Expression of lipid transport-associated genes in lipid-deprived cancer cells.

Cancer cells are known to significantly alter their lipid profiles in response to changes in extracellular lipid availability. Recent studies have shown that in response to lipid deprivation, cancer cells display significant changes in their cellular lipid homeostasis. These changes have been linked to the modulation of de novo lipid synthesis pathways that are markedly altered under lipid-deprived growth conditions. However, the effects of such environment on intracellular lipid trafficking-that could also affect cellular lipid homeostasis-have not been widely investigated. The presented work studies the effect of lipid deprivation on expression of genes for lipid transport proteins (LTPs) in cancer cell lines.

Cancer cell lipid class homeostasis is altered under nutrient-deprivation but stable under hypoxia.

BACKGROUND: Cancer cells modify the balance between fatty acid (FA) synthesis and uptake under metabolic stress, induced by oxygen/nutrient deprivation. These modifications were shown to alter the levels of individual triglyceride (TG) or phospholipid sub-species. To attain a holistic overview of the lipidomic profiles of cancer cells under stress we performed a broad lipidomic assay, comprising 244 lipids from six major classes. This assay allowed us to perform robust analyses and assess the changes in averages of broader lipid-classes, stratified on the basis of saturation index of their fatty-acyl side chains. METHODS: Global lipidomic profiling using Liquid Chromatography-Mass Spectrometry was performed to assess lipidomic profiles of biologically diverse cancer cell lines cultivated under metabolically stressed conditions. RESULTS: Neutral lipid compositions were markedly modified under serum-deprived conditions and, strikingly, the cellular level of triglyceride subspecies decreased with increasing number of double bonds in their fatty acyl chains. In contrast and unexpectedly, no robust changes were observed in lipidomic profiles of hypoxic (2% O2) cancer cells despite concurrent changes in proliferation rates and metabolic gene expression. CONCLUSIONS: Serum-deprivation significantly affects lipidomic profiles of cancer cells. Although, the levels of individual lipid moieties alter under hypoxia (2% O2), the robust averages of broader lipid classes remain unchanged.

Lipid-load in peripheral blood mononuclear cells: Impact of food-consumption, dietary-macronutrients, extracellular lipid availability and demographic factors.

Lipid-load in peripheral blood mononuclear cells (PBMCs) has recently gained attention of the researchers working on nutritional regulation of metabolic health. Previous works have indicated that the metabolic circuitries in the circulating PBMCs are influenced by dietary-intake and macronutrient composition of diet. In the present work, we analyzed the impact of diet and dietary macronutrients on PBMCs' lipid-load. The overall analyses revealed that dietary carbohydrates and fats combinatorially induce triglyceride accumulation in PBMCs. On the other hand, dietary fats were shown to induce significant decrease in PBMCs' cholesterol-load. The effects of various demographic factors -including age, gender and body-weight- on PBMCs' lipid-load were also examined. Body-weight and age were both shown to affect PBMC's lipid-load. Our study fails to provide any direct association between extracellular lipid availability and cholesterol-load in both, freshly isolated and cultured PBMCs. The presented work significantly contributes to the current understanding of the impact of food-consumption, dietary macronutrients, extracellular lipid availability and demographic factors on lipid-load in PBMCs.

Correction to: Anthropometric and metabolic indices in assessment of type and severity of dyslipidemia.

After the publication of this work [1] an error was noticed in one of the formulas.

Anthropometric and metabolic indices in assessment of type and severity of dyslipidemia.

BACKGROUND: It has been shown that obesity is associated with increased rates of dyslipidemia. The present work revisits the association between plasma lipid levels and classical indicators of obesity including body mass index (BMI). The significance of various anthropometric/metabolic variables in clinical assessment of type and severity of dyslipidemia was also determined. Recently described body indices, a body shape index (ABSI) and body roundness index (BRI), were also assessed in this context. METHODS: For the present cross-sectional analytical study, the participants (n = 275) were recruited from the patients visiting different health camps. Participants were anthropometrically measured and interviewed, and their fasting intravenous blood was collected. Plasma lipid levels were accordingly determined. RESULTS: The values for different anthropometric parameters are significantly different between dyslipidemic and non-dyslipidemic participants. Receiver operating characteristics curve analyses revealed that all the tested variables gave the highest area under the curve (AUC) values for predicting hypertriglyceridemia in comparison to other plasma lipid abnormalities. BRI gave slightly higher AUC values in predicting different forms of dyslipidemia in comparison to BMI, whereas ABSI gave very low values. CONCLUSIONS: Several anthropometric/metabolic indices display increased predictive capabilities for detecting hypertriglyceridemia in comparison to any other form of plasma lipid disorders. The capacity of BRI to predict dyslipidemia was comparable but not superior to the classical indicators of obesity, whereas ABSI could not detect dyslipidemia.

Aberrant de novo cholesterogenesis: Clinical significance and implications.

Human cells can acquire cholesterol from the circulation but also have the ability to synthesize it via de novo cholesterogenesis (DC). Cholesterol absorption and de novo cholesterogenesis are the key processes that modulate cholesterol homeostasis in the human body. The endogenous biosynthesis of cholesterol substantially contributes to the whole-body cholesterol pool. Additionally, dysregulation of this pathway is associated with diverse medical conditions. The present review focuses on our current understanding of the cholesterogenic pathway and the various different factors regulating this pathway. It also highlights dysregulation of this pathway in various physiological and pathological conditions including cardiovascular diseases, type II diabetes, obesity and viral infections.

Revisiting the dyslipidemia associated with acute leukemia.

BACKGROUND: Previous studies appreciate the leukemia-associated alterations in plasma lipid profiles but fail to provide a consistent pattern of lipid anomalies in leukemia patients. These inconsistencies could be due to overlooking the effects of related confounding risk-factors and comorbidities. METHODS: The plasma lipid profiles of acute-leukemia and control groups were compared. RESULTS: We observed that acute lymphocytic leukemia (ALL) patients display significantly higher triglycerides and very low-density lipoproteins, whereas, acute myeloid leukemia (AML) patients display significantly lower high-density lipoproteins. To assess the confounding effects of related risk factors gender-, age- and BMI-based analyses were performed. We observed that the aforementioned significant differences in the lipid profiles of leukemia patients were restricted to female participants of the respective groups. Moreover, a significant decrease in total cholesterol and low-density lipoprotein levels was observed only in male participants of the AML population. Various age-specific trends in plasma lipid profile of the leukemia patients were also observed. BMI-based analysis did not display many significant differences from the overall analyses. In addition to comparing the absolute values of plasma lipids in leukemia and control groups we also compared and observed significant differences in prevalence of various isolated- and mixed-dyslipidemias in these groups. CONCLUSIONS: These findings may help in outlining the prevalence and types of dyslipidemia in leukemia patients that may emerge as diagnostic/prognostic factors for the management of acute leukemia.