Distribution Of Lipids Research Articles

Lipid parameters, adipose tissue distribution and prognosis prediction in chronic kidney Disease patients

BackgroundLipid management in clinic is critical to the prevention and treatment of Chronic kidney disease (CKD), while the manifestations of lipid indicators vary in types and have flexible association with CKD prognosis.PurposeExplore the associations between the widely used indicators of lipid metabolism and their distribution in clinic and CKD prognosis; provide a reference for lipid management and inform treatment decisions for patients with non-dialysis CKD stage 3–5.MethodsThis is a retrospective cohort study utilizing the Self-Management Program for Patients with Chronic Kidney Disease Cohort (SMP-CKD) database of 794 individuals with CKD stages 3–5. It covers demographic data, clinical diagnosis and medical history collection, laboratory results, circulating lipid profiles and lipid distribution assessments. Primary endpoint was defined as a composite outcome(the initiation of chronic dialysis or renal transplantation, sustained decline of 40% or more in estimated glomerular filtration rate (eGFR), doubled of serum creatinine (SCr) from the baseline, eGFR less than 5 mL/min/1.73m2, or all-cause mortality). Exposure variables were circulating lipid profiles and lipid distribution measurements. Association were assessed using Relative risks (RRs) (95% confidence intervals (CIs)) computed by multivariate Poisson models combined with least absolute shrinkage and selection operator (LASSO) regression according to categories of lipid manifestations. The best model was selected via akaike information criterion (AIC), area under curve (AUC), receiver operating characteristic curve (ROC) and net reclassification index (NRI). Subgroup analysis and sensitivity analysis were performed to assess the interaction effects and robustness..Results255 individuals reached the composite outcome. Median follow-up duration was 2.03 [1.06, 3.19] years. Median age was 58.8 [48.7, 67.2] years with a median eGFR of 33.7 [17.6, 47.8] ml/min/1.73 m2. Five dataset were built after multiple imputation and five category-based Possion models were constructed for each dataset. Model 5 across five datasets had the best fitness with smallest AIC and largest AUC. The pooled results of Model 5 showed that total cholesterol (TC) (RR (95%CI) (per mmol/L) :1.143[1.023,1.278], P = 0.018) and percentage of body fat (PBF) (RR (95%CI) (per percentage):0.976[0.961,0.992], P = 0.003) were significant factors of composite outcome. The results indicated that comprehensive consideration of lipid metabolism and fat distribution is more critical in the prediction of CKD prognosis..ConclusionComprehensive consideration of lipid manifestations is optimal in predicting the prognosis of individuals with non-dialysis CKD stages 3–5.

Ultrahigh resolution lipid mass spectrometry imaging of high-grade serous ovarian cancer mouse models.

No effective screening tools for ovarian cancer (OC) exist, making it one of the deadliest cancers among women. Considering that little is known about the detailed progression and metastasis mechanism of OC at a molecular level, it is crucial to gain more insights into how metabolic and signaling alterations accompany its development. Herein, we present a comprehensive study using ultra-high-resolution Fourier transform ion cyclotron resonance matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to investigate the spatial distribution and alterations of lipids in ovarian tissues collected from double knockout (n = 4) and triple mutant mouse models (n = 4) of high-grade serous ovarian cancer (HGSOC). Lipids belonging to a total of 15 different classes were annotated and their abundance changes were compared to those in healthy mouse reproductive tissue (n = 4), mapping onto major lipid pathways involved in OC progression. From intermediate-stage OC to advanced HGSC, we provide direct visualization of lipid distributions and their biological links to inflammatory response, cellular stress, cell proliferation, and other processes. We also show the ability to distinguish tumors at different stages from healthy tissues via a number of highly specific lipid biomarkers, providing targets for future panels that could be useful in diagnosis.

Thin Calcification Predicts Lipid Component in Carotid Plaque—Relationship Between Lipid Distribution and Thin Calcification

BackgroundAccurately evaluating plaque characteristics is essential because lesions with lipid-rich plaque put patients at risk of thromboembolic complications from carotid artery stenting (CAS). Near-infrared spectroscopy (NIRS) is a diagnostic imaging modality that identifies lipid components from the near-infrared absorption pattern, but does not reveal the distribution of calcification. The purpose of this study was to investigate the calcification characteristics of unstable carotid plaques, focusing on relationships between the calcification characteristics revealed by computed tomography angiography (CTA) and the lipid core distribution derived from NIRS. MethodsParticipants in this retrospective analysis comprised 35 patients (29 men, 6 women; mean age, 76.0 years; range, 52–89 years) who underwent CAS in our institute between January 2021 and December 2022. We evaluated the thickness and length of carotid calcifications at the minimal lumen level from preoperative CTA and analyzed the relationship with maximal lipid core burden index (max-LCBI) from NIRS. ResultsStrong, negative linear correlations were observed between the thickness of calcification and max-LCBI at Area (any segment in a target lesion) (r=-0.795, p<0.001), max-LCBI at minimal lumen area (MLA) (r=-0.795, p<0.001) and LCBI at Lesion (rate of LCBI in entire plaque lesion) (r=-0.788, p<0.001), respectively. Significant negative linear correlations were observed between distribution of calcification length and max-LCBI at Area (r=-0.429, p=0.01), max-LCBI at MLA (r=-0.373, p=0.027) and LCBI at Lesion (r=-0.443, p=0.008). ConclusionsThin and ubiquitous carotid calcification was associated with LCBI values derived from NIRS indicative of carotid lipid plaque distribution, implying the possibility of predicting lesion instability.

Curvature sensing lipid dynamics in a mitochondrial inner membrane model

Membrane curvature is essential for many cellular structures and processes, and factors such as leaflet asymmetry, lipid composition, and proteins all play important roles. Cardiolipin is the signature lipid of mitochondrial membranes and is essential for maintaining the highly curved shapes of the inner mitochondrial membrane (IMM) and the spatial arrangement of membrane proteins. In this study, we investigate the partitioning behavior of various lipids present in the IMM using coarse-grained molecular dynamics simulations. This study explores curved bilayer systems containing phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CDL) in binary and ternary component mixtures. Curvature properties such as mean and Gaussian curvatures, as well as the distribution of lipids into the various curved regions of the cristae models, are quantified. Overall, this work represents an advance beyond previous studies on lipid curvature sensing by simulating these systems in a geometry that has the morphological features and scales of curvature consistent with regions of the IMM. We find that CDL has a stronger preference for accumulating in regions of negative curvature than PE lipids, in agreement with previous results. Furthermore, we find lipid partitioning propensity is dominated by sensitivity to mean curvature, while there is a weaker correlation with Gaussian curvature.

Studying lipid flip-flop in asymmetric liposomes using 1H NMR and TR-SANS.

The specific spatial and temporal distribution of lipids in membranes play a crucial role in determining the biochemical and biophysical properties of the system. In nature, the asymmetric distribution of lipids is a dynamic process with ATP-dependent lipid transporters maintaining asymmetry, and passive transbilayer diffusion, that is, flip-flop, counteracting it. In this chapter, two probe-free techniques, 1H NMR and time-resolved small angle neutron scattering, are described in detail as methods of investigating lipid flip-flop rates in synthetic liposomes that have been generated with an asymmetric bilayer composition.

Lipid Content Distribution and its Clinical Implication in Patients with Acute Myocardial Infarction-Plaque Erosion: Results from the Prospective OCTAMI Study.

Plaque erosion (PE) is one of the main plaque phenotypes of acute coronary syndrome (ACS). However, the underlying plaque component and distribution have not been systematically analysed. This study aims to investigate the distribution of lipid and calcium content in culprit lesions assessed by optical coherence tomography (OCT) in patients with PE and explore its relationship with prognosis in a cohort of ST segment elevation myocardial infarction (STEMI) patients. A prospective cohort of 576 patients with STEMI was enrolled in our study. After exclusion, 152 PE patients with clear underlying plaque components were ultimately analysed. The culprit lesion was divided into the border zone, external erosion zone and erosion site in the longitudinal view. Each pullback of the culprit lesions was assessed by 3 independent investigators frame-by-frame, and the quantity and distribution of lipid and calcium components were recorded. Of the 152 PE patients, lipid and calcium contents were more likely to exist in the external erosion zone than in the other regions. In particular, a high level of lipid content proximal to the erosion site was significantly associated with plaque vulnerability and a higher incidence of MACEs. This study revealed that high level of lipid content in the proximal external erosion zone was related to high-risk plaque characteristics and poor prognosis, which provided a novel method for risk stratification and precise management in patients with plaque erosion.

Estimation of biological variance in coherent Raman microscopy data of two cell lines using chemometrics.

Broadband Coherent Anti-Stokes Raman Scattering (BCARS) is a valuable spectroscopic imaging tool for visualizing cellular structures and lipid distributions in biomedical applications. However, the inevitable biological changes in the samples (cells/tissues/lipids) introduce spectral variations in BCARS data and make analysis challenging. In this work, we conducted a systematic study to estimate the biological variance in BCARS data of two commonly used cell lines (HEK293 and HepG2) in biomedical research. The BCARS data were acquired from two different experimental setups (Leibniz Institute of Photonics Technology (IPHT) in Jena and Politecnico di Milano (POLIMI) in Milano) to evaluate the reproducibility of results. Also, spontaneous Raman data were independently acquired at POLIMI to validate those results. First, Kramers-Kronig (KK) algorithm was utilized to retrieve Raman-like signals from the BCARS data, and a pre-processing pipeline was subsequently used to standardize the data. Principal component analysis - Linear discriminant analysis (PCA-LDA) was performed using two cross-validation (CV) methods: batch-out CV and 10-fold CV. Additionally, the analysis was repeated, considering different spectral regions of the data as input to the PCA-LDA. Finally, the classification accuracies of the two BCARS datasets were compared with the results of spontaneous Raman data. The results demonstrated that the CH band region (2770-3070 cm-1) and spectral data in the 1500-1800 cm-1 region have significantly contributed to the classification. A maximum of 100% balanced accuracies were obtained for the 10-fold CV for both BCARS setups. However, in the case of batch-out CV, it is 92.4% for the IPHT dataset and 98.8% for the POLIMI dataset. This study offers a comprehensive overview for estimating biological variance in biomedical applications. The insights gained from this analysis hold promise for improving the reliability of BCARS measurements in biomedical applications, paving the way for more accurate and meaningful spectroscopic analyses in the study of biological systems.

Ketone bodies promote epididymal white adipose expansion to alleviate liver steatosis in response to a ketogenic diet

Liver can sense the nutrient status and send signals to other organs to regulate overall metabolic homoeostasis. Herein, we demonstrate that ketone bodies act as signals released from the liver that specifically determine the distribution of excess lipid in epididymal white adipose tissue (eWAT) when exposed to a ketogenic diet (KD). An acute KD can immediately result in excess lipid deposition in the liver. Subsequently, the liver sends the ketone body β-hydroxybutyrate (BHB) to regulate white adipose expansion, including adipogenesis and lipogenesis, to alleviate hepatic lipid accumulation. When ketone bodies are depleted by deleting 3-Hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) gene in liver, the enhanced lipid deposition in eWAT but not in inguinal white adipose tissue (iWAT) is preferentially blocked, while lipid accumulation in liver is not alleviated. Mechanistically, ketone body BHB can significantly decrease lysine acetylation of peroxisome proliferator-activated receptor gamma (PPARγ) in eWAT, causing enhanced activity of PPARγ, the key adipogenic transcription factor. These observations suggest that the liver senses metabolic stress first and sends a corresponding signal, that is, ketone body BHB, to specifically promote eWAT expansion to adapt to metabolic challenges.

Substrate-induced assembly of cascade enzymes and catalytic surfactants: nanoarchitectonics at the oil-in-water droplet interface.

The heterogeneous distribution of lipids and lipid-bound proteins in a plasma membrane has functional advantages. Herein, in a synthetic system, we demonstrate the assembly of three enzymes involved in cascade reactions, in response to the substrate of the first enzyme at the oil-water interface being stabilized by a Zn(II)-metallosurfactant. Then we show substrate-mediated catalytically-active cluster formation of the metallosurfactant in a binary mixture with another non-catalytic surfactant at the interface. The catalytic ability can be tuned by controlling clustering through the addition of phosphate ions. Overall this work demonstrates functionally diverse supramolecular nanoarchitectonics at the oil-water interface.

Применение нового комбинированного препарата, содержащего среднецепочечные триглицериды, в лечении синдрома «сухого глаза»

Background: the outer layer of the tear film is composed of nonpolar lipids, including free fatty acid esters, triglycerides (TG), and cholesterol esters. Alterations in their qualitative and quantitative composition can result in evaporative dry eye, which requires pathogenic treatment. Somatic comorbidities, particularly type 2 diabetes (T2D), may act as a potential etiological factor. Aim: to assess the efficacy of a new complex medication containing medium chain TGs for the treatment of dry eye. Patients and Methods: a single-center, observational, single-stage, controlled single-sample, non-randomized study was conducted. Twenty-seven patients (mean age 52.5±0.5 years) were included in the study. Group 1 included 12 patients with dry eye and T2D. Group 2 included 15 patients with dry eye but no T2D. Patients received a complex medication containing medium chain TGs and carbomer for one month. In addition to standard and additional eye examinations, tearscopy and low-resolution mass spectrometry using LCQ Fleet (Thermo Scientific, Germany) were performed. Results: a reduction in the levels of TG and cholesterol was demonstrated in both groups. The reduction was more significant in group 1. A complex medication containing medium chain TGs and carbomer for one month improved functional indices in group 1 patients compared with baseline (p &lt;0.05). Corneal staining grade 1 was reported in 94% of group 1 patients. In group 2, corneal staining did not change significantly. Tearscopy revealed a significant improvement in the tear film lipid layer in group 1 (an increase in the lipid distribution coefficient and lipid thickness by 0.2 and 0.03, respectively) in comparison to group 2 (an increase by 0.1 and 0.02). Conclusions: decreased levels of TGs and cholesterol in T2D induce cellular dysfunction and inflammation in meibomian glands, thereby triggering dry eye development and/or worsening its course. In light of these considerations, complex medications containing TGs are necessary and reasonable. KEYWORDS: medium chain triglycerides, carbomer, meibomian gland dysfunction, dry eye, mass spectrometry, diabetes. FOR CITATION: Safonova T.N., Zaytseva G.V., Kravets K.Yu., Polyakov N.B. Novel complex medication containing medium chain triglycerides for the treatment of dry eye. Russian Journal of Clinical Ophthalmology. 2024;24(2):64–68 (in Russ.). DOI: 10.32364/2311- 7729-2024-24-2-4.

Methyl-β-cyclodextrin asymmetrically extracts phospholipid from bilayers, granting tunable control over differential stress in lipid vesicles.

Lipid asymmetry - that is, a nonuniform lipid distribution between the leaflets of a bilayer - is a ubiquitous feature of biomembranes and is implicated in several cellular phenomena. Differential tension - that is, unequal lateral monolayer tensions comparing the leaflets of a bilayer- is closely associated with lipid asymmetry underlying these varied roles. Because differential tension is not directly measurable in combination with the fact that common methods to adjust this quantity grant only semi-quantitative control over it, a detailed understanding of lipid asymmetry and differential tension are impeded. To overcome these challenges, we leveraged reversible complexation of phospholipid by methyl-β-cyclodextrin (mbCD) to tune the direction and magnitude of lipid asymmetry in synthetic vesicles. Lipid asymmetry generated in our study induced (i) vesicle shape changes and (ii) gel-liquid phase coexistence in 1-component vesicles. By applying mass-action considerations to interpret our findings, we discuss how this approach provides access to phospholipid thermodynamic potentials in bilayers containing lipid asymmetry (which are coupled to the differential tension of a bilayer). Because lipid asymmetry yielded by our approach is (i) tunable and (ii) maintained over minute to hour timescales, we anticipate that this approach will be a valuable addition to the experimental toolbox for systematic investigation into the biophysical role(s) of lipid asymmetry (and differential tension).

Predicting lipid sorting in curved membranes.

Most biological membranes are curved, and both lipids and proteins play a role in generating curvature. For any given membrane shape and composition, it is not trivial to determine whether lipids are laterally distributed in a homogeneous or inhomogeneous way, and whether the inter-leaflet distribution is symmetric or not. Here we present a simple computational tool that allows to predict the preference of any lipid type for membranes with positive vs. negative curvature, for any given value of curvature. The tool is based on molecular dynamics simulations of tubular membranes with hydrophilic pores. The pores allow spontaneous, barrierless flip-flop of most lipids, while also preventing differences in pressure between the inner and outer water compartments and minimizing membrane asymmetric stresses. Specifically, we provide scripts to build and analyze the simulations. We test the tool by performing simulations on simple binary lipid mixtures, and we show that, as expected, lipids with negative intrinsic curvature distribute to the tubule inner leaflet, the more so when the radius of the tubular membrane is small. Compared to other existing computational methods, relying on membrane buckles and tethers, our method is based on spontaneous inter-leaflet transport of lipids, and therefore allows to explore lipid distribution in asymmetric membranes. The method can easily be adapted to work with any molecular dynamics code and any force field.

Macromolecular Interactions of Lipoprotein Lipase (LPL).

Lipoprotein lipase (LPL) is a critical enzyme in humans that provides fuel to peripheral tissues. LPL hydrolyzes triglycerides from the cores of lipoproteins that are circulating in plasma and interacts with receptors to mediate lipoprotein uptake, thus directing lipid distribution via catalytic and non-catalytic functions. Functional losses in LPL or any of its myriad of regulators alter lipid homeostasis and potentially affect the risk of developing cardiovascular disease-either increasing or decreasing the risk depending on the mutated protein. The extensive LPL regulatory network tunes LPL activity to allocate fatty acids according to the energetic needs of the organism and thus is nutritionally responsive and tissue dependent. Multiple pharmaceuticals in development manipulate or mimic these regulators, demonstrating their translational importance. Another facet of LPL biology is that the oligomeric state of the enzyme is also central to its regulation. Recent structural studies have solidified the idea that LPL is regulated not only by interactions with other binding partners but also by self-associations. Here, we review the complexities of the protein-protein and protein-lipid interactions that govern LPL structure and function.

Analyzing lipid distributions and curvature in molecular dynamics simulations of complex membranes.

We describe methods to analyze lipid distributions and curvature in membranes with complex lipid mixtures and embedded membrane proteins. We discuss issues involved in these analyses, available tools to calculate curvature preferences of lipids and proteins, and focus on tools developed in our group for visual analysis of lipid-protein interactions and the analysis of membrane curvature.

Metal ion cofactors modulate integral enzyme activity by varying differential membrane curvature stress.

Metal ions are well-known cofactors of protein function and stability. In the case of the integral membrane enzyme OmpLA (outer membrane phospholipase A) the active dimer is stabilized by calcium ions. We studied the lipid hydrolysis kinetics of OmpLA in charge-neutral and charged membranes with symmetric or asymmetric transbilayer lipid distributions. In charge-neutral membranes, OmpLA was more active in symmetric bilayers due to the lower differential curvature stress between membrane leaflets. Strikingly, this behavior was completely reversed in charged bilayers. Measurements revealed intrinsic molecular shape changes in the charged lipids upon addition of calcium. This effectively reduces the differential curvature stress in charged asymmetric membranes leading to increased protein activity. This conclusion is further supported by similar effects observed upon the addition of sodium ions, which also alter the shape of the lipids, but do not specifically interact with the protein. Additional lipid-protein interactions likely contribute to this phenomenon. Our findings demonstrate that ion cofactors not only interact directly with membrane proteins but also modulate protein activity indirectly by altering the effective molecular shape of charged lipid species.

Size-fractionated distribution of glycerol dialkyl glycerol tetraether core lipids in surface sediments of a large-river delta-front estuary

Glycerol dialkyl glycerol tetraether core lipids (GDGTs) are microbial biomarkers ubiquitously distributed in terrestrial and marine environments. Dispersal and fate of GDGTs in an estuary largely depends on sediment grain size, however, their size distribution patterns remain poorly understood. Here, surface sediments collected from the Changjiang Estuary were separated into <20, 20–32, 32–63, 63–125 and >125 μm fractions, and analyzed for GDGTs as well as total organic carbon (TOC), stable isotopic composition (δ13C) of TOC and lignin phenols, to investigate the size and spatial distributions of GDGTs and the particle size effects on GDGTs proxies in this large river delta-front estuary. The concentrations of isoprenoidal GDGTs (isoGDGTs) were higher in the finest fractions and in off-estuary sites. On the contrary, branched GDGTs (brGDGTs) were high not only in the finest fractions but in coarser fractions (>32 μm fractions), and thus at both near- and off-estuary sites. The branched and isoprenoid tetraether (BIT) index increased with increasing grain size, and decreased sharply from the estuary (~0.52) to the shelf (~0.16). BrGDGTs were positively correlated with crenarcheaol in both high and low BIT regions. The brGDGTIIIa/IIa ratios in all size fractions were <0.59, further indicating that the brGDGTs were mainly derived from terrestrial input with minimum in-situ production. Fractional TOC source assignments derived from the BIT index was significantly positively correlated with the fractions of terrestrial OC from a mixing model based on δ13C-TOC and lignin contents, indicating that BIT may track a broader pool of terrestrial OC than just soil OC. This work provides novel, yet preliminary insights into the size fractionated distribution characteristics of GDGTs and the applicability of BIT as a proxy for OC sources in estuarine sediments. More work is needed to further clarify the particle size effects on other GDGTs proxies in estuarine systems.

FEATURES OF THE LIPID PROFILE AND ADIPOSE TISSUE IN PATIENTS WITH CAROTID ARTERY STENOSIS ON THE BACKGROUND OF CORONARY ARTERY DISEASE

HighlightsIntra-abdominal adipose tissue thickness (IAAT) was statistically significantly greater in patients with hypertriglyceridemia compared to patients with normal triglyceride levels. Linear regression analysis confirmed the following findings: the greater the thickness of IAAT and preperitoneal fat thickness (PFT), the higher the levels of triglycerides and very-low-density lipoproteins.AbstractAim. To assess the lipid profile and distribution of adipose tissue (based on ultrasound parameters) and their role in the development of carotid artery stenosis in patients with coronary heart disease (CHD).Methods. Ultrasound parameters of adipose tissue in 125 patients, diagnosed with coronary heart disease (CHD), were studied. The average age of the patients was 68 (61.0; 74.0) years old. The sample was represented predominantly by males (58.4%).Results. It was determined that in patients who did not reach the target levels of triglycerides (TG), the thickness of the IAAT is 15 mm more than in patients with the adequate level of this indicator (p = 0.031). Subcutaneous adipose tissue (SAT) values also exceeded the values ​​in individuals with low HDL levels (p = 0.050), in contrast to patients with normal HDL. Linear regression analysis (after adjusting for gender and age) showed that the increase in IAAT thickness was associated with the increase in TG (b = 0.002, p = 0.028) and VLDL (b = 0.001, p = 0.023). It was also found that only 43.4% of the examined individuals received lipid-lowering therapy, and 17.3% received an adequate dose of statins (reached the target LDL values).Conclusion. No statistically significant patterns were found between the achievement of lipid targets and the presence of carotid stenosis. An extremely low percentage of patients taking adequate lipid-lowering therapy (17.3%) was determined, and the proportion of the people with carotid stenosis who reached the target levels of total cholesterol was 58.4%, TG – 79.3%, HDL – 31.7%, LDL – 12.2%. The thickness of the IAAT is statistically significantly higher in individuals with hypertriglyceridemia, in contrast to patients with normal TG levels. The tendencies towards statistical significance of PFT indicators in individuals with hypertriglyceridemia, minimum and maximum SAT values, depending on the level of HDL, were determined. Linear regression analysis confirmed the data obtained: the higher the thickness of IAAT and PFT, the higher the levels of TG and VLDL.

Composition and structure analysis of different depths in the stratum corneum using confocal Raman microscopy combined with two-dimensional correlation spectroscopy

The chemical composition and structure of the stratum corneum (SC) play a crucial role in the skin barrier function. Therefore, accurately determining the SC thickness and studying the changes in lipid and keratin structure and distribution within it are key aspects of skin barrier research. Currently, there are limited analytical tools and data analysis methods available for real-time and online studies of SC composition and structural changes. In this study, we focus on depth as a perturbation and employ confocal Raman microscopy combined with moving-window two-dimensional correlation spectroscopy (MW2D) technique to investigate the SC thickness. Additionally, we employ confocal Raman microscopy combined with perturbation-correlation moving-window two-dimensional correlation spectroscopy (PCMW2D) to precisely characterize the stratification of the SC. Furthermore, the two-dimensional correlation spectroscopy (2DCOS) method is utilized to examine the content of various conformations in the keratin secondary structure within the SC, as well as the subtle interrelationships between lipid and keratin structures.

Zonated iron deposition in the periportal zone of the liver is associated with selectively enhanced lipid synthesis.

Disorders in liver lipid metabolism have been implicated in a range of metabolic conditions, including fatty liver and liver cancer. Altered lipid distribution within the liver, shifting from the pericentral to the periportal zone under pathological circumstances, has been observed; however, the underlying mechanism remains elusive. Iron, an essential metal, exhibits a zonal distribution in the liver similar to that of lipids. Nevertheless, the precise relationship between iron and lipid distribution, especially in the pericentral and periportal zones, remains poorly understood. We conducted comprehensive invitro and invivo experiments, combining with insitu analysis and RNA sequencing, aiming for a detailed exploration of the causal relationship between iron accumulation and lipid metabolism. Our research suggests that iron overload can disrupt the normal distribution of lipids within the liver, particularly in the periportal zone. Through meticulous gene expression profiling in both the pericentral and periportal zones, we identified pyruvate carboxylase (PC) as a pivotal regulator in iron overload-induced lipid accumulation. Additionally, we revealed that the activation of cyclic adenosine monophosphate response element binding protein (CREB) was indispensable for Pc gene expression when in response to iron overload. In summary, our investigation unveils the crucial involvement of iron overload in fostering hepatic lipid accumulation in the periportal zone, at least partly mediated by the modulation of Pc expression. These insights offer new perspectives for understanding the pathogenesis of fatty liver diseases and their progression.

68 Characteristics of guinea pig oocytes at two stages of the estrous cycle on lipid distribution and apoptosis rate

68 Characteristics of guinea pig oocytes at two stages of the estrous cycle on lipid distribution and apoptosis rate