Silencing the triacylglycerol lipase (TGL) gene decreases the number of apyrene sperm and inhibits oviposition in Sitotroga cerealella.

Triacylglycerol lipase (TGL) is an essential lipid metabolism enzyme that also plays a critical role in energy metabolism; however, how it regulates other life processes is unknown. To investigate the functional role of TGL in moth reproduction, males Sitotroga cerealella were used as a model. The TGL gene was cloned and analysed. The results showed that the open reading frame of TGL was 1968 bp long and contained three conserved regions. TGL gene expression was higher in the larval and early adult stages than in the pupal stage, with the highest levels observed in the fat body, testis and accessory glands during the early adult stage. Moreover, after TGL in male adults was silenced through RNAi, the protein content in male accessory glands remained unchanged, and the spermatophore transferred into females mated with TGL-silenced males became small and empty; meanwhile, the number of apyrene sperm in the spermatophore was significantly reduced due to the reduction of apyrene sperm in males, which eventually led to the significant reduction of egg-laying amount. All of the findings suggest that TGL regulates the amount of sperm in male moths as well as the morphology and quality of spermatophores transferred to females after mating with treated males, implying that TGL is critical for Sitotroga cerealella's reproductive process.

Lipase - The fascinating dynamics of enzyme in seed storage and germination - A real challenge to pearl millet.

Pearl millet is considered as 'nutri-cereal' because of high nutrient density of the seeds. The grain has limited use because of low keeping quality of the flour due to the activities of rancidity causing enzymes like lipase, lox, pox and PPO. Among all the enzymes, lipase is most notorious because of its robust nature and high activity under different conditions. we have identified 2180 putative transcripts showing homology with different variants of lipase precursor through transcriptome data mining (NCBI BioProject acc. no. PRJNA625418). Lipase plays dual role of facilitating the germination of seeds and deteriorating the quality of the pearl millet flour through hydrolytic rancidity. Different physiochemical methods like heat treatment, micro oven, hydrothermal, etc. have been developed to inhibit lipase activity in pearl millet flour. There is further need to develop improved processing technologies to inhibit the hydrolytic and oxidative rancidity in the floor with enhanced shelf-life.

Cannabis and synaptic reprogramming of the developing brain.

Recent years have been transformational in regard to the perception of the health risks and benefits of cannabis with increased acceptance of use. This has unintended neurodevelopmental implications given the increased use of cannabis and the potent levels of Δ9-tetrahydrocannabinol today being consumed by pregnant women, young mothers and teens. In this Review, we provide an overview of the neurobiological effects of cannabinoid exposure during prenatal/perinatal and adolescent periods, in which the endogenous cannabinoid system plays a fundamental role in neurodevelopmental processes. We highlight impaired synaptic plasticity as characteristic of developmental exposure and the important contribution of epigenetic reprogramming that maintains the long-term impact into adulthood and across generations. Such epigenetic influence by its very nature being highly responsive to the environment also provides the potential to diminish neural perturbations associated with developmental cannabis exposure.

Adipose triglyceride lipase protects renal cell endocytosis in a Drosophila dietary model of chronic kidney disease.

Obesity-related renal lipotoxicity and chronic kidney disease (CKD) are prevalent pathologies with complex aetiologies. One hallmark of renal lipotoxicity is the ectopic accumulation of lipid droplets in kidney podocytes and in proximal tubule cells. Renal lipid droplets are observed in human CKD patients and in high-fat diet (HFD) rodent models, but their precise role remains unclear. Here, we establish a HFD model in Drosophila that recapitulates renal lipid droplets and several other aspects of mammalian CKD. Cell type-specific genetic manipulations show that lipid can overflow from adipose tissue and is taken up by renal cells called nephrocytes. A HFD drives nephrocyte lipid uptake via the multiligand receptor Cubilin (Cubn), leading to the ectopic accumulation of lipid droplets. These nephrocyte lipid droplets correlate with endoplasmic reticulum (ER) and mitochondrial deficits, as well as with impaired macromolecular endocytosis, a key conserved function of renal cells. Nephrocyte knockdown of diglyceride acyltransferase 1 (DGAT1), overexpression of adipose triglyceride lipase (ATGL), and epistasis tests together reveal that fatty acid flux through the lipid droplet triglyceride compartment protects the ER, mitochondria, and endocytosis of renal cells. Strikingly, boosting nephrocyte expression of the lipid droplet resident enzyme ATGL is sufficient to rescue HFD-induced defects in renal endocytosis. Moreover, endocytic rescue requires a conserved mitochondrial regulator, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC1α). This study demonstrates that lipid droplet lipolysis counteracts the harmful effects of a HFD via a mitochondrial pathway that protects renal endocytosis. It also provides a genetic strategy for determining whether lipid droplets in different biological contexts function primarily to release beneficial or to sequester toxic lipids.

Adipose-specific knockout of ubiquitin-conjugating enzyme E2L6 (Ube2l6) reduces diet-induced obesity, insulin resistance, and hepatic steatosis.

Ubiquitin/ISG15-conjugating enzyme E2 L6 (UBE2L6/Ube2l6) catalyzes protein ISGylation and ubiquitylation, post-translational modifications which regulate protein stability. Ube2l6 plays a role in promoting in vitro adipogenesis; however, its mechanism(s) of action and in vivo effects remain unknown. Here, we discovered that UBE2L6 levels were upregulated, and UBE2L6 and adipose triglyceride lipase (ATGL/Atgl) levels were negatively correlated, in white adipose tissue (WAT) from obese humans and obese mice. Therefore, we employed adipose-specific Ube2l6 knockout (Ube2l6AKO) mice and age-matched Ube2l6flox/flox controls to assess adipocyte Ube2l6's role in high-fat diet (HFD)-induced obesity, insulin resistance, and hepatic steatosis. HFD-fed Ube2l6AKO mice displayed lower subcutaneous and visceral WAT mass levels relative to controls. HFD-fed Ube2l6AKO mice also showed WAT adipocyte hypoplasia and hypotrophy as well as enhanced whole-body metabolic activity relative to controls. Furthermore, glucose intolerance, insulin resistance, compensatory hyperinsulinemia, hypercholesterolemia, and hepatic steatosis were lower in HFD-fed Ube2l6AKO mice as compared to controls. Mechanistically, we found that Atgl protein expression and Atgl-mediated lipolysis were negatively regulated by Ube2l6's promotion of Atgl protein ubiquitylation. Collectively, adipocyte Ube2l6 functions as a negative regulator of Atgl protein stability and, consequently, promotes HFD-induced obesity, insulin resistance, and hepatic steatosis.

An In-Silico Comparative Study of Lipases from the Antarctic Psychrophilic Ciliate Euplotes focardii and the Mesophilic Congeneric Species Euplotes crassus: Insight into Molecular Cold-Adaptation.

Cold-adapted enzymes produced by psychrophilic organisms have elevated catalytic activities at low temperatures compared to their mesophilic counterparts. This is largely due to amino acids changes in the protein sequence that often confer increased molecular flexibility in the cold. Comparison of structural changes between psychrophilic and mesophilic enzymes often reveal molecular cold adaptation. In the present study, we performed an in-silico comparative analysis of 104 hydrolytic enzymes belonging to the family of lipases from two evolutionary close marine ciliate species: The Antarctic psychrophilic Euplotes focardii and the mesophilic Euplotes crassus. By applying bioinformatics approaches, we compared amino acid composition and predicted secondary and tertiary structures of these lipases to extract relevant information relative to cold adaptation. Our results not only confirm the importance of several previous recognized amino acid substitutions for cold adaptation, as the preference for small amino acid, but also identify some new factors correlated with the secondary structure possibly responsible for enhanced enzyme activity at low temperatures. This study emphasizes the subtle sequence and structural modifications that may help to transform mesophilic into psychrophilic enzymes for industrial applications by protein engineering.

The PNPLA3-I148M Variant Confers an Antiatherogenic Lipid Profile in Insulin-resistant Patients.

CONTEXT: The I148M (rs738409-G) variant in PNPLA3 increases liver fat content but may be protective against cardiovascular disease. Insulin resistance (IR) amplifies the effect of PNPLA3-I148M on liver fat. OBJECTIVE: To study whether PNPLA3-I148M confers an antihyperlipidemic effect in insulin-resistant patients. DESIGN: Cross-sectional study comparing the impact of PNPLA3-I148M on plasma lipids and lipoproteins in 2 cohorts, both divided into groups based on rs738409-G allele carrier status and median HOMA-IR. SETTING: Tertiary referral center. PATIENTS: A total of 298 obese patients who underwent a liver biopsy during bariatric surgery (bariatric cohort: age 49 ±â€…9 years, body mass index [BMI] 43.2 ±â€…6.8 kg/m2), and 345 less obese volunteers in whom liver fat was measured by proton magnetic resonance spectroscopy (nonbariatric cohort: age 45 ±â€…14 years, BMI 29.7 ±â€…5.7 kg/m2). MAIN OUTCOME MEASURES: Nuclear magnetic resonance profiling of plasma lipids, lipoprotein particle subclasses and their composition. RESULTS: In both cohorts, individuals carrying the PNPLA3-I148M variant had significantly higher liver fat content than noncarriers. In insulin-resistant and homozygous carriers, PNPLA3-I148M exerted a distinct antihyperlipidemic effect with decreased very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) particles and their constituents, and increased high-density lipoprotein particles and their constituents, compared with noncarriers. VLDL particles were smaller and LDL particles larger in PNPLA3-I148M carriers. These changes were geometrically opposite to those due to IR. PNPLA3-I148M did not have a measurable effect in patients with lower IR, and its effect was smaller albeit still significant in the less obese than in the obese cohort. CONCLUSIONS: PNPLA3-I148M confers an antiatherogenic plasma lipid profile particularly in insulin-resistant individuals.

Bile salt-dependent lipase promotes the barrier integrity of Caco-2 cells by activating Wnt/ß-catenin signaling via LRP6 receptor.

Bile salt-dependent lipase (BSDL) within intestinal lumen can be endocytosed by enterocytes and support the intestinal barrier function. However, the epithelial-supporting effect of this protein has not been verified in a human cell line and neither the direct signaling pathway nor the function of endocytosis in this process has been clearly identified. We sought to investigate the signaling pathway and the membrane receptor through which BSDL might exert these effects using intestinal epithelial cells. Caco-2 cells were treated with recombinant BSDL, and the barrier function, cell proliferation, and activation of the Wnt signaling pathway were assessed. The effect of Wnt signaling activation induced by BSDL and BSDL endocytosis was investigated in LRP6-silenced and non-silenced cells. Moreover, caveolae- and clathrin-dependent endocytosis inhibitors were also applied respectively to analyze their effects on Wnt signaling activation induced by BSDL. BSDL treatment increased the barrier function but not proliferation of Caco-2 cells. It also induced ß-catenin nuclear translocation and activated Wnt target gene transcription. Moreover, in the Wnt pathway, BSDL increased the levels of non-phosphorylated-ß-catenin (Ser33/37/Thr41) and phosphorylated-ß-catenin (Ser552). Notably, the silencing of LRP6 expression impaired BSDL endocytosis and decreased BSDL-induced ß-catenin nuclear translocation. The inhibition of BSDL endocytosis induced by caveolae-mediated endocytosis inhibitor was stronger than that by clathrin-mediated endocytosis inhibitor, and the Wnt signaling activation associated with its endocytosis was also most likely caveolae-dependent. Our findings suggested that LRP6, a canonical Wnt pathway co-receptor, can mediate BSDL endocytosis and then activate Wnt signaling in Caco-2 cells.

Effect of Tricaprin on Cardiac Proteome in a Mouse Model for Triglyceride Deposit Cardiomyovasculopathy.

Triglyceride deposit cardiomyovasculopathy (TGCV), a rare cardiovascular disorder caused by genetic or acquired dysfunction of adipose triglyceride lipase (ATGL), is marked by defective intracellular lipolysis that results in excessive accumulation of triglycerides (TGs) in the myocardium and coronary arteries, leading to intractable heart failure (HF). We have developed a specific treatment for TGCV using tricaprin, a medium chain TG, as part of a governmental rare disease project in Japan. We recently reported that tricaprin diet improved cardiac TG metabolism and left ventricular function in an ATGL-knockout (KO) mouse, a mouse model for TGCV. Here, we report the effect of tricaprin on the myocardial proteome of KO mice to elucidate the mechanisms of action of tricaprin at protein expression levels. We compared proteomic changes in the hearts of KO mice fed control or tricaprin diet. Tandem mass tag-based shotgun proteomics identified 1832 proteins common to all sample groups. Whole proteomic distribution in the heart was largely up-regulated in KO mice fed control diet. When using cut-off values (>1.5 or <0.67, FDR-adjusted p value<0.01), in fact, 65 proteins were up-regulated whereas only 2 proteins were down-regulated in the hearts of KO mice fed control diet. The former included proteins assigned to "Cardiac Arrhythmia", and "Cardiac Damage" reflecting HF by a toxicity function analysis. One of the latter was Ces1d, which is known to regulate intracellular TG metabolism. These proteomic changes observed in KO mice were dramatically rescued by the tricaprin diet. These results indicated that tricaprin diet ameliorated HF in a TGCV mouse model at protein expression levels and also provided important clues to understand mechanisms for the beneficial effect of tricaprin.

Role of Patatin-Like Phospholipase Domain-Containing 3 Gene for Hepatic Lipid Content and Insulin Resistance in Diabetes.

OBJECTIVE: The rs738409(G) single nucleotide polymorphism (SNP) in the patatin-like phospholipase domain-containing 3 (PNPLA3) gene associates with increased risk and progression of nonalcoholic fatty liver disease (NAFLD). As the recently described severe insulin-resistant diabetes (SIRD) cluster specifically relates to NAFLD, this study examined whether this SNP differently associates with hepatic lipid content (hepatocellular lipids [HCL]) and insulin sensitivity in recent-onset diabetes. RESEARCH DESIGN AND METHODS: A total of 917 participants in the German Diabetes Study (GDS) underwent genotyping, hyperinsulinemic-euglycemic clamps with stable isotopic tracer dilution, and MRS. RESULTS: The G allele associated positively with HCL (ß = 0.36, P < 0.01), independent of age, sex, and BMI across the whole cohort, but not in the individual clusters. Those with SIRD exhibited lowest whole-body insulin sensitivity compared with those with severe insulin-deficient (SIDD), moderate obesity-related (MOD), moderate age-related (MARD), and severe autoimmune diabetes (SAID) clusters (all P < 0.001). Interestingly, the SIRD group presented with higher prevalence of the rs738409(G) SNP compared with other clusters and the glucose-tolerant control group (P < 0.05). HCL was higher in the SIRD group (median 13.6% [1st quartile 5.8; 3rd quartile 19.1] compared with the MOD (6.4 % [2.1; 12.4], P < 0.05), MARD (3.0% [1.0; 7.9], P < 0.001), SAID (0.4% [0.0; 1.5], P < 0.001), and glucose-tolerant (0.9% [0.4; 4.9), P < 0.001) group. Although the PNPLA3 polymorphism did not directly associate with whole-body insulin sensitivity in SIRD, the G-allele carriers had higher circulating free fatty acid concentrations and greater adipose tissue insulin resistance compared with noncarriers (both P < 0.001). CONCLUSIONS: Members of the SIRD cluster are more frequently carriers of the rs738409(G) variant. The SNP-associated adipose tissue insulin resistance and excessive lipolysis may contribute to their NAFLD.

The novel non-steroidal MR antagonist finerenone improves metabolic parameters in high-fat diet-fed mice and activates brown adipose tissue via AMPK-ATGL pathway.

Mineralocorticoid receptor antagonists (MRAs) are recommended for the treatment of heart failure and hypertension, mainly due to their natriuretic and anti-fibrotic mode of action. Rodent studies have shown that MRAs can prevent adverse metabolic consequences of obesity but an elucidation of underlying molecular mechanisms is missing. Here, we investigated metabolic effects of the novel non-steroidal MRA finerenone (FIN) in a mouse model of high-fat diet (HFD)-induced obesity and the signaling pathways activated by MR antagonism at level of interscapular brown adipose tissue (iBAT). C57BL/6J male mice were fed a normal diet or a HFD (with60% kcal from fat) containing or not FIN for 3 months. Metabolic parameters, adipose tissue morphology, gene and protein expression analysis were assessed. We also used brown adipocyte cultures (T37i cells) to investigate the effects of FIN-mediated MR antagonism upon lipid and mitochondrial metabolism. HFD + FIN-treated mice showed improved glucose tolerance together with increased multilocularity and higher expression of thermogenic markers at the level of iBAT, without differences in white adipose depots, suggesting an iBAT-specific effect of FIN. Mechanistically, FIN increased activation of AMP-activated protein kinase which, in turn, stimulated adipose triglyceride lipase activation, with subsequent increased expression of uncoupling protein-1 in brown adipocytes.

The Role of Metabolic Lipases in the Pathogenesis and Management of Liver Disease.

Intracellular lipolysis is an enzymatic pathway responsible for the catabolism of triglycerides (TGs) that is complemented by lipophagy as the autophagic breakdown of lipid droplets. The hydrolytic cleavage of TGs generates free fatty acids (FFAs), which can serve as energy substrates, precursors for lipid synthesis, and mediators in cell signaling. Despite the fundamental and physiological importance of FFAs, an oversupply can trigger lipotoxicity with impaired membrane function, endoplasmic reticulum stress, mitochondrial dysfunction, cell death, and inflammation. Conversely, impaired release of FFAs and other lipid mediators can also disrupt key cellular signaling functions that regulate metabolism and inflammatory processes. This review will focus on specific functions of intracellular lipases in lipid partitioning, covering basic and translational findings in the context of liver disease. In addition, the clinical relevance of genetic mutations in human disease and potential therapeutic opportunities will be discussed.

A role for triglyceride lipase brummer in the regulation of sex differences in Drosophila fat storage and breakdown.

Triglycerides are the major form of stored fat in all animals. One important determinant of whole-body fat storage is whether an animal is male or female. Here, we use Drosophila, an established model for studies on triglyceride metabolism, to gain insight into the genes and physiological mechanisms that contribute to sex differences in fat storage. Our analysis of triglyceride storage and breakdown in both sexes identified a role for triglyceride lipase brummer (bmm) in the regulation of sex differences in triglyceride homeostasis. Normally, male flies have higher levels of bmm mRNA both under normal culture conditions and in response to starvation, a lipolytic stimulus. We find that loss of bmm largely eliminates the sex difference in triglyceride storage and abolishes the sex difference in triglyceride breakdown via strongly male-biased effects. Although we show that bmm function in the fat body affects whole-body triglyceride levels in both sexes, in males, we identify an additional role for bmm function in the somatic cells of the gonad and in neurons in the regulation of whole-body triglyceride homeostasis. Furthermore, we demonstrate that lipid droplets are normally present in both the somatic cells of the male gonad and in neurons, revealing a previously unrecognized role for bmm function, and possibly lipid droplets, in these cell types in the regulation of whole-body triglyceride homeostasis. Taken together, our data reveal a role for bmm function in the somatic cells of the gonad and in neurons in the regulation of male-female differences in fat storage and breakdown and identify bmm as a link between the regulation of triglyceride homeostasis and biological sex.

ATGL/CGI-58-Dependent Hydrolysis of a Lipid Storage Pool in Murine Enterocytes.

As circulating lipid levels are balanced by the rate of lipoprotein release and clearance from the plasma, lipid absorption in the small intestine critically contributes to the maintenance of whole-body lipid homeostasis. Within enterocytes, excessive triglycerides are transiently stored as cytosolic lipid droplets (cLDs), and their mobilization sustains lipid supply during interprandial periods. Using mice lacking adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) exclusively in the intestine (intestine-specific double KO [iDKO]), we show that ATGL/CGI-58 are not involved in providing substrates for chylomicron synthesis. Massive intestinal cLD accumulation in iDKO mice independent of dietary lipids together with inefficient lipid incorporation into cLDs in the early absorption phase demonstrate the existence of a secretion/re-uptake cycle, corroborating the availability of two diverse cLD pools. This study identified ATGL/CGI-58 as critical players in the catabolism of basolaterally (blood) derived lipids and highlights the necessity to modify the current model of intestinal lipid metabolism.

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.

Molecular Genetic Study of a Large Inbred Pakistani Family Affected with Autosomal Recessive Congenital Ichthyosis Through Whole Exome Sequencing.

Background: Autosomal recessive congenital ichthyoses (ARCI) are a group of rare nonsyndromic genodermatoses characterized by generalized scaly appearance of the epidermis with markedly impaired cutaneous barriers owing to defects in keratinization related genes. In this study, we ascertained a consanguineous Pakistani family affected with ARCI. Aims: To investigate genetic defect underlying disease phenotype in the affected family. Methods: All available members of the family (affected and unaffected) were sampled. Whole exome sequencing (WES) was performed on DNA of the proband and the data were analyzed for probable pathogenic variants. Segregation of the identified variant was validated by Sanger sequencing. Results: Analysis of the WES data identified a novel nonsense mutation, c.762C>G, in the PNPLA1 (patatin-like phospholipase domain containing 1) gene. The protein product of of this gene is involved in lipid organization during cornified cell envelope formation. The variant is predicted to result in the generation of a premature truncation site at amino acid position 254 (p.Tyr254*). This would result in the loss of a large C-terminal portion of the protein suggesting it to be rendered nonfunctional. In silico protein structure modeling confirmed a detrimental effect of the variation on protein structure. Conclusions: The study supports the evidence for the prevalence of PNPLA1 mutations in distant ethnic groups. Despite the significant number of reported ARCI cases with PNPLA1 variants, a straightforward genotype-phenotype correlation cannot be established.

Lipases associated with plant defense against pathogens.

When facing microbe invaders, plants activate genetic and metabolic defense mechanisms and undergo extracellular and intracellular changes to obtain a certain level of host resistance. Dynamic adjustment and adaptation occur in structures containing lipophilic compounds and cellular metabolites. Lipids encompassing fatty acids, fatty acid-based polymers, and fatty acid derivatives are part of the fundamental architecture of cells and tissues and are essential compounds in numerous biological processes. Lipid-associated plant defense responses are mostly facilitated by the activation of lipases (lipid hydrolyzing proteins), which cleave or transform lipid substrates in various subcellular compartments. In this review, several types of plant defense-associated lipases are described, including their molecular aspects, enzymatic actions, cellular functions, and possible functional relevance in plant defense. Defensive roles are discussed considering enzyme properties, lipid metabolism, downstream regulation, and phenotypic traits in loss-of-function mutants.

Sphk2-/- mice are protected from obesity and insulin resistance.

Sphingosine kinases phosphorylate sphingosine to sphingosine 1­phosphate (S1P), which functions as a signaling molecule. We have previously shown that sphingosine kinase 2 (Sphk2) is important for insulin secretion. To obtain a better understanding of the role of Sphk2 in glucose and lipid metabolism, we have characterized 20- and 52-week old Sphk2-/- mice using glucose and insulin tolerance tests and by analyzing metabolic gene expression in adipose tissue. A detailed metabolic characterization of these mice revealed that aging Sphk2-/- mice are protected from metabolic decline and obesity compared to WT mice. Specifically, we found that 52-week old male Sphk2-/- mice had decreased weight and fat mass, and increased glucose tolerance and insulin sensitivity compared to control mice. Indirect calorimetry studies demonstrated an increased energy expenditure and food intake in 52-week old male Sphk2-/- versus control mice. Furthermore, expression of adiponectin gene in adipose tissue was increased and the plasma levels of adiponectin elevated in aged Sphk2-/- mice compared to WT. Analysis of lipid metabolic gene expression in adipose tissue showed increased expression of the Atgl gene, which was associated with increased Atgl protein levels. Atgl encodes for the adipocyte triglyceride lipase, which catalyzes the rate-limiting step of lipolysis. In summary, these data suggest that mice lacking the Sphk2 gene are protected from obesity and insulin resistance during aging. The beneficial metabolic effects observed in aged Sphk2-/- mice may be in part due to enhanced lipolysis by Atgl and increased levels of adiponectin, which has lipid- and glucose-lowering effects.

A cold and organic solvent tolerant lipase produced by Antarctic strain Rhodotorula sp. Y-23.

Psychrotolerant yeast Rhodotorula sp. Y-23 was isolated from the sediment core sub-samples of Nella Lake, East Antarctica. Isolate was screened for lipase production using plate assay method followed by submerged fermentation. Production optimization revealed the maximum lipase production by using palmolein oil (5% v/v), pH 8.0 and inoculum size of 2.5% v/v at 15 °C. The potential inducers for lipase were 1% w/v of galactose and KNO3 , and MnCl2 (0.1% w/v). Final productions with optimized conditions gave 5.47-fold increase in lipase production. Dialyzed product gave a purification fold of 5.63 with specific activity of 26.83 U mg-1 and 15.67% yields. This lipase was more stable at pH 5.0 and -20 °C whereas more activity was found at pH 8.0 and 35 °C. Stability was more in 50 mM Fe3+ , EDTA-Na (20 mM), sodium deoxycholate (20 mM), H2 O2 (1% v/v), and almost all organic solvents (50% v/v). Tolerance capacity at wider range of pH and temperature with having lower Km value i.e., 0.08 mg ml-1 and higher Vmax 385.68 U mg-1 at 15 °C make the studied lipase useful for industrial applications. Besides this, the lipase was compatible with commercially available detergents, and its addition to them increases lipid degradation performances making it a potential candidate in detergent formulation.

Adipose tissue ATGL modifies the cardiac lipidome in pressure-overload-induced left ventricular failure.

Adipose tissue lipolysis occurs during the development of heart failure as a consequence of chronic adrenergic stimulation. However, the impact of enhanced adipose triacylglycerol hydrolysis mediated by adipose triglyceride lipase (ATGL) on cardiac function is unclear. To investigate the role of adipose tissue lipolysis during heart failure, we generated mice with tissue-specific deletion of ATGL (atATGL-KO). atATGL-KO mice were subjected to transverse aortic constriction (TAC) to induce pressure-mediated cardiac failure. The cardiac mouse lipidome and the human plasma lipidome from healthy controls (n = 10) and patients with systolic heart failure (HFrEF, n = 13) were analyzed by MS-based shotgun lipidomics. TAC-induced increases in left ventricular mass (LVM) and diastolic LV inner diameter were significantly attenuated in atATGL-KO mice compared to wild type (wt) -mice. More importantly, atATGL-KO mice were protected against TAC-induced systolic LV failure. Perturbation of lipolysis in the adipose tissue of atATGL-KO mice resulted in the prevention of the major cardiac lipidome changes observed after TAC in wt-mice. Profound changes occurred in the lipid class of phosphatidylethanolamines (PE) in which multiple PE-species were markedly induced in failing wt-hearts, which was attenuated in atATGL-KO hearts. Moreover, selected heart failure-induced PE species in mouse hearts were also induced in plasma samples from patients with chronic heart failure. TAC-induced cardiac PE induction resulted in decreased PC/ PE-species ratios associated with increased apoptotic marker expression in failing wt-hearts, a process absent in atATGL-KO hearts. Perturbation of adipose tissue lipolysis by ATGL-deficiency ameliorated pressure-induced heart failure and the potentially deleterious cardiac lipidome changes that accompany this pathological process, namely the induction of specific PE species. Non-cardiac ATGL-mediated modulation of the cardiac lipidome may play an important role in the pathogenesis of chronic heart failure.