Ghrelin, a stomach-derived orexigenic hormone, has stimulated great interest as a potential target for obesity control. Pharmacological evidence indicates that ghrelin’s effects on food intake are ...mediated by neuropeptide Y (NPY) and agouti-related protein (AgRP) in the central nervous system. These include intracerebroventricular application of antibodies to neutralize NPY and AgRP, and the application of an NPY Y1 receptor antagonist, which blocks some of the orexigenic effects of ghrelin. Here we describe treatment of Agrp−/−;Npy−/− and Mc3r−/−;Mc4r−/− double knockout mice as well as Npy−/− and Agrp−/− single knockout mice with either ghrelin or an orally active nonpeptide ghrelin agonist. The data demonstrate that NPY and AgRP are required for the orexigenic effects of ghrelin, as well as the involvement of the melanocortin pathway in ghrelin signaling. Our results outline a functional interaction between the NPY and AgRP pathways. Although deletion of either NPY or AgRP caused only a modest or nondetectable effect, ablation of both ligands completely abolished the orexigenic action of ghrelin. Our results establish an in vivo orexigenic function for NPY and AgRP, mediating the effect of ghrelin.
Melanin-concentrating hormone (MCH) is a cyclic 19-aa hypothalamic neuropeptide derived from a larger prohormone precursor of MCH (Pmch), which also encodes neuropeptide EI (NEI) and neuropeptide GE ...(NGE). Pmch-deficient (Pmch-/-) mice are lean, hypophagic, and have an increased metabolic rate. Transgenic mice overexpressing Pmch are hyperphagic and develop mild obesity. Consequently, MCH has been implicated in the regulation of energy homeostasis. The MCH 1 receptor (MCH1R) is one of two recently identified G protein-coupled receptors believed to be responsible for the actions of MCH. We evaluated the physiological role of MCH1R by generating MCH1R-deficient (Mch1r-/-) mice. Mch1r-/-mice have normal body weights, yet are lean and have reduced fat mass. Surprisingly, Mch1r-/-mice are hyperphagic when maintained on regular chow, and their leanness is a consequence of hyperactivity and altered metabolism. Consistent with the hyperactivity, Mch1r-/-mice are less susceptible to diet-induced obesity. Importantly, chronic central infusions of MCH induce hyperphagia and mild obesity in wild-type mice, but not in Mch1r-/-mice. We conclude that MCH1R is a physiologically relevant MCH receptor in mice that plays a role in energy homeostasis through multiple actions on locomotor activity, metabolism, appetite, and neuroendocrine function.
The stability of electrochemical double layer capacitors (EDLC) utilizing an ionic liquid and tetraethylammoninium tetrafluoroborate (TEABF4) in acetonitrile electrolyte was tested by cycling and by ...constant voltage hold tests. It turned out that possible degradation of the EDLC is visible in the voltage hold test after a time period which is typically much shorter if compared to the cycle tests. A constant capacitance during several thousands of cycles does not necessarily indicate stability. For capacitor cells using a carbon black as active material and an ionic liquid as electrolyte constant capacitance could be demonstrated over 12,000 cycles between 0 V and 3.75 V. Clear ageing was observed, however, during the voltage hold test at 3.75 V after 300 h. For a maximum voltage of 3.5 V both the cycle and the voltage hold test indicated stable performance over 12,000 cycles or 500 h, respectively. For capacitors using an activated carbon as active material and standard electrolyte TEABF4 in acetonitrile both tests clearly demonstrated degradation for a maximum cell voltage of 3.5 V. The evolution of capacitance loss observed for the voltage hold test at 3.25 V is in good agreement with the degradation observed at 3.5 V for the voltage hold test.
► Stability tests for double layer capacitors by cycling and voltage hold were compared. ► The voltage hold test turns out to be more demanding than the cycle test. ► The same capacitance loss was observed after much shorter test time for the voltage hold test. ► The cycle test overestimated the voltage limit for stability by about 0.3 V.
A reliable method for the determination of regions of electrochemical stability of electrolytes for electrochemical double layer capacitors (EDLC) by means of potential window opening measurements is ...presented. For this purpose, a new evaluation method for the anodic and cathodic potential limits of electrochemical systems utilizing high surface area carbon electrodes is suggested. A change of 5% in the faradaic current contribution within a potential step of 1V to the overall current is proposed as new stability criterion. The results of seven ionic liquids (IL) and three standard electrolytes dissolved in acetonitrile (AN) or propylene carbonate (PC) at RT are presented. For two electrolytes a temperature dependent study is conducted. The feasibility of the new criterion is verified by full cell constant voltage aging experiments. The IL EMIMBF4 displays a maximum cell voltage of 3.5V at RT, which is, compared to standard electrolytes, an increase of about 0.5V.
Genome-wide association studies (GWAS) have demonstrated the ability to identify the strongest causal common variants in complex human diseases. However, to date, the massive data generated from GWAS ...have not been maximally explored to identify true associations that fail to meet the stringent level of association required to achieve genome-wide significance. Genetics of gene expression (GGE) studies have shown promise towards identifying DNA variations associated with disease and providing a path to functionally characterize findings from GWAS. Here, we present the first empiric study to systematically characterize the set of single nucleotide polymorphisms associated with expression (eSNPs) in liver, subcutaneous fat, and omental fat tissues, demonstrating these eSNPs are significantly more enriched for SNPs that associate with type 2 diabetes (T2D) in three large-scale GWAS than a matched set of randomly selected SNPs. This enrichment for T2D association increases as we restrict to eSNPs that correspond to genes comprising gene networks constructed from adipose gene expression data isolated from a mouse population segregating a T2D phenotype. Finally, by restricting to eSNPs corresponding to genes comprising an adipose subnetwork strongly predicted as causal for T2D, we dramatically increased the enrichment for SNPs associated with T2D and were able to identify a functionally related set of diabetes susceptibility genes. We identified and validated malic enzyme 1 (Me1) as a key regulator of this T2D subnetwork in mouse and provided support for the association of this gene to T2D in humans. This integration of eSNPs and networks provides a novel approach to identify disease susceptibility networks rather than the single SNPs or genes traditionally identified through GWAS, thereby extracting additional value from the wealth of data currently being generated by GWAS.
The energy storage mechanism of electric double-layer capacitors is governed by ion electrosorption at the electrode surface. This process requires high surface area electrodes, typically highly ...porous carbons. In common organic electrolytes, bare ion sizes are below one nanometer but they are larger when we consider their solvation shell. In contrast, ionic liquid electrolytes are free of solvent molecules, but cation-anion coordination requires special consideration. By matching pore size and ion size, two seemingly conflicting views have emerged: either an increase in specific capacitance with smaller pore size or a constant capacitance contribution of all micro- and mesopores. In our work, we revisit this issue by using a comprehensive set of electrochemical data and a pore size incremental analysis to identify the influence of certain ranges in the pore size distribution to the ion electrosorption capacity. We see a difference in solvation of ions in organic electrolytes depending on the applied voltage and a cation-anion interaction of ionic liquids in nanometer sized pores.
•Pore size incremental analysis shows non-constant capacitive contribution.•Differential capacitance depends on type of ion and solvent.•Ion desolvation may become more important at higher electrode potentials.•Ionic liquids exhibit cation-anion coordination.
Polyvinylpyrrolidone (PVP) is presented as a “greener” alternative to commonly used supercapacitor binders, namely polyvinylidenedifluoride (PVDF) or polytetrafluoroethylene (PTFE). The key ...advantages of using PVP are that it is non-toxic and soluble in ethanol and it can be used to spray coat or drain cast activated carbon (AC) electrodes directly on a current collector such as aluminum foil – in contrast to PTFE that requires rolling or PVDF that requires toxic N-methylpyrrolidone (NMP). The electrodes with the best mechanical stability incorporated 3.5 mass% of 1.300.000 g mol−1 PVP. Compared to PTFE or PVDF, the resulting pore volume was significantly higher and the specific surface area significantly larger when using PVP (normalized to the amount of AC). A good electrochemical performance was observed in organic electrolytes for AC–PVP electrodes: 112 or 97 F g−1 at 0.1 A g−1 in 1 M TEA–BF4 in propylene carbonate or acetonitrile, respectively. The performance stability was comparable to PTFE-bound electrodes when adjusting the maximum cell voltage to 2.5 V while preserving the manufacturing features of PVDF–AC films. (Electro)chemical stability is shown by electrochemical testing and infrared vibrational spectroscopy for propylene carbonate and acetonitrile.
•Polyvinylpyrrolidone (PVP) can be used as a binder in supercapacitors.•PVP-electrodes can be casted or sprayed and used in organic electrolytes.•PVP as a binder yields better performance as polyvinylidenedifluoride (PVDF).
This study investigates carbon onions (~400 m super(2) g super(-1)) as a conductive additive for supercapacitor electrodes of activated carbon and compares their performance with carbon black with ...high or low internal surface area. We provide a study of the electrical conductivity and electrochemical behavior between 2.5 and 20 mass% addition of each of these three additives to activated carbon. Structural characterization shows that the density of the resulting film electrodes depends on the degree of agglomeration and the amount of additive. Addition of low surface area carbon black (~80 m super(2) g super(-1)) enhances the power handling of carbon electrodes but significantly lowers the specific capacitance even when adding small amounts of carbon black. A much lower decrease in specific capacitance is observed for carbon onions and the best values are seen for carbon black with a high surface area (~1390 m super(2) g super(-1)). The overall performance benefits from the addition of any of the studied additives only at either high scan rates and/or electrolytes with high ion mobility. Normalization to the volume shows a severe decrease in volumetric capacitance and only at high current densities nearing 10 A g super(-1) we can see an improvement of the electrode capacitance.
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