Candida lipases: a review on biochemical, molecular and pathogenic aspects. / [Lipasas de especies Candida: una revisión sobre aspectos bioquímicos, moleculares y patogénicos.]

In the last half century there was a significant increase in the incidence of fungal infections being likely to become a global health priority. The sophisticated degree of host-Candida interaction is the product of different virulence strategies used by the fungus to invade the tissues and the various defense mechanisms that it develops to control it. There is a significant amount of literature that indicates that this opportunistic commensal fungus has components that can be considered virulence factors related to the stage of the infectious process. Among the virulence factors of this fungus can be mentioned the adherence to cell surfaces, the formation of biofilms and the production of hydrolytic enzymes. The most studied hydrolases secreted by C. albicans are aspartyl proteinases, phospholipases and esterases, while lipases have been the least studied. These enzymes would have the function to facilitate active penetration into the cells, participating in the digestion and synthesis of lipid esters for their nutrition and contributing to the invasion of the tissue by hydrolyzing the lipid components of the host cell membranes. There is also bibliographic evidence that these enzymes are capable to damage cells and molecules of the immune system to avoid the antimicrobial activity.Taking into account the foregoing, this review provides an updated description of biochemical and molecular characteristics of the lipases secreted by Candida, its role as a virulence factor and its potential for the development of new antifungal drugs.

En el último medio siglo se produjo un aumento significativo en la incidencia de infecciones fúngicas siendo probable que se conviertan en una prioridad de salud global. El sofisticado grado de interacción hospedador-Candida es producto de diferentes estrategias de virulencia que utiliza el hongo para invadir los tejidos y de los diversos mecanismos de defensa que este último desarrolla para controlarlo. Existe bibliografía que indica que este hongo comensal oportunista posee componentes que pueden ser considerados factores de virulencia asociados a la etapa del proceso infeccioso. Dentro de los factores de virulencia de este hongo pueden mencionarse la adherencia a las superficies celulares, la formación de biofilms y la producción de enzimas hidrolíticas. Las hidrolasas secretadas por C. albicans más estudiadas son las aspartil proteinasas, las fosfolipasas y las esterasas, mientras que las lipasas han sido las menos exploradas. Estas enzimas tendrían como función facilitar la penetración activa en las células, participar en la digestión y síntesis de ésteres de lípidos para su nutrición y contribuir a la invasión del tejido al hidrolizar los componentes lipídicos de las membranas celulares del hospedador. También hay evidencia bibliográfica que indica que estas enzimas son capaces de dañar células y moléculas del sistema inmune para evitar la actividad antimicrobiana. Teniendo en cuenta lo precedente, esta revisión, proporciona una actualizada descripción de las características bioquímicas y moleculares de las lipasas secretadas por el hongo Candida, su rol como factor de virulencia y su potencial para el desarrollo de nuevos fármacos antifúngicos.

Lipolysis and lipases in white adipose tissue - An update.

Lipolysis is defined as the sequential hydrolysis of triacylglycerol (TAG) stored in cell lipid droplets. For many years, it was believed that hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL) were the main enzymes catalyzing lipolysis in the white adipose tissue. Since the discovery of adipose triglyceride lipase (ATGL) in 2004, many studies were performed to investigate and characterize the actions of this lipase, as well as of other proteins and possible regulatory mechanisms involved, which reformulated the concept of lipolysis. Novel findings from these studies include the identification of lipolytic products as signaling molecules regulating important metabolic processes in many non-adipose tissues, unveiling a previously underestimated aspect of lipolysis. Thus, we present here an updated review of concepts and regulation of white adipocyte lipolysis with a special emphasis in its role in metabolism homeostasis and as a source of important signaling molecules.

Lipolysis and lipases in white adipose tissue – An update

Lipolysis is defined as the sequential hydrolysis of triacylglycerol (TAG) stored in cell lipid droplets. For many years, it was believed that hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL) were the main enzymes catalyzing lipolysis in the white adipose tissue. Since the discovery of adipose triglyceride lipase (ATGL) in 2004, many studies were performed to investigate and characterize the actions of this lipase, as well as of other proteins and possible regulatory mechanisms involved, which reformulated the concept of lipolysis. Novel findings from these studies include the identification of lipolytic products as signaling molecules regulating important metabolic processes in many non-adipose tissues, unveiling a previously underestimated aspect of lipolysis. Thus, we present here an updated review of concepts and regulation of white adipocyte lipolysis with a special emphasis in its role in metabolism homeostasis and as a source of important signaling molecules.

[The role of endothelial lipase in atherogenesis]. / Lipasa endotelial y su relación con la enfermedad cardiovascular y diabetes mellitus tipo 2.

Endothelial lipase (EL) is synthetized by endothelial cells and its main substrates are lipoprotein phospholipids. Over expression of EL reduces high density lipoprotein (HDL) cholesterol and phospholipids, in vivo and in vitro. Inhibition of the enzyme achieves the opposite effects. The synthesis of the enzyme is regulated by interleukin 1 and tumor necrosis factor a. These inflammatory cytokines play a role in diabetes and vascular disease. An increase in vascular mechanical forces, that play a role in atherogenesis, also increase the synthesis of EL. There is expression of EL in endothelial cells, macrophages and muscle cells of atherosclerotic lesions of coronary arteries of humans. This evidence leads to the suspicion that EL plays a role in atherogenesis. There are also higher plasma levels of EL in subjects with type 2 diabetes, who are especially susceptible to the development of vascular lesions. Therefore the inhibition of EL could play an important role in HDL metabolism and could be a new therapeutic strategy for the prevention of atherosclerosis.

Lipasa endotelial y su relación con la enfermedad cardiovascular y diabetes mellitus tipo 2 / The role of endothelial lipase in atherogenesis

Endothelial lipase (EL) is synthetized by endothelial cells and its main substrates are lipoprotein phospholipids. Over expression of EL reduces high density lipoprotein (HDL) cholesterol and phospholipids, in vivo and in vitro. Inhibition of the enzyme achieves the opposite effects. The synthesis of the enzyme is regulated by interleukin 1 and tumor necrosis factor a. These inflammatory cytokines play a role in diabetes and vascular disease. An increase in vascular mechanical forces, that play a role in atherogenesis, also increase the synthesis of EL. There is expression of EL in endothelial cells, macrophages and muscle cells of atherosclerotic lesions of coronary arteries of humans. This evidence leads to the suspicion that EL plays a role in atherogenesis. There are also higher plasma levels of EL in subjects with type 2 diabetes, who are especially susceptible to the development of vascular lesions. Therefore the inhibition of EL could play an important role in HDL metabolism and could be a new therapeutic strategy for the prevention of atherosclerosis.

Composição corporal: influência na ação da insulina, leptina, lipase lipoprotéica e lipase hormônio-sensível / Body composition: influence on insulin action, leptin, lipoproteic-and hormone-sensitive lipase

The balance between food intake and energy expenditure is of major importance for weight control and prevention of non-transmissible diseases. Within this context body composition profile is a determining factor for the adequate functioning of neuroendocrine mechanisms; body fat, especially that localized around the abdomen, plays a major role in these mechanisms. Fat tissue may be considered an endocrine organ since hormones such as insulin and leptin, are directly linked to its storage acting in the control of food intake, energy expenditure and nutrient metabolism. In addition, enzymes such as lipoproteic- and hormone-sensitive lipase, which are directly related to lipid metabolism, are regulated by several hormones, including insulin, which in turn are influenced by fat storages. Usually, alteration of these enzymes trigger important metabolic changes, such as elevated serum tryglicerides, which is involved with onset of diabetes and dislipidemia. Considering the influence of body composition on the body's functioning itis essential to stimulate the practice of regular physical activity and incorporation of adequate feeding habits and life style, since these could contribute to a better body composition profile. Moreover, with relatively simple and inexpensive anthropometric measurements it is possible to detect high percentage of body fat, and by means of appropriate interventions, prevent and control many non-transmissible diseases

El equilibrio entre la ingestión alimentar y elgasto de energía es de importancia fundamental para el control del peso y prevención de las enfermedades crónico-degenerativas. En esse contexto, la composición corpórea es un fator determinante en el funcionamiento correcto delos mecanismos neuroendocrinos, y la grasa corpórea, principalmente aquella localizada enel área abdominal, ejerce gran influencia en esos mecanismos.El tejido adiposo puede ser considerado un órganoendocrino, porque se relacionan hormonas, como insulina y leptina, directamente al tamaño de su depósito y ellos actúan en el control de la ingesta alimentar, en el gasto de energía y en el metabolismo de los nutrientes. Además, enzimas como las lipoprotéica, lipasa y lipasa sensible a hormona que participan directamente en el metabolismo de lípidos tiene su actividad controlada por varias hormonas, como la insulina que es fuertemente influenciada por los depósitos de grasa corpórea existentes. Normalmente, la alteración de esas enzimas desencadena alteraciones metabólicas importantes como la elevación de los niveles séricos de triglicéridos,involucrados principalmente en el aparecimiento de diabetes y dislipidemias.Considerando que la influencia de la composición corpórea en el funcionamiento del organismo semanifiesta la importancia del incentivo de la práctica de actividad física de una manera regulary la adopción de hábitos alimentarios y de estilo devida adecuados. Esto contribuiría a un mejor perfil de la composición corpórea. Además, por médio de medidas antropométricas relativamente simples y de bajo costo es posible descubrir los porcentajes elevados de grasa corpórea y a través de las intervenciones prevenir y controlar muchas de las enfermedades crónico-degenerativas.

O equilíbrio entre a ingestão alimentar e o gasto energético é de fundamental importância para o controle do peso e prevenção de doenças não transmissíveis. Nesse contexto, o padrão de composição corporal é fator determinante no funcionamento adequado dos mecanismos neuro-endócrinos, sendo que a gordura corporal, principalmente a localizada na região abdominal, exerce grande influência nesses mecanismos. O tecido adiposo pode ser considerado um órgão endócrino, visto que hormônios, como insulina e leptina, estão diretamente ligados ao tamanho do seu estoque e atuam no controle da ingestão alimentar, gasto energético e metabolismo dos nutrientes. Além disso, enzimas como lipase lipoprotéica e lipase hormônio sensível, as quais estão envolvidas diretamente no metabolismo de lipídios, têm sua atividade controlada por diversos hormônios, como a insulina, que por sua vez sofrem grande influência dos estoques de gordura corporal. Normalmente, a alteração dessas enzimas desencadeia alterações metabólicas importantes como a elevação dos níveis séricos de triglicerídeos, envolvidos principalmente no aparecimento de diabetes e dislipidemias. Considerando essa influência da composição corporal sobre o funcionamento do organismo torna-se importante o incentivo à prática da atividade física, de forma regular, e a adoção de hábitos alimentares e de estilo de vida adequados, já que isto contribuiria para um melhor perfil da composição corporal. Além disso, por meio de medidas antropométricas ,relativamente simples e de baixo custo, é possível detectar elevados percentuais de gordura corporal e por meio de intervenções, prevenir e controlar muitas das doenças não transmissíveis

Influência de produtos naturais na ativação da lipase pancreática humana / Influence of natural products in the human pancreatic lipase activation

O presente trabalho objetivou caracterizar a ação de alguns compostos naturais (baicaleína, quercitrina, isoquercitrina, bicina, xantona) sobre a lipase pancreática humana in vitro, na tentativa de elucidar seus mecanismos de ação relacionados com o catabolismo de triacilgliceróis. Na pesquisa com vários fármacos, que é o centro de nossos estudos, buscas com relação a mecanismo de ação estão relacionadas aos efeitos de substâncias teste sobre a atividade de enzimas. Assim, a atividade enzimática da lipase foi medida na presença de cada uma dessas substâncias, variando a concentração do substrato e fixando a concentração do agente, e variando a concentração do agente e fixando a concentração do substrato. Os resultados mostraram que todas as combinações testadas apresentaram ativação sobre a lipase, enquanto que a quercitrina na concentração de 1,6 x 10-5mol/L com um volume de substrato de 24,19 ml/L apresentou uma porcentagem de ativação maior (35,2%). Ao se fixar a concentração do substrato, foi observado que a bicina na concentração de 5,5 x 10-5 mol/L apresentou porcentagem de ativação maior (20,6%)

Lipasa hepática: efectos sobre el metabolismo lipídico y lipoproteico / Hepatic lipase: its effects on lipids and lipoproteins metabolism

La Lipasa Hepática (LH) es una enzima de síntesis y localización principalmente hepática. Como triglicérido hidrolasa y fosfolipasa interviene en la transformación de la lipoproteína de densidad intermedia (IDL) en lipoproteína de baja densidad (LDL) y en el catabolismo de la lipoproteína de alta densidad (HDL). Además actúa como ligando entre las lipoproteínas y distintos receptores de la superficie celular, en el catabolismo lipoproteico. En los últimos años, el estudio del polimorfisismo de su gen promotor (LIPC), ha esclarecido el comportamiento de la LH en diferentes situaciones metabólicas. Para la medida de su actividad, se validaron las condiciones finales del ensayo: sustrato de trioleína, sonicado en presencia de albúmina, en buffer Tris-HCl pH=9, con lisolecitina como emulgente, incubado en presencia de plasma post-heparínico. La actividad de la LH se encuentra bajo control hormonal; una disminución en su actividad genera un cuadro aterogénico, con hiperlipemia combinada y presencia de lipoproteínas aterogénicas. Por otro lado, un aumento marcado de LH, produce disminución de HDL y presencia de LDL pequeñas y densas. En este trabajo, se presentan los papeles lipolítico y no lipolítico de la LH, así como distintos factores que regulan su actividad y por lo tanto, su intervención en el proceso aterogénico (AU)