Leptin signaling in breast cancer and its crosstalk with peroxisome proliferator-activated receptors α and γ

Obesity may create a mitogenic microenvironment that influences tumor initiation and progression. The obesity-associated adipokine, leptin regulates energy metabolism and has been implicated in cancer development. It has been shown that some cell types other than adipocytes can express leptin and leptin receptors in tumor microenvironments. It has been shown that peroxisome proliferator-activated receptors (PPAR) agonists can affect leptin levels and vice versa leptin can affect PPARs. Activation of PPARs affects the expression of several genes involved in aspects of lipid metabolism. In addition, PPARs regulate cancer cell progression through their action on the tumor cell proliferation, metabolism, and cellular environment. Some studies have shown an association between obesity and several types of cancer, including breast cancer. There is some evidence that suggests that there is crosstalk between PPARs and leptin during the development of breast cancer. Through a systematic review of previous studies, we have reviewed the published relevant articles regarding leptin signaling in breast cancer and its crosstalk with peroxisome proliferator-activated receptors α and γ (AU)

Potential molecular mechanism of the Xiexin capsule in the intervention of dyslipidemia based on bioinformatics and molecular docking / Posible mecanismo molecular de la cápsula Xiexin en la intervención de la dislipidemia basada en la bioinformática y el acoplamiento molecular

Objective: bioinformatic methods and molecular docking technology were used to predict the active components, targets, and related biological pathways of the Xiexin capsule in the intervention for dyslipidemia, exploring its mechanism. Methods: the active components and targets of the Xiexin capsule were screened by the TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform )database. Genecards (The Human Gene Database), OMIM (Online Mendelian Inheritance in Man), PharmGkb (Pharmacogenomics Knowledge Base database), TTD (Therapeutic Target Database), and Drugbank platforms were used to search the disease targets of dyslipidemia. The Cytoscape 3.8.0 software was used to construct the 'component-target' network diagram, and the STRING (functional protein association networks) platform was used to analyze protein-protein interaction (PPI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) enrichment analyses were performed by R language data packets to predict the mechanism of action. The AutoDockVina and PyMol software were used to dock the key active components in the Xiexin capsule and the core proteins in PPI. Results: a total of 66 effective components were screened, involving 114 targets; 87 key active compounds were screened from the 'drug-component-target' diagram. The PPI network mainly involved core proteins such as PTGS2 (prostaglandin-endoperoxide synthase 2), PTGS1 (prostaglandin-endoperoxide synthase 1), and HSP90AA1 (heat shock protein 90 alpha family class A member 1). GO and KEGG enrichment analysis results of common targets mainly involved hormone-mediated signaling pathway, steroid hormone response, lipid transport and metabolism, regulation of cholesterol storage, cyclooxygenase pathway, and other biological pathways, as well asMM PPAR (peroxisome proliferators-activated receptor) signaling pathway, IL-17 (interleukin 17) signaling pathway (AU)

Objetivo: se utilizaron métodos bioinformáticos y técnicas de acoplamiento molecular para predecir los componentes efectivos, los objetivos y las vías biológicas relacionadas de la cápsula Xiexin en la intervención de la dislipidemia y explorar su mecanismo. Métodos: los componentes activos y los objetivos de la cápsula Xiexin fueron seleccionados por la base de datos TCMSP. Se utilizaron las plataformas Genecards, OMIM, PharmGkb, TTD (Therapeutic Target Database) y Drugbank para buscar las dianas de la enfermedad en la dislipidemia. El diagrama reticular “componente-diana” fue construido por el software Cytoscape 3.7.0, y la interacción proteína-proteína (PPI) fue analizada por la plataforma STRING. Los análisis de enriquecimiento de Gene Ontology (GO) y Kyoto Encyclopedia of Genes and Genomics (KEGG) se realizaron mediante paquetes de datos en lenguaje R para predecir el mecanismo de acción. El software AutoDockVina y PyMol se utilizó para unir los componentes activos clave de la cápsula Xiexin y las proteínas clave de la PPI. Resultados: se seleccionaron 65 componentes activos y 114 dianas. Veintitrés compuestos activos clave fueron seleccionados a partir de la tabla “componentes farmacéuticos-dianas”. Las redes PPI incluyen principalmente proteínas básicas como PTGS2, PTGS1 y HSP90AA1. Los resultados del análisis de enriquecimiento de GO y KEGG en los objetivos comunes se refieren principalmente a la vía de señalización mediada por esteroides, la respuesta hormonal esteroidea, el transporte y metabolismo lipídicos, la regulación del almacenamiento de colesterol, la vía de la ciclooxigenasa y otras vías biológicas, así como la vía de señalización de PPAR, la vía de señalización de IL-17, la vía de señalización de PI3K-Akt (AU)

Difference in fatty acids composition of breast adipose tissue in women with breast cancer and benign breast disease / Diferencia en la composición de ácidos grasos del tejido adiposo de la mama en mujeres con cáncer de mama y enfermedad benigna de la mama

Introduction: Breast cancer is the second most common cancer in the world, and the most frequent cancer among women. Moreover, there are factors that influence the risk for breast cancer including the age, genetic and endocrine factors, and lifestyle. Objectives: To evaluate the consumption of fatty acids; compare the fatty acids composition in the breast adipose tissue of women with breast cancer and benign breast disease as well as potential risk factors; and describe the genotypic frequency of the Pro12Ala PPARγ polymorphism. Material and methods: A hospital-based case-control study was conducted including incident cases (n = 38 breast cancer; n = 75 benign breast disease; n = 166 control). Lifestyle features, socioeconomic issues, dietary intake, anthropometry, and blood and tissue data were assessed. Results: No differences were observed for fatty acids intake. Interestingly, lauric acid (p = 0.001), myristic acid (p = 0.036), stearic acid (p = 0.031), and total saturated fatty acids (SFAs) (p = 0.048) had lower concentrations in BC than in BBD women, while palmitoleic acid (p = 0.022), erucic acid (p = 0.002), total monounsaturated fatty acids (MUFAs) (p = 0.039) and oleic acid/stearic acid ratio (p = 0.015) increased. There was no significant association between PPARγ polymorphism and studied groups (p = 0.977). The age at first full pregnancy (p = 0.004) was significantly associated with the development BC, whereas BMI (p = 0.005); percentage of body fat (p = 0.024); physical activity (p = 0.036); and age at menarche (p = 0.008), at first full pregnancy (p < 0.001), and of first mammogram (p = 0.018) were significantly associated with the development of BBD. Conclusion: The results suggest a different fatty acids composition of breast adipose tissue, a biomarker of long-term dietary intake, particularly for SFAs, MUFA and 18: 1 n-9/18: 00 ratio. Our findings also show that are differences in the factors related to the development of BC and BBC (AU)

Introducción: el cáncer de mama (CM) es el segundo cáncer más común en el mundo, y el cáncer más frecuente entre las mujeres. Por otra parte, hay factores que influyen en el riesgo de padecer CM, entre los que se encuentran la edad, factores genéticos y endocrinos, y el estilo de vida. Objetivos: evaluar el consumo de ácidos grasos; comparar la composición de ácidos grasos en el tejido adiposo de mama de las mujeres con CM y enfermedad benigna de mama (EBM), así como los posibles factores de riesgo; y describir la frecuencia genotípica del polimorfismo Pro12Ala PPARγ. Material y métodos: se llevó a cabo un estudio caso-control basado en hospitales, incluyendo casos incidentes (n = 38 cáncer de mama, n = 75 enfermedad benigna de mama, n = 166 control). Se evaluaron las características del estilo de vida, las cuestiones socioeconómicas, la ingesta dietética, la antropometría y los datos de sangre y tejidos. Resultados: no se observaron diferencias para la ingesta de ácidos grasos. Curiosamente, ácido láurico (p = 0,001), ácido mirístico (p = 0,036), ácido esteárico (p = 0,031) y los ácidos grasos totales saturados (AGS) (p = 0,048) tenían concentraciones más bajas en CM que en mujeres EBM, mientras ácido palmitoleico (p = 0,022), ácido erúcico (p = 0,002), los ácidos totales grasos monoinsaturados (MUFA) (p = 0,039) y la relación ácido oleico/ácido esteárico (p = 0,015) aumentó. No hubo asociación significativa entre el polimorfismo PPAR gamma y los grupos de estudio (p = 0,977). La edad al primer embarazo (p = 0,004) se asoció de forma signifi cativa con el desarrollo de CM, mientras que el IMC (p = 0,005), porcentaje de grasa corporal (p = 0,024), la actividad física (p = 0,036) y la edad de la menarquia (p = 0,008), al primer embarazo (p < 0,001), y de la primera mamografía (p = 0,018), fueron significativamente asociados con el desarrollo de EBM. Conclusiones: los resultados sugieren una composición diferente de ácidos grasos del tejido adiposo de la mama, un biomarcador de la ingesta dietética a largo plazo, particularmente para SFA, MUFA y 18: 1 n-9/18: 00. Nuestros hallazgos también muestran que existen diferencias en los factores relacionados con el desarrollo de CM y EBM (AU)

Importancia de los obesógenos en la adipogénesis y obesidad / Role of obesogens in adipogenicity and obesity

La incidencia y prevalencia de sobrepeso y obesidad ha experimentado un gran incremento en las últimas décadas. Aunque el balance entre ingreso y gasto energético es clave en la inducción y establecimiento de la obesidad, otros factores parecen estar netamente implicados. A este respecto la hipótesis de los obesógenos ambientales, ha ganado credibilidad en los años recientes, al identificarse agentes químicos que promueven la adipogénesis y obesidad en animales y humanos. En esta revisión, se hace un estudio de los disruptores endocrinos que son sustancias químicas contaminantes del medio ambiente y su relación con la obesidad. Se revisan los principales tipos de obesógenos, p.ej. dietilestilbestrol, bisfenol A, los compuestos orgánicos derivados del estaño, la genisteína y los ftalatos y sus características diferenciales y mecanismos de acción. Se ultima con unas reflexiones sobre la necesidad de profundizar en el conocimiento de estos compuestos tan abundantes hoy en día (AU)

Overweight and obesity incidence and prevalence have increased during the last decades. Although the energy intake/expenditure balance is a key factor in the obesity induction and development, other factors seem clearly implicated. In fact the environmental obesogens hypothesis has gain importance in the last years, as different chemical agents have been found to adipogenics and obesogenics in animal models and humans. In this review we study the role of environmental chemical polluting as endocrine disruptors and their relationship with obesity. Major obesogen types, e.g. diethylstilboestrol, bisphenol A, tinorganic derived compounds, genistein and ftalates are described. Their differential characteristics and action mechanisms are defined. The review ends with some considerations on the need to get knowledge on such abundant compounds (AU)

Irisin, a unique non-inflammatory myokine in stimulating skeletal muscle metabolism

Exercise offers several benefits for health, including increased lean body mass and heightened energy expenditure, which may be partially attributable to secretory factors known as myokines. Irisin, a recently identified myokine, was shown to increase metabolic rate and mitochondrial content in both myocytes and adipocytes; however, the mechanism(s) of action still remain largely unexplained. This work investigated if irisin functions by acting as an inflammatory myokine leading to cellular stress and energy expenditure. C2C12 myotubes were treated with various concentrations of irisin, TNFAlpha, or IL6 for various durations. Glycolytic and oxidative metabolism, as well as mitochondrial uncoupling, were quantified by measurement of acidification and oxygen consumption, respectively. Metabolic gene and protein expression were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and immunoblotting, respectively. Mitochondrial content was assessed by fluorescent imaging. NFkappaB activity was assessed using an NFkappaB GFP-linked reporter system. Consistent with previous findings, irisin significantly increased expression of several genes including peroxisome proliferator-activated receptor Alpha coactivator-1Alpha (PGC-1Alpha) leading to increased mitochondrial content and oxygen consumption. Despite some similarities between TNFAlpha and irisin treatment, irisin failed to activate the NFkappaB pathway like TNFAlpha, suggesting that irisin may not act as an inflammatory signal. Irisin has several effects on myotube metabolism which appear to be dependent on substrate availability; however, the precise mechanism(s) by which irisin functions in skeletal muscle remain unclear. Our observations support the hypothesis that irisin does not function through inflammatory NFkappaB activation like other myokines (such as TNFAlpha)

Los niveles en sangre de PGC-1alfa predice miocardio salvado y remodelado ventricular tras infarto agudo de miocardio con elevación del segmento ST / Blood pgc-1α concentration predicts myocardial salvage and ventricular remodeling after st-segment elevation acute myocardial infarction

Introducción y objetivos: El coactivador 1alfa del receptor activado gamma del proliferador de peroxisoma (PGC-1alfa) es un regulador metabólico que se induce durante la isquemia y previene el remodelado cardiaco en modelos animales. Su actividad puede estimarse en pacientes con infarto agudo de miocardio con elevación del segmento ST. Nuestro objetivo es evaluar el valor predictivo de los niveles en sangre de PGC-1α en la extensión del área necrótica y el remodelado ventricular tras infarto. Métodos: Estudio prospectivo de 31 pacientes con primer infarto de miocardio de localización anterior y reperfusión exitosa. Se determinó la expresión de PGC-1α en sangre periférica al ingreso y a las 72 h, evaluando su correlación con el daño miocárdico y el volumen ventricular y la función sistólica a los 6 meses. El edema y la necrosis miocárdica se estimaron mediante resonancia magnética cardiaca durante la primera semana. A los 6 meses, una resonancia de control evaluó tamaño del infarto y remodelado ventricular, definido como el incremento > 10% del volumen telediastólico del ventrículo izquierdo. Se definió miocardio salvado como la diferencia entre las áreas de edema y de necrosis. Resultados: Se observó más miocardio salvado en los pacientes con expresión de PGC-1α detectable al ingreso (el 18,3% ± 5,3% frente al 4,5% ± 3,9%; p = 0,04). La inducción de PGC-1α a las 72 h se correlacionó con mayor remodelado ventricular (variación del volumen telediastólico del ventrículo izquierdo a los 6 meses, el 29,7% ± 11,2% frente al 1,2% ± 5,8%; p = 0,04). Conclusiones: El grado de expresión basal de PGC–1α y una respuesta atenuada del sistema tras infarto agudo de miocardio se asocian con más miocardio salvado y predicen menos remodelado ventricular (AU)

Introduction and objectives: Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) is a metabolic regulator induced during ischemia that prevents cardiac remodeling in animal models. The activity of PGC-1α can be estimated in patients with ST-segment elevation acute myocardial infarction. The aim of the present study was to evaluate the value of blood PGC-1α levels in predicting the extent of necrosis and ventricular remodeling after infarction. Methods: In this prospective study of 31 patients with a first myocardial infarction in an anterior location and successful reperfusion, PGC-1α expression in peripheral blood on admission and at 72 hours was correlated with myocardial injury, ventricular volume, and systolic function at 6 months. Edema and myocardial necrosis were estimated using cardiac magnetic resonance imaging during the first week. At 6 months, infarct size and ventricular remodeling, defined as an increase > 10% of the left ventricular end-diastolic volume, was evaluated by follow-up magnetic resonance imaging. Myocardial salvage was defined as the difference between the edema and necrosis areas. Results: Greater myocardial salvage was seen in patients with detectable PGC-1α levels at admission (mean [standard deviation (SD)], 18.3% [5.3%] vs 4.5% [3.9%]; P = .04). Induction of PGC–1α at 72 hours correlated with greater ventricular remodeling (change in left ventricular end-diastolic volume at 6 months, 29.7% [11.2%] vs 1.2% [5.8%]; P = .04). Conclusions: Baseline PGC–1α expression and an attenuated systemic response after acute myocardial infarction are associated with greater myocardial salvage and predict less ventricular remodeling (AU)

PPARalfa atenúa el estrés del retículo endoplasmático inducido por palmitato en células cardíacas humanas por medio de la inducción de la actividad AMPK / PPARalpha attenuates palmitate-induced endoplasmic reticulum stress in human cardiac cells by enhancing AMPK activity

Introducción El estrés del retículo endoplasmático (RE) se ha relacionado con distintas enfermedades cardiovasculares, como la arteriosclerosis y la hipertrofia e insuficiencia cardíacas. Este estrés del RE altera la señalización de la insulina, contribuyendo al desarrollo de la resistencia a la insulina y la diabetes. Diversos estudios han demostrado que PPARalfa inhibe el estrés del RE, por lo que el objetivo de este trabajo consistió en investigar si la activación de este receptor nuclear era capaz de prevenir el estrés del RE inducido por ácidos grasos saturados en células cardíacas, así como los mecanismos implicados. Métodos: Cardiomiocitos humanos AC16 fueron tratados con palmitato en presencia de diferentes activadores e inhibidores de AMPK y PPARalfa. Para los estudios in vivo, ratones macho fueron alimentados con una dieta rica en grasa (HFD). Posteriormente, se determinó la presencia de distintos marcadores de estrés del RE en células cardíacas por medio del análisis de la expresión génica y la acumulación proteica. Resultados: El palmitato y la dieta HFD indujeron el estrés del RE en células cardíacas, pues incrementaron diversos marcadores de este, como son la expresión génica de ATF3, BiP/GRP78 y CHOP, el splicing de XBP1 y la fosforilación de IRE-1α y eIF2alfa. El tratamiento con Wy-14,643, un agonista de PPARalfa, previno el incremento del estrés del RE inducido por palmitato por medio de la activación de la AMPK. Conclusión: Wy-14,643 podría ser útil para prevenir el estrés del RE y las enfermedades cardiovasculares asociadas en pacientes obesos, e incluso durante la cardiomiopatía diabética, por medio de la activación de AMPK

Introduction Endoplasmic reticulum (ER) stress has been linked to several cardiovascular diseases, such as atherosclerosis, heart failure and cardiac hypertrophy. ER stress impairs insulin signalling, thus contributing to the development of insulin resistance and diabetes. Since several studies have reported that PPARalfa may inhibit ER stress, the main aim of this study consisted in investigating whether activation of this nuclear receptor is able to prevent lipid-induced ER stress in cardiac cells, as well as studying the mechanisms involved. Methods: A cardiomyocyte cell line of human origin, AC16, was treated with palmitate in the presence or absence of several AMPK and PPARα pharmacological agonists and antagonists. For the in vivo studies, wild-type male mice were fed a standard diet, or a high-fat diet (HFD), for two months. At the end of the experiments, several ER stress markers were assessed in cardiac cells or in the mice hearts, using real-time RT-PCR and Western-blot analyses. Results: The results demonstrate that both palmitate and the HFD induced ER stress in cardiac cells, since they upregulated the expression (ATF3, BiP/GRP78 and CHOP), splicing (sXBP1), and phosphorylation (IRE-1α and eIF2α) of several ER stress markers. Interestingly, treatment with the PPARalfa agonist Wy-14,643 prevented an increase in the majority of these ER stress markers in human cardiac cells by means of AMPK activation. Conclusion: These data indicate that PPARα activation by Wy-14,643 might be useful to prevent the harmful effects of ER stress and associated cardiovascular diseases in obese patients, and even during diabetic cardiomyopathy, by enhancing AMPK activity

Effects of binge ethanol on lipid homeostasis and oxidative stress in a rat model of nonalcoholic fatty liver disease

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Excess fat accumulation renders the liver more vulnerable to ethanol, but it is still unclear how alcohol enhances lipid dysmetabolism and oxidative stress in a pre-existing steatosis condition. The effects produced by binge ethanol consumption in the liver of male Wistar rats fed a standard (Ctrl) or a high-fat diet HFD were compared. The liver status was checked through tissue histology and standard serum parameters. Alteration of hepatic lipid homeostasis and consequent oxidative unbalance were assessed by quantifying the mRNA expression of the lipid-regulated peroxisome proliferator-activated receptors (PPARs), of the cytochromes CYP2E1 and CYP4A1, and of some antioxidant molecules such as the metallothionein isoforms MT1 and MT2 and the enzymes catalase and superoxide dismutase. The number of adipose differentiation-related protein (ADRP)-positive lipid droplets (LDs) was evaluated by immunohistochemical staining. As a response to the double insult of diet and ethanol the rat liver showed: (1) a larger increase in fat accumulation within ADRP-positive LDs; (2) stimulation of lipid oxidation in the attempt to limit excess fat accumulation; (3) induction of antioxidant proteins (MT2, in particular) to protect the liver from the ethanol-induced overproduction of oxygen radicals. The data indicate an increased susceptibility of fatty liver to ethanol and suggest that the synergistic effect of diet and ethanol on lipid dysmetabolism might be mediated, at least in part, by PPARs and cytochromes CYP4A1 and CYP2E1 (AU)

La activación de PPARβ/δ previene la hipertrigliceridemia causada por una dieta rica en grasas. Implicación de la AMPK y de la vía PGC-1α-lipina 1-PPAR / PPARβ/δ Activation prevents hypertriglyceridemia caused by a high fat diet. Involvement of AMPK and PGC-1α-Lipin 1-PPARα pathway

Introducción El consumo excesivo de alimentos hipercalóricos y de alto contenido en grasas saturadas produce una dislipidemia aterogénica. En este estudio hemos analizado los efectos del activador de PPARβ/δ GW501516 sobre la hipertrigliceridemia inducida por una dieta rica en grasas. Metodología Ratones macho fueron distribuidos aleatoriamente en 3 grupos: control (dieta estándar), dieta grasa (high fat diet [HFD], 35% grasa en peso, 58% kcal procedentes de grasa) y dieta grasa más GW501516 (3 mg/kg/día). La duración del tratamiento fue de 3 semanas. Resultados La HFD causó hipertrigliceridemia acompañada de una reducción de los niveles hepáticos de la proteína AMPK fosforilada y de los niveles de ARNm Pgc-1α y lipina 1. Estos efectos fueron revertidos por el tratamiento con GW501516. El mantenimiento de la AMPK fosforilada tras el tratamiento con GW501516 podría deberse al aumento de la relación AMP/ATP. GW501516 incrementó los niveles de proteína lipina 1 nuclear acompañado por una amplificación de la vía PGC-1α-PPARα y un aumento de la actividad de unión al ADN de PPARα, así como el incremento en la expresión de los genes diana de PPARα implicados en la β-oxidación de ácidos grasos. GW501516 también aumentó los niveles plasmáticos de β-hidroxibutirato, producto final de la β-oxidación hepática. Finalmente, GW501516 incrementó los niveles del ligando endógeno de PPARα, 16:0/18:1-fosfatidilcolina, y aumentó la expresión del receptor de las VLDL en hígado. Conclusión El efecto hipotrigliceridemiante de GW501516 en ratones sometidos a HFD se acompaña de un aumento de los niveles de la AMPK fosforilada y de un aumento de la vía PGC-1α-lipina 1-PPARα (AU)

Introduction Excessive consume of hypercaloric and high in saturated fat food causes an atherogenic dyslipidemia. In this study we analyzed the effects of PPARβ/δ activator GW501516 on the hypertriglyceridemia induced by a high-fat diet. Methods Male mice were randomized in three groups: control (standard chow), high fat diet (HFD, 35% fat by weight, 58% Kcal from fat) and high fat diet plus GW501516 (3 mg/Kg/day). Treatment duration was three weeks. Results HFD-induced hypertriglyceridemia was accompanied by a reduction in hepatic levels of phospho-AMPK and in PGC-1α and Lipin 1 mRNA levels. All these effects were reversed by GW501516 treatment. The lack of changes in phospho-AMPK levels after GW501516 treatment in HFD-fed animals could be the result of an increase in the AMP/ATP ratio. GW501516 treatment also increased Lipin 1 protein levels in the nucleus, led to the amplification of the PGC-1α-PPARα pathway and increased PPARα DNA-binding activity, as well as the expression of PPARα-target genes involved in fatty acid oxidation. GW501516 also increased β-hydroxibutirate plasmatic levels, a hepatic β-oxidation end product. Finally, GW501516 increased the hepatic levels of the PPARα endogenous ligand 16:0/18:1-PC and the expression of the VLDL receptor. Conclusion These data indicate that the hypotriglyceridemic effect of GW501516 in mice subjected to HFD-fed mice is accompanied by an increase in phospho-AMPK levels and the amplification of the PGC-1α-Lipin 1-PPARα pathway (AU)

The effect of troglitazone on lipid accumulation and related gene expression in Hanwoo muscle satellite cell

The current study was undertaken to determine the effect of the troglitazone (TGZ) on the expression of peroxisome proliferator-activating receptor (PPARã), CCAAT/enhancer-binding protein, fatty acid binding protein 4, calpain 1 (CAPN1), and lipid accumulation in the myotube of Hanwoo muscle satellite cells. The satellite cells were treated with 5, 10, and 50 ìM of TGZ for indicated time intervals. TGZ promoted the trans-differentiation with significant increase in glycerol accumulation. Polymerase chain reaction (PCR) and microarray results indicated that the TGZ treatment significantly increased the expression of adipogenic transcription factors. TGZ (10 and 50 ìM) increased the CAPN1 gene expression 2.2- and 2.6-fold in real-time polymerase chain reaction analysis and 0.52- and 0.25-fold in microarray analysis, respectively, when compared with their respective controls. This result suggests that CAPN1 gene might be involved in the adipogenic differentiation programs. In addition, 13 genes were upregulated and 12 genes were downregulated in microarray analysis. Most of the up/downregulated genes were directly linked with adipogenesis (AU)

Papel de PP2A en el control de la expresión de PPARalfa; por fructosa en células FaO de hepatoma de rata / No disponible

Introducción La suplementación de la dieta con un 10% (p/v) de fructosa en el agua de bebida durante 14 días en ratas produce hipertrigliceridemia y esteatosis hepática como consecuencia de una reducción en la expresión y en la actividad transcripcional de (..) (AU)

Introduction The addition of fructose in drinking water (10% w/v) for two weeks to rats induces hypertriglyceridemia and fatty liver by reducing the expression and transcriptional activity of (..) (AU)

Expression of nuclear-encoded genes involved in mitochondrial biogenesis and dynamics in experimentally denervated muscle

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The abundance, morphology, and functional properties of mitochondria become altered in response to denervation. To gain insight into the regulation of this process, mitochondrial enzyme activities and gene expression involved in mitochondrial biogenesis and dynamics in mouse gastrocnemius muscle was investigated. Sciatic nerve transactions were performed on mice, and then gastrocnemius muscles were isolated at days 5 and 30 after surgery. Muscle weight was decreased significantly by 15% and 62% at days 5 and 30 after surgery, respectively. The activity (..) (AU)

RARã and TRBeta expressions are decreased in PBMC and SWAT of obese subjects in weight gain

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In order to evaluate the expression of nuclear receptors at the peripheral level in obese subjects,messenger RNA (mRNA) levels of different isoforms of retinoic acid receptor (RAR), triiodothyronine(TR), and peroxisome proliferator-activated receptor (PPAR) were determined and compared in peripheral mononuclear blood cells (PBMC) and subcutaneous white adipose tissue (SWAT). Twelve lean subjects and 68 obese subjects divided into weight gain (WG), weight-stable (WS), and weight loss (WL) groups were studied. Nuclear receptor mRNA levels were assessed in PBMC and SWAT using a quantitative real-time reverse transcription polymerase chain (..) (AU)

Efectos metabólicos del tratamiento con antagonistas de los receptores de la angiotensina II / Metabolic effect of treatment with angiotensin-II receptor antagonists

El objetivo del tratamiento de los pacientes hipertensos no sólo es reducir las cifras de presión arterial, sino también disminuir su riesgo cardiovascular total. Es importante, por lo tanto, que los fármacos utilizados, además de su acción hipotensora, posean un perfil metabólico beneficioso. Los antagonistas de los receptores de angiotensina II (AR-II) son de demostrada eficacia antihipertensiva y también tienen efectos beneficiosos en cuanto al metabolismo de los lípidos y los hidratos de carbono y en la prevención de nuevos casos de diabetes mellitus. Estas acciones se deben al bloqueo de los receptores AT1, pero en algunos ARA-II, aunque no parece que se trate de un efecto de clase, también a través de una acción parcialmente agonista de los receptores nucleares PPARγ. Si estos efectos metabólicos beneficiosos, demostrados hasta ahora experimentalmente y en algunos estudios, se corroboran en ensayos clínicos más amplios, los convertirían en los fármacos ideales para el tratamiento de los pacientes hipertensos con otros factores de riesgo cardiovascular y/o con síndrome metabólico (AU)

The aim of treatment in hypertensive patients is not only to reduce blood pressure but also to minimize the overall cardiovascular risk. It is important, therefore, that the drugs administered have a beneficial influence on metabolic parameters as well as an antihypertensive effect. It has been shown that angiotensin-II receptor antagonists (ARA IIs) are effective antihypertensives that also have a positive influence on lipid and carbohydrate metabolism. Moreover, they can help prevent the development of new-onset diabetes. These actions arise from the blockade of angiotensin-II type-1 (AT-1) receptors, while some ARA IIs, though this does not appear to be a class effect, are also able to act like partial agonists of the nuclear receptor peroxisome proliferatoractivated receptor-gamma (PPAR-Á). If these beneficial metabolic effects, which have been found in experimental studies and in a few clinical studies, are confirmed in larger clinical trials, ARA IIs will become the ideal drugs for treating hypertensive patients with other cardiovascular risk factors or with metabolic syndrome (AU)

Relationship between lipoprotein lipase and peroxisome proliferator-activated receptor-alpha expression in rat liver during development

The present study was addressed to determine whether the high expression of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) in rat liver during the perinatal stage plays a role in the induction of liver lipoprotein lipase (LPL) expression and activity. Parallel increases in liver mRNA PPAR-alpha and LPL activity were found in newborn rats, and after a slight decline, values remained elevated until weaning. Anticipated weaning for 3 days caused a decline in those two variables as well as in the mRNA LPL level, and a similar change was also found in liver triacylglycerol concentration. Force-feeding with Intralipid in 10-day-old rats or animals kept fasted for 5 h showed high mRNA-PPARalpha and-LPL levels as well as LPL activity with low plasma insulin and high FFA levels, whereas glucose and a combination of glucose and Intralipid produced low mRNA-PPARalpha and-LPL levels as well as LPL activity. Under these latter conditions, plasma insulin and FFA levels were high in those rats receiving the combination of glucose and Intralipid, whereas plasma FFA levels were low in those force-fed with glucose. It is proposed that the hormonal and nutritional induction of liver PPAR-alpha expression around birth and its maintained elevated level throughout suckling is responsible for the induction of liver LPL-expression and activity during suckling (AU)

Se estudia si la alta expresión del receptor activado por proliferadores peroxisomales-alpha (PPAR-alpha) que se observa en el hígado de la rata durante la etapa perinatal, contribuye a la inducción de la expresión y actividad de la lipoproteína lipasa (LPL) que se presenta en este órgano. Se observó un incremento paralelo en el mRNA del PPAR-alpha y en la actividad LPL del hígado en ratas recién nacidas, y tras un ligero descenso, los valores se mantuvieron elevados hasta el destete. Un destete anticipado de 3 días causó un descenso en esas dos variables y en el nivel de mRNA LPL, así como un cambio semejante en la concentración de triacilgliceroles en el hígado. Animales de 10 días de edad sometidos a alimentación forzada con Intralipid o mantenidos en ayunas durante 5 h mostraron valores altos de mRNA-PPARalpha y-LPL así como de la actividad de la LPL en hígado, y niveles bajos de insulina y altos de FFA en plasma, mientras que la administración de glucosa o la combinación de glucosa e Intralipid produjeron valores bajos de mRNA-PPARalpha y-LPL así como de actividad LPL en hígado. Los niveles plasmáticos de insulina y FFA fueron altos en las ratas que recibieron la combinación de glucosa e Intralipid, mientras que los niveles de FFA plasmáticos fueron bajos en los sometidos a alimentación forzada con glucosa. En consecuencia, se propone que la inducción hormonal y nutricional de la expresión del PPAR-alpha en hígado alrededor del nacimiento y su mantenimiento en valores elevados a lo largo de la lactancia es responsable de la inducción de la expresión y la actividad de la LPL durante esta etapa del desarrollo (AU)

D) ¿Modula el metabolismo lipídico del miocardio la hipertrofia cardíaca? / No disponible

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