The reflectance spectra of the most abundant meteorites, ordinary chondrites, are different from those of the abundant S-type (mnemonic for siliceous) asteroids. This discrepancy has been thought to ...be due to space weathering, which is an alteration of the surfaces of airless bodies exposed to the space environment. Here we report evidence of space weathering on particles returned from the S-type asteroid 25143 Itokawa by the Hayabusa spacecraft. Surface modification was found in 5 out of 10 particles, which varies depending on mineral species. Sulfur-bearing Fe-rich nanoparticles exist in a thin (5 to 15 nanometers) surface layer on olivine, low-Ca pyroxene, and plagioclase, which is suggestive of vapor deposition. Sulfur-free Fe-rich nanoparticles exist deeper inside (<60 nanometers) ferromagnesian silicates. Their texture suggests formation by metamictization and in situ reduction of Fe2+.
Purpose
The present study was aimed to demonstrate the recuperative effect of nesfatin-1 on testicular dysfunction in the high-fat diet (HFD)/streptozotocin (STZ)-induced type-2 diabetes mellitus ...(T2DM) mice.
Method and results
Three experimental groups were formed: (1) vehicle control (VC), (2) T2DM mice, (3) T2DM + nesf-1. The mice with blood glucose level higher than 300 mg/dL following HFD and a single dose of STZ were used for the experiment. The T2DM mice showed increases in body mass, blood glucose and insulin levels, reductions in spermatogenesis and steroidogenesis, production of antioxidative enzymes, and disturbed lipid profile. These alterations were all ameliorated by administration of nesfatin-1 at 20 μg/Kg BW for 15 days. Nesfatin-1 treatment also increased the production of testosterone (T), improved insulin sensitivity, and effectively ameliorated the testicular aberrations, and increased spermatogenesis and steroidogenesis. In addition, nesfatin-1 treatment upregulated the PCNA and Bcl2 expression and inhibited the caspase-3 and prohibitin expression in T2DM mice. Nesfatin-1 increased insulin receptor (IR) and GLUT8 expressions, and lactate production, the changes that further substantiate the increase of energy influx to the testis.
Conclusion
Altogether, the results suggest the ameliorative effect of nesfatin-1 against T2DM-associated testicular dysfunctions and improved insulin sensitivity along with promoting T production and fertility in T2DM mice.
Caloric restriction (CR) is known to retard aging and delay functional decline as well as the onset of diseases in most organisms. Ghrelin is secreted from the stomach in response to CR and regulates ...energy metabolism. We hypothesized that in CR ghrelin has a role in protecting aging-related diseases. We examined the physiological mechanisms underlying the ghrelin system during the aging process in three mouse strains with different genetic and biochemical backgrounds as animal models of accelerated or normal human aging. The elevated plasma ghrelin concentration was observed in both klotho-deficient and senescence-accelerated mouse prone/8 (SAMP8) mice. Ghrelin treatment failed to stimulate appetite and prolong survival in klotho-deficient mice, suggesting the existence of ghrelin resistance in the process of aging. However, ghrelin antagonist hastened death and ghrelin signaling potentiators rikkunshito and atractylodin ameliorated several age-related diseases with decreased microglial activation in the brain and prolonged survival in klotho-deficient, SAMP8 and aged ICR mice. In vitro experiments, the elevated sirtuin1 (SIRT1) activity and protein expression through the cAMP-CREB pathway was observed after ghrelin and ghrelin potentiator treatment in ghrelin receptor 1a-expressing cells and human umbilical vein endothelial cells. Furthermore, rikkunshito increased hypothalamic SIRT1 activity and SIRT1 protein expression of the heart in the all three mouse models of aging. Pericarditis, myocardial calcification and atrophy of myocardial and muscle fiber were improved by treatment with rikkunshito. Ghrelin signaling may represent one of the mechanisms activated by CR, and potentiating ghrelin signaling may be useful to extend health and lifespan.
Nesfatin-1 is a novel satiety molecule in the hypothalamus and is also present in peripheral tissues. Here we sought to identify the active segment of nesfatin-1 and to determine the mechanisms of ...its action after peripheral administration in mice. Intraperitoneal injection of nesfatin-1 suppressed food intake in a dose-dependent manner. Nesfatin-1 has three distinct segments; we tested the effect of each segment on food intake. Injection of the midsegment decreased food intake under leptin-resistant conditions such as db/db mice and mice fed a high-fat diet. After injection of the midsegment, expression of c-Fos was significantly activated in the brainstem nucleus tractus solitarius (NTS) but not in the hypothalamic arcuate nucleus; the nicotinic cholinergic pathway to the NTS contributed to midsegment-induced anorexia. Midsegment injection significantly increased expression of proopiomelanocortin and cocaine- and amphetamine-regulated transcript genes in the NTS but not in the arcuate nucleus. Investigation of mutant midsegments demonstrated that a region with amino acid sequence similarity to the active site of agouti-related peptide was indispensable for anorexigenic induction. Our findings indicate that the midsegment of nesfatin-1 causes anorexia, possibly by activating POMC and CART neurons in the NTS via a leptin-independent mechanism after peripheral stimulation.
Peripherally administered nesfatin-1 and its mid-segment suppress food intake in mice. The nicotinic cholinergic pathway to the nucleus tractus solitarius contributes to the anorexigenic action of the mid-segment.
Hyperlipidaemia often occurs in patients with type 2 diabetes mellitus. Though HMG-CoA reductase inhibitors (statins) are widely used for controlling hypercholesterolemia, atorvastatin has also been ...reported to have an adverse effect on glucose metabolism. Based on these findings, the aim of this study was to investigate the effects of statins on adipocytes, which play pivotal roles in glucose metabolism.
In 3T3-L1 cells, effects of statins on adipocyte maturation were determined morphologically. Protein and mRNA levels of SLC2A4 and adipocyte marker proteins were determined by immunoblotting and RT-PCR, respectively. Type 2 diabetic NSY mice were treated with atorvastatin for 15 weeks, followed by glucose and insulin tolerance tests and examination of SLC2A4 expression in white adipose tissue (WAT). Seventy-eight Japanese subjects with type 2 diabetes and hypercholesterolaemia were treated with atorvastatin (10 mg/day), and its effects on lipid and glycaemic profiles were measured 12 weeks after treatment initiation.
Treatment with atorvastatin inhibited adipocyte maturation, SLC2A4 and C/EBPalpha expressions and insulin action in 3T3-L1 cells. Atorvastatin also attenuated SLC2A4 and C/EBPalpha expressions in differentiated 3T3-L1 adipocytes. These effects were reversed by L. mevalonate or geranylgeranyl pyrophosphate. In NSY mice, atorvastatin accelerated glucose intolerance as a result of insulin resistance and decreased SLC2A4 expression in WAT. In addition to improving hyperlipidaemia, atorvastatin treatment significantly increased HbA(1c) but not fasting glucose levels in diabetic patients, and this effect was greater in the non-obese subgroup.
These results demonstrate that atorvastatin attenuates adipocyte maturation and SLC2A4 expression by inhibiting isoprenoid biosynthesis, and impairs glucose tolerance. These actions of atorvastatin could potentially affect the control of type 2 diabetes.
Abstract The recent return of samples from asteroid 162173 Ryugu provides a first insight into early Solar System prebiotic evolution from known planetary bodies. Ryugu’s samples are CI ...chondrite-like, rich in water and organic material, and primarily composed of phyllosilicate. This phyllosilicate surrounds micron to submicron macromolecular organic particles known as insoluble organic matter. Using advanced microscopy techniques on Hayabusa-2 samples, we find that aqueous alteration on Ryugu produced organic particles richer in aromatics compared to less altered carbonaceous chondrites. This challenges the view that aromatic-rich organic matter formed pre-accretion. Additionally, widespread diffuse organic material occurs in phyllosilicate more aliphatic-, carboxylic-rich, and aromatic-poor than the discrete organic particles, likely preserving the soluble organic material. Some organic particles evolved to encapsulate phyllosilicate, indicating that aqueous alteration on Ryugu led to the containment of soluble organic matter within these particles. Earth therefore has been, and continues to be, delivered micron-sized polymeric organic objects containing biologically relevant molecules.
Obesity and metabolic syndrome are the major risk factors for cardiovascular disease. Obesity is caused by increased food intake and/or decreased energy expenditure. Leptin potently inhibits food ...intake and promotes energy expenditure. These effects of leptin involve the activation of proopiomelanocortin (POMC) neurons in the hypothalamus arcuate nucleus (ARC). Disruption of leptin signaling in POMC neuron is considered one of the major causes for obesity.
The present study aimed to examine whether overexpression of interleukin-10 (IL-10) could substitute for the leptin action and ameliorate obesity in leptin-deficient Lep(ob/ob) mice.
Adeno-associated virus (AAV) expressing murine IL-10 (AAV-mIL-10) was injected into the skeletal muscle to overexpress IL-10 in mice. These mice were subsequently subjected to analysis of body weight, food intake, glucose metabolism and underlying mechanisms.
In Lep(ob/ob) mice, AAV-IL-10 ameliorated hyperphagia, obesity, glucose intolerance and insulin resistance, as well as attenuated tumor necrosis factor-α expression. The IL-10 treatment also improved glucose-induced insulin release. Furthermore, IL-10 treatment increased POMC mRNA expression in ARC and phosphorylation of signal transducer and activator of transcription-3 (STAT3) in ARC and white adipose tissue (WAT). In neuron-specific STAT3-null mice that exhibited obesity and hyperphagia, AAV-mIL-10 administration failed to affect food intake, body weight and phosphorylation of STAT3 in WAT.
These results demonstrate that peripheral overexpression of IL-10 induces STAT3 phosphorylation in ARC POMC neurons, and thereby ameliorates hyperphagia and obesity caused by leptin deficiency. IL-10 gene transfer may provide an effective approach for preventing progression of metabolic syndrome due to leptin resistance.
Abstract
Ryugu is a second-generation C-type asteroid formed by the reassembly of fragments of a previous larger body in the main asteroid belt. While the majority of Ryugu samples returned by ...Hayabusa2 are composed of a lithology dominated by aqueously altered minerals, clasts of pristine olivine and pyroxene remain in the least-altered lithologies. These clasts are objects of great interest for revealing the composition of the dust from which the original building blocks of Ryugu's parent asteroid formed. Here we show that some grains rich in olivine, pyroxene, and amorphous silicates discovered in one millimeter-sized stone of Ryugu have infrared spectra similar to the D-type asteroid Hektor (a Jupiter Trojan), to comet Hale–Bopp, and to some anhydrous interplanetary dust particles of probable cometary origin. This result indicates that Ryugu's primary parent body incorporated anhydrous ingredients similar to the building blocks of asteroids (and possibly some comets) formed in the outer solar system, and that Ryugu retained valuable information on the formation and evolution of planetesimals at different epochs of our solar system's history.
We developed a novel technique called “analytical dual-energy microtomography” that uses the linear attenuation coefficients (LACs) of minerals at two different X-ray energies to nondestructively ...obtain three-dimensional (3D) images of mineral distribution in materials such as rock specimens. The two energies are above and below the absorption edge energy of an abundant element, which we call the “index element”. The chemical compositions of minerals forming solid solution series can also be measured. The optimal size of a sample is of the order of the inverse of the LAC values at the X-ray energies used. We used synchrotron-based microtomography with an effective spatial resolution of >200nm to apply this method to small particles (30–180μm) collected from the surface of asteroid 25143 Itokawa by the Hayabusa mission of the Japan Aerospace Exploration Agency (JAXA). A 3D distribution of the minerals was successively obtained by imaging the samples at X-ray energies of 7 and 8keV, using Fe as the index element (the K-absorption edge of Fe is 7.11keV). The optimal sample size in this case is of the order of 50μm. The chemical compositions of the minerals, including the Fe/Mg ratios of ferromagnesian minerals and the Na/Ca ratios of plagioclase, were measured. This new method is potentially applicable to other small samples such as cosmic dust, lunar regolith, cometary dust (recovered by the Stardust mission of the National Aeronautics and Space Administration NASA), and samples from extraterrestrial bodies (those from future sample return missions such as the JAXA Hayabusa2 mission and the NASA OSIRIS-REx mission), although limitations exist for unequilibrated samples. Further, this technique is generally suited for studying materials in multicomponent systems with multiple phases across several research fields.
Leptin, an adipocytokine encoded by an obesity gene and expressed in adipose tissue, affects feeding behavior, thermogenesis, and neuroendocrine status via leptin receptors distributed in the brain, ...especially in the hypothalamus. Leptin may also modulate the synaptic plasticity and behavioral performance related to learning and memory since: leptin receptors are found in the hippocampus, and both leptin and its receptor share structural and functional similarities with the interleukin-6 family of cytokines that modulate long-term potentiation (LTP) in the hippocampus. We therefore examined the effect of leptin on (1) behavioral performance in emotional and spatial learning tasks, (2) LTP at Schaffer collateral-CA1 synapses, (3) presynaptic and postsynaptic activities in hippocampal CA1 neurons, (4) the intracellular Ca
2+ concentration (Ca
2+
i) in CA1 neurons, and (5) the activity of Ca
2+/calmodulin protein kinase II (CaMK II) in the hippocampal CA1 tissue that exhibits LTP. Intravenous injection of 5 and/or 50
μg/kg, but not of 500
μg/kg leptin, facilitated behavioral performance in passive avoidance and Morris water-maze tasks. Bath application of 10
−12
M leptin in slice experiments enhanced LTP and increased the presynaptic transmitter release, whereas 10
−10
M leptin suppressed LTP and reduced the postsynaptic receptor sensitivity to
N-methyl-
d-aspartic acid. The increase in the Ca
2+
i induced by 10
−10
M leptin was two times greater than that induced by 10
−12
M leptin. In addition, the facilitation (10
−12
M) and suppression (10
−10
M) of LTP by leptin was closely associated with an increase and decrease in Ca
2+-independent activity of CaMK II. Our results show that leptin not only affects hypothalamic functions (such as feeding, thermogenesis, and neuroendocrine status), but also modulates higher nervous functions, such as the behavioral performance related to learning and memory and hippocampal synaptic plasticity.
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