Role Of Lipase Research Articles

The Bursaphelenchus xylophilus candidate effector BxLip-3 targets the class I chitinases to suppress immunity in pine.

Lipase is involved in lipid hydrolysis, which is related to nematodes' energy reserves and stress resistance. However, the role of lipases in Bursaphelenchus xylophilus, a notorious plant-parasitic nematode responsible for severe damage to pine forest ecosystems, remains largely obscure. Here, we characterized a class III lipase as a candidate effector and named it BxLip-3. It was transcriptionally up-regulated in the parasitic stages of B. xylophilus and specifically expressed in the oesophageal gland cells and the intestine. In addition, BxLip-3 suppressed cell death triggered by the pathogen-associated molecular patterns PsXEG1 and BxCDP1 in Nicotiana benthamiana, and its Lipase-3 domain is essential for immunosuppression. Silencing of the BxLip-3 gene resulted in a delay in disease onset and increased the activity of antioxidant enzymes and the expression of pathogenesis-related (PR) genes. Plant chitinases are thought to be PR proteins involved in the defence system against pathogen attack. Using yeast two-hybrid and co-immunoprecipitation assays, we identified two class I chitinases in Pinus thunbergii, PtChia1-3 and PtChia1-4, as targets of BxLip-3. The expression of these two chitinases was up-regulated during B. xylophilus inoculation and inhibited by BxLip-3. Overall, this study illustrated that BxLip-3 is a crucial virulence factor that plays a critical role in the interaction between B. xylophilus and host pine.

Endocannabinoids regulate cocaine-associated memory through brain AEA–CB1R signalling activation

ObjectiveContextual drug-associated memory precipitates craving and relapse in substance users, and the risk of relapse is a major challenge in the treatment of substance use disorders. Thus, understanding the neurobiological underpinnings of how this association memory is formed and maintained will inform future advances in the treatment of drug addiction. Brain endocannabinoids (eCBs) signalling has been associated with drug-induced neuroadaptations, but the role of lipases that mediate small lipid ligand biosynthesis and metabolism in regulating drug-associated memory has not been examined. Here, we explored how manipulation of the lipase fatty acid amide hydrolase (FAAH), which is involved in mediating the level of the lipid ligand anandamide (AEA), affects cocaine-associated memory formation. MethodsWe applied behavioural, pharmacological and biochemical methods to detect cocaine-associated memory formation, eCBs in the dorsal dentate gyrus (dDG), and the activity of related enzymes. We further examined the roles of abnormal FAAH activity and AEA–CB1R signalling in the regulation of cocaine-associated memory formation and granule neuron dendritic structure alterations in the dDG through Western blotting, electron microscopy and immunofluorescence. ResultsIn the present study, we found that cocaine induced a decrease in the level of FAAH in the dDG and increased the level of AEA. A high level of AEA activated cannabinoid type 1 receptors (CB1Rs) and further triggered CB1R signalling activation and granule neuron dendritic remodelling, and these effects were reversed by blockade of CB1Rs in the brain. Furthermore, inhibition of FAAH in the dDG markedly increased AEA levels and promoted cocaine-associated memory formation through CB1R signalling activation. ConclusionsTogether, our findings demonstrate that the lipase FAAH influences CB1R signalling activation and granule neuron dendritic structure alteration in the dDG by regulating AEA levels and that AEA and AEA metabolism play a key role in cocaine-associated memory formation. Manipulation of AEA production may serve as a potential therapeutic strategy for drug addiction and relapse prevention.

The Role of Lipid Sensing Nuclear Receptors (PPARs and LXR) and Metabolic Lipases in Obesity, Diabetes and NAFLD

Obesity and type 2 diabetes mellitus (T2DM) are metabolic disorders characterized by metabolic inflexibility with multiple pathological organ manifestations, including non-alcoholic fatty liver disease (NAFLD). Nuclear receptors are ligand-dependent transcription factors with a multifaceted role in controlling many metabolic activities, such as regulation of genes involved in lipid and glucose metabolism and modulation of inflammatory genes. The activity of nuclear receptors is key in maintaining metabolic flexibility. Their activity depends on the availability of endogenous ligands, like fatty acids or oxysterols, and their derivatives produced by the catabolic action of metabolic lipases, most of which are under the control of nuclear receptors. For example, adipose triglyceride lipase (ATGL) is activated by peroxisome proliferator-activated receptor γ (PPARγ) and conversely releases fatty acids as ligands for PPARα, therefore, demonstrating the interdependency of nuclear receptors and lipases. The diverse biological functions and importance of nuclear receptors in metabolic syndrome and NAFLD has led to substantial effort to target them therapeutically. This review summarizes recent findings on the roles of lipases and selected nuclear receptors, PPARs, and liver X receptor (LXR) in obesity, diabetes, and NAFLD.

A role for the endocannabinoid enzymes monoacylglycerol and diacylglycerol lipases in cue-induced cocaine craving following prolonged abstinence.

Following exposure to drugs of abuse, long-term neuroadaptations underlie persistent risk to relapse. Endocannabinoid signaling has been associated with drug-induced neuroadaptations, but the role of lipases that mediate endocannabinoid biosynthesis and metabolism in regulating relapse behaviors following prolonged periods of drug abstinence has not been examined. Here, we investigated how pharmacological manipulation of lipases involved in regulating the expression of the endocannabinoid 2-AG in the nucleus accumbens (NAc) influence cocaine relapse via discrete neuroadaptations. At prolonged abstinence (30days) from cocaine self-administration, there is an increase in the NAc levels of diacylglycerol lipase (DAGL), the enzyme responsible for the synthesis of the endocannabinoid 2-AG, along with decreased levels of monoacylglycerol lipase (MAGL), which hydrolyzes 2-AG. Since endocannabinoid-mediated behavioral plasticity involves phosphatase dysregulation, we examined the phosphatase calcineurin after 30days of abstinence and found decreased expression in the NAc, which we demonstrate is regulated through the transcription factor EGR1. Intra-NAc pharmacological manipulation of DAGL and MAGL with inhibitors DO-34 and URB-602, respectively, bidirectionally regulated cue-induced cocaine seeking and altered the phosphostatus of translational initiation factor, eIF2α. Finally, we found that cocaine seeking 30days after abstinence leads to decreased phosphorylation of eIF2α and reduced expression of its downstream target NPAS4, a protein involved in experience-dependent neuronal plasticity. Together, our findings demonstrate that lipases that regulate 2-AG expression influence transcriptional and translational changes in the NAc related to drug relapse vulnerability.

Oxidation reactions in model systems simulating the processing of soybeans into soymilk: role of lipase and lipoxygenase in volatile flavors formation

ABSTRACT In recent decades, the process of lipase (LIP) activation hydrolysis and lipoxygenase (LOX) oxidation for energy supply during soybean germination has been well understood, but the formation mechanism of volatile flavor substances in soymilk grinding has not been understood in detail. Different model systems were prepared using protein, LOX, LIP, and triacylglycerol (TAG) derived from soybeans to study the reaction process of soymilk flavor. The study revealed that the simultaneous existence of LOX, LIP, and TAG was a necessary condition for flavor formation, and the type and amount of volatile flavor substances were related to the composition of the lipid substrates. Compared with soymilk, the model system with LOX and LIP had a high degree of similarity in the composition of volatile flavors, but there were differences in quantity. This indicates that the flavor formation of soymilk is also positively influenced by other ingredients in soymilk.

Lipolytic Enzymes Involved in the Virulence of Human Pathogenic Fungi

Pathogenic microbes secrete various enzymes with lipolytic activities to facilitate their survival within the host. Lipolytic enzymes include extracellular lipases and phospholipases, and several lines of evidence have suggested that these enzymes contribute to the virulence of pathogenic fungi. Candida albicans and Cryptococcus neoformans are the most commonly isolated human fungal pathogens, and several biochemical and molecular approaches have identified their extracellular lipolytic enzymes. The role of lipases and phospholipases in the virulence of C. albicans has been extensively studied, and these enzymes have been shown to contribute to C. albicans morphological transition, colonization, cytotoxicity, and penetration to the host. While not much is known about the lipases in C. neoformans, the roles of phospholipases in the dissemination of fungal cells in the host and in signaling pathways have been described. Lipolytic enzymes may also influence the survival of the lipophilic cutaneous pathogenic yeast Malassezia species within the host, and an unusually high number of lipase-coding genes may complement the lipid dependency of this fungus. This review briefly describes the current understanding of the lipolytic enzymes in major human fungal pathogens, namely C. albicans, C. neoformans, and Malassezia spp.

Evaluation of Expression of Lipases and Phospholipases ofMalassezia restrictain Patients with Seborrheic Dermatitis

BackgroundMalassezia species (spp.) are cutaneous opportunistic pathogens and associated with various dermatological diseases including seborrheic dermatitis, dandruff and atopic dermatitis. Almost all Malassezia spp. are obligatorily lipid-dependent, which might be caused by lack of the myristic acid synthesis. Recent genome analysis of M. restricta and M. globosa suggested that the absence of a gene encoding fatty acid synthesis might be compensated by abundant genes encoding hydrolases, which produce fatty acids, and that lipases and phospholipases may play a role in virulence of the fungus.ObjectiveThe current study aimed to investigate the contribution of lipases and phospholipases in virulence of the M. restricta as being the most frequently isolated Malassezia spp. from the human skin.MethodsSwap samples of two different body sites of at least 18 patients with seborrheic dermatitis were obtained and in vivo expression of lipases and phospholipases of M. restricta was analyzed by the gene specific two-step nested RT-PCR.ResultsThe results of the current study suggest that majority of the patients display expression of lipase RES_0242.ConclusionThese data imply a possible role of lipase in the host environment to produce free fatty acids for the fungus.

Phospholipase A2 Mediates Apolipoprotein-Independent Uptake of Chylomicron Remnant-Like Particles by Human Macrophages

Apolipoprotein E-receptor-mediated pathways are the main routes by which macrophages take up chylomicron remnants, but uptake may also be mediated by receptor-independent routes. To investigate these mechanisms, triacylglycerol (TG) accumulation induced by apolipoprotein-free chylomicron remnant-like particles (CRLPw/o) in human monocyte-derived macrophages was evaluated. Macrophage TG content increased about 5-fold after incubation with CRLPw/o, and this effect was not reduced by the inhibition of phagocytosis, macropinocytosis, apolipoprotein E function, or proteoglycan bridging. The role of lipases, including lipoprotein lipase, cholesteryl ester hydrolase, and secretory (sPLA2) and cytosolic phospholipase A2, was studied using [3H]TG-labelled CRLPw/o. Total cell radioactivity after incubation with [3H]TG CRLPw/o was reduced by 15–30% by inhibitors of lipoprotein lipase and cholesteryl ester hydrolase and by about 45% by inhibitors of sPLA2 and cytosolic PLA2 . These results suggest that macrophage lipolytic enzymes mediate the internalization of postprandial TG-rich lipoproteins and that sPLA2 and cytosolic PLA2, play a more important role than extracellular lipoprotein lipase-mediated TG hydrolysis.

The role of lipase in blood lipoprotein metabolism and accumulation of lipids in oocytes of the Siberian sturgeon Acipenser baerii during maturation

Summary The purpose of this study was to investigate the role of lipoprotein lipase (LPL) and hepatic lipase (HL) played in accumulating lipid into oocytes and serum lipid metabolism in Siberian sturgeon Acipenser baerii. We determined ovarian LPL activity, serum LPL and HL activity, and several serum lipid amounts in different ovary development stages. Our results shown that LPL activity in ovaries during vitellogenesis, serum LPL and HL activity were increased during vitellogenesis with a significant high level in stage V, and decreased fast after ovulation. Serum very low density lipoprotein (VLDL), triglycerides (TG), and phospholipids (PL) concentrations were increased since stage II to IV, and then decreased till stage VI. Serum cholesterol (TC) and low-density lipoprotein (LDL) amounts were gradually increasing during ovaries development. Moreover, we found that serum two lipases activity positively correlated with serum VLDL, TG and, TC and negatively correlated with high-density lipoprotein (HDL). The variation tendency of serum LPL, HL activity and lipids concentration, and the close correlationship between the two lipases and lipids during ovarian development suggest that LPL and HL participate in regulating blood lipid metabolism.

Lipase of Candida albicans induces activation of NADPH oxidase and l-arginine pathways on resting and activated macrophages

Candida albicans secretes various hydrolytic enzymes which are considered to be an integral part in the pathogenesis. However, the role of lipases is far from being completely understood and the direct effects of these fungal enzymes during the host–pathogen interaction remain to be established. We recently isolated and characterized an extracellular C. albicans lipase (CaLIP), and demonstrated the ability of this fungal enzyme to interact directly with macrophages (Mϕ) and hepatocytes and to operate as a virulence factor. Herein, we explored the effects of CaLIP on Mϕ functions such as oxidative burst and l-arginine metabolism. The study was performed in cells with different activation status: normal-resting Mϕs and Mϕs primed in vivo or in vitro with C. albicans. The ability of this fungal factor to modulate the above-mentioned parameters was dependent on cells status, dose, and microenvironment, where the interaction took place. These results constitute a new finding in the biology of candidiasis and could illustrate an additional evolutive advantage for the fungus in the framework of the bidirectional host–pathogen interaction.

The Role of Lipase and α-Amylase in the Degradation of Starch/Poly(ɛ-Caprolactone) Fiber Meshes and the Osteogenic Differentiation of Cultured Marrow Stromal Cells

The present work studies the influence of hydrolytic enzymes (alpha-amylase or lipase) on the degradation of fiber mesh scaffolds based on a blend of starch and poly(epsilon-caprolactone) (SPCL) and the osteogenic differentiation of osteogenic medium-expanded rat bone marrow stromal cells (MSCs) and subsequent formation of extracellular matrix on these scaffolds under static culture conditions. The biodegradation profile of SPCL fiber meshes was investigated using enzymes that are specifically responsible for the enzymatic hydrolysis of SPCL using concentrations similar to those found in human serum. These degradation studies were performed under static and dynamic conditions. After several degradation periods (3, 7, 14, 21, and 30 days), weight loss measurements and micro-computed tomography analysis (specifically porosity, interconnectivity, mean pore size, and fiber thickness) were performed. The SPCL scaffolds were seeded with rat MSCs and cultured for 8 and 16 days using complete osteogenic media with and without enzymes (alpha-amylase or lipase). Results indicate that culture medium supplemented with enzymes enhanced cell proliferation after 16 days of culture, whereas culture medium without enzymes did not. No calcium was detected in groups cultured with alpha-amylase or without enzymes after each time period, although groups cultured with lipase presented calcium deposition after the eighth day, showing a significant increase at the sixteenth day. Lipase appears to positively influence osteoblastic differentiation of rat MSCs and to enhance matrix mineralization. Furthermore, scanning electron microscopy images showed that the enzymes did not have a deleterious effect on the three-dimensional structure of SPCL fiber meshes, meaning that the scaffolds did not lose their structural integrity after 16 days. Confocal micrographs have shown cells to be evenly distributed and infiltrated within the SPCL fiber meshes up to 410 microm from the surface. This study demonstrates that supplementation of culture media with lipase holds great potential for the generation of bone tissue engineering constructs from MSCs seeded onto SPCL fiber meshes, because lipase enhances the osteoblastic differentiation of the seeded MSCs and promotes matrix mineralization without harming the structural integrity of the meshes over 16 days of culture.

Advances in adipose tissue metabolism

This review will focus on the recent findings in adipose tissue metabolism with special attention to human adipocyte biology and physiology. There are major advances stemming from the concomitant results obtained from studies on mature human adipocytes, human preadipocytes differentiated in vitro and murine adipose cell lines. Physiological developments have been based on the expanded utilization of various kinds of murine transgenic models and physiological techniques such as microdialysis, open-flow microperfusion, arteriovenous techniques and the utilization of deuterium- or tritium-labelled metabolites that have provided a number of physiological advances in the understanding of human adipose tissue physiology. Gene expression profiling studies and nutrigenomics are emerging methods that herald interesting approaches for the future. An overview of recent discoveries in the mechanisms involved in the control of free fatty acid uptake, triacylglycerol synthesis and fat deposition will be discussed, as well as recent advances in the mechanisms involved in the lipolytic pathways, the role of lipases and perilipins. In addition, the in vivo validation of catecholamine action and the discovery of the lipolytic effects of natriuretic peptides will also be covered.

Prevalence and Determinants of Increased Serum Lipase Levels in a General Population

There is little information on the prevalence of increased serum lipase levels and its determinants from population-based studies. The present study was performed to provide such information. We used data from the 4275 subjects aged 20 to 79 years who were recruited for the population-based Study of Health in Pomerania. Serum lipase levels were determined colorimetrically; levels > or =3.17 micromol/s x l were considered increased. The prevalence of increased serum lipase levels was 3.4%. The prevalence of self-reported chronic pancreatitis in this population was 0.7%. Subjects with and without increased serum lipase levels did not differ with respect to symptoms indicative of pancreatitis including abdominal feeling of fullness, abdominal pain, nausea, and loss of weight. High serum lipase levels correlated with advanced age, increased serum creatinine levels, and use of steroids or enalapril. Increased serum lipase levels are unrelated to pancreatitis-related symptoms. Renal insufficiency and prevalent pancreatitis explain increased serum lipase levels in a minority of subjects. In clinical practice, drugs including steroids and enalapril should be excluded as cause of increased serum lipase levels. The predictive roleof lipase measurements with respect to other pancreatic or extrapancreatic disorders has to be investigated in cohort studies.

Role of lipase in Burkholderia cepacia complex (Bcc) invasion of lung epithelial cells

The Burkholderia cepacia complex (Bcc) is a group of ten closely related species associated with life-threatening infection in cystic fibrosis (CF). These bacteria are highly antibiotic resistant, with some strains transmissible, and in a subgroup of patients, they can cause a rapid and fatal necrotising pneumonia. The Bcc organisms produce a range of exoproducts with virulence potential, including exopolysaccharide, proteases and lipases. Many members of the Bcc are also capable of epithelial cell invasion, although the mechanism(s) involved are poorly understood. This study investigates a role for Bcc lipase in epithelial cell invasion by Bcc strains. Lipase activity was measured in eight species of the Bcc. Strains that produced high levels of lipase were predominantly from the B. multivorans and B. cenocepacia species. Pre-treatment of two epithelial cell lines with Bcc lipase significantly increased invasion by two B. multivorans strains and one B. cenocepacia strain and did not affect either plasma membrane or tight junction integrity. Inhibition of Bcc lipase production by the lipase inhibitor Orlistat significantly decreased invasion by both B. multivorans and B. cenocepacia strains in a concentration-dependent manner. This study demonstrates the extent of lipase production across the Bcc and establishes a potential role for lipase in Bcc epithelial cell invasion.

The Bald Truth About Lipids

Hair loss can be traumatic, whether it is linked to illness or simply part of the natural aging process, and there is considerable interest in dissecting its underlying mechanisms. Kazantseva et al . identify a culprit gene in a group of Russian families who show an inherited deficiency in hair growth but are otherwise healthy. The mutant gene, LIPH , encodes lipase H, a phospholipase thought to regulate the production of lipid signaling molecules. This discovery will likely stimulate investigations aimed at understanding the precise role of lipase H in hair follicle biology and whether the LIPH gene also contributes to the more common forms of baldness in the general population. A. Kazantseva, A. Goltsov, R. Zinchenko, A. P. Grigorenko, A. V. Abrukova, Y. K. Moliaka, A. G. Kirillov, Z. Guo, S. Lyle, E. K. Ginter, E. I. Rogaev, Human hair growth deficiency is linked to a genetic defect in the phospholipase gene LIPH . Science 314 , 982-985 (2006). [Abstract] [Full Text]

The molecular machinery of autophagy: unanswered questions

Autophagy is a process in which cytosol and organelles are sequestered within double-membrane vesicles that deliver the contents to the lysosome/vacuole for degradation and recycling of the resulting macromolecules. It plays an important role in the cellular response to stress, is involved in various developmental pathways and functions in tumor suppression, resistance to pathogens and extension of lifespan. Conversely, autophagy may be associated with certain myopathies and neurodegenerative conditions. Substantial progress has been made in identifying the proteins required for autophagy and in understanding its molecular basis; however, many questions remain. For example, Tor is one of the key regulatory proteins at the induction step that controls the function of a complex including Atg1 kinase, but the target of Atg1 is not known. Although autophagy is generally considered to be nonspecific, there are specific types of autophagy that utilize receptor and adaptor proteins such as Atg11; however, the means by which Atg11 connects the cargo with the sequestering vesicle, the autophagosome, is not understood. Formation of the autophagosome is a complex process and neither the mechanism of vesicle formation nor the donor membrane origin is known. The final breakdown of the sequestered cargo relies on well-characterized lysosomal/vacuolar proteases; the roles of lipases, by contrast, have not been elucidated, and we do not know how the integrity of the lysosome/vacuole membrane is maintained during degradation.

Highly active, lipase silicone elastomers

Lipase Candida rugosa was entrapped in silicone rubber via condensation-cure room temperature vulcanization of silanol-terminated poly(dimethylsiloxane) with tetraethyl orthosilicate as a crosslinker, to give a highly active silicone-enzyme elastomer. The effect on enzyme activity of addition of water and hydrophilic polymeric moieties based on poly(ethylene oxide) 2 was examined, as were crosslinker concentration, enzyme concentration, and elastomer thickness. It was demonstrated that lipase is most active in silicone elastomers and more active in silicone oils than simple hydrocarbons. Crosslink density in these elastomers was not an important factor in the reactivity of the rubber. However, the addition of hydrophilic species prior to elastomer formation decreased the efficiency both of the dispersion of the enzyme and the resulting activity of the elastomer. This effect could be moderated by prior exposure of the lipase to silicone oil. Thus, hydrophobic silicones play a protective/activating role for lipase.

Lipases in racemic resolutions

Lipases are enzymes that hydrolyse lipids into triglycerides and fatty acids. Due to the unique environment around their active site, they are capable of a wide range of racemic resolutions. This review article deals with the role of Lipases in racemic resolutions with specific references to the stereospecificity, role of solvents and enzyme structure. (C) 2001 Society of Chemical Industry.

Role of lipase in the regulation of postprandial gastric acid secretion and emptying of fat in humans: a study with orlistat, a highly specific lipase inhibitor

BACKGROUND AND AIMSTo investigate the importance of lipase on gastric functions, we studied the effects of orlistat, a potent and specific inhibitor of lipase, on postprandial gastric acidity and gastric...

Role of lipase in the regulation of gastric secretion and gastric emptying in humans: A study with orlistat, a highly specific lipase inhibitor: [formula omitted], J. Borovicka, G. Gutmann, C. Güzelhan, D. Hartmann, M. Fried. Gastroenterology, University Hospitals Zurich and Lausanne, and Hoffmann-LaRoche, Basel, Switzerland

Role of lipase in the regulation of gastric secretion and gastric emptying in humans: A study with orlistat, a highly specific lipase inhibitor: [formula omitted], J. Borovicka, G. Gutmann, C. Güzelhan, D. Hartmann, M. Fried. Gastroenterology, University Hospitals Zurich and Lausanne, and Hoffmann-LaRoche, Basel, Switzerland