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Background: The triglyceride-glucose (TyG) index is a risk marker for arterial stiffness; however, the extent to which the TyG index is associated with arterial stiffness via lipids and inflammation remains unknown. The first aim was to probe the relationship between the TyG index and arterial stiffness in two surveys. The second aim was to clarify whether lipids and inflammation mediate this relationship. Methods: The sample size of 13,726 U.S. individuals from the National Examination Survey (NHANES) and 3,964 Chinese individuals from the China Health and Retirement Longitudinal Study (CHARLS 2015) were enrolled. Weighted multivariate logistic and linear regression models, as well as restricted cubic spline (RCS) and mediation analyses, were utilized to estimate complex relationships between the TyG index, arterial stiffness, lipids (non-high-density lipoprotein cholesterol [non-HDL-C]) and inflammation (C-reactive protein [CRP]) biomarkers. Results: A total of 3,420 U.S. patients and 992 Chinese patients were diagnosed with increased arterial stiffness. Regression analyses demonstrated that higher quartiles of the TyG index were associated with a greater incidence of increased arterial stiffness (NHANES: OR = 2.610, 95% CI = 2.043–3.334, P < 0.001; CHARLS: OR = 1.579, 95% CI = 1.057–2.360, P < 0.001). Participants with a higher TyG index/higher CRP level or with a higher TyG index/higher non-HDL-C level had the highest incidence of increased arterial stiffness in the two surveys. The results were still consistent when the sensitivity analysis was implemented with stricter clinical cut-off values of non-HDL-C. Mediation analysis verified that lipids (mediated effect: β = 0.012, P < 0.001 in NHANES; β = 0.020, P < 0.001 in CHARLS) and inflammation (mediated effect: β = 0.003, P < 0.001 in NHANES; β = 0.006, P < 0.001 in CHARLS) partially mediated this relationship. Conclusions: These results indicated a positive linear correlation between the TyG index, non-HDL-C level, CRP level and increased arterial stiffness in two surveys. Furthermore, lipids and inflammation could partly mediate the correlation of the TyG index with arterial stiffness in both surveys. [ABSTRACT FROM AUTHOR]

Backgrounds: A growing body of evidence has highlighted the interactions of lipids metabolism and immune regulation. Nevertheless, there is still a lack of evidence regarding the causality between lipids and autoimmune diseases (ADs), as well as their possibility as drug targets for ADs. Objectives: This study was conducted to comprehensively understand the casual associations between lipid traits and ADs, and evaluate the therapeutic possibility of lipid-lowering drug targets on ADs. Methods: Genetic variants for lipid traits and variants encoding targets of various lipid-lowering drugs were derived from Global Lipid Genetics Consortium (GLGC) and verified in Drug Bank. Summary data of ADs were obtained from MRC Integrative Epidemiology Unit (MER-IEU) database and FinnGen consortium, respectively. The causal inferences between lipid traits/genetic agents of lipid-lowering targets and ADs were evaluated by Mendelian randomization (MR), summary data-based MR (SMR), and multivariable MR (MVMR) analyses. Enrichment analysis and protein interaction network were employed to reveal the functional characteristics and biological relevance of potential therapeutic lipid-lowering targets. Results: There was no evidence of causal effects regarding 5 lipid traits and 9 lipid-lowering drug targets on ADs. Genetically proxied 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibition was associated with a reduced risk of rheumatoid arthritis (RA) in both discovery (OR [odds ratio] = 0.45, 95%CI: 0.32, 0.63, P = 6.79 × 10− 06) and replicate datasets (OR = 0.37, 95%CI: 0.23, 0.61, P = 7.81 × 10− 05). SMR analyses supported that genetically proxied HMGCR inhibition had causal effects on RA in whole blood (OR = 0.48, 95%CI: 0.29, 0.82, P = 6.86 × 10− 03) and skeletal muscle sites (OR = 0.75, 95%CI: 0.56, 0.99, P = 4.48 × 10− 02). After controlling for blood pressure, body mass index (BMI), smoking and drinking alchohol, HMGCR suppression showed a direct causal effect on a lower risk of RA (OR = 0.33, 95%CI: 0.40, 0.96, P = 0.042). Conclusions: Our study reveals causal links of genetically proxied HMGCR inhibition (lipid-lowering drug targets) and HMGCR expression inhibition with a decreased risk of RA, suggesting that HMGCR may serve as candidate drug targets for the treatment and prevention of RA. [ABSTRACT FROM AUTHOR]

Background: Global per capita meat consumption continues to rise, especially pork. Meat quality is influenced by the content of intramuscular fat (IMF) as a key factor. The longissimus dorsi muscle of Dahe pigs (DHM, IMF: 7.98% ± 1.96%) and Dahe black pigs (DHBM, IMF: 3.30% ± 0.64%) was studied to explore cellular heterogeneity and differentially expressed genes (DEGs) associated with IMF deposition using single-nucleus RNA sequencing (snRNA-seq). The lipid composition was then analyzed using non-targeted lipidomics. Results: A total of seven cell subpopulations were identified, including myocytes, fibroblast/fibro/adipogenic progenitors (FAPs), satellite cells, endothelial cells, macrophages, pericytes, and adipocytes. Among them, FAPs and adipocytes were more focused because they could be associated with lipid deposition. 1623 DEGs in the FAPs subpopulation of DHBM were up-regulated compared with DHM, while 1535 were down-regulated. These DEGs enriched in the glycolysis/gluconeogenesis pathway. 109 DEGs were up-regulated and 806 were down-regulated in the adipocyte subpopulation of DHBM compared with DHM, which were mainly enriched in the PPAR signaling pathway and fatty acid (FA) biosynthesis. The expression level of PPARG, ABP4, LEP, and ACSL1 genes in DHM was higher than that in DHBM. Lipidomics reveals porcine lipid composition characteristics of muscle tissue. A total of 41 lipid classes and 2699 lipid species were identified in DHM and DHBM groups. The top ten relative peak areas of lipid classes in DHM and DHBM were triglyceride (TG), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), diglyceride (DG), cardiolipin (CL), ceramides (Cer), Simple Glc series (Hex1Cer), sphingomyelin (phSM), and phosphatidylinositol (PI). The relative peak areas of 35 lipid species in DHM were lower than DHBM, and 28 lipid species that were higher. There was a significant increase in the TG fatty acyl chains C6:0, C17:0, and C11:4, and a significant decrease in C16:0, C18:1, C18:2, and C22:4 in DHBM (p < 0.05). Conclusions: C16:0 FA may downregulate the expression level of PPARG gene, which leads to the downregulation of fat metabolism-related genes such as ACSL, PLIN2, and FABP4 in DHBM compared with DHM. This may be the reason that the lipid deposition ability of Dahe pigs is stronger than that of Dahe black pigs, which need further investigation. [ABSTRACT FROM AUTHOR]

The motor features of Parkinson's disease result from loss of dopaminergic neurons in the substantia nigra with autophagy dysfunction being closely linked to this disease. While a large body of work focusing on protein effectors of autophagy has been reported, regulation of autophagy by lipids has garnered far less attention. Therefore, we sought to identify endogenous lipid molecules that act as signaling mediators of autophagy in differentiated SH-SY5Y cells, a commonly used dopaminergic neuron-like cell model. In order to accomplish this goal, we assessed the role of a fatty acid-binding protein (FABP) family member on autophagy due to its function as an intracellular lipid chaperone. We focused specifically upon FABP5 due to its heightened expression in dopaminergic neurons within the substantia nigra and SH-SY5Y cells. Here, we report that knockdown of FABP5 resulted in suppression of autophagy in differentiated SH-SY5Y cells suggesting the possibility of an autophagic role for an interacting lipid. A lipidomic screen of FABP5-interacting lipids uncovered hits that include 5-oxo-eicosatetraenoic acid (5OE) and its precursor metabolite, arachidonic acid (AA). Additionally, other long-chain fatty acids were found to bind FABP5, such as stearic acid (SA), hydroxystearic acid (HSA), and palmitic acid (PA). The addition of 5OE, SA, and HSA but not AA or PA, led to potent inhibition of autophagy in SH-SY5Y cells. To identify potential molecular mechanisms for autophagy inhibition by these lipids, RNA-Seq was performed which revealed both shared and divergent signaling pathways between the lipid-treated groups. These findings suggest a role for these lipids in modulating autophagy through diverse signaling pathways and could represent novel therapeutic targets for Parkinson's disease. [ABSTRACT FROM AUTHOR]

Background: The dietary inflammatory index (DII) serves as a tool to assess the inflammatory impact of an individual's diet. This study aimed to investigate the association between DII and some cardio-metabolic risk indices among patients with T2DM. Methods: Data from the Hoveyzeh Cohort Study, encompassing 2045 adults with T2DM, were analyzed. DII scores were calculated based on food frequency questionnaires. Anthropometric measurements and biochemical tests were performed to assess cardio-metabolic risk factors. Results: Higher DII scores were positively associated with elevated triglyceride levels, triglyceride-glucose (TyG) index, lipid accumulation product (LAP), anthropometric indices including a body shape index (ABSI), body roundness index (BRI), body mass index (BMI), hip, waist circumferences (WC), and waist-to-height ratio (all Ptrend < 0.05). Notably, no significant association was observed between DII and fasting blood sugar (FBS) levels (Ptrend > 0.05). Additionally, dietary intake analysis revealed a negative correlation between DII scores and intake of fiber, fruits, vegetables, legumes, fish, seafood, dairy products, magnesium, and vitamins A, C, D, and E (all Ptrend < 0.05). Conversely, higher DII scores were associated with increased consumption of red meat, processed meat, refined cereals, potatoes, and soft drinks (all Ptrend < 0.05). Conclusion: This study underscores the critical link between dietary inflammation, assessed by the DII score, and a multitude of cardio-metabolic risk factors in patients with T2DM. Notably, while the study did not find a significant association between DII and fasting blood sugar levels, it identified robust associations with novel anthropometric and biochemical indices indicative of cardio-metabolic risk. These findings highlight the potential of dietary interventions as a cornerstone strategy for managing T2DM and mitigating its associated complications. [ABSTRACT FROM AUTHOR]

The current study aimed to assess the influence of dietary inclusion of cyanobacterium Arthrospira platensis NIOF17/003 as a dry material and as a free-lipid biomass (FL) on the growth performance, body composition, redox status, immune responses, and gene expression of whiteleg shrimp, Litopenaeus vannamei postlarvae. L. vannamei were fed five different supplemented diets; the first group was fed on an un-supplemented diet as a negative control group (C-N), the second group was fed on a commercial diet supplemented with 2% of A. platensis complete biomass as a positive control group (C-P20), whereas, the three remaining groups were fed on a commercial diet supplemented with graded amounts of FL at 1%, 2%, and 3% (FL10, FL20, and FL30, respectively). The obtained results indicated that the diet containing 1% FL significantly increased the growth performance, efficiency of consumed feed, and survival percentage of L. vannamei compared to both C-N and C-P20 groups. As for the carcass analysis, diets containing A. platensis or its FL at higher levels significantly increased the protein, lipid, and ash content compared to the C-N group. Moreover, the shrimp group fed on C-P20 and FL10 gave significantly stimulated higher digestive enzyme activities compared with C-N. The shrimp fed C-P20 or FL exhibited higher innate immune responses and promoted their redox status profile. Also, the shrimp fed a low FL levels significantly upregulated the expression of both the peroxiredoxin (Prx) and prophenoloxidase (PPO1) genes than those receiving C-N. The current results recommended that dietary supplementation with 1% FL is the most effective treatment in promoting the performance and immunity of whiteleg shrimp. [ABSTRACT FROM AUTHOR]

[Display omitted] Conjugating biomolecules, such as antibodies, to bioconjugate moieties on lipid surfaces is a powerful tool for engineering the surface of diverse biomaterials, including cells and nanoparticles. We developed supported lipid bilayers (SLBs) presenting well-defined spatial distributions of functional moieties as models for precisely engineered functional biomolecular-lipid surfaces. We used quartz crystal microbalance with dissipation (QCM-D) and atomic force microscopy (AFM) to determine how vesicles containing a mixture of 1,2-dipalmitoyl- sn - glycero -3-phosphatidylcholine (DPPC) and 1,2-distearoyl- sn - glycero -3-phosphoethanolamine-N-[azido(polyethylene glycol)-2000] (DSPE-PEG-N 3) form SLBs as a function of the lipid phase transition temperature (T m). Above the DPPC T m , DPPC/DSPE-PEG-N 3 vesicles form SLBs with functional azide moieties on SiO 2 substrates via vesicle fusion. Below this T m , DPPC/DSPE-PEG-N 3 vesicles attach to SiO 2 intact. Intact DPPC/DSPE-PEG-N 3 vesicles on the SiO 2 surfaces fuse and rupture to form SLBs when temperature is brought above the DPPC T m. AFM studies show uniform and complete DPPC/DSPE-PEG-N 3 SLB coverage of SiO 2 surfaces for different DSPE-PEG-N 3 concentrations. As the DSPE-PEG-N 3 concentration increases from 0.01 to 6 mol%, the intermolecular spacing of DSPE-PEG-N 3 in the SLBs decreases from 4.6 to 1.0 nm. The PEG moiety undergoes a mushroom to brush transition as DSPE-PEG-N 3 concentration varies from 0.1 to 2.0 mol%. Via copper-free click reaction, IgG was conjugated to SLB surfaces with 4.6 nm or 1.3 nm inter-DSPE-PEG-N 3 spacing. QCM-D and AFM data show; 1) uniform and complete IgG layers of similar mass and thickness on the two types of SLB; 2) a higher-viscosity/less rigid IgG layer on the SLB with 4.6 nm inter-DSPE-PEG-N 3 spacing. Our studies provide a blueprint for SLBs modeling spatial control of functional macromolecules on lipid surfaces, including surfaces of lipid nanoparticles and cells. [ABSTRACT FROM AUTHOR]

The stemness loss-associated dysregeneration of impaired alveolar type 2 epithelial (AT2) cells abolishes the reversible therapy of idiopathic pulmonary fibrosis (IPF). We here report an inhalable mucus-penetrating lipid nanoparticle (LNP) for codelivering dual mRNAs, promoting realveolarization via restoring AT2 stemness for IPF treatment. Inhalable LNPs were first formulated with dipalmitoylphosphatidylcholine and our in-house-made ionizable lipids for high-efficiency pulmonary mucus penetration and codelivery of dual messenger RNAs (mRNAs), encoding cytochrome b5 reductase 3 and bone morphogenetic protein 4, respectively. After being inhaled in a bleomycin model, LNPs reverses the mitochondrial dysfunction through ameliorating nicotinamide adenine dinucleotide biosynthesis, which inhibits the accelerated senescence of AT2 cells. Concurrently, pathological epithelial remodeling and fibroblast activation induced by impaired AT2 cells are terminated, ultimately prompting alveolar regeneration. Our data demonstrated that the mRNA-LNP system exhibited high protein expression in lung epithelial cells, which markedly extricated the alveolar collapse and prolonged the survival of fibrosis mice, providing a clinically viable strategy against IPF. [ABSTRACT FROM AUTHOR]

The current consensus holds that optically‐cleared specimens are unsuitable for Magnetic Resonance Imaging (MRI); exhibiting absence of contrast. Prior studies combined MRI with tissue‐clearing techniques relying on the latter's ability to eliminate lipids, thereby fostering the assumption that lipids constitute the primary source of ex vivo MRI‐contrast. Nevertheless, these findings contradict an extensive body of literature that underscores the contribution of other features to contrast. Furthermore, it remains unknown whether non‐delipidating clearing methods can produce MRI‐compatible specimens or whether MRI‐contrast can be re‐established. These limitations hinder the development of multimodal MRI‐light‐microscopy (LM) imaging approaches. This study assesses the relation between MRI‐contrast, and delipidation in optically‐cleared whole brains following different tissue‐clearing approaches. It is demonstrated that uDISCO and ECi‐brains are MRI‐compatible upon tissue rehydration, despite both methods' substantial delipidating‐nature. It is also demonstrated that, whereas Scale‐clearing preserves most lipids, Scale‐cleared brain lack MRI‐contrast. Furthermore, MRI‐contrast is restored to lipid‐free CLARITY‐brains without introducing lipids. Our results thereby dissociate between the essentiality of lipids to MRI‐contrast. A tight association is found between tissue expansion, hyperhydration and loss of MRI‐contrast. These findings then enabled us to develop a multimodal MRI‐LM‐imaging approach, opening new avenues to bridge between the micro‐ and mesoscale for biomedical research and clinical applications. [ABSTRACT FROM AUTHOR]

Background: Shift work has been identified as a risk factor for several chronic health conditions including obesity. This study evaluated the impact of a low-calorie meal replacement (MR) as a dinner substitute on body composition and metabolic parameters in shift workers with overweight and obesity. Methods: An 8-week parallel, randomized controlled trial was conducted on overweight and obese shift workers in a large hospital. An intervention group (IG) (n = 25) was provided with a low-calorie MR shake (∼200 kcal) as a replacement for dinner, every day for 8 weeks, while the control group (CG) (n = 25) continued their habitual diet. Anthropometric measurements, body composition, biochemical, and lifestyle data were assessed at the first and last visits. Analyses were done per protocol (PP) and by intention to treat (ITT). Results: Over the study duration, both groups displayed moderate changes in anthropometric measurements and body composition, although these were not statistically significant according to the PP analysis. In the ITT analysis, apart from the hip circumference (HC), all other anthropometric parameters demonstrated significant group and time interactions, suggesting the advantageous effects of the meal replacement over the study period (P < 0.05). HDL and VLDL cholesterol measures showed significant main effects, influenced by both group (P = 0.031) and time (P = 0.050) respectively. The most pronounced dietary shift in the IG was a reduction in carbohydrate consumption and an increase in protein intake. Throughout the study, the meal replacement was well-tolerated, with no adverse events reported. Conclusions: The meal replacement dietary intervention appears to offer beneficial health effects over time. Extended research is crucial to understand the broader implications of meal replacements across diverse populations. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12622000231741. Registered on 09 February 2022. https://www.anzctr.org.au/ACTRN12622000231741.aspx. [ABSTRACT FROM AUTHOR]

Background: The causal associations of lipids and the drug target genes with atrial fibrillation (AF) risk remain obscure. We aimed to investigate the causal associations using genetic evidence. Methods: Mendelian randomization (MR) analyses were conducted using summary-level genome-wide association studies (GWASs) in European and East Asian populations. Lipid profiles (low-density lipoprotein cholesterol, triglyceride, and lipoprotein[a]) and lipid-modifying drug target genes (3-hydroxy-3-methylglutaryl-CoA reductase, proprotein convertase subtilisin/kexin type 9, NPC1-like intracellular cholesterol transporter 1, apolipoprotein C3, angiopoietin-like 3, and lipoprotein[a]) were used as exposures. AF was used as an outcome. The inverse variance weighted method was applied as the primary method. Summary-data-based Mendelian randomization analyses were performed for further validation using expression quantitative trait loci data. Mediation analyses were conducted to explore the indirect effect of coronary heart disease. Results: In the European population, MR analyses demonstrated that elevated levels of lipoprotein(a) increased AF risk. Moreover, analyses focusing on drug targets revealed that the genetically proxied target gene LPA, which simulates the effects of drug intervention by reducing lipoprotein(a), exhibited an association with AF risk. This association was validated in independent datasets. There were no consistent and significant associations observed for other traits when analyzed in different datasets. This finding was also corroborated by Summary-data-based Mendelian randomization analyses between LPA and AF. Mediation analyses revealed that coronary heart disease plays a mediating role in this association. However, in the East Asian population, no statistically significant evidence was observed to support these associations. Conclusions: This study provided genetic evidence that Lp(a) may be a causal factor for AF and that LPA may represent a promising pharmacological target for preventing AF in the European population. [ABSTRACT FROM AUTHOR]

Chronic feeding of a high fat diet (HFD) in preclinical species induces broad metabolic dysfunction characterized by body weight gain, hyperinsulinemia, dyslipidemia and impaired insulin sensitivity. The plasma lipidome is not well characterized in dogs with HFD-induced metabolic dysfunction. We therefore aimed to describe the alterations that occur in the plasma lipid composition of dogs that are fed a HFD and examine the association of these changes with the clinical signs of metabolic dysfunction. Dogs were fed a normal diet (ND) or HFD for 12 weeks. Insulin sensitivity (SI) and beta cell compensation (AIRG) were assessed through an intravenous glucose tolerance test (IVGTT) and serum biochemistry was analyzed before the introduction of HFD and again after 12 weeks of continued ND or HFD feeding. Plasma lipidomics were conducted prior to the introduction of HFD and again at week 8 in both ND and HFD-fed dogs. 12 weeks of HFD feeding resulted in impaired insulin sensitivity and increased beta cell compensation measured by SI (ND mean: 11.5 [mU/l]–1 min–1, HFD mean: 4.7 [mU/l]–1 min–1) and AIRG (ND mean: 167.0 [mU/l]min, HFD mean: 260.2 [mU/l]min), respectively, compared to dogs fed ND over the same duration. Chronic HFD feeding increased concentrations of plasma lipid species and deleterious fatty acids compared to dogs fed a ND. Saturated fatty acid (SFA) concentrations were significantly associated with fasting insulin (R2 = 0.29), SI (R2 = 0.49) and AIRG (R2 = 0.37) in all dogs after 12 weeks, irrespective of diet. Our results demonstrate that chronic HFD feeding leads to significant changes in plasma lipid composition and fatty acid concentrations associated with metabolic dysfunction. High SFA concentrations may be predictive of deteriorated insulin sensitivity in dogs. [ABSTRACT FROM AUTHOR]

Physical activity (PA) positively influences pregnancy, a critical period for health promotion, and affects placental structure and function in ways previously overlooked. Here, we summarize the current body of literature examining the association between PA, placenta biology, and physiology while also highlighting areas where gaps in knowledge exist. PA during pregnancy induces metabolic changes, influencing nutrient availability and transporter expression in the placenta. Hormones and cytokines secreted during PA contribute to health benefits, with intricate interactions in pro‐ and anti‐inflammatory markers. Extracellular vesicles and placental "‐omics" data suggest that gestational PA can shape placental biology, affecting gene expression, DNA methylation, metabolite profiles, and protein regulation. However, whether cytokines that respond to PA alter placental proteomic profiles during pregnancy remains to be elucidated. The limited research on placenta mitochondria of physically active gestational parents (gesP), has shown improvements in mitochondrial DNA and antioxidant capacity, but the relationship between PA, placental mitochondrial dynamics, and lipid metabolism remains unexplored. Additionally, PA influences the placenta‐immune microenvironment, angiogenesis, and may confer positive effects on neurodevelopment and mental health through placental changes, vascularization, and modulation of brain‐derived neurotrophic factor. Ongoing exploration is crucial for unraveling the multifaceted impact of PA on the intricate placental environment. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) is a significant hepatic condition that has gained worldwide attention. Kaempferol (Kae), renowned for its diverse biological activities, including anti-inflammatory, antioxidant, anti-aging, and cardio-protective properties, has emerged as a potential therapeutic candidate for non-alcoholic steatohepatitis (NASH). Despite its promising therapeutic potential, the precise underlying mechanism of Kae's beneficial effects in NASH remains unclear. Therefore, this study aims to clarify the mechanism by conducting comprehensive in vivo and in vitro experiments. Results: In this study, a murine model of non-alcoholic steatohepatitis (NASH) was established by feeding C57BL/6 female mice a high-fat diet for 12 weeks. Kaempferol (Kae) was investigated for its ability to modulate systemic inflammatory responses and lipid metabolism in this model (20 mg/kg per day). Notably, Kae significantly reduced the expression of NLRP3-ASC/TMS1-Caspase 3, a crucial mediator of liver tissue inflammation. Additionally, in a HepG2 cell model induced with palmitic acid/oleic acid (PA/OA) to mimic NASH conditions, Kae demonstrated the capacity to decrease lipid droplet accumulation and downregulate the expression of NLRP3-ASC/TMS1-Caspase 3 (20 µM and the final concentration to 20 nM). These findings suggest that Kae may hold therapeutic potential in the treatment of NASH by targeting inflammatory and metabolic pathways. Conclusions: These findings suggest that kaempferol holds potential as a promising therapeutic intervention for ameliorating non-alcoholic fatty liver disease (NAFLD). [ABSTRACT FROM AUTHOR]

Many different types of nanoparticles have been suggested for tumor-targeted theranosis. However, most systems were prepared through a series of complicated processes and could not even overcome the blood–immune barriers. For the accurate diagnosis and effective treatment of cancers, herein we suggested the lipid micellar structure capturing quantum dot (QD) for cancer theranosis. The QD/lipid micelles (QDMs) were prepared using a simple self-assembly procedure and then conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for tumor targeting. As a therapeutic agent, Bcl2 siRNA-cholesterol conjugates were loaded on the surface of QDMs. The EGFR-directed QDMs containing Bcl2 siRNA, so-called immuno-QDM/siBcl2 (iQDM/siBcl2), exhibited the more effective delivery of QDs and siBcl2 to target human colorectal cancer cells in cultures as well as in mouse xenografts. The effective in vivo targeting of iQDM/siBcl2 resulted in a more enhanced therapeutic efficacy of siBcl2 to the target cancer in mice. Based on the results, anti-EGFR QDM capturing therapeutic siRNA could be suggested as an alternative modality for tumor-targeted theranosis. [ABSTRACT FROM AUTHOR]

While edible algae might seem low in fat, the lipids they contain are crucial for good health and preventing chronic diseases. This study introduces a binary matrix to analyze all the polar lipids in both macroalgae (Wakame—Undaria pinnatifida, Dulse—Palmaria palmata, and Nori—Porphyra spp.) and microalgae (Spirulina—Arthrospira platensis, and Chlorella—Chlorella vulgaris) using matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). The key lies in a new dual matrix made by combining equimolar amounts of 1,5-diaminonaphthalene (DAN) and 9-aminoacridine (9AA). This combination solves the limitations of single matrices: 9AA is suitable for sulfur-containing lipids and acidic phospholipids, while DAN excels as an electron-transfer secondary reaction matrix for intact chlorophylls and their derivatives. By employing the equimolar binary matrix, a wider range of algal lipids, including free fatty acids, phospholipids, glycolipids, pigments, and even rare arsenosugarphospholipids were successfully detected, overcoming drawbacks related to ion suppression from readily ionizable lipids. The resulting mass spectra exhibited a good signal-to-noise ratio at a lower laser fluence and minimized background noise. This improvement stems from the binary matrix's ability to mitigate in-source decay effects, a phenomenon often encountered for certain matrices. Consequently, the data obtained are more reliable, facilitating a faster and more comprehensive exploration of algal lipidomes using high-throughput MALDI-MS/MS analysis. [ABSTRACT FROM AUTHOR]

Simple Summary: This review aims to deepen the understanding of buffalo farming in the Amazon, presenting the quality and nutritional value of buffalo meat and liver. We will explore the characteristics of nutrients and their influence on human health, with a special focus and particular emphasis in vitamins, minerals, and lipids. By investigating fatty acids and cholesterol, we seek to understand the complexity of lipids and their contribution to nutritional quality. The main objective of this study was to provide subsidies to improve buffalo farming practices, promote a healthier human diet and contribute to environmental sustainability in the Amazon region. Thus, this review aims to deepen the understanding of buffalo farming in the Amazon, presenting the quality and nutritional value of buffalo meat and liver. This information serves as a subsidy to improve practices related to the breeding system, nutrition, health and sustainability associated with aquatic buffaloes. For this, a review of the databases was carried out using the descriptors "nutritional value of buffalo meat", "nutritional value of buffalo liver" and "buffalo breeding in the Amazon". Thus, the consumption of foods derived from aquatic buffaloes has important nutritional value for human consumption. In view of this, it is possible to conclude that the nutrition of these animals is influenced by the biodiversity of the Amazon, giving unique characteristics to its products, also highlighting the importance of carrying out research that aims to value the potential use of this species and strengthen the economy of the region. [ABSTRACT FROM AUTHOR]

Simple Summary: Cholesterol and cholesterol derivatives accumulate in prostate cancer cells. Epidemiologic studies about diet and/or treatment with cholesterol-lowering drugs indicate that this metabolite plays a role in cancer progression, but they do not discriminate its possible role in cancer incidence. The goal of this study is so to determine whether cholesterol availability impacts tumor formation itself. Using a drosophila model specifically dedicated to the study of early epithelial tumorigenesis, we find that basal extrusion, a critical step of tumor formation, directly depends on cholesterol availability through dietary intake, and on cholesterol metabolization by the tumor cells. As we find that many genes related to cholesterol homeostasis and metabolism are ill-expressed in primary prostate cancer samples, this work indicates that cholesterol levels and metabolism could play a crucial role in the early phases of prostate cancer as well. Epidemiological studies point to cholesterol as a possible key factor for both prostate cancer incidence and progression. It could represent a targetable metabolite as the most aggressive tumors also appear to be sensitive to therapies designed to decrease hypercholesterolemia, such as statins. However, it remains unknown whether and how cholesterol, through its dietary uptake and its metabolism, could be important for early tumorigenesis. Oncogene clonal induction in the Drosophila melanogaster accessory gland allows us to reproduce tumorigenesis from initiation to early progression, where tumor cells undergo basal extrusion to form extra-epithelial tumors. Here we show that these tumors accumulate lipids, and especially esterified cholesterol, as in human late carcinogenesis. Interestingly, a high-cholesterol diet has a limited effect on accessory gland tumorigenesis. On the contrary, cell-specific downregulation of cholesterol uptake, intracellular transport, or metabolic response impairs the formation of such tumors. Furthermore, in this context, a high-cholesterol diet suppresses this impairment. Interestingly, expression data from primary prostate cancer tissues indicate an early signature of redirection from cholesterol de novo synthesis to uptake. Taken together, these results reveal that during early tumorigenesis, tumor cells strongly increase their uptake and use of dietary cholesterol to specifically promote the step of basal extrusion. Hence, these results suggest the mechanism by which a reduction in dietary cholesterol could lower the risk and slow down the progression of prostate cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Cervical cancer is the fourth most prominent cancer in women worldwide. Early cancer detection, timely treatment, and prognostic marker identification are vital to ensure that patients have improved outcomes. Magnetic resonance spectroscopy (MRS) is a powerful tool for detecting metabolites in vivo. This review article covers the role of MRS for cervical cancer for diagnosis, treatment response evaluation, and future applications of this technology. This review article investigates the utilization of MRS in the setting of cervical cancer. A variety of different techniques have been used in this space including single-voxel techniques such as point-resolved spectroscopy (PRESS) and stimulated echo acquisition mode spectroscopy (STEAM). Furthermore, the experimental parameters for these acquisitions including field strength, repetition times (TR), and echo times (TE) vary greatly. This study critically examines eleven MRS studies that focus on cervical cancer. Out of the eleven studies, ten studies utilized PRESS acquisition, while the remaining study used STEAM acquisition. These studies generally showed that the choline signal is altered in cervical cancer (4/11 studies), the lipid signal is generally increased in cervical cancer or the lipid distribution is changed (5/11 studies), and that diffusion-weighted imaging (DWI) can quantitatively detect lower apparent diffusion coefficient (ADC) values in cervical cancer (2/11 studies). Two studies also investigated the role of MRS for monitoring treatment response and demonstrated mixed results regarding choline signal, and one of these studies showed increased lipid signal for non-responders. There are several new MRS technologies that have yet to be implemented for cervical cancer including advanced spectroscopic imaging and artificial intelligence, and those technologies are also discussed in the article. [ABSTRACT FROM AUTHOR]

Simple Summary: Cell–cell communication mechanisms are gathering growing scientific interest, particularly in the context of cancer cells and the tumor microenvironment. Extracellular vesicles are gaining increased interest due to their relevance in tumor molecular characterization, classification, diagnosis, prognosis evaluation, and response to treatment. Many advances have been made in the clinical and therapeutic fields, exploiting increasingly precise biomolecular engineering strategies. This review aims to focus on the role of extracellular vesicles (EVs) as diagnostic and therapeutic tools in lung cancer. Lung cancer represents the leading cause of cancer-related mortality worldwide, with around 1.8 million deaths in 2020. For this reason, there is an enormous interest in finding early diagnostic tools and novel therapeutic approaches, one of which is extracellular vesicles (EVs). EVs are nanoscale membranous particles that can carry proteins, lipids, and nucleic acids (DNA and RNA), mediating various biological processes, especially in cell–cell communication. As such, they represent an interesting biomarker for diagnostic analysis that can be performed easily by liquid biopsy. Moreover, their growing dataset shows promising results as drug delivery cargo. The aim of our work is to summarize the recent advances in and possible implications of EVs for early diagnosis and innovative therapies for lung cancer. [ABSTRACT FROM AUTHOR]

Sausage is susceptible to oxidative changes in lipids and microbial spoilage due to the presence of water, fat, protein, and vitamins. Bee pollen (BP) as a source of potential antioxidants and antibacterial compounds can effectively prevent lipid peroxidation and microbial spoilage in meat products. The aim of the present study was to investigate the antibacterial and antioxidant activities of BP and the effects of nano/microparticles of bee pollen extract (n/m BP) at a concentration of 125 and 250 mg/100 g meat on the oxidative stability and microbial growth of high‐fat sausage during 30 days of storage at 4°C. The formation of BP particles in the nano/micro range was confirmed by scanning electron microscopy. High concentrations of total phenolic compounds (28.26 ± 0.10 mg GAE/g BP) with antioxidant activity (EC50 = 5.4 ± 0.07 mg/mL) were detected in BP. Based on the microdilution assay, the minimum inhibitory concentration of n/m BP for all test bacteria was 1000 (μg/mL) and the minimum bactericidal concentration of n/m BP was 2000 (μg/mL) for Staphylococcus aureus and Bacillus cereus and 4000 (μg/mL) for Escherichia coli and Pseudomonas aeruginosa. The n/m BP treatment (250 mg/100 g meat) showed a higher pH value (p <.05) and lower TBARS values (p <.05) than the ascorbic acid treatment (100 mg/100 g meat) and the control during the storage period. The microbial analysis showed that the addition of n/m BP led to a significant decrease (p <.05) in the total bacterial count, coliforms, S. aureus, and fungal population compared to the other samples. The results show that the addition of n/m BP (125 mg/100 g) can improve the texture, taste, and overall acceptability of the sausage compared to the control sample. In conclusion, this study suggests that BP can replace synthetic antioxidants in high‐fat sausages at the nano/microparticle level. [ABSTRACT FROM AUTHOR]

Health concerns regarding fat consumption, as well as shifts in customer preference, have prompted substantial studies into low‐fat products. This study examined the nutritional, color, functional, and antioxidant properties of Bambara groundnut (BGN) flour varieties (cream, brown, and red‐coated) grains as well as their influence on the physicochemical properties, lipid oxidation, and sensory acceptability of low‐fat mutton patties. The patties were formulated with 2.5%, 5%, 7.5%, and 10% of BGN flour for each variety, and 100% mutton patties were used as a control. The BGN flours showed significant (p <.05) differences in their nutritional composition (except for ash content), color, functional (excluding emulsion stability), and antioxidant properties. The increase in the percentage of substitution of BGN flours significantly increased the fiber (0.00% to 0.79%), ash (1.16% to 1.99%), and carbohydrates (2.14% to 1.99%) contents of the formulated mutton patties. However, moisture and protein contents decreased. The cooking yield of the formulated patties significantly increased with the increase in the percentage substitution of BGN flours (2.5%–10%), with values ranging from 76.39% to 86.80%, but the diameter reduction was limited. The increase in the inclusion of BGN flours significantly increased the lightness, hue angle, color difference, and whiteness of patties. Nevertheless, the redness, yellowness, chroma, and yellowness index of the patties decreased. The hardness and resilience of formulated patties significantly increased, with values varying from 16.41 to 17.66 N, and from 0.35 to 0.48 J/J, respectively, whereas the springiness, cohesiveness, and chewiness decreased. The lipid oxidation of formulated mutton patties significantly increased from Days 7 to 21, but was still less than that of the control sample within storage days. The sensory properties of formulated patties were not significantly different from the control sample and were above the acceptable score of five. All BGN varieties had positive effects on the mutton patties, more especially red, followed by brown, and cream, respectively. The inclusion of a 10% red BGN flour variety is highly recommended due to its significant impact on mutton patties. Nevertheless, different types of BGN varieties can each be used as additives in mutton patties without having detrimental effects on the quality parameters of the patties. [ABSTRACT FROM AUTHOR]

The self‐assembly of amphiphilic molecules produces structures of diverse dimensions, encompassing micelles, tubules, lamellae, and vesicles. This study focuses on elucidating the controllability of amphiphilic lipid molecule self‐assembly in size and uniformity to facilitate our understanding of the molecular characteristics that correlate with the functions and attributes of the assembled structures. Electrospray deposition allows micropatterning of lipid molecules in conjunction with a conductive–nonconductive patterned substrate. The solvent in the sprayed mist undergoes evaporation during flight, leading to the deposition of dry lipids exclusively on the conductive regions of the substrate. This process enables homogeneous lipid micropatterning, effectively circumventing the coffee‐ring effect. Subsequent hydration of the lipid pattern triggers the spontaneous formation of a size‐controlled, unilamellar vesicle array on the substrate, spanning an area of a few square millimeters. The vesicles exhibits monodispersity, with a coefficient of variation below 8% for sizes ranging from 5 to 20 μm. The size‐controlled self‐assembly process is adaptable to various lipid compositions, thereby demonstrating that the molecular characteristics manifest in the morphological features appear as phase separation, budding, and curvature of vesicle membranes. The approach further validates its suitability for conducting time‐resolved analyses of molecular transport and ligand binding on the monodispersed vesicle array. [ABSTRACT FROM AUTHOR]

Aging coincides with the progressive loss of muscle mass and strength, increased adiposity, and diminished physical function. Accordingly, interventions aimed at improving muscle, metabolic, and/or physical health are of interest to mitigate the adverse effects of aging. In this study, we tested a stem cell secretome product, which contains extracellular vesicles and growth, cytoskeletal remodeling, and immunomodulatory factors. We examined the effects of 4 weeks of 2×/week unilateral intramuscular secretome injections (quadriceps) in ambulatory aged male C57BL/6 mice (22–24 months) compared to saline‐injected aged‐matched controls. Secretome delivery substantially increased whole‐body lean mass and decreased fat mass, corresponding to higher myofiber cross‐sectional area and smaller adipocyte size, respectively. Secretome‐treated mice also had greater whole‐body physical function (grip strength and rotarod performance) and had higher energy expenditure and physical activity levels compared to control mice. Furthermore, secretome‐treated mice had greater skeletal muscle Pax7+ cell abundance, capillary density, collagen IV turnover, reduced intramuscular lipids, and greater Akt and hormone sensitive lipase phosphorylation in adipose tissue. Finally, secretome treatment in vitro directly enhanced muscle cell growth and IL‐6 production, and in adipocytes, it reduced lipid content and improved insulin sensitivity. Moreover, indirect treatment with secretome‐treated myotube culture media also enhanced muscle cell growth and adipocyte size reduction. Together, these data suggest that intramuscular treatment with a stem cell secretome improves whole‐body metabolism, physical function, and remodels skeletal muscle and adipose tissue in aged mice. [ABSTRACT FROM AUTHOR]

New advancements in nanocarrier technologies are revolutionizing the delivery of drugs through the skin, allowing for precise treatment with better absorption, stability, and bioavailability. This review investigates lipid and inorganic nanocarriers like liposomes, ethosomes, and inorganic nanoparticles and assesses their potential for delivering drugs through the skin. It emphasizes the mechanisms that enable controlled release and deeper skin penetration, which are crucial for ensuring effectiveness in clinical applications. The review synthesizes existing research, acknowledging that only few nanocarriers are successfully deployed in clinical settings. By offering a comprehensive overview, it sheds light on the progress and future obstacles to using nanocarriers for drug delivery through the skin. [ABSTRACT FROM AUTHOR]

The B‐cell lymphoma 2 (BCL2) family members, BCL2‐associated protein X (BAX) and BCL2 homologous antagonist killer (BAK), are required for programmed cell death via the mitochondrial pathway. When cells are stressed, damaged or redundant, the balance of power between the BCL2 family of proteins shifts towards BAX and BAK, allowing their transition from an inactive, monomeric state to a membrane‐active oligomeric form that releases cytochrome c from the mitochondrial intermembrane space. That oligomeric state has an essential intermediate, a symmetric homodimer of BAX or BAK. Here we describe crystal structures of dimers of the core domain of BAX, comprising its helices α2–α5. These structures provide an atomic resolution description of the interactions that drive BAX homo‐dimerisation and insights into potential interaction between core domain dimers and membrane lipids. The previously identified BAK lipid‐interacting sites are not conserved with BAX and are likely to determine the differences between them in their interactions with lipids. We also describe structures of heterodimers of BAK/BAX core domains, yielding further insight into the differences in lipid binding between BAX and BAK. [ABSTRACT FROM AUTHOR]

[Display omitted] Lipid nanoparticles containing a cationic lipid are increasingly used in drug and gene delivery as they can display improved cellular uptake, enhanced loading for anionic cargo such as siRNA and mRNA or exhibit additional functionality such as cytotoxicity against cancer cells. This research study tests the hypothesis that the molecular structure of the cationic lipid influences the structure of the lipid nanoparticle, the cellular uptake, and the resultant cytotoxicity. Three potentially cytotoxic cationic lipids, with systematic variations to the hydrophobic moiety, were designed and synthesised. All the three cationic lipids synthesised contain pharmacophores such as the bicyclic coumarin group (CCA12), the tricyclic etodolac moiety (ETD12), or the large pentacyclic triterpenoid "ursolic" group (U12) conjugated to a quaternary ammonium cationic lipid containing twin C12 chains. The cationic lipids were doped into monoolein cubosomes at a range of concentrations from 0.1 mol% to 5 mol% and the effect of the lipid molecular architecture on the cubosome phase behaviour was assessed using a combination of Small Angle X-Ray Scattering (SAXS), Dynamic Light Scattering (DLS), zeta-potential and cryo-Transmission Electron Microscopy (Cryo-TEM). The resulting cytotoxicity of these particles against a range of cancerous and non-cancerous cell-lines was assessed, along with their cellular uptake. The molecular architecture of the cationic lipid was linked to the internal nanostructure of the resulting cationic cubosomes with a transition to more curved cubic and hexagonal phases generally observed. Cubosomes formed from the cationic lipid CCA12 were found to have improved cellular uptake and significantly higher cytotoxicity than the cationic lipids ETD12 and U12 against the gastric cancer cell-line (AGS) at lipid concentrations ≥ 75 µg/mL. CCA12 cationic cubosomes also displayed reasonable cytotoxicity against the prostate cancer PC-3 cell-line at lipid concentrations ≥ 100 µg/mL. In contrast, 2.5 mol% ETD12 and 2.5 mol% U12 cubosomes were generally non-toxic against both cancerous and non-cancerous cell lines over the entire concentration range tested. The molecular architecture of the cationic lipid was found to influence the cubosome phase behaviour, the cellular uptake and the toxicity although further studies are necessary to determine the exact relationship between structure and cellular uptake across a range of cell lines. [ABSTRACT FROM AUTHOR]

This article explores the recruitment of arbuscular mycorrhizal (AM) conserved genes for ectomycorrhizal (ECM) symbiosis. ECM symbiosis, which is a more recent form of symbiosis than AM symbiosis, involves the formation of a mantle around the root and an intercellular Hartig net. The study found that ECM host species from the Fagales order maintained the majority of AM-conserved genes, unlike other non-AM hosts. Transcriptome analysis revealed that several of these maintained genes were induced in ECM symbiosis, suggesting that ECM formation recruits AM-derived mechanisms. The study focuses on ECM-only hosts, which are plant species that exclusively engage in ECM symbiosis and have lost the ability to form AM symbiosis. The researchers discovered that ECM-only hosts maintain 64% of the AM-conserved orthologous groups (OGs), highlighting the importance of these genes in ECM symbiosis. They also identified specific genes, such as RAM2, involved in lipid biosynthesis and arbuscule formation in ECM roots. The study suggests that the preservation of AM-conserved genes in ECM-only hosts supports their role in ECM symbiosis. [Extracted from the article]

Objective: Statin treatment compliance and achieving target levels differ between populations. This study aimed to determine the status of achieving the lipid targets and evaluate patients' compliance to statin treatment in type 2 diabetic patients with dyslipidemia. Method: This cross-sectional study included type 2 diabetes mellitus (T2DM) patients with dyslipidemia who applied for treatment at our polyclinics. Statin compliance was evaluated using the Modified Morisky Adherence Scale (MMAS-8) through a face-to-face interview. Cardiovascular (CV) risk was calculated according to the 2019 ESC (European Society of Cardiology) criteria by evaluating the patients' individual risk factors. LDL targets were determined according to risk categories with the same criteria. Results: A total of 504 patients (F/M: 274/230) were included. The serum LDL levels were 102.6 ± 39.2 mg/dL. Of the patients, 56.1% were under statin treatment. CV risk was very high in 73.6% of patients. LDL levels were significantly lower in users than in non-users (91.2 ± 26.0, 117.3 ± 38.4, p < 0.0001). The rate of reaching the LDL target was 14.8% in statin users. Treatment compliance was low for 40.6% of statin users. Discontinuation of statin treatment due to side effects was 15.7% (n = 14). N = 49 patients willingly discontinued statin treatment. They reported that 40.8% considered the treatment unnecessary. Conclusion: It was observed that 56.1% of type 2 diabetic patients were on statin therapy. A small percentage of them 14.8% (n = 42) reached the LDL target. Statin non-compliance and a lack of awareness of the statin treatment are the main reasons for high LDL levels in type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Human iPSC-derived airway organoids (iPSC-AOs) exhibit cellular heterogenicity resembling the human native airway. Bioinformatics analysis revealed a robust dysregulation in inflammation, lipid-metabolism pathway, and alternative splicing in SARS-CoV-2 infected airway organoids. Manipulating lipid homeostasis using cholesterol-lowering drugs (e.g. Statins) relocated the viral entry receptor angiotensin-converting enzyme-2 (ACE-2), leading to the reduction of SARS-CoV-2 entry and replication. [Display omitted] • Single-cell RNA sequencing showed that iPSC-AOs exhibition of the genetic profiles highly resembling the genotypes of human airways. • iPSC-AOs are susceptible to SARS-COV-2 infection and the expressions of S and N proteins after viral infection. • Bioinformatics analysis indicated the involvement of aberrant enrichment of lipid transport and lipid pathways in infected iPSC-AOs. • Statin preincubation relocated ACE2, reduced N protein, and limited SARS-CoV-2 infection in iPSC-AOs. • Lipid modifications consistently inhibited viral entry of various SARS-CoV-2 strains (wild-type, alpha, delta, omicron). Modifications of lipid metabolism were closely associated with the manifestations and prognosis of coronavirus disease of 2019 (COVID-19). Pre-existing metabolic conditions exacerbated the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection while modulations of aberrant lipid metabolisms alleviated the manifestations. To elucidate the underlying mechanisms, an experimental platform that reproduces human respiratory physiology is required. Here we generated induced pluripotent stem cell-derived airway organoids (iPSC-AOs) that resemble the human native airway. Single-cell sequencing (ScRNAseq) and microscopic examination verified the cellular heterogeneity and microstructures of iPSC-AOs, respectively. We subjected iPSC-AOs to SARS-CoV-2 infection and investigated the treatment effect of lipid modifiers statin drugs on viral pathogenesis, gene expression, and the intracellular trafficking of the SARS-CoV-2 entry receptor angiotensin-converting enzyme-2 (ACE-2). In SARS-CoV-2-infected iPSC-AOs, immunofluorescence staining detected the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins and bioinformatics analysis further showed the aberrant enrichment of lipid-associated pathways. In addition, SARS-CoV-2 hijacked the host RNA replication machinery and generated the new isoforms of a high-density lipoprotein constituent apolipoprotein A1 (APOA1) and the virus-scavenging protein deleted in malignant brain tumors 1 (DMBT1). Manipulating lipid homeostasis using cholesterol-lowering drugs (e.g. Statins) relocated the viral entry receptor angiotensin-converting enzyme-2 (ACE-2) and decreased N protein expression, leading to the reduction of SARS-CoV-2 entry and replication. The same lipid modifications suppressed the entry of luciferase-expressing SARS-CoV-2 pseudoviruses containing the S proteins derived from different SARS-CoV-2 variants, i.e. wild-type, alpha, delta, and omicron. Together, our data demonstrated that modifications of lipid pathways restrict SARS-CoV-2 propagation in the iPSC-AOs, which the inhibition is speculated through the translocation of ACE2 from the cell membrane to the cytosol. Considering the highly frequent mutation and generation of SARS-CoV-2 variants, targeting host metabolisms of cholesterol or other lipids may represent an alternative approach against SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Whole-body vibration (WBV), a training method based on the stimulation of muscle contraction by mechanical vibration generated in a vibrating platform, is claimed to be effective in diabetes management. This meta-analysis evaluated WBV effects against other exercises, placebo, or no intervention in type-2 diabetes. Medline, Scopus, and Web of Science databases were systematically searched through June 2023. Randomized controlled trials reported the effect of WBV on glucose (hemoglobin A1C and fasting blood glucose), and lipid profiles (total cholesterol, triglycerides, high, and low-density lipoprotein) were included. Two researchers independently extracted the characteristics of the studies, participants, WBV intervention and comparisons, and the outcomes from the included articles. The Physiotherapy Evidence Database (PEDro) scale assessed trial quality. In this review, all articles had no high risk of bias according to the PEDro scale, with studies achieving optimal, excellent, and good scores. Network meta-analysis revealed that WBV was effective for reducing hemoglobin A1C when compared with conventional (mean difference: − 1.58%, 95%CrI: − 2.51, − 0.47) and resistance exercise (mean difference: − 1.32%, 95%CrI: − 1.96, − 0.33). WBV had also a desirable but insignificant effect on hemoglobin A1C compared to stretching and balance exercises, placebo, and no intervention. The current pairwise meta-analysis did not show that WBV favors fasting blood glucose and lipids. WBV may have potential advantages for glycemic control in type-2 diabetes. However, uncertainties in the findings remain due to the limited number of studies and their heterogeneity. [ABSTRACT FROM AUTHOR]

Lipid-lowering therapies, particularly non-statin regimens, are underutilized as ~2/3 of patients with atherosclerotic cardiovascular (CV) disease (CVD) are not optimally managed, and do not attain target low-density lipoprotein cholesterol (LDL-C) concentrations, despite statin treatment. Statins have been the mainstay of hypolipidemic therapies; however, they are plagued by adverse effects, which have partly hindered their more widespread use. Ezetimibe is often the first added mode of treatment to attain LDL-C goals as it is efficacious and also allows the use of a smaller dose of statin, while the need for more expensive therapies is obviated. We herein provide a comprehensive review of the effects of ezetimibe in lipid lowering and reducing CV events and improving outcomes. Of the hypolipidemic therapies, oral ezetimibe, in contrast to newer agents, is the most convenient and/or affordable regimen to be utilized as mono- or combined therapy supported by data from CV outcomes studies attesting to its efficacy in reducing CVD risk and events. When combined with a statin, the statin dose could be lower, thus curtailing side-effects, while the hypolipidemic effect is enhanced (by ~20%) as the percentage of patients with target level LDL-C (<70 mg/dL) is higher with combined treatment versus a high-intensity statin. Ezetimibe could also serve as an alternative treatment in cases of statin intolerance. In conclusion, ezetimibe has an excellent safety/tolerability profile; it is the first added treatment to a statin that can attain LDL-C targets. In the combined therapy, the hypolipidemic effect is enhanced while the dose of statin could be lower, thus limiting the occurrence of side-effects. Ezetimibe could also serve as an alternative mode of treatment in cases of statin intolerance. [ABSTRACT FROM AUTHOR]

Diosgenin (DG), a well-known steroidal sapogenin, is abundantly found in the plants of the Dioscoreaceae family and exhibits diverse pharmacological properties. In our previous study, we demonstrated that DG supplementation protected Caenorhabditis elegans from high glucose-induced lipid deposition, oxidative damage, and lifespan reduction. Nevertheless, the precise biological mechanisms underlying the beneficial effects of DG have not yet been described. In this context, the present study aims to elucidate how DG reduces molecular and cellular declines induced by high glucose, using the powerful genetics of the C. elegans model. Treatment with DG significantly (p < 0.01) prevented fat accumulation and extended lifespan under high-glucose conditions without affecting physiological functions. DG-induced lifespan extension was found to rely on longevity genes daf-2, daf-16, skn-1, glp-1, eat-2, let-363, and pha-4. Specifically, DG regulates lipophagy, the autophagy-mediated degradation of lipid droplets, in C. elegans, thereby inhibiting fat accumulation. Furthermore, DG treatment did not alter the triglyceride levels in the fat-6 and fat-7 single mutants and fat-6;fat-7 double mutants, indicating the significant role of stearoyl-CoA desaturase genes in mediating the reduction of fat deposition by DG. Our results provide new insight into the fat-reducing mechanisms of DG, which might develop into a multitarget drug for preventing obesity and associated health complications; however, preclinical studies are required to investigate the effect of DG on higher models. [ABSTRACT FROM AUTHOR]

Calcification of aortic valve leaflets is a growing mortality threat for the 18 million human lives claimed globally each year by heart disease. Extensive research has focused on the cellular and molecular pathophysiology associated with calcification, yet the detailed composition, structure, distribution and etiological history of mineral deposition remains unknown. Here transdisciplinary geology, biology and medicine (GeoBioMed) approaches prove that leaflet calcification is driven by amorphous calcium phosphate (ACP), ACP at the threshold of transformation toward hydroxyapatite (HAP) and cholesterol biomineralization. A paragenetic sequence of events is observed that includes: (1) original formation of unaltered leaflet tissues: (2) individual and coalescing 100’s nm- to 1 μm-scale ACP spherules and cholesterol crystals biomineralizing collagen fibers and smooth muscle cell myofilaments; (3) osteopontin coatings that stabilize ACP and collagen containment of nodules preventing exposure to the solution chemistry and water content of pumping blood, which combine to slow transformation to HAP; (4) mm-scale nodule growth via ACP spherule coalescence, diagenetic incorporation of altered collagen and aggregation with other ACP nodules; and (5) leaflet diastole and systole flexure causing nodules to twist, fold their encasing collagen fibers and increase stiffness. These in vivo mechanisms combine to slow leaflet calcification and establish previously unexplored hypotheses for testing novel drug therapies and clinical interventions as viable alternatives to current reliance on surgical/percutaneous valve implants. [ABSTRACT FROM AUTHOR]

Nesfatin-1 (NESF-1) has been shown to modulate lipid metabolism. We have identified a nesfatin-1-like-peptide (NLP) processed from a related precursor nucleobindin 1 (NUCB1). Here we determined if NLP, like NESF-1, regulates lipid accumulation in vitro, and tested if the disruption of nucb1 gene affects hepatic lipid metabolism genes in mice. Hepatocytes (HepG2/C3A cells) express NLP and NESF-1 and both peptides significantly reduced lipogenic enzyme mRNAs and enhanced beta-oxidation enzyme mRNAs. Lipid contents in oleic acid induced HepG2/C3A cells were attenuated by NESF-1 and NLP. The inhibitory effect on cellular lipid content was blocked by compound C, an inhibitor of AMPK. The disruption of nucb1 gene affected lipid metabolism-related enzyme mRNAs, endogenous nucb2 mRNA and AMPK phosphorylation. The lipid-lowering effects identified here highlights the potential of nucleobindins and peptides processed from them to address lipid disorders, and its possible benefits in metabolic disease management. Nesfatin-1 and nesfatin-1-like peptide reduced lipid content in oleic acid-induced HepG2/C3A cells, an effect that was blocked by an AMPK inhibitor compound C. This highlights the therapeutic potential for nesfatin-1 and NLP in lipid disorders. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to evaluate the effects on the clinical signs of poisoning and adverse effects of intravenous lipid emulsion treatment in 82 animals (dogs and cats) with suspected poisonings over 18 months. Physical examination parameters and state of consciousness were documented every hour after the intravenous administration of a bolus of 2 ml/kg and 0.25 ml/kg/min over 60 minutes of a 20% intravenous lipid emulsion. The modified Glasgow coma scale and laboratory findings (blood gas analysis, triglyceride, lactate) were evaluated initially and three hours after discontinuing intravenous lipid emulsion administration. A statistical evaluation of the occurrence of adverse effects and the development of laboratory values was performed. A decrease in respiratory rate in the second control (8–12 hours) after ILE was observed. Three hours after completing of the intravenous lipid emulsion, triglyceride concentration increased about 10 times (p <0.001). Venous carbon dioxide partial pressure, bicarbonate, base excess, as well as the electrolytes sodium, potassium and ionized calcium decreased significantly (p <0.001). Patients who experienced a worsening of the modified Glasgow coma scale had a higher increase in triglyceride concentrations (p = 0.041) and plasma lactate (p = 0.034) and a larger decrease in bicarbonate concentrations (p = 0.053) compared to others. About 54% (n = 44) of the patients showed adverse effects which could be attributed to the administration of intravenous lipid emulsion and may be associated with a higher triglyceride increase. All of them were completely reversible within 33 hours. Adverse effects associated with intravenous lipid emulsion therapy were observed in half of the patients and were associated with a higher increase in triglycerides. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia, which is characterized by an unfavorable lipid profile, is a key risk factor for cardiovascular disease (CVD). Understanding the relationships between epigenetic aging and lipid levels may help guide early prevention and treatment efforts for dyslipidemia. Methods: We used weighted linear regression to cross-sectionally investigate the associations between five measures of epigenetic age acceleration estimated from whole blood DNA methylation (HorvathAge Acceleration, HannumAge Acceleration, PhenoAge Acceleration, GrimAge Acceleration, and DunedinPACE) and four blood lipid measures (total cholesterol (TC), LDL-C, HDL-C, and triglycerides (TG)) in 3,813 participants (mean age = 70 years) from the Health and Retirement Study (HRS). As a sensitivity analysis, we examined the same associations in participants who fasted prior to the blood draw (n = 2,531) and in participants who did not take lipid-lowering medication (n = 1,869). Using interaction models, we also examined whether demographic factors including age, sex, and educational attainment modified the relationships between epigenetic age acceleration and blood lipids. Results: After adjusting for age, race/ethnicity, sex, fasting status, and lipid-lowering medication use, greater epigenetic age acceleration was associated with lower TC, HDL-C, and LDL-C, and higher TG (p < 0.05), although the effect sizes were relatively small (e.g., < 7 mg/dL of TC per standard deviation in epigenetic age acceleration). GrimAge acceleration and DunedinPACE associations with all lipids remained significant after further adjustment for body mass index, smoking status, and educational attainment. These associations were stronger in participants who fasted and who did not use lipid-lowering medication, particularly for LDL-C. We observed the largest number of interactions between DunedinPACE and demographic factors, where the associations with lipids were stronger in younger participants, females, and those with higher educational attainment. Conclusion: Multiple measures of epigenetic age acceleration are associated with blood lipid levels in older adults. A greater understanding of how these associations differ across demographic groups can help shed light on the relationships between aging and downstream cardiovascular diseases. The inverse associations between epigenetic age and TC and LDL-C could be due to sample limitations or non-linear relationships between age and these lipids, as both TC and LDL-C decrease faster at older ages. [ABSTRACT FROM AUTHOR]

Cancer prognosis remains a critical clinical challenge. Lipidomic analysis via mass spectrometry (MS) offers the potential for objective prognostic prediction, leveraging the distinct lipid profiles of cancer patient-derived specimens. This review aims to systematically summarize the application of MS-based lipidomic analysis in prognostic prediction for cancer patients. Our systematic review summarized 38 studies from the past decade that attempted prognostic prediction of cancer patients through lipidomics. Commonly analyzed cancers included colorectal, prostate, and breast cancers. Liquid (serum and urine) and tissue samples were equally used, with liquid chromatography–tandem MS being the most common analytical platform. The most frequently evaluated prognostic outcomes were overall survival, stage, and recurrence. Thirty-eight lipid markers (including phosphatidylcholine, ceramide, triglyceride, lysophosphatidylcholine, sphingomyelin, phosphatidylethanolamine, diacylglycerol, phosphatidic acid, phosphatidylserine, lysophosphatidylethanolamine, lysophosphatidic acid, dihydroceramide, prostaglandin, sphingosine-1-phosphate, phosphatidylinosito, fatty acid, glucosylceramide and lactosylceramide) were identified as prognostic factors, demonstrating potential for clinical application. In conclusion, the potential for developing lipidomics in cancer prognostic prediction was demonstrated. However, the field is still nascent, necessitating future studies for validating and establishing lipid markers as reliable prognostic tools in clinical practice. [ABSTRACT FROM AUTHOR]

The use of new materials in the field of biofuel production has been represented as a step in the development of remarkable catalysts. The use of lipases in the production of biodiesel is often seen as a cost-limiting step, as the operating expenses in recovering such catalysts can lead to unfeasible market expectations. In this study, hydroxyapatite (HAp) particles were evaluated as a support to immobilize commercial lipase, following application in ethyl ester synthesis. First, hydroxyapatite was synthesized through the co-precipitation method at constant pH and selected as a support to be used in enzyme immobilization. The characterization of the biocatalyst support materials produced was carried out using DRX, BET, FTIR, TGA, and SEM analysis. The lipase from Thermomyces lanuginosus was then immobilized in the matrices, and, subsequently, there was transesterification of the vegetable oil deodorization distillate (VODD). The biodiesel samples generated showed that they were within commercial standards, achieving ester conversion greater than 96.5%. Other properties such as density (0.87 g.cm−3) and viscosity (4.36 mm2.s−1) meet the specifications required by ASTM to be used as a biofuel. In the experiment planning technique, the results revealed an experimental trend and a defined behavior: a higher lipase loading in the immobilization and the use of temperatures in the range of 40–50 °C favor high conversions of ethyl esters. Thus, this confirms that the enzymatic chemical catalyst was able to form the main fatty acid esters even using a residual lipid raw material. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) is a cluster of risk factors related to diabetes and cardiovascular disease (CVD). Given that early identification of MetS might decrease CVD risk, it is imperative to establish a simple and cost-effective method to identify individuals at risk of MetS. The purpose of this study was to explore the relationships between several atherogenic indices (including AIP, TyG index, non-HDL-C, LDL-c/HDL-c, and TC/HDL-c) and MetS, and to assess the ability of these indices to predict MetS. Methods: The present cross-sectional study was conducted using baseline data from 9809 participants of the Hoveyzeh Cohort Study (HCS). MetS was defined based on the International Diabetes Federation (IDF). To examine the discriminatory abilities of each atherogenic indices in the identification of MetS, a receiver-operating characteristic curve was conducted. Logistic regression analysis was also performed to evaluate the relationship between atherogenic indices and MetS. Results: All of the atherogenic indices including the TyG index, AIP, non-HDL-C, TC/HDL-c, and LDL-c/HDL-c were significantly higher in participants with MetS than in those without MetS. According to the ROC curve analysis, the TyG index revealed the highest area under the curve (0.79 and 0.85 in men and women, respectively), followed by the AIP (0.76 and 0.83 in men and women, respectively). The best cutoff values for the TyG index and AIP were 8.96 and 0.16 for men and 8.84 and 0.05 for women, respectively. The TyG index and AIP were also strongly associated with MetS. Conclusion: Among the 5 atherogenic indices evaluated, the TyG index and AIP were strongly related to MetS. The TyG index also demonstrated superior discriminative ability compared to other atherogenic indices in predicting MetS. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis B Virus (HBV) is widely recognized as a "metabolic virus" that disrupts hepatic metabolic homeostasis, rendering it one of the foremost risk factors for hepatocellular carcinoma (HCC). Except for antiviral therapy, the fundamental principles underlying HBV− and HBV+ HCC have remained unchanged, limiting HCC treatment options. Objectives: In this study, we aim to identify the distinctive metabolic profile of HBV-associated HCC, with the promise of identifying novel metabolic targets that confer survival advantages and ultimately impede cancer progression. Methods: We employed a comprehensive methodology to evaluate metabolic alterations systematically. Initially, we analyzed transcriptomic and proteomic data obtained from a public database, subsequently validating these findings within our test cohort at both the proteomic and transcriptomic levels. Additionally, we conducted a comprehensive analysis of tissue metabolomics profiles, lipidomics, and the activity of the MAPK and AKT signaling pathway to corroborate the abovementioned changes. Results: Our multi-omics approach revealed distinct metabolic dysfunctions associated with HBV-associated HCC. Specifically, we observed upregulated steroid hormone biosynthesis, primary bile acid metabolism, and sphingolipid metabolism in HBV-associated HCC patients' serum. Notably, metabolites involved in primary bile acid and sphingolipids can activate the MAPK/mTOR pathway. Tissue metabolomics and lipidomics analyses further validated the serum metabolic alterations, particularly alterations in lipid composition and accumulation of unsaturated fatty acids. Conclusion: Our findings emphasize the pivotal role of HBV in HCC metabolism, elucidating the activation of a unique MAPK/mTOR signaling axis by primary bile acids and sphingolipids. Moreover, the hyperactive MAPK/mTOR signaling axis transduction leads to significant reprogramming in lipid metabolism within HCC cells, further triggering the activation of the MAPK/mTOR pathway in turn, thereby establishing a self-feeding circle driven by primary bile acids and sphingolipids. [ABSTRACT FROM AUTHOR]

Background: The placenta plays a crucial role in supporting and influencing fetal development. We compared the effects of prepartum supplementation with omega-3 (n-3) fatty acid (FA) sources, flaxseed oil (FLX) and fish oil (FO), on the expression of genes and proteins related to lipid metabolism, inflammation, oxidative stress, and the endocannabinoid system (ECS) in the expelled placenta, as well as on FA profile and inflammatory response of neonates. Late-pregnant Holstein dairy cows were supplemented with saturated fat (CTL), FLX, or FO. Placental cotyledons (n = 5) were collected immediately after expulsion, and extracted RNA and proteins were analyzed by RT-PCR and proteomic analysis. Neonatal blood was assessed for FA composition and concentrations of inflammatory markers. Results: FO increased the gene expression of fatty acid binding protein 4 (FABP4), interleukin 10 (IL-10), catalase (CAT), cannabinoid receptor 1 (CNR1), and cannabinoid receptor 2 (CNR2) compared with CTL placenta. Gene expression of ECS-enzyme FA-amide hydrolase (FAAH) was lower in FLX and FO than in CTL. Proteomic analysis identified 3,974 proteins; of these, 51–59 were differentially abundant between treatments (P ≤ 0.05, |fold change| ≥ 1.5). Top canonical pathways enriched in FLX vs. CTL and in FO vs. CTL were triglyceride metabolism and inflammatory processes. Both n-3 FA increased the placental abundance of FA binding proteins (FABPs) 3 and 7. The abundance of CNR1 cannabinoid-receptor-interacting-protein-1 (CNRIP1) was reduced in FO vs. FLX. In silico modeling affirmed that bovine FABPs bind to endocannabinoids. The FLX increased the abundance of inflammatory CD44-antigen and secreted-phosphoprotein-1, whereas prostaglandin-endoperoxide synthase 2 was decreased in FO vs. CTL placenta. Maternal FO enriched neonatal plasma with n-3 FAs, and both FLX and FO reduced interleukin-6 concentrations compared with CTL. Conclusion: Maternal n-3 FA from FLX and FO differentially affected the bovine placenta; both enhanced lipid metabolism and modulated oxidative stress, however, FO increased some transcriptional ECS components, possibly related to the increased FABPs. Maternal FO induced a unique balance of pro- and anti-inflammatory components in the placenta. Taken together, different sources of n-3 FA during late pregnancy enhanced placental immune and metabolic processes, which may affect the neonatal immune system. [ABSTRACT FROM AUTHOR]

Food allergy is widely recognized as a significant health issue, having escalated into a global epidemic, subsequently giving rise to the development of numerous additional complications. Currently, the sole efficient method to curb the progression of allergy is through the implementation of an elimination diet. The increasing number of newly identified allergens makes it harder to completely remove or avoid them effectively. The immunoreactivity of proteins of bacterial origin remains an unexplored topic. Despite the substantial consumption of microbial proteins in our diets, the immunologic mechanisms they might induce require thorough validation. This stands as the primary objective of this study. The primary objective of this study was to evaluate the effects of bacterial proteins on the intestinal barrier and immune system parameters during hypersensitivity induction in both developing and mature organisms. The secondary objective was to evaluate the role of lipids in the immunoreactivity programming of these bacterial proteins. Notably, in this complex, comprehensively designed in vitro, in vivo, and ex vivo trial, the immunoreactivity of various bacterial proteins will be examined. In summary, the proposed study intends to address the knowledge gaps regarding the effects of Lactobacillus microbial proteins on inflammation, apoptosis, autophagy, and intestinal barrier integrity in a single study. [ABSTRACT FROM AUTHOR]

Phosphatidylinositol (PI) is the precursor lipid for the minor phosphoinositides (PPIns), which are critical for multiple functions in all eukaryotic cells. It is poorly understood how phosphatidylinositol, which is synthesized in the ER, reaches those membranes where PPIns are formed. Here, we used VT01454, a recently identified inhibitor of class I PI transfer proteins (PITPs), to unravel their roles in lipid metabolism, and solved the structure of inhibitor-bound PITPNA to gain insight into the mode of inhibition. We found that class I PITPs not only distribute PI for PPIns production in various organelles such as the plasma membrane (PM) and late endosomes/lysosomes, but that their inhibition also significantly reduced the levels of phosphatidylserine, di- and triacylglycerols, and other lipids, and caused prominent increases in phosphatidic acid. While VT01454 did not inhibit Golgi PI4P formation nor reduce resting PM PI(4,5)P2 levels, the recovery of the PM pool of PI(4,5)P2 after receptor-mediated hydrolysis required both class I and class II PITPs. Overall, these studies show that class I PITPs differentially regulate phosphoinositide pools and affect the overall cellular lipid landscape. Synopsis: Class I phosphatidylinositol (PI) transfer proteins (PITPs) have been proposed to supply PI to the lipid kinases that produce mono-phosphorylated phosphoinositides, PI4P and PI3P. A novel inhibitor of class I PITPs illuminates how these proteins contribute to the maintenance of various phosphoinositide pools in intact cells. PITPs provide PI to the plasma membrane and late endosomes for generation of PI4P in those organelle membranes. Acute PITP inhibition does not affect PI4P levels in the Golgi and only has a small impact on PI3P levels in early endosomes. PI(4,5)P2 maintenance in the plasma membrane upon phospholipase C activation requires both class I and class II PITPs. The crystal structure of inhibitor-bound PITPNA reveals an "open" structure identical to the reported cargo-free structures. PTIP Inhibition affects the levels of several lipid classes. Inhibition of specific lipid transfer proteins reveals how pools of key signalling lipids are maintained in the plasma membrane and late endosome. [ABSTRACT FROM AUTHOR]

Lipid nanoparticles own a remarkable potential in nanomedicine, only partially disclosed. While the clinical use of liposomes and cationic lipid-nucleic acid complexes is well-established, liquid lipid nanoparticles (nanoemulsions), solid lipid nanoparticles, and nanostructured lipid carriers have even greater possibilities. However, they face obstacles in being used in clinics due to a lack of understanding about the molecular mechanisms controlling their drug loading and release, interactions with the biological environment (such as the protein corona), and shelf-life stability. To create effective drug delivery carriers and successfully translate bench research to clinical settings, it is crucial to have a thorough understanding of the internal structure of lipid nanoparticles. Through synchrotron small-angle X-ray scattering experiments, we determined the spatial distribution and internal structure of the nanoparticles' lipid, surfactant, and the bound water in them. The nanoparticles themselves have a barrel-like shape that consists of coplanar lipid platelets (specifically cetyl palmitate) that are covered by loosely spaced polysorbate 80 surfactant molecules, whose polar heads retain a large amount of bound water. To reduce the interface cost of bound water with unbound water without stacking, the platelets collapse onto each other. This internal structure challenges the classical core-shell model typically used to describe solid lipid nanoparticles and could play a significant role in drug loading and release, biological fluid interaction, and nanoparticle stability, making our findings valuable for the rational design of lipid-based nanoparticles. [ABSTRACT FROM AUTHOR]

Background/Objectives: Lipid metabolism plays an important role in maternal health and fetal development. There is a gap in the knowledge of how lipid metabolism changes during pregnancy for Black women who are at a higher risk of adverse outcomes. We hypothesized that the comprehensive lipidome profiles would show variation across pregnancy indicative of requirements during gestation and fetal development. Methods: Black women were recruited at prenatal clinics. Plasma samples were collected at 8–18 weeks (T1), 22–29 weeks (T2), and 30–36 weeks (T3) of pregnancy. Samples from 64 women who had term births (≥37 weeks gestation) were subjected to "shotgun" Orbitrap mass spectrometry. Mixed-effects models were used to quantify systematic changes and dimensionality reduction models were used to visualize patterns and identify reliable lipid signatures. Results: Total lipids and major lipid classes showed significant increases with the progression of pregnancy. Phospholipids and glycerolipids exhibited a gradual increase from T1 to T2 to T3, while sphingolipids and total sterol lipids displayed a more pronounced increase from T2 to T3. Acylcarnitines, hydroxy acylcarnitines, and Lyso phospholipid levels significantly decreased from T1 to T3. A deviation was that non-esterified fatty acids decreased from T1 to T2 and increased again from T2 to T3, suggestive of a potential role for these lipids during the later stages of pregnancy. The fatty acids showing this trend included key fatty acids—non-esterified Linoleic acid, Arachidonic acid, Alpha-linolenic acid, Eicosapentaenoic acid, Docosapentaenoic acid, and Docosahexaenoic acid. Conclusions: Mapping lipid patterns and identifying lipid signatures would help develop intervention strategies to reduce perinatal health disparities among pregnant Black women. [ABSTRACT FROM AUTHOR]

The metabolism of glucose and lipids plays a crucial role in the normal homeostasis of the body. Although glucose is the main energy substrate, in its absence, lipid metabolism becomes the primary source of energy. The main means of fatty acid oxidation (FAO) takes place in the mitochondrial matrix through β-oxidation. Glioblastoma (GBM) is the most common form of primary malignant brain tumor (45.6%), with an incidence of 3.1 per 100,000. The metabolic changes found in GBM cells and in the surrounding microenvironment are associated with proliferation, migration, and resistance to treatment. Tumor cells show a remodeling of metabolism with the use of glycolysis at the expense of oxidative phosphorylation (OXPHOS), known as the Warburg effect. Specialized fatty acids (FAs) transporters such as FAT, FABP, or FATP from the tumor microenvironment are overexpressed in GBM and contribute to the absorption and storage of an increased amount of lipids that will provide sufficient energy used for tumor growth and invasion. This review provides an overview of the key enzymes, transporters, and main regulatory pathways of FAs and ketone bodies (KBs) in normal versus GBM cells, highlighting the need to develop new therapeutic strategies to improve treatment efficacy in patients with GBM. [ABSTRACT FROM AUTHOR]

Supplementation with fish oil rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) effectively reduces acute and chronic alcohol-induced hepatic steatosis. We aimed to find molecular mechanisms underlying the effects of n-3 PUFAs in alcohol-induced hepatic steatosis. Because free fatty acid receptor 4 (FFA4, also known as GPR120) has been found as a receptor for n-3 PUFAs in an ethanol-induced liver steatosis model, we investigated whether n-3 PUFAs protect against liver steatosis via FFA4 using AH7614, an FFA4 antagonist, and Ffa4 knockout (KO) mice. N-3 PUFAs and compound A (CpdA), a selective FFA4 agonist, reduced the ethanol-induced increase in lipid accumulation in hepatocytes, triglyceride content, and serum ALT levels, which were not observed in Ffa4 KO mice. N-3 PUFAs and CpdA also reduced the ethanol-induced increase in lipogenic sterol regulatory element-binding protein-1c expression in an FFA4-dependent manner. In Kupffer cells, treatment with n-3 PUFA and CpdA reversed the ethanol-induced increase in tumor necrosis factor-α, cyclooxygenase-2, and NLR family pyrin domain-containing 3 expression levels in an FFA4-dependent manner. In summary, n-3 PUFAs protect against ethanol-induced hepatic steatosis via the anti-inflammatory actions of FFA4 on Kupffer cells. Our findings suggest FFA4 as a therapeutic target for alcoholic hepatic steatosis. [ABSTRACT FROM AUTHOR]

Lipid droplet (LD) accumulation in hepatocytes is one of the major symptoms associated with fatty liver disease. Mitochondria play a key role in catabolizing fatty acids for energy production through β-oxidation. The interplay between mitochondria and LD assumes a crucial role in lipid metabolism, while it is obscure how mitochondrial morphology affects systemic lipid metabolism in the liver. We previously reported that cilnidipine, an already existing anti-hypertensive drug, can prevent pathological mitochondrial fission by inhibiting protein–protein interaction between dynamin-related protein 1 (Drp1) and filamin, an actin-binding protein. Here, we found that cilnidipine and its new dihydropyridine (DHP) derivative, 1,4-DHP, which lacks Ca2+ channel-blocking action of cilnidipine, prevent the palmitic acid-induced Drp1–filamin interaction, LD accumulation and cytotoxicity of human hepatic HepG2 cells. Cilnidipine and 1,4-DHP also suppressed the LD accumulation accompanied by reducing mitochondrial contact with LD in obese model and high-fat diet-fed mouse livers. These results propose that targeting the Drp1–filamin interaction become a new strategy for the prevention or treatment of fatty liver disease. [ABSTRACT FROM AUTHOR]

Alzheimer disease (AD) is a heterogeneous and complex disease in which different pathophysiological mechanisms are involved. This heterogenicity can be reflected in different atrophy patterns or clinical manifestations. Regarding biochemical pathways involved in early AD, lipid metabolism plays an important role; therefore, lipid levels have been evaluated as potential AD diagnosis biomarkers, and their levels could be related to different AD clinical manifestations. Therefore, the aim of this work is to study AD lipid profiles from early AD patients and evaluate their clinical significance. For this purpose, untargeted plasma lipidomic analysis was carried out in early AD patients (n = 31) diagnosed with cerebrospinal fluid (CSF) biomarkers. Cluster analysis was carried out to define early AD subgroups according to the lipid levels. Then, the clinical significance of each lipid profile subgroup was studied, analyzing differences for other variables (cognitive status, CSF biomarkers, medication, comorbidities, age, and gender). The cluster analysis revealed two different groups of AD patients. Cluster 1 showed higher levels of plasma lipids and better cognitive status than Cluster 2. However, no differences were found for the other variables (age, gender, medication, comorbidities, cholesterol, and triglycerides levels) between both groups. Plasma lipid levels could differentiate two early AD subgroups, which showed different cognitive statuses. However, further research with a large cohort and longitudinal study evaluating the clinical evolution of these patients is required. In general, it would involve a relevant advance in the knowledge of AD pathological mechanisms, potential treatments, and precision medicine. [ABSTRACT FROM AUTHOR]