Lipidomics reveals perturbations in the liver lipid profile of iron-overloaded mice.

Iron overload is an important contributor to disease. The liver, the major site of iron storage in the body, is a key organ impacted by iron overload. While several studies have reported perturbations in liver lipids in iron overload, it is not clear, on a global scale, how individual liver lipid ions are altered. Here, we used lipidomics to study the changes in hepatic lipid ions in iron-overloaded mice. Iron overload was induced by daily intraperitoneal injections of 100 mg/kg body weight iron dextran for 1 week. Iron overload was verified by serum markers of iron status, liver iron quantitation, and Perls stain. Compared with the control group, the serum of iron-overload mice exhibited low levels of urea nitrogen and high-density lipoprotein (HDL), and high concentrations of total bile acid, low-density lipoprotein (LDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH), suggestive of liver injury. Moreover, iron overload disrupted liver morphology, induced reactive oxygen species (ROS) production, reduced superoxide dismutase (SOD) activity, caused lipid peroxidation, and led to DNA fragmentation. Iron overload altered the overall composition of lipid ions in the liver, with significant changes in over 100 unique lipid ions. Notably, iron overload selectively increased the overall abundance of glycerolipids and changed the composition of glycerophospholipids and sphingolipids. This study, one of the first to report iron-overload induced lipid alterations on a global lipidomics scale, provides early insight into lipid ions that may be involved in iron overload-induced pathology.

A case of homozygous familial hypercholesterolemia with an atypical phenotype and delayed clinical symptoms.

We describe the casuistry of a homozygous familial hypercholesterolemia female patient with a biallelic missense variant (NM_000527.4:c.1775G>A, p.Gly592Glu) in the LDLR gene, severe hypertriglyceridemia and late manifestation of coronary heart disease not earlier than at the age of 45 years. An atypical phenotype led to a delayed diagnosis.

Stage-Specific De Novo Synthesis of Very-Long-Chain Dihydroceramides Confers Dormancy to Entamoeba Parasites.

Amoebiasis is a parasitic disease caused by Entamoeba histolytica infection and is a serious public health problem worldwide due to ill-prepared preventive measures as well as its high morbidity and mortality rates. Amoebiasis transmission is solely mediated by cysts. Cysts are produced by the differentiation of proliferative trophozoites in a process termed "encystation." Entamoeba encystation is a fundamental cell differentiation process and proceeds with substantial changes in cell metabolites, components, and morphology, which occur sequentially in an orchestrated manner. Lipids are plausibly among these metabolites that function as key factors for encystation. However, a comprehensive lipid analysis has not been reported, and the involved lipid metabolic pathways remain largely unknown. Here, we exploited the state-of-the-art untargeted lipidomics and characterized 339 molecules of 17 lipid subclasses. Of these, dihydroceramide (Cer-NDS) was found to be among the most induced lipid species during encystation. Notably, in encysting cells, amounts of Cer-NDS containing very long N-acyl chains (≥26 carbon) were more than 30-fold induced as the terminal product of a de novo metabolic pathway. We also identified three ceramide synthase genes responsible for producing the very-long-chain Cer-NDS molecules. These genes were upregulated during encystation. Furthermore, these ceramide species were shown to be indispensable for generating membrane impermeability, a prerequisite for becoming dormant cyst that shows resistance to environmental assault inside and outside the host for transmission. Hence, the lipid subclass of Cer-NDS plays a crucial role for Entamoeba cell differentiation and morphogenesis by alternating the membrane properties.IMPORTANCEEntamoeba is a protozoan parasite that thrives in its niche by alternating its two forms between a proliferative trophozoite and dormant cyst. Cysts are the only form able to transmit to a new host and are differentiated from trophozoites in a process termed "encystation." During Entamoeba encystation, cell metabolites, components, and morphology drastically change, which occur sequentially in an orchestrated manner. Lipids are plausibly among these metabolites. However, the involved lipid species and their metabolic pathways remain largely unknown. Here, we identified dihydroceramides (Cer-NDSs) containing very long N-acyl chains (C26 to C30) as a key metabolite for Entamoeba encystation by our state-of-the-art untargeted lipidomics. We also showed that these Cer-NDSs are critical to generate the membrane impermeability, a prerequisite for this parasite to show dormancy as a cyst that repels substances and prevents water loss. Hence, ceramide metabolism is essential for Entamoeba to maintain the parasitic lifestyle.

Bioactive Lipids in MSCs Biology: State of the Art and Role in Inflammation.

Lipidomics is a lipid-targeted metabolomics approach that aims to the comprehensive analysis of lipids in biological systems in order to highlight the specific functions of lipid species in health and disease. Lipids play pivotal roles as they are major structural components of the cellular membranes and energy storage molecules but also, as most recently shown, they act as functional and regulatory components of intra- and intercellular signaling. Herein, emphasis is given to the recently highlighted roles of specific bioactive lipids species, as polyunsaturated fatty acids (PUFA)-derived mediators (generally known as eicosanoids), endocannabinoids (eCBs), and lysophospholipids (LPLs), and their involvement in the mesenchymal stem cells (MSCs)-related inflammatory scenario. Indeed, MSCs are a heterogenous population of multipotent cells that have attracted much attention for their potential in regulating inflammation, immunomodulatory capabilities, and reparative roles. The lipidomics of the inflammatory disease osteoarthritis (OA) and the influence of MSCs-derived lipids have also been addressed.

Efficacy of coenzyme Q10 supplementation on glucose metabolism, lipid profiles, and biomarkers of inflammation in women with polycystic ovary syndrome: A protocol for a systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the common gynecological endocrine system diseases. It is characterized by excessive androgen, rare or anovulation, and polycystic ovary morphology. Coenzyme Q10 (CoQ10) is a fat-soluble natural vitamin, which has a continuous oxidation-reduction cycle and is an effective antioxidant that can protect ovaries from oxidative damage. This study aims to systematically summarize and analyze the scientific literatures on glucose metabolism index, lipid profiles, inflammatory factor, and sex hormone level of PCOS patients treated with CoQ10 to provide a reference basis for clinical treatment. METHODS: We will retrieve the following electronic databases from the built-in until March 2021: Cochrane Library, PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Clinical Trials. gov, Chinese Scientific Journal Database (VIP), and Wang-fang database. Two reviewers will independently scan the articles searched, de-duplication, filtering, quality assessment. Differences will be resolved by discussion between the 2 reviewers or by a third reviewers. All analyses were systematic to evaluate interventions based on the Cochrane handbook. Meta-analysis and/or subgroup analysis will be performed on the basis of the included studies. DISCUSSION: This review will be to investigate the efficacy of CoQ10 supplementation on glucose metabolism, lipid profiles, and biomarkers of inflammation in women with PCOS and provide a high-quality synthesis to assess whether CoQ10 is an effective and safe intervention for PCOS. The results of the analysis will be published in a scientific journal after peer-review. SYSTEMATIC REVIEW REGISTRATION: INPLASY 2020100013.

Adipose Tissue Lipokines: Recent Progress and Future Directions.

Beyond classical metabolic functions in energy storage and energy expenditure, adipose tissue is also a dynamic endocrine organ that secretes bioactive factors into blood plasma. Historically, studies of the adipose secretome have predominantly focused on polypeptide adipokines. Recently, adipose-derived blood-borne lipids ("lipokines") have emerged as a distinct class of endocrine factors. Lipokines are intimately connected to intracellular pathways of fatty acid metabolism and therefore uniquely poised to communicate the intracellular energy status of adipocytes to other nonadipose tissues including liver, muscle, and pancreas. Here, we discuss recent progress on our understanding of adipose-secreted lipokines as endocrine regulators of glucose and lipid metabolism. We also provide our perspective on future directions for adipose-secreted lipids, including limitations of the currently available experimental data as well as potential strategies for addressing the remaining open questions.

Biosurfactants as a Novel Additive in Pharmaceutical Formulations: Current Trends and Future Implications.

BACKGROUND: Surfactants are an important category of additives that are used widely in most of the formulations as solubilizers, stabilizers, and emulsifiers. Current drug delivery systems comprise of numerous synthetic surfactants (such as Cremophor EL, polysorbate 80, Transcutol-P), which are associated with several side effects though used in many formulations. Therefore, to attenuate the problems associated with conventional surfactants, a new generation of surface-active agents is obtained from the metabolites of fungi, yeast, and bacteria, which are termed as biosurfactants. OBJECTIVES: In this article, we critically analyze the different types of biosurfactants, their origin along with their chemical and physical properties, advantages, drawbacks, regulatory status, and detailed pharmaceutical applications. METHODS: 243 papers were reviewed and included in this review. RESULTS: Briefly, Biosurfactants are classified as glycolipids, rhamnolipids, sophorolipids, trehalolipids, surfactin, lipopeptides & lipoproteins, lichenysin, fatty acids, phospholipids, and polymeric biosurfactants. These are amphiphilic biomolecules with lipophilic and hydrophilic ends and are used as drug delivery vehicles (foaming, solubilizer, detergent, and emulsifier) in the pharmaceutical industry. Despite additives, they have some biological activity as well (anti-cancer, anti-viral, anti-microbial, P-gp inhibition, etc.). These biomolecules possess better safety profiles and are biocompatible, biodegradable, and specific at different temperatures. CONCLUSION: Biosurfactants exhibit good biomedicine and additive properties that can be used in developing novel drug delivery systems. However, more research should be driven due to the lack of comprehensive toxicity testing and high production cost which limits their use.

"Lipidomics": Mass spectrometric and chemometric analyses of lipids.

Lipids are ubiquitous in the human organism and play essential roles as components of cell membranes and hormones, for energy storage or as mediators of cell signaling pathways. As crucial mediators of the human metabolism, lipids are also involved in metabolic diseases, cardiovascular and renal diseases, cancer and/or hepatological and neurological disorders. With rapidly growing evidence supporting the impact of lipids on both the genesis and progression of these diseases as well as patient wellbeing, the characterization of the human lipidome has gained high interest and importance in life sciences and clinical diagnostics within the last 15 years. This is mostly due to technically advanced molecular identification and quantification methods, mainly based on mass spectrometry. Mass spectrometry has become one of the most powerful tools for the identification of lipids. New lipidic mediators or biomarkers of diseases can be analysed by state-of-the art mass spectrometry techniques supported by sophisticated bioinformatics and biostatistics. The lipidomic approach has developed dramatically in the realm of life sciences and clinical diagnostics due to the available mass spectrometric methods and in particular due to the adaptation of biostatistical methods in recent years. Therefore, the current knowledge of lipid extraction methods, mass-spectrometric approaches, biostatistical data analysis, including workflows for the interpretation of lipidomic high-throughput data, are reviewed in this manuscript.

Untargeted Lipidomics Highlight the Depletion of Deoxyceramides during Therapy-Induced Senescence.

Therapy-induced senescence is a state of cell cycle arrest that occurs as a response to various chemotherapeutic reagents, especially ones that cause DNA damage. Senescent cells display resistance to cell death and can impair the efficacy of chemotherapeutic strategies. Since lipids can exhibit pro-survival activity, it is envisioned in this article that probing the lipidome could provide insights into novel lipids that are involved in senescence. Therefore, a tissue culture model system is established and the cellular lipidomes of senescent and proliferating cells are comparatively analyzed. Out of thousands of features detected, 17 species are identified that show significant changes in senescent cells. The majority of these species (11 out of 17) are atypical sphingolipids, 1-deoxyceramides/dihydroceramides, which are produced as a result of the utilization of alanine, instead of serine during sphingolipid biosynthesis. These lipids are depleted in senescent cells. Elevating the levels of deoxyceramides by supplementing the growth medium with metabolic precursors or by directly adding deoxyceramide result in decreased senescence, suggesting that these species might play a key role in this process.

Milk Polar Lipids: Underappreciated Lipids with Emerging Health Benefits.

Milk fat is encased in a polar lipid-containing tri-layer milk fat globule membrane (MFGM), composed of phospholipids (PLs) and sphingolipids (SLs). Milk PLs and SLs comprise about 1% of total milk lipids. The surfactant properties of PLs are important for dairy products; however, dairy products vary considerably in their polar lipid to total lipid content due to the existence of dairy foods with different fat content. Recent basic science and clinical research examining food sources and health effects of milk polar lipids suggest they may beneficially influence dysfunctional lipid metabolism, gut dysbiosis, inflammation, cardiovascular disease, gut health, and neurodevelopment. However, more research is warranted in clinical studies to confirm these effects in humans. Overall, there are a number of potential effects of consuming milk polar lipids, and they should be considered as food matrix factors that may directly confer health benefits and/or impact effects of other dietary lipids, with implications for full-fat vs. reduced-fat dairy.

Proteomic and lipidomic analysis of exosomes derived from ovarian cancer cells and ovarian surface epithelial cells.

BACKGROUND: The limitation of current biomarker of early stage ovarian cancer and the anatomical location of ovarian (depths of the pelvic) make ovarian cancer difficult to be detected in early stage. Growing evidence shows exosomes as key information transmitters, it carried molecules, such as miRNAs, proteins, lipids, double-stranded DNA have been reported as promising biomarkers in many diseases. However, little is known about the protein and lipid composition of ovarian cancer. METHODS: Here, we report proteomic and lipidomic analysis of exosomes derived from ovarian cancer cells (SKOV-3) and ovarian surface epithelial cells (HOSEPiC). RESULTS: A total of 1433 proteins and 1227 lipid species were identified from two cell line derived exosomes. Several lipid species and proteins significantly differ in SKOV-3 derived exosomes compared to those from HOSEPiC. For example, we noted that ChE and ZyE species were in general more abundant in exosomes from SKOV-3 than from HOSEPiC; Collagen type V alpha 2 chain (COL5A2) and lipoprotein lipase (LPL) were significantly higher in SKOV-3 derived exosomes than HOSEpic (p < 0.05). CONCLUSIONS: Our research indicates the promising role of exosomal proteins and lipids in the early diagnosis of ovarian cancer.

A comparative study of the effects of palm olein, cocoa butter and extra virgin olive oil on lipid profile, including low-density lipoprotein subfractions in young healthy Chinese people.

The aim of this study is to investigate the effects of palm olein (POL), cocoa butter (CB) and extra virgin olive oil (EVOO) on the lipid profile and low-density lipoprotein subfractions in a young, healthy Chinese population. After screening, 72 subjects were randomly assigned to three groups, and an 18-week randomized crossover trial was conducted. The first phase was a 2-week run-in period, followed by three phases of the 4-week experimental periods with a 2-week washout period between experimental periods. Three groups of subjects alternately consumed a Chinese diet enriched with the different test oils. The various indices of subjects were collected before and after each experimental period. Sixty-seven subjects completed the study, and there were no significant differences in conventional indices amongst the three groups at the beginning of the three experimental periods (p > .05). Each test oil accounted for approximately 40% of total fat intake and approximately 11.3% of the total energy supply. After controlling for dietary interventions, only the serum triglyceride level of the POL-Diet was significantly lower than that of the EVOO-Diet (p = .034), and most indices did not significantly differ amongst the three test oil diets (p > .05). POL, CB and EVOO have almost identical effects on serum lipids.

Lipid profiling of pre-treatment plasma reveals biomarker candidates associated with response rates and hand-foot skin reactions in sorafenib-treated patients.

Sorafenib is a multi-kinase inhibitor for treatment of advanced hepatocellular carcinoma (HCC). Beyond its clinical benefit against advanced HCC, the efficacy and safety of sorafenib chemotherapy are critical concerns. In this study, we addressed the lipid profiles associated with the efficacy and safety of sorafenib chemotherapy. Plasma samples from HCC patients before sorafenib chemotherapy (N = 44) were collected and subjected to lipidomic analysis. We measured the levels of 176 lipids belonging to 8 classes of phosphoglycerolipids, 2 classes of sphingolipids, 3 classes of neutral lipids, and 4 other classes of lipids. To characterize lipids associated with efficacy, we compared the responder group (N = 21; partial response and stable disease) with non-responder group (N = 22; progressive disease). To characterize lipids associated with hand-foot skin reaction (HFSR), we compared the susceptible group (N = 12; grade 2 and 3) with non-susceptible group (N = 32; grade 0 and 1). The levels of 8 lipids, including phosphatidylcholine (PC)[34:2], PC[34:3]a, PC[35:2], PC[36:4]a, PC[34:3e], acylcarnitine (Car)[18:0], cholesterol ester[20:2], and diacylglycerol (DG)[34:2], were significantly lower in the responder group, and 6 out of 8 these lipids contained FA(18:2). In addition, the levels of 7 lipids (Car[12:0], Car[18:0], Car[18:1], Car[20:1] and fatty acid amides (FAA[16:0], FAA[18:0], and FAA[18:1]b)) were significantly lower in the group susceptible to HFSR. Our comprehensive lipidomics study using samples from sorafenib-treated patients with HCC revealed that significant differences in the lipid profiles of pre-treatment plasma were associated with sorafenib efficacy and sorafenib-induced HFSR. Validation using another set of patient plasma samples and elucidating the molecular basis of these changes will lead to better treatment with sorafenib chemotherapy.

Heterogeneity of lipidomic profiles among lung cancer subtypes of patients.

Lung cancer is a leading cause of cancer-related deaths with an increasing incidence and poor prognoses. To further understand the regulatory mechanisms of lipidomic profiles in lung cancer subtypes, we measure the profiles of plasma lipidome between health and patients with lung cancer or among patients with squamous cell carcinomas, adenocarcinoma or small cell lung cancer and to correct lipidomic and genomic profiles of lipid-associated enzymes and proteins by integrating the data of large-scale genome screening. Our studies demonstrated that circulating levels of PS and lysoPS significantly increased, while lysoPE and PE decreased in patients with lung cancer. Our data indicate that lung cancer-specific and subtype-specific lipidomics in the circulation are important to understand mechanisms of systemic metabolisms and identify diagnostic biomarkers and therapeutic targets. The carbon atoms, dual bonds or isomerism in the lipid molecule may play important roles in lung cancer cell differentiations and development. This is the first try to integrate lipidomic data with lipid protein-associated genomic expression among lung cancer subtypes as the part of clinical trans-omics. We found that a large number of lipid protein-associated genes significantly change among cancer subtypes, with correlations with altered species and spatial structures of lipid metabolites.

Oil Characterization and Lipids Class Composition of Pomegranate Seeds.

This study aims to investigate the physicochemical characteristics, phenolics content, and oil composition of pomegranate oil seeds (PSO). Quality indices, pigments, phenolics content, and antioxidant activity were determined. PSO was fractioned into polar lipids: glycolipids (GL) and phospholipids (PL). Sterols profile and fatty acids composition of total lipids (TL), GL, and PL were determined by GC/FID. The free acidity, the peroxide value, and the specific extinction coefficients were, respectively, 1.69%, 3.42 in milliequivalents of active oxygen per kilogram of oil, 4.15, and 3.95. PSO is rich in phenols (93.42 mg/Kg) but poor in pigments. The sterols markers were ß-sitosterol (77.94%), Δ5-avenasterol (7.45%), and campesterol (6.35%). Oil content was 12.2%, wherein 23.9% were GL and 24.35% were PL. TL were rich in unsaturated fatty acids (63.17%), while saturated fatty acids were more present in PL and GL (71.97% and 66.29%, resp.). Conjugated fatty acids were about 13.30%, 2.03%, and 4.91%, respectively, in TL, PL, and GL. The cis/trans ratio of TL, PL, and GL was, respectively, 49.82%, 42.91%, and 27.39%. Monounsaturated fatty acids were more bound in PL, whereas polyunsaturated fatty acids were more bound in GL. PSO is a good source of essential fatty acids, phenolics compounds, phytosterols, and lipid-soluble fractions.

UPLC-QqQ/MS-Based Lipidomics Approach To Characterize Lipid Alterations in Inflammatory Macrophages.

In this study, UPLC-QqQ/MS-based lipidomics was applied to profile various lipids from RAW264.7 macrophages treated with different concentrations of lipopolysaccharide (LPS). The degree of inflammation increased with the LPS concentration. To elucidate the altered lipid metabolism of inflammatory macrophages, we targeted to analyze 25 lipid classes from LPS-treated RAW264.7 cells. As a result, 523 lipid species were successfully profiled by using the optimal UPLC and MRM. Statistical data analyses such as PCA, PLS-DA, and HCA differentiated five RAW264.7 cells treated with different concentrations of LPS. VIP plot, heat map, and bar plot also provided lists of up- or down-regulated lipids according to the LPS concentration. From the results, 11 classes of lipids, TG, DG, ChE, PE, PS, PI, PA, LyPC, LyPE, Cer, and dCer, were increased, and three classes, cholesterol, PC, and LyPA, were decreased in an LPS concentration-dependent manner. Furthermore, the treatment of an anti-inflammatory compound recovered the levels of PC, PE, PI, PA, LyPE, LyPA, and Cer from the activated macrophages. Finally, these results demonstrate the correlation between inflammation and lipid metabolism in macrophages. The differentially regulated lipids also have the potential to be used as biomarkers for inflammation.

Aging and caloric restriction impact adipose tissue, adiponectin, and circulating lipids.

Adipose tissue expansion has been associated with system-wide metabolic dysfunction and increased vulnerability to diabetes, cancer, and cardiovascular disease. A reduction in adiposity is a hallmark of caloric restriction (CR), an intervention that extends longevity and delays the onset of these same age-related conditions. Despite these parallels, the role of adipose tissue in coordinating the metabolism of aging is poorly defined. Here, we show that adipose tissue metabolism and secretory profiles change with age and are responsive to CR. We conducted a cross-sectional study of CR in adult, late-middle-aged, and advanced-aged mice. Adiposity and the relationship between adiposity and circulating levels of the adipose-derived peptide hormone adiponectin were age-sensitive. CR impacted adiposity but only levels of the high molecular weight isoform of adiponectin responded to CR. Activators of metabolism including PGC-1a, SIRT1, and NAMPT were differentially expressed with CR in adipose tissues. Although age had a significant impact on NAD metabolism, as detected by biochemical assay and multiphoton imaging, the impact of CR was subtle and related to differences in reliance on oxidative metabolism. The impact of age on circulating lipids was limited to composition of circulating phospholipids. In contrast, the impact of CR was detected in all lipid classes regardless of age, suggesting a profound difference in lipid metabolism. These data demonstrate that aspects of adipose tissue metabolism are life phase specific and that CR is associated with a distinct metabolic state, suggesting that adipose tissue signaling presents a suitable target for interventions to delay aging.

Assessment of altered lipid homeostasis by HILIC-ion mobility-mass spectrometry-based lipidomics.

Ion mobility-mass spectrometry (IM-MS) has proven to be a highly informative technique for the characterization of lipids from cells and tissues. We report the combination of hydrophilic-interaction liquid chromatography (HILIC) with traveling-wave IM-MS (TWIM-MS) for comprehensive lipidomics analysis. Main lipid categories such as glycerolipids, sphingolipids, and glycerophospholipids are separated on the basis of their lipid backbones in the IM dimension, whereas subclasses of each category are mostly separated on the basis of their headgroups in the HILIC dimension, demonstrating the orthogonality of HILIC and IM separations. Using our previously established lipid calibrants for collision cross-section (CCS) measurements in TWIM, we measured over 250 CCS values covering 12 lipid classes in positive and negative modes. The coverage of the HILIC-IM-MS method is demonstrated in the analysis of Neuro2a neuroblastoma cells exposed to benzalkonium chlorides (BACs) with C10 or C16 alkyl chains, which we have previously shown to affect gene expression related to cholesterol and lipid homeostasis. We found that BAC exposure resulted in significant changes to several lipid classes, including glycerides, sphingomyelins, phosphatidylcholines, and phosphatidylethanolamines. Our results indicate that BAC exposure modifies lipid homeostasis in a manner that is dependent upon the length of the BAC alkyl chain.

The Lipidomic Analyses in Low and Highly Aggressive Ovarian Cancer Cell Lines.

Despite huge advances in the research of epithelial ovarian cancer (EOC), it remains the most lethal gynecological malignancy. Peritoneal tumor cell dissemination with cell survival and drug-resistance to taxane and platinum-based chemotherapy are two of the major challenges of EOC treatment. We have generated highly aggressive EOC cell lines (ID8-P1 lines or P1) from ID8-P0 (without in vivo passage, or P0) through in vivo passage in mice. We conducted lipidomic analyses in cells from ID8-P0 versus three ID8-P1 cell lines using ultra-high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry. A total of 16 classes of lipids (149 individual lipids) were analyzed and compared between P0 and P1 cells. In addition to overall lipid profiles in EOC cells, we had several novel observations. Several classes and species of lipids have been identified to be differentially present in P0 versus P1 cells, which are potentially involved in the acquired aggressiveness of P1 cells. Triacylglycerols (TAG) were dramatically increased under detachment stress in EOC cells. Since survival of EOC cells under detachment is one of the major obstacles for EOC treatment, further studies identifying the molecular mechanisms controlling TAG increase may lead to new treatment modalities for EOC.

Unknown aspect of the old disease: does dyslipidemia in systemic AA amyloidosis differ from the dyslipidemia in primary glomerulonephritis?

AIM: To investigate the nature of dyslipidemia and its diversity in patients with systemic AA amyloidosis. METHODS: The reports of the kidney biopsies performed due to nephrotic proteinuria (>3.5 g/day/1.73 m(2)) with preserved renal function [glomerular filtration rate (GFR) >60 mL/min/1.73 m(2)] were reviewed. Clinical and laboratory data of the patients with systemic AA amyloidosis and primary glomerulonephritis (PG) were analyzed. RESULTS: A total of 104 (systemic AA amyloidosis: 43, PG: 61) patients were included in the study. Proteinuria and GFR levels were similar in both the groups. Patients with systemic AA amyloidosis group had lower serum albumin (p = 0.002), lower hemoglobin levels (p = 0.001), higher platelet counts (p = 0.002) and higher C-reactive protein levels (p = 0.001) compared to patients in PG group. Although the frequency of dyslipidemia was similar in the groups (86.0 vs. 93.4%), patients with systemic amyloidosis had both lower values of LDL-C (4.56 ± 2.05 vs. 5.49 ± 2.23 mmol/L, p = 0.028) and HDL-C (1.19 ± 0.36 vs. 1.35 ± 0.39 mmol/L, p = 0.035). Serum lipid levels were correlated with serum total protein, albumin and proteinuria levels in PG group. However, in the systemic amyloidosis group, only one clear correlation between serum lipid and hemoglobin levels was estimated. A multivariate analysis demonstrated that LDL-C was independently associated with the etiology of nephrotic proteinuria, serum total protein, serum albumin (inversely) and hemoglobin levels. CONCLUSIONS: Although dyslipidemia is closely associated with serum total protein, albumin and proteinuria in patients with PG, there is no clear such association in patients with systemic amyloidosis. Correlation between serum lipid and hemoglobin levels in this group and other findings point out that probably complex mechanisms take place in dyslipidemia of nephrotic syndrome caused by systemic AA amyloidosis.