a 24-h urine collection were obtained for other kidney function assessments. Results No significant differences were observed for 51Cr-EDTA clearance throughout the trial (Creatine: Pre 101.42 ± 13.11, Post 108.78 ± 14.41 mL/min/1.73m2; Placebo: Pre 103.29 ± 17.64, Post 106.68 ± 16.05 mL/min/1.73m2; group x time interaction: F = 0.21, p = 0.64). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria remained virtually unchanged. Conclusions A 12-week creatine supplementation protocol did not affect kidney function in resistance-trained healthy individuals consuming a high-protein diet; thus reinforcing the safety of this dietary supplement. Trial registration ClinicalTrials.gov NCT01817673

On Ti-18Si-6B and Ti-7.5Si-22.5B powder alloys prepared by high-energy ball milling and sintering

Recently, a new ternary phase was discovered in the Ti-Si-B system, located near the Ti6Si2B composition. The present study concerns the preparation of titanium alloys that contain such phase mixed with α-titanium and other intermetallic phases. High-purity powders were initially processed in a planetary ball-mill under argon atmosphere with Ti-18Si-6B and Ti-7.5Si-22.5B at. (%) initial compositions. Variation of parameters such as rotary speed, time, and ball diameters were adopted. The as-milled powders were pressureless sintered and hot pressed. Both the as-milled and sintered materials were characterized by X-ray diffraction, scanning electron microscopy and energy-dispersive spectrometry. Sintered samples have presented equilibrium structures formed mainly by the α-Ti+Ti6Si2B+Ti5Si3+TiB phases. Silicon and boron peaks disappear throughout the milling processes, as observed in the powder diffraction data. Furthermore, an iron contamination of up to 10 at. (%) is measured by X-ray spectroscopy analysis on some regions of the sintered samples. Density, hardness and tribological results for these two compositions are also presented here.

Exercise and caloric restriction alter the immune system of mice submitted to a high-fat diet

As the size of adipocytes increases during obesity, the establishment of resident immune cells in adipose tissue becomes an important source of proinflammatory mediators. Exercise and caloric restriction are two important, nonpharmacological tools against body mass increase. To date, their effects on the immune cells of adipose tissue in obese organisms, specifically when a high-fat diet is consumed, have been poorly investigated. Thus, after consuming a high-fat diet, mice were submitted to chronic swimming training or a 30% caloric restriction in order to investigate the effects of both interventions on resident immune cells in adipose tissue. These strategies were able to reduce body mass and resulted in changes in the number of resident immune cells in the adipose tissue and levels of cytokines/chemokines in serum. While exercise increased the number of NK cells in adipose tissue and serum levels of IL-6 and RANTES, caloric restriction increased the CD4+/CD8+ cell ratio and MCP-1 levels. Together, these data demonstrated that exercise and caloric restriction modulate resident immune cells in adipose tissues differently in spite of an equivalent body weight reduction. Additionally, the results also reinforce the idea that a combination of both strategies is better than either individually for combating obesity

Metformin attenuates the exacerbation of the allergic eosinophilic inflammation in high fat-diet-induced obesity in mice

A positive relationship between obesity and asthma has been well documented. The AMP-activated protein kinase (AMPK) activator metformin reverses obesity-associated insulin resistance (IR) and inhibits different types of inflammatory responses. This study aimed to evaluate the effects of metformin on the exacerbation of allergic eosinophilic inflammation in obese mice. Male C57BL6/J mice were fed for 10 weeks with high-fat diet (HFD) to induce obesity. The cell infiltration and inflammatory markers in bronchoalveolar lavage (BAL) fluid and lung tissue were evaluated at 48 h after ovalbumin (OVA) challenge. HFD obese mice displayed peripheral IR that was fully reversed by metformin (300 mg/kg/day, two weeks). OVA-challenge resulted in higher influx of total cell and eosinophils in lung tissue of obese mice compared with lean group. As opposed, the cell number in BAL fluid of obese mice was reduced compared with lean group. Metformin significantly reduced the tissue eosinophil infiltration and prevented the reduction of cell counts in BAL fluid. In obese mice, greater levels of eotaxin, TNF-α and NOx, together with increased iNOS protein expression were observed, all of which were normalized by metformin. In addition, metformin nearly abrogated the binding of NF-κB subunit p65 to the iNOS promoter gene in lung tissue of obese mice. Lower levels of phosphorylated AMPK and its downstream target acetyl CoA carboxylase (ACC) were found in lung tissue of obese mice, which were restored by metformin. In separate experiments, the selective iNOS inhibitor aminoguanidine (20 mg/kg, 3 weeks) and the anti-TNF-α mAb (2 mg/kg) significantly attenuated the aggravation of eosinophilic inflammation in obese mice. In conclusion, metformin inhibits the TNF-α-induced inflammatory signaling and NF-κB-mediated iNOS expression in lung tissue of obese mice. Metformin may be a good pharmacological strategy to control the asthma exacerbation in obese individuals.

Bounds on the density of sources of ultra-high energy cosmic rays from the Pierre Auger Observatory

We derive lower bounds on the density of sources of ultra-high energy cosmic rays from the lack of significant clustering in the arrival directions of the highest energy events detected at the Pierre Auger Observatory. The density of uniformly distributed sources of equal intrinsic intensity was found to be larger than ~(0.06 - 5) × '10 POT. -4' 'Mpc POT. -3' at 95% CL, depending on the magnitude of the magnetic deflections. Similar bounds, in the range (0.2 - 7) × '10 POT. -4' 'Mpc POT. -3', were obtained for sources following the local matter distribution.

A high energy perspective of the co-evolution of black holes and their host galaxies

Thanks to the Chandra and XMM–Newton surveys, the hard X-ray sky is now probed down to a flux limit where the bulk of the X-ray background is almost completely resolved into discrete sources, at least in the 2–8 keV band. Extensive programs of multiwavelength follow-up observations showed that the large majority of hard X–ray selected sources are identified with Active Galactic Nuclei (AGN) spanning a broad range of redshifts, luminosities and optical properties. A sizable fraction of relatively luminous X-ray sources hosting an active, presumably obscured, nucleus would not have been easily recognized as such on the basis of optical observations because characterized by “peculiar” optical properties. In my PhD thesis, I will focus the attention on the nature of two classes of hard X-ray selected “elusive” sources: those characterized by high X-ray-to-optical flux ratios and red optical-to-near-infrared colors, a fraction of which associated with Type 2 quasars, and the X-ray bright optically normal galaxies, also known as XBONGs. In order to characterize the properties of these classes of elusive AGN, the datasets of several deep and large-area surveys have been fully exploited. The first class of “elusive” sources is characterized by X-ray-to-optical flux ratios (X/O) significantly higher than what is generally observed from unobscured quasars and Seyfert galaxies. The properties of well defined samples of high X/O sources detected at bright X–ray fluxes suggest that X/O selection is highly efficient in sampling high–redshift obscured quasars. At the limits of deep Chandra surveys (∼10−16 erg cm−2 s−1), high X/O sources are generally characterized by extremely faint optical magnitudes, hence their spectroscopic identification is hardly feasible even with the largest telescopes. In this framework, a detailed investigation of their X-ray properties may provide useful information on the nature of this important component of the X-ray source population. The X-ray data of the deepest X-ray observations ever performed, the Chandra deep fields, allows us to characterize the average X-ray properties of the high X/O population. The results of spectral analysis clearly indicate that the high X/O sources represent the most obscured component of the X–ray background. Their spectra are harder (G ∼ 1) than any other class of sources in the deep fields and also of the XRB spectrum (G ≈ 1.4). In order to better understand the AGN physics and evolution, a much better knowledge of the redshift, luminosity and spectral energy distributions (SEDs) of elusive AGN is of paramount importance. The recent COSMOS survey provides the necessary multiwavelength database to characterize the SEDs of a statistically robust sample of obscured sources. The combination of high X/O and red-colors offers a powerful tool to select obscured luminous objects at high redshift. A large sample of X-ray emitting extremely red objects (R−K >5) has been collected and their optical-infrared properties have been studied. In particular, using an appropriate SED fitting procedure, the nuclear and the host galaxy components have been deconvolved over a large range of wavelengths and ptical nuclear extinctions, black hole masses and Eddington ratios have been estimated. It is important to remark that the combination of hard X-ray selection and extreme red colors is highly efficient in picking up highly obscured, luminous sources at high redshift. Although the XBONGs do not present a new source population, the interest on the nature of these sources has gained a renewed attention after the discovery of several examples from recent Chandra and XMM–Newton surveys. Even though several possibilities were proposed in recent literature to explain why a relatively luminous (LX = 1042 − 1043erg s−1) hard X-ray source does not leave any significant signature of its presence in terms of optical emission lines, the very nature of XBONGs is still subject of debate. Good-quality photometric near-infrared data (ISAAC/VLT) of 4 low-redshift XBONGs from the HELLAS2XMMsurvey have been used to search for the presence of the putative nucleus, applying the surface-brightness decomposition technique. In two out of the four sources, the presence of a nuclear weak component hosted by a bright galaxy has been revealed. The results indicate that moderate amounts of gas and dust, covering a large solid angle (possibly 4p) at the nuclear source, may explain the lack of optical emission lines. A weak nucleus not able to produce suffcient UV photons may provide an alternative or additional explanation. On the basis of an admittedly small sample, we conclude that XBONGs constitute a mixed bag rather than a new source population. When the presence of a nucleus is revealed, it turns out to be mildly absorbed and hosted by a bright galaxy.

4H silicon carbide particle detectors: study of the defects induced by high energy neutron irradiation

During the last decade advances in the field of sensor design and improved base materials have pushed the radiation hardness of the current silicon detector technology to impressive performance. It should allow operation of the tracking systems of the Large Hadron Collider (LHC) experiments at nominal luminosity (1034 cm-2s-1) for about 10 years. The current silicon detectors are unable to cope with such an environment. Silicon carbide (SiC), which has recently been recognized as potentially radiation hard, is now studied. In this work it was analyzed the effect of high energy neutron irradiation on 4H-SiC particle detectors. Schottky and junction particle detectors were irradiated with 1 MeV neutrons up to fluence of 1016 cm-2. It is well known that the degradation of the detectors with irradiation, independently of the structure used for their realization, is caused by lattice defects, like creation of point-like defect, dopant deactivation and dead layer formation and that a crucial aspect for the understanding of the defect kinetics at a microscopic level is the correct identification of the crystal defects in terms of their electrical activity. In order to clarify the defect kinetic it were carried out a thermal transient spectroscopy (DLTS and PICTS) analysis of different samples irradiated at increasing fluences. The defect evolution was correlated with the transport properties of the irradiated detector, always comparing with the un-irradiated one. The charge collection efficiency degradation of Schottky detectors induced by neutron irradiation was related to the increasing concentration of defects as function of the neutron fluence.