El tejido adiposo marrón, una estrategia terapéutica prometedora contra las enfermedades asociadas a la obesidad

Los niveles alarmantes de prevalencia de la obesidad a nivel mundial han llevado a la Organización Mundial de la Salud a considerar esta enfermedad como la epidemia del Siglo XXI. Además, es un reconocido factor de riesgo para otras enfermedades como la diabetes, enfermedades cardiovasculares, dislipemias y algunos tipos de cáncer. Es por ello que se dedican grandes recursos tanto a la investigación de las bases moleculares de esta enfermedad como a la búsqueda de nuevas terapias. Hasta hace unos años, el tejido adiposo blanco era el protagonista principal en la investigación dedicada a una búsqueda de una diana terapéutica contra la obesidad y las enfermedades relacionadas con ésta. En cambio, el papel del tejido adiposo marrón (BAT) pasaba desapercibido, debido a su menor abundancia y que se consideraba exclusivo de los roedores y en neonatos humanos. Sin embargo, en la década pasada, se redescubrió la presencia y actividad del BAT en humanos adultos mediante la combinación de las técnicas de tomografía de emisión de positrones (PET) y la tomografía computarizada (CT). Con el redescubrimiento en 2009 del tejido adiposo marrón se abrió una nueva puerta para el tratamiento de la obesidad y sus complicaciones asociadas. Este tejido posee un elevado potencial termogénico y de oxidación de sustratos, por lo que incrementar su actividad supondría una prometedora estrategia en la homeostasis energética corporal. Esto abrió un nuevo campo y destacó al BAT como un nuevo objetivo terapéutico para luchar contra los trastornos relacionados con la obesidad.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Esta conferencia se impartirá con el apoyo económico de una ayuda para conferenciantes de los fondos que para tal fin tiene asignado el presupuesto del Departamento de Biología Molecular y Bioquímica

Alexander Von Humboldt, perfil de un sabio

2009 has been a year of celebrations for science. It has been the year of Galileo and Darwin. But few remember that in 2009 the 150th anniversary of the death of a great scientific figure was also celebrated, the considered ‘Father of Universal Modern Geography’, Alexander Von Humboldt (1769-1859), a naturalist of extraordinary versatility that was not repeated after his disappearanceEl 2009 ha sido un año de celebraciones para la ciencia. Ha sido el año de Galileo y Darwin. Pero poco se acuerdan que en 2009 también se ha celebrado el  150 aniversario de la muerte de una gran figura científica. el considerado ''Padre de la Geografía Moderna Universal '', Alexander Von Humboldt (1769-1859), un naturalista de una polivalencia extraordinari que no volvió a repetirse tras su desaparició

Plasma microrna expression profile for reduced ejection fraction in dilated cardiomyopathy

The left ventricular (LV) ejection fraction (EF) is key to prognosis in dilated cardiomyopathy (DCM). Circulating microRNAs have emerged as reliable biomarkers for heart diseases, included DCM. Clinicians need improved tools for greater clarification of DCM EF categorization, to identify highrisk patients. Thus, we investigated whether microRNA profiles can categorize DCM patients based on their EF. 179-differentially expressed circulating microRNAs were screened in two groups: (1) non-idiopathic DCM; (2) idiopathic DCM. Then, 26 microRNAs were identified and validated in the plasma of ischemic-DCM (n = 60), idiopathic-DCM (n = 55) and healthy individuals (n = 44). We identified fourteen microRNAs associated with echocardiographic variables that differentiated idiopathic DCM according to the EF degree. A predictive model of a three-microRNA (miR-130b-3p, miR-150-5p and miR-210-3p) combined with clinical variables (left bundle branch block, left ventricle end-systolic dimension, lower systolic blood pressure and smoking habit) was obtained for idiopathic DCM with a severely reduced-EF. The receiver operating characteristic curve analysis supported the discriminative potential of the diagnosis. Bioinformatics analysis revealed that miR-150-5p and miR-210-3p target genes might interact with each other with a high connectivity degree. In conclusion, our results revealed a three-microRNA signature combined with clinical variables that highly discriminate idiopathic DCM categorization. This is a potential novel prognostic biomarker with high clinical value

Estratègies de modulació de l'oxidació d'àcids grassos com a tractament per combatre l'obesitat

L'estil de vida actual, amb dietes d'alt contingut calòric i falta d'exercici físic, fa que la incidència d'obesitat s'incrementi notablement. Augmentar la degradació de greixos o bé reduir la ingesta calòrica poden ser potencials estratègies terapèutiques. L'enzim carnitina palmitoïltransferasa I (CPT1) és el pas limitant de l'oxidació dels àcids grassos. En aquest article, es mostra com la modulació de la seva activitat en diferents teixits, com el fetge, el teixit adipós o l'hipotàlem, pot ser clau a l'hora d'augmentar la despesa energètica i controlar la ingesta d'aliments.Current lifestyles, with high-energy diets and little exercise, are triggering an alarming growth in obesity. Strategies that enhance fat degradation or reduce caloric food intake could be considered therapeutic interventions to reduce not only obesity, but also its associated disorders. The enzyme carnitine palmitoyltransferase I (CPT1) is the critical rate-determining regulator of fatty acid oxidation. In this paper, we show that this enzyme might play a key role in different tissues, such as liver, adipose tissue and hypothalamus, increasing energy expenditure and controlling food intake

Mechanisms of Impaired Brown Adipose Tissue Recruitment in Obesity

Brown adipose tissue (BAT) dissipates energy to produce heat. Thus, it has the potential to regulate body temperature by thermogenesis. For the last decade, BAT has been in the spotlight due to its rediscovery in adult humans. This is evidenced by over a hundred clinical trials that are currently registered to target BAT as a therapeutic tool in the treatment of metabolic diseases, such as obesity or diabetes. The goal of most of these trials is to activate the BAT thermogenic program via several approaches such as adrenergic stimulation, natriuretic peptides, retinoids, capsinoids, thyroid hormones, or glucocorticoids. However, the impact of BAT activation on total body energy consumption and the potential effect on weight loss is still limited. Other studies have focused on increasing the mass of thermogenic BAT. This can be relevant in obesity, where the activity and abundance of BAT have been shown to be drastically reduced. The aim of this review is to describe pathological processes associated with obesity that may influence the correct differentiation of BAT, such as catecholamine resistance, inflammation, oxidative stress, and endoplasmic reticulum stress. This will shed light on the thermogenic potential of BAT as a therapeutic approach to target obesity-induced metabolic diseases. Keywords: differentiation, BAT recruitment, preadipocyte, obesity, catecholamine, inflammation, oxidative stress, endoplasmic reticulum stres

Deconstructing sugarcane bagasse lignocellulose by acid-based deep eutectic solvents to enhance enzymatic digestibility

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGBiorefinery with deep eutectic solvent (DES) is an emerging processing technology to overcome the shortcomings of conventional biomass pretreatments. This work evaluates the biorefinery of sugarcane bagasse (SCB) with DES formulated with choline chloride as hydrogen bond acceptor and three hydrogen bond donors: lactic acid, citric acid, and acetic acid. Acetic acid showed unique ionic properties responsible for the selective removal of lignin and the deconstruction of cellulose to improve the digestibility of up to 97.61 % of glucan and 63.95 % of xylan during enzymatic hydrolysis. In addition, the structural characteristics of the polysaccharide-rich material (PRM) were analyzed by X-rays, ATR-FTIR, SEM, and enzymatic hydrolysis, and compared with the original material sample, for a comprehensive understanding of biomass deconstruction using different hydrogen bond donors (HBD) as DES pretreatment.Ministerio de Ciencia e Innovación | Ref. PID2020-115879RB-I00São Paulo​ Research Foundation | Ref. 2018/25511-1São Paulo​ Research Foundation | Ref. 2021/15138-4National Council for Scientific and Technological Development—CNPq | Ref. 312923/2020-1National Council for Scientific and Technological Development—CNPq | Ref. 408783/2021-4Xunta de Galicia | Ref. GPC-ED431B 2021/2

Mitochondrial free [Ca2+] levels and the permeability transition

Producción CientíficaMitochondrial Ca2+ activates many processes, from mitochondrial metabolism to opening of the permeability transition pore (PTP) and apoptosis. However, there is considerable controversy regarding the free mitochondrial [Ca2+] ([Ca2+]M) levels that can be attained during cell activation or even in mitochondrial preparations. Studies using fluorescent dyes (rhod-2 or similar), have reported that phosphate precipitation precludes [Ca2+]M from increasing above 2–3 M. Instead, using low-Ca2+-affinity aequorin probes, we have measured [Ca2+]M values more than two orders of magnitude higher. We confirm here these values by making a direct in situ calibration of mitochondrial aequorin, and we show that a prolonged increase in [Ca2+]M to levels of 0.5–1mM was actually observed at any phosphate concentration (0–10mM) during continuous perfusion of 3.5–100 MCa2+-buffers. In spite of this high and maintained (>10 min) [Ca2+]M, mitochondria retained functionality and the [Ca2+]M drop induced by a protonophore was fully reversible. In addition, this high [Ca2+]M did not induce PTP opening unless additional activators (phenyl arsine oxide, PAO) were present. PAO induced a rapid, concentration-dependent and irreversible drop in [Ca2+]M. In conclusion [Ca2+]M levels of 0.5–1mM can be reached and maintained for prolonged periods (>10 min) in phosphate-containing medium, and massive opening of PTP requires additional pore activators

Ca2+ Dynamics in the Secretory Vesicles of Neurosecretory PC12 and INS1 Cells

Producción CientíficaWe have investigated the dynamics of the free [Ca2+] inside the secretory granules of neurosecretory PC12 and INS1 cells using a low-Ca2+-affinity aequorin chimera fused to synaptobrevin-2. The steady-state secretory granule [Ca2+] ([Ca2+]SG] was around 20–40 lM in both cell types, about half the values previously found in chromaffin cells. Inhibition of SERCA-type Ca2+ pumps with thapsigargin largely blocked Ca2+ uptake by the granules in Ca2+-depleted permeabilized cells, and the same effect was obtained when the perfusion medium lacked ATP. Consistently, the SERCA-type Ca2+ pump inhibitor benzohydroquinone induced a rapid release of Ca2+ from the granules both in intact and permeabilized cells, suggesting that the continuous activity of SERCA-type Ca2+ pumps is essential to maintain the steady-state [Ca2+]SG. Both inositol 1,4, 5-trisphosphate (InsP3) and caffeine produced a rapid Ca2+ release from the granules, suggesting the presence of InsP3 and ryanodine receptors in the granules. The response to high-K+ depolarization was different in both cell types, a decrease in [Ca2+]SG in PC12 cells and an increase in [Ca2+]SG in INS1 cells. The difference may rely on the heterogeneous response of different vesicle populations in each cell type. Finally, increasing the glucose concentration triggered a decrease in [Ca2+]SG in INS1 cells. In conclusion, our data show that the secretory granules of PC12 and INS1 cells take up Ca2+ through SERCA-type Ca2+ pumps and can release it through InsP3 and ryanodine receptors, supporting the hypothesis that secretory granule Ca2+ may be released during cell stimulation and contribute to secretion

A confocal study on the visualization of chromaffin cell secretory vesicles with fluorescent targeted probes and acidic dyes

Producción CientíficaSecretory vesicles have low pH and have been classically identified as those labelled by a series of acidic fluorescent dyes such as acridine orange or neutral red, which accumulate into the vesicles according to the pH gradient. More recently, several fusion proteins containing enhanced green fluorescent protein (EGFP) and targeted to the secretory vesicles have been engineered. Both targeted fluorescent proteins and acidic dyes have been used, separately or combined, to monitor the dynamics of secretory vesicle movements and their fusion with the plasma membrane. We have now investigated in detail the degree of colocalization of both types of probes using several fusion proteins targeted to the vesicles (synaptobrevin2- EGFP, Cromogranin A-EGFP and neuropeptide Y-EGFP) and several acidic dyes (acridine orange, neutral red and lysotracker red) in chromaffin cells, PC12 cells and GH3 cells. We find that all the acidic dyes labelled the same population of vesicles. However, that population was largely different from the one labelled by the targeted proteins, with very little colocalization among them, in all the cell types studied. Our data show that the vesicles containing the proteins more characteristic of the secretory vesicles are not labelled by the acidic dyes, and vice versa. Peptide glycyl-L-phenylalanine 2-naphthylamide (GPN) produced a rapid and selective disruption of the vesicles labelled by acidic dyes, suggesting that they could be mainly lysosomes. Therefore, these labelling techniques distinguish two clearly different sets of acidic vesicles in neuroendocrine cells. This finding should be taken into account whenever vesicle dynamics is studied using these techniques

Estratègies de modulació de l'oxidació d'àcids grassos com a tractament per combatre l'obesitat

L'estil de vida actual, amb dietes d'alt contingut calòric i falta d'exercici físic, fa que la incidència d'obesitat s'incrementi notablement. Augmentar la degradació de greixos o bé reduir la ingesta calòrica poden ser potencials estratègies terapèutiques. L'enzim carnitina palmitoïltransferasa I (CPT1) és el pas limitant de l'oxidació dels àcids grassos. En aquest article, es mostra com la modulació de la seva activitat en diferents teixits, com el fetge, el teixit adipós o l'hipotàlem, pot ser clau a l'hora d'augmentar la despesa energètica i controlar la ingesta d'aliments