Ghrelin requires p53 to stimulate lipid storage in fat and liver

Ghrelin, a stomach-derived peptide, stimulates feeding behavior and adiposity. For its orexigenic action, ghrelin triggers a central SIRT1/p53/AMPK pathway. The tumor suppressor p53 also plays an important role in white adipose tissue (WAT), where it is up-regulated in the adipocytes of obese mice. It is not known, however, whether p53 has any role in mediating the peripheral action of ghrelin. In the present study, chronic peripheral ghrelin treatment resulted in increased body weight and fat-mass gain in wild-type mice. Correspondingly, mRNA levels of several adipogenic and fat-storage-promoting enzymes were up-regulated in WAT, whereas hepatic triglyceride content and lipogenic enzymes were also increased in wild-type mice following ghrelin treatment. In contrast, mice lacking p53 failed to respond to ghrelin treatment, with their body weight, fat mass, and adipocyte and hepatic metabolism remaining unchanged. Thus, our results show that p53 is necessary for the actions of ghrelin on WAT and liver, leading to changes in expression levels of lipogenic and adipogenic genes, and modifying body weight

A gliclazide complex based on palladium towards Alzheimer's disease: promising protective activity against Aβ-induced toxicity in C. elegans

A new palladium coordination compound based on gliclazide with the chemical formula [Pd(glz)2] (where glz = gliclazide) has been synthesized and characterised. The structural characterization reveals that this material consists of mononuclear units formed by a Pd2+ ion coordinated to two molecules of the glz ligand, in which palladium ions exhibit a distorted plane-square coordination sphere. This novel material behaves like a good and selective inhibitor of butyrylcholinesterase, one of the most relevant therapeutic targets against Alzheimer’s disease. Analysis of the enzyme kinetics showed a mixed mode of inhibition, the title compound being capable of interacting with both the free enzyme and the enzyme–substrate complex. Finally, the palladium compound shows promising protective activity against Ab-induced toxicity in the Caenorhabditis elegans model, which has never been reported

A Mixed Heterobimetallic Y/Eu-MOF for the Cyanosilylation and Hydroboration of Carbonyls

Supplementary Materials The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/catal12030299/s1. Table S1: Elemental analysis of compounds Y/Eu-MOF. Table S2: ICP-AES results of compound Y/Eu-MOF. Table S3: Crystallographic data and structure refinement details of compound Y/Eu-MOF. Table S4: Selected bond lengths (Å) and angles (°) for compound Y/Eu-MOF. Table S5: Table of the continuous Shape Measurements for the MN3O6 coordination environment. Table S6: Table of the continuous Shape Measurements for the MO8 coordination environment. Table S7: Electrophoretic mobility and ζ-potential dependence, with the pH of the Y/Eu-MOFs particles dispersed in water. Conductivity fixed at 330 µS/cm. Table S8: Optimization of the reaction conditions in the hydroboration reaction. Table S9: Green metrics calculated for Y/Eu-MOF catalyst. Table S10: Catalytic cyanosilylation of benzaldehyde performances of Ln-MOFs, as reported in the literature. Figure S1: Figure of the pattern matching analysis and experimental PXRD for Y/Eu-MOF. Figure S2: Figure of the infrared spectra of the ligand and Y/Eu-MOF. Figure S3: SEM and EDS mapping of bulk material of Y/Eu-MOF. Figure S4: Images and particle size distribution (an overall of 250 particles) in the deposited fraction of Y/Eu-MOF catalyst non-suspended in water (about a 68% of the total amount), determined from optical microscope images. Figure S5: Images and particle size distribution (an overall of 250 particles) of Y/Eu-MOF crystals in the fraction steadily suspended in water (about a 32% of the total amount), determined from optical microscope images. Figure S6: Comparation of the particle size distribution of Y/Eu-MOF in the fraction steadily suspended in water and the non-suspended, determined from optical microscope images. Figure S7: Calibration line of conductivity (µS/cm) vs [NaCl] (mol/L). Figure S8: ζ-potential (mV) dependence with the pH of the Y/Eu-MOF. All the measurements were performed with constant conductivity of 330 µS/cm. Figure S9: Electrophoretic mobility (µm·cm/V·s) dependence with the pH of the Y/Eu-MOF. All the measurements were performed with constant conductivity of 330 µS/cm. Figure S10: Study of the recyclability of Y/Eu-MOF (0.5 mol%) catalyst on the cyanosilylation and hydroboration reaction of acetophenone as carbonyl substrate. Figure S11: Analysis of the TOF (h−1) obtained in the cyanosilylation reaction of acetophenone at different times of reaction with Y/Eu-MOF (0.5 mol%), with the optimized reaction conditions. Figure S12: Analysis of the TOF (h−1) obtained in the hydroboration reaction acetophenone at different times of reaction with Y/Eu-MOF (0.5 mol%), with the optimized reaction conditions. Scheme S1: Reaction conditions used for the study of recyclability of Y/Eu-MOF catalysts in the cyanosilylation reaction. Scheme S2: Reaction conditions used for the study of recyclability of Y/Eu-MOF catalysts in the hydroboration reaction. Scheme S3: Leaching test, carried out after the first and second cycles.Funding: This research has been funded by the State Research Agency (grants CTQ2017-84334-R and PGC2018-102052-B-C21) of the Spanish Ministry of Science, Innovation and Universities, the European Union (European Regional Development Fund—ERDF), Junta de Andalucía (P20_01041, UAL2020-AGR-B1781, B-FQM-734-UGR20 and FQM-394). E.E., S.R., and J.P. acknowledge the Government of the Basque Country, Juan de la Cierva Incorporación (grant no. IJC2019-038894-I) and University of Almeria (grant no. HIPATIA2021_04) for their respective fellowsHerein, to the best of our knowledge, the first heterobimetallic Y/Eu porous metal–organic framework (MOF), based on 3-amino-4-hydroxybenzoic acid (H2L) ligand, with the following formulae {[Y3.5Eu1.5L6(OH)3(H2O)3]·12DMF}n (in advance, namely Y/Eu-MOF), is described. The three-dimensional structure has been synthesized by solvothermal routes and thoroughly characterized, by means of single crystal X-ray diffraction, powder X-ray diffraction, electronic microscopy, ICP-AES, electrophoretic mobility, and FTIR spectra. Intriguingly, the porous nature allows for coordinated solvent molecules displacement, yielding unsaturated metal centers, which can act as a Lewis acid catalyst. This novel supramolecular entity has been tested in cyanosilylation and hydroboration reactions on carbonyl substrates of a diverse nature, exhibiting an extraordinary activity.Cierva Incorporación IJC2019-038894-IState Research Agency CTQ2017-84334-R, PGC2018-102052-B-C21University of Almeria HIPATIA2021_04Ministerio de Ciencia, Innovación y UniversidadesEuropean CommissionEuropean Regional Development FundJunta de Andalucía B-FQM-734-UGR20, FQM-394, IJC2019-038894-I, P20_01041, UAL2020-AGR-B178

2D-Coordination polymers based on 1H-indazole4-carboxylic acid and transition metal ions: magnetic, luminescence and biological properties

We report the formation of five novel multifunctional coordination polymers based on 1H-indazole-4- carboxylic acid (HL). To the best of our knowledge, these complexes are the first examples of coordination compounds constructed with this interesting ligand. These materials were synthesized by solvothermal routes, possess different 2D-structures and show interesting magnetic properties due to the copper compound showing an unusual spin-canted effect while the anisotropic cobalt material behaves as a fieldinduced single molecule magnet. MTT assays performed on human embryonic kidney (HEK293) and mouse skin melanoma (B16-F10) cell lines indicated that the Cd-based compound was the only one exhibiting dose-dependent toxicity on B16-F10 cells, most likely due to the release of toxic Cd(II). Cadmium and zinc polymers exhibit interesting luminescence properties. The fact that zinc polymers did not exhibit inherent toxicity against both cancer and non-cancerous cells make this new family an excellent candidate for further investigation in the field of luminescent materials with biomedical applications.Junta de Andalucia FQM-394 FQM-1484Red Guipuzcoana de Ciencia, Tecnologia e Innovacion OF218/2018University of Basque Country GIU 17/13Basque Government IT1005-16Spanish Ministry of Science, Innovation and Universities (MCIU/AEI/FEDER, UE) PGC2018-102052-A-C22 PGC2018-102052-B-C21Junta de Andalucia FQM-394 FQM-1484European Union (EU)ESFGovernment of the Basque CountryFEDER/MCIU/AEI RYC-2016-21042 JdC-201

Caliope: an operational air quality forecasting system for the Iberian Peninsula, Balearic Islands and Canary Islands ? first annual evaluation and ongoing developments

International audienceThe Caliope project funded by the Spanish Ministry of the Environment establishes an air quality forecasting system for Spain to increase the knowledge on transport and dynamics of pollutants in Spain, to assure the accomplishment of legislation and to inform the population about the levels of pollutants, topics in which the European Commission has shown a great concern. The present contribution describes the first quantitative verification study performed so far with two chemistry transport models (CMAQ and CHIMERE) for a reference year (2004) at medium spatial resolution (around 20×20 km for the Iberian Peninsula). Both models perform similarly in the case of ground-level ozone. The mean normalised gross error MNGE remains below 15?20% during summertime, when ozone episodes occur, outlining the good skills of the system concerning the forecasting of air quality in Spain. Furthermore, the ongoing developments of the system towards high resolution modelling (4×4 km for Spain, 12×12 km for Europe, 1 h temporal resolution) and the integration with observations within the Caliope umbrella are described

Sequential Exposure to Obesogenic Factors in Females Rats: From Physiological Changes to Lipid Metabolism in Liver and Mesenteric Adipose Tissue

During their lifetime, females are subjected to different nutritional and hormonal factors that could increase the risk of obesity and associated comorbidities. From early postnatal periods until the postmenopausal phase, exposure to over nutrition, high-energy diet and oestrogen deficiency, are considered as significant obesity risk factors in women. In this study, we assessed how key transitional life events and exposure to different nutrition influence energy homeostasis in a rat model. Specifically, we assessed the sequential exposure to postnatal over nutrition, high-fat diet (HFD) after weaning, followed later by ovariectomy (OVX; as a model of menopause). Each obesity risk factor increased significantly body weight (BW) and adiposity, with additive effects after sequential exposure. Increased energy intake in both HFD and/or OVX groups, and decreased locomotor activity and energy expenditure after OVX can explain these metabolic changes. Our study also documents decreased lipogenic pathway in mesenteric adipose tissue after HFD and/or OVX, independent of previous postnatal programming, yet only HFD evoked this effect in liver. In addition, we report an increase in the expression of the hepatic PEPCK depending on previous metabolic status. Overall, our results identify the impact of different risk factors, which will help in understanding the development of obesity in females

Lack of Hypophagia in CB1 Null Mice is Associated to Decreased Hypothalamic POMC and CART Expression

Background: Cumulative data indicate that the endocannabinoid system plays a major role in feeding behavior and energy balance. Genetic silencing of cannabinoid receptor type 1 (CB1) reduces body weight gain, independently of food intake. Methods: In this work, we investigated whether the hypothalamic neuropeptide expression pattern supports the absence of the anorexigenic response observed under constitutive CB1 ablation, by using neuronal CB1 conditional null mice (CamK-CB1-KO) and whole body CB1 null mice (CB1-KO). Results: Our data showed that both CB1 null models display a marked decrease in proopiomelanocortin (POMC) and cocaine-amphetamine-regulated transcript (CART) expression in the arcuate nucleus of the hypothalamus (ARC). Conclusions: This evidence suggests that a lack of hypophagia is associated with the suppression of ARC anorexigenic neuropeptides and that behavioral changes in food intake (or lack thereof) after constitutive CB1 ablation are likely mediated by impaired melanocortin and CART signaling in the hypothalamus.The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement nº 281854 of the ObERStress European Research Council Project (Dr López) and 245009 of the Neurofast project (Drs Nogueiras, Diéguez, and López); Xunta de Galicia (Dr Nogueiras: EM 2012/039 and 2012-CP069; Dr López: 2012-CP070); the Frank Mohn Foundation, Bergen (Dr Fernø); Instituto de Salud Carlos III (ISCIII; Dr López: PI12/01814 and PIE13/00024); and MINECO, co-funded by the FEDER Program of EU (Dr Nogueiras: RyC-2008-02219 and BFU2012-35255; Dr Diéguez: BFU2011-29102). CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIIIS