Lipidology, Volume 2, Issue 4 (December 2025) – 9 articles

Liposomes started to be studied for drug delivery in 1970s, taking advantage of their ability to encapsulate hydrophilic and hydrophobic drugs using biodegradable and biocompatible molecules. Nowadays, they remain one of the most promising strategies for drug delivery not only in cancer treatment but also in gene therapies and vaccines. The design and development of liposomal systems have evolved significantly over the past decades, moving from conventional formulations to advanced, stimulus-responsive, and multifunctional nanocarriers. Analogous to the myth of the Trojan Horse, liposomes must mislead the host immune system to reach the interior of cancer cells in order to deliver the therapeutic payload. There are many barriers that liposomes have to overcome to circulate through the bloodstream and specifically target cancer cells without damaging other tissues. Crucial parameters such as lipid composition, particle size, zeta potential, and PEGylation have been systematically optimized to enhance pharmacokinetics and biodistribution and to improve delivery efficiency. Furthermore, conjugation with antibodies, peptides, or small molecules has enabled active targeting, while stimuli such as pH, temperature, and enzymatic activity have been exploited for controlled drug release within the tumor microenvironment. Such innovations have laid the groundwork for translating liposomal formulations from the bench to clinical applications. In this paper, we evaluate the physicochemical features of liposomal design that underpin their suitability and efficacy for anticancer drug delivery. We aimed to focus on two main aspects: conducting an exhaustive review of the physicochemical parameters of liposomal drugs that have already been approved by regulatory agencies, while maintaining a pedagogical approach when explaining the key design parameters for the optimal design of liposomes in oncology in detail. Full article

Milk fatty acid (FA) synthesis and enteric methanogenesis share common biochemical pathways related to rumen fermentation patterns and microbial volatile FA production. The FA profile of milk is known to correlate with methane (CH₄) emissions; thus, FA profiling has been proposed as an indirect method to predict CH₄ emissions from dairy cattle. This study aimed to (1) investigate the milk FA profiles of Holstein cows to identify candidate biomarkers for predicting CH₄ output (g/d), CH₄ yield (g/kg dry matter intake), and CH₄ intensity (g/kg energy-corrected milk), and (2) develop and compare regression models predicting CH₄ emissions. Forty-eight cows, fed industry standard diets, were enrolled in an exploratory trial. Milk samples and CH₄ measurements were collected thrice per day, and intake was recorded daily. Milk lipids were extracted, transesterified, and subsequently analyzed via gas–liquid chromatography. Three penalized regression models were compared for predicting CH₄ emission metrics using milk FAs and management variables. Methane emission metrics corelated positively with short- and medium-chain FAs, polyunsaturated FAs, and branched-chain FAs, while monounsaturated FAs correlated negatively. Notably, this study observed novel correlations between 11-cyclohexyl-11:0; and 20:3 c5,c8,c11 and CH₄ metrics (|r| = 0.58–0.79). Across all CH₄ metrics, the models demonstrated high predictive accuracy (R² = 0.71–0.87; concordance correlation coefficient = 0.83–0.93). The findings of this study indicate that milk FA profiling may be an effective method to detect CH₄ emissions from cows fed industry standard diets and highlight the need for further refinement of prediction models. Full article

Background/objectives: Plant-based meat analogues (PBMAs) are designed to mimic meat products and to be cooked under similar conditions by consumers. There have been few studies into the lipid stability of PBMAs, and no published studies have investigated the effect of cooking on the lipid stability of PBMAs. Methods: This study analysed the effect of recommended cooking conditions on the lipid oxidation of three commercial chicken schnitzel PBMAs with differing fatty acid composition. Fatty acids and lipid classes were analysed using gas chromatography (GC) and capillary chromatography (Iatroscan) with flame ionisation detectors, respectively. Lipid oxidation was analysed using multiple tests, including peroxide value (POV), p-Anisidine value, acid value, and thiobarbituric acid reactive substance (TBARS) tests, which then allowed for the total oxidation (TOTOX) to be calculated. Results: Fatty acid analysis by GC showed different levels of saturated and unsaturated fatty acid contents in all PBMAs, with oleic acid (C18:1) being the most abundant (product A = 52%; product B = 62%; product C = 37%). Meanwhile, lipid class analyses by Iatroscan revealed that the oils used in the PBMAs were composed of triacylglycerol (TAG), which remained intact after cooking. Lipid oxidation tests showed no major increases between the raw and cooked PBMA. Also, the TOTOX values for each product did not increase significantly (p < 0.05) due to cooking (TOTOX values for raw/cooked product A = 9.36/9.99; product B = 5.88/6.19; product C = 11.31/11.92), suggesting a broad stability of the lipids. Conclusions: Therefore, if the on-package cooking instructions are followed for these three PBMA products, their lipid oxidation levels remain within safe limits. Full article

Background: Familial hypercholesterolemia (FH) is a monogenic disorder causing markedly elevated low-density lipoprotein cholesterol (LDL-C) and premature atherosclerosis. Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in antioxidant defense via NADPH production. G6PD deficiency, an X-linked disorder impairing redox homeostasis, may contribute to cardiovascular disease (CVD) risk. This study examined whether G6PD deficiency increases CVD risk in FH patients. Methods: We retrospectively analyzed 217 FH patients. Clinical data included demographics, lipid profiles, G6PD status, and atherosclerotic CVD outcomes (coronary, cerebrovascular, or peripheral arterial disease). In a subset, FH was confirmed by LDLR gene sequencing, and G6PD Mediterranean and Seattle variants were genotyped. Cumulative CVD prevalence was compared between G6PD-deficient and G6PD-normal FH patients. Multivariable logistic regression was adjusted for age, sex, body mass index, high blood pressure, and smoking. Results: Participants (mean age 47 years, 60% female) had markedly elevated LDL-C (mean 292 mg/dL at diagnosis). Atherosclerotic CVD was present in 119 (55%) patients. G6PD-deficient FH patients had a significantly higher CVD prevalence than those with normal G6PD activity (77.4% vs. 39.8%, p < 0.0001). LDL-C levels were higher in the G6PD-deficient group than in the non-deficient group, and this difference reached statistical significance in the univariate analysis. In the multivariable analysis, G6PD deficiency remained an independent CVD predictor (adjusted OR 3.57, 95% CI 1.30–9.83) after controlling for conventional risk factors. Conclusions: In FH, hereditary G6PD deficiency is associated with a markedly increased risk of atherosclerotic CVD. A pro-oxidative state in G6PD-deficient FH patients may play a role in premature atherogenesis. G6PD status may represent a cardiovascular risk modifier in FH, warranting further research into underlying mechanisms and targeted management. Full article

This systematic review examines the impact of vegetable oil consumption, such as extra virgin olive, olive, soybean, palm olein, corn, and camellia seed oils, on both human and animal health, alongside factors influencing oil quality and safety. A variety of studies were included, such as clinical trials, cohort studies, animal experiments, and reports on production methods and contamination (polycyclic aromatic hydrocarbons (PAHs) and heavy metals). The literature search was performed in scientific databases indexed up to September 2025, and risk of bias was assessed using specific tools appropriate for each study design. The findings suggest that, among the oils studied, extra virgin olive oil showed the most consistent benefits, including improvements in endothelial function, lipid profiles, weight management, and reduced mortality in humans. Animal studies corroborate hepatoprotective effects and weight regulation benefits. Oil quality is influenced by genetic, environmental, and technological factors, including cultivar selection, pollination, post-harvest handling, and extraction techniques (cold, hot, DIC, MFA, encapsulation) and refining processes, which can affect both nutritional benefits and contaminant levels. Although contaminants such as PAHs and heavy metals (Cd, Pb, As) are generally below regulatory thresholds, some contexts may present health risks. High-quality vegetable oils confer cardiovascular, metabolic, and hepatic benefits. However, their contribution to public health relies on strict production practices, continuous monitoring of contaminants, and the implementation of technological innovations to ensure both safety and optimal health outcomes. Full article

ATP citrate lyase (ACL) is a highly conserved enzyme across eukaryotes that catalyzes the generation of cytosolic acetyl-CoA from citrate—a pivotal step linking central carbon metabolism to lipid biosynthesis. In the oleaginous yeast Yarrowia lipolytica, ACL is encoded by two genes, ACL1 and ACL2, forming a heteromeric complex that mirrors the multidomain architecture of the single-chain ACL enzymes found in mammals and plants. This conservation of catalytic architecture reflects a shared catalytic strategy across kingdoms, underscoring ACL’s fundamental role in metabolic integration. In Y. lipolytica, ACL is essential for directing mitochondrial citrate toward acetyl-CoA production and subsequent lipid accumulation. Yet, in contrast to well-characterized ACLs in animals and plants, the functional mechanisms and regulation of yeast ACL remain incompletely understood. A deeper understanding of ACL in Y. lipolytica offers not only evolutionary insights but also potential avenues for engineering lipid overproduction in microbial systems. Full article

In the last twenty years, an increasing volume of research has characterized lipids as dynamic signaling molecules that play essential roles in various physiological and pathological processes, especially concerning chronic diseases such as cardiovascular disorders, diabetes, liver disease, neurodegeneration, cancer, obesity, diabetic and chronic kidney diseases and atherosclerosis. Dysregulation of lipid synthesis and storage, lipolysis, fatty acid oxidation, lipid signaling pathways, and organelle-specific lipid modifications, including mitochondrial phospholipid remodeling and endoplasmic reticulum stress induced by saturated fatty acids, are recognized as contributors to the initiation and progression of this pathogenesis. Concurrently with the increasing comprehension of lipid metabolism, the last decade has seen progress in the understanding of genome control, especially with non-coding RNAs (ncRNAs). MicroRNAs, long non-coding RNAs, and circular RNAs, as ncRNAs, are essential modulators of gene expression at the epigenetic, transcriptional, and post-transcriptional levels that affect a number of lipid metabolism-related processes, such as fatty acid synthesis and oxidation, cholesterol homeostasis, and lipid droplet dynamics. Therapeutically, ncRNAs hold considerable promise owing to their tissue specificity and modularity, with antisense oligonucleotides and CRISPR-based editing currently under preclinical evaluation. In this context, we review recent studies exploring the interplay between ncRNAs and the regulatory networks governing lipid metabolism, and how disruptions in these networks contribute to chronic disease. This emerging paradigm underscores the role of ncRNA–lipid metabolism interactions as central nodes in metabolic and inflammatory pathways, highlighting the need for a holistic approach to therapeutic targeting. Full article

Background: Dyslipidaemia promotes atherosclerotic plaque formation. Plaques that are vulnerable to rupture have a higher proportion of inflammatory (M1:CD86) macrophages in their cap. Many plaque macrophages are derived from blood monocytes which have been exposed to elevated blood lipid levels. Here, we explored whether the inflammatory state of monocyte-derived macrophages is associated with blood lipid levels and assessed whether oxidised low-density lipoprotein (oxLDL) directly induces some of the observed changes. Method: Blood was collected from 20 individuals. Lipid profiles were measured, and monocytes differentiated into macrophages. Macrophage inflammatory state was assessed by flow cytometry for phenotypic markers (e.g., CD86 and CD163) and cytokine production: TNF, IL-1β, and IL-6. Furthermore, monocytes were isolated from 6 normo-lipidaemic individuals and cultured with oxLDL, followed by stimulation with LPS/IFNγ and assessment of the cytokine response. Results: The inflammatory phenotype acquired by macrophages (ex vivo) was related to levels of in vivo circulating lipids. Correlations for CD86/CD163 were found with CVD risk markers; most strongly with triglycerides (TG) and TG/HDL-C, but also with cholesterol/HDL-C and ApoB/ApoA1 and inversely with LDL particle size. Functionally, macrophage production of inflammatory cytokines (TNF and IL-1β) correlated with oxLDL levels and inversely with ApoA1. Macrophages differentiated from monocytes cultured with oxLDL produced significantly higher IL-1β but lower IL-10 (in response to LPS/IFNγ), compared to control cells. Conclusions: Monocyte-derived macrophages adopt an inflammatory phenotype relative to the levels of circulating lipid factors that are characteristic of atherogenic dyslipidaemia (such as high TG, TG/HDL-C and low LDL particle size), but not LDL-C. Full article

It has long been recognized that elevated circulating lipid levels are among the strongest risk factors for the development of plaques within the arterial wall that are characteristic of atherosclerotic cardiovascular disease. Indeed, decades of studies have identified the deposition of low-density lipoprotein as an initiator of this disease, which coordinates the vascular and immune dysfunction that fuels the advancement of the atherosclerotic plaque. However, in the vessel wall, deposited cholesterol and fatty acids are dynamic in nature and engage signaling pathways. Shifting from metabolic-related pathways, lipid modifications and their conversion to intermediates engage signaling cascades that further perpetuate the inflammatory milieu of the atherosclerotic plaque and its progression towards the fatal end-stage events associated with cardiovascular disease, including myocardial infarction. In this review, we will cover the cellular and molecular mechanisms that preserve homeostasis and advance disease, including how lipid species induce endothelial dysfunction and drive the development of macrophage foam cells. We will additionally discuss ongoing therapeutic strategies to combat the hyperlipidemia that underlies atherogenesis. Full article