Chylomicrons Research Articles

Glucagon-Like-Peptide-2 Stimulates Lacteal Contractility and Enhances Chylomicron Transport in the Presence of an Intact Enteric Nervous System

Secretion and transport of intestinal chylomicrons (CMs) via lymphatics to the blood circulation is stimulated primarily by fat ingestion, whereas several other factors have also been shown to play important roles in regulating CM secretion rate. Among these factors, active regulation of lymphatic pumping has not been appreciated to date. The gut peptide and intestinal growth factor glucagon-like peptide-2 (GLP-2) has emerged as a robust enhancer of intestinal lipid mobilization and secretion. The present study aims to elucidate GLP-2's impact on lacteal contractility and assess enteric nervous system (ENS) involvement in GLP-2-induced effects on lipid mobilization. Using intravital imaging of a prospero-related homeobox 1-enhanced green fluorescent protein rat model, we assessed GLP-2's effect on lacteal contractility, in the presence and absence of the ENS inhibitor mecamylamine (MEC). Concurrently, to explore the physiological relevance, we examined GLP-2's impact on lymph flow and triglyceride (TG) output invivo in a rat lymph fistula model. GLP-2 significantly increased lacteal contractility, and this effect was inhibited by MEC. In the rat lymph fistula model, GLP-2 increased lymph flow, lymph volume, cumulative lymph volume, and TG output while reducing lymph TG concentration. MEC administration blocked these effects of GLP-2. Peak enhancement of lacteal contractility and enhancement of lymph flow invivo occurred simultaneously with maximal effect at 15-20 minutes post GLP-2 administration, suggesting that GLP-2 enhances lipid transport by stimulating lymphatic contractility. For the first time, through imaging and concurrent rat lymphatic fistula studies, we demonstrated active regulation of lymphatic contractility as a key determinant of CM secretion and that intact ENS was required to observe this effect.

#213 : Causal Associations Between Different Plasma Lipid and Apolipoprotein Parameters with the Risk of Endometriosis: A Two-Sample Mendelian Randomization Study

Background and Aims: Endometriosis is a chronic gynecological disease with a high prevalence among reproductive-aged women. Several studies have investigated the causal effect of different plasma lipid and apolipoprotein parameters on the occurrence and progression of endometriosis. However, the results of these studies remained controversial. Herein, this study aims to analyze the causal associations of genetically predicted levels of different blood lipid and apolipoprotein traits with the risk of endometriosis using a two-sample Mendelian randomization (MR) approach. Methods: The single-nucleotide polymorphisms (SNPs) of exposures which indicate the genetic variants were used as instrumental variables (IVs). We assessed the correlation between each blood lipid and apolipoprotein parameter and the occurrence of endometriosis from various cohorts of European ancestry, and the SNPs of them were obtained from the genome-wide association study (GWAS) from the IEU GWAS database. The causal effects were estimated through the inverse-variance weighted method (IVW). The sensitivity examinations of each result after the MR analysis were performed to detect if any heterogeneity and pleiotropy existed. Besides, sub-analyses were performed to provide more detailed information about the actual associations. Results: Our results demonstrated that cholesterol in chylomicron (CM) and extremely large very low-density lipoprotein (VLDL) was causally linked to higher odds of endometriosis, while high-density lipoprotein (HDL) cholesterol showed the opposite correlation. No evidence was detected on the causal relations of low-density lipoprotein (LDL) cholesterol, VLDL cholesterol, triglyceride (TG), apolipoprotein A1 and apolipoprotein B with endometriosis. Neither pleiotropy nor heterogeneity was found in our study. In addition, subgroup analyses about subtypes of endometriosis suggested the causal association of several serum lipids with peritoneal endometriosis. Conclusion: Our results suggested that dysregulated lipid metabolism is causally associated with the occurrence of endometriosis, especially peritoneal endometriosis. Our findings provided genetic insights on potential novel strategies in the primary prevention and treatment of endometriosis.

Severe hypertriglyceridemia and its correlation with clinical atherosclerosis and pancreatitis investigated in beta-quantification

Abstract Background Severe hypertriglyceridemia is commonly associated with pancreatitis and questionably atherosclerotic cardiovascular disease (ASCVD). However, while some patients develop those sequelae at relatively low levels, others with extreme levels remain spared from it. Purpose This study serves to validate, whether the distribution of triglycerides (TG), either in very-low-density lipoprotein (VLDL) particles or chylomicrons (CM) can be decisive for the development of clinical disease. Methods Patients with TG levels above 500 mg/dL, who routinely visited our lipid outpatient clinic between 2016 and 2021 with their lipid panel done via beta-quantification were retrospectively investigated for the presence of clinical pancreatitis and ASCVD via electronic chart-review. Results In total, 221 patients met eligibility criteria, with a mean age of 48 years, BMI of 29.7, with 72.4% males. Median TG and low-density lipoprotein cholesterol levels were 827 mg/dL and 62 mg/dL, respectively. A history of pancreatitis was present in 13.7% of patients, while ASCVD was present in 20.7%. TG distribution, described as the ratio of TG in VLDL per TG in CM showed no significant differences with regards to pancreatitis incidence (p=0.393). For ASCVD, the ratio was significantly higher in those with ASCVD vs those without (3.54 vs 2.25) (p=0.008). CM-dominant TG distribution was present in 19.5% of patients and was associated with higher total TG levels (2122 mg/dL vs 825 mg/dL), compared to VLDL-dominant TG distribution. Conclusion A higher relative amount of TGs in VLDL compared to CM, as most prevalent pattern, was associated with ASCVD, while very high levels of TG frequently relate to hyperchylomicronemia.

Postprandial Hyperlipidemia: Its Pathophysiology, Diagnosis, Atherogenesis, and Treatments.

Postprandial hyperlipidemia showing postprandial increases in serum triglyceride (TG) is associated with the development of atherosclerotic cardiovascular disease (ASCVD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed; however, this test is very time-consuming and is difficult to perform. Elevated serum TG levels reflect an increase in TG-rich lipoproteins (TRLs), such as chylomicrons (CM), very low-density lipoproteins (VLDL), and their remnants (CM remnants [CMRs] and VLDL remnants [VLDLRs]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurement of apo B48, which is a constituent of CM and CMR; non-fasting TG, which includes TG content in all lipoproteins including CM and CMR; non-high-density lipoprotein cholesterol (non-HDL-C), which includes TRLs and low-density lipoprotein; and remnant cholesterol are useful to reveal the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an inducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with postprandial hyperlipidemia have various atherogenic properties such as induction of inflammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss, and exercise positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, fenofibrate, bezafibrate, ezetimibe, and eicosapentaenoic acid have been shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide 1 analogues have been shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments. However, there are some problems with the diagnosis for postprandial hyperlipidemia. Postprandial hyperlipidemia cannot be specifically defined by measures such as TG levels 2 h after a meal. To study interventions for postprandial hyperlipidemia with the outcome of preventing the onset of ASCVD, it is necessary to define postprandial hyperlipidemia using reference values such as IGT.

Sugar and Dyslipidemia: A Double-Hit, Perfect Storm.

The availability of sugar has expanded over the past 50 years, due to improved industrial processes and corn subsidies, particularly in the form of sweetened beverages. This correlates with a surge in the prevalence of cardiometabolic disorders, which has brought this issue back into the spotlight for public health. In this narrative review, we focus on the role of fructose in the genesis of cardiometabolic dyslipidemia (an increase in serum triglyceride-rich lipoproteins (TRL): VLDL, chylomicrons (CM), and their remnants) bringing together the most recent data on humans, which demonstrates the crucial interaction between glucose and fructose, increasing the synthesis while decreasing the catabolism of these particles in a synergistic downward spiral. After reviewing TRL metabolism, we discuss the fundamental principles governing the metabolism of fructose in the intestine and liver and the effects of dysregulated fructolysis, in conjunction with the activation of carbohydrate-responsive element-binding protein (ChREBP) by glucose and the resulting crosstalk. The first byproduct of fructose catabolism, fructose-1-P, is highlighted for its function as a signaling molecule that promotes fat synthesis. We emphasize the role of fructose/glucose interaction in the liver, which enhances de novo lipogenesis, triglyceride (TG) synthesis, and VLDL production. In addition, we draw attention to current research that demonstrates how fructose affects the activity of lipoprotein lipase by increasing the concentration of inhibitors such as apolipoprotein CIII (apoCIII) and angiopoietin-like protein 3 (ANGPTL3), which reduce the catabolism of VLDL and chylomicrons and cause the building up of their atherogenic remnants. The end outcome is a dual, synergistic, and harmful action that encourages atherogenesis. Thus, considering the growing concerns regarding the connection between sugar consumption and cardiometabolic disease, current research strongly supports the actions of public health organizations aimed at reducing sugar intake, including dietary guidance addressing "safe" limits for sugar consumption.

Development of lipophilic ester prodrugs of dolutegravir for intestinal lymphatic transport

The establishment of latent cellular and anatomical viral reservoirs is a major obstacle to achieving a cure for people infected by HIV. Mesenteric lymph nodes (MLNs) are one of the most important anatomical reservoirs of HIV. Suboptimal levels of antiretroviral (ARVs) drugs in these difficult-to-penetrate viral reservoirs is one of the limitations of current antiretroviral therapy (ART) regimens. This study aimed to design and assess highly lipophilic ester prodrugs of dolutegravir (DTG) formulated with long-chain triglyceride (LCT) for delivery of DTG to the viral reservoir in mesenteric lymph and MLNs. A number of alkyl ester prodrugs of DTG were designed based on the predicted affinity to chylomicrons (CM), and the six most promising prodrugs were selected and synthesised. The synthesised prodrugs were further assessed for their intestinal lymphatic transport potential and biotransformation in biorelevant media in vitro and ex vivo. DTG and the most promising prodrug (prodrug 5) were then assessed in pharmacokinetic and biodistribution studies in rats. Although oral administration of 5 mg/kg of unmodified DTG (an allometrically scaled dose from humans) with or without lipids achieved concentrations above protein binding-adjusted IC90 (PA-IC90) (64 ng/mL) in most tissues, the drug was not selectively targeted to MLNs. The combination of lipophilic ester prodrug and LCT-based formulation approach improved the targeting selectivity of DTG to MLNs 4.8-fold compared to unmodified DTG. However, systemic exposure to DTG was limited, most likely due to poor intestinal absorption of the prodrug following oral administration. In vitro lipolysis showed a good correlation between micellar solubilisation of the prodrug and systemic exposure to DTG in rats in vivo. Thus, it is prudent to include in vitro lipolysis in the early assessment of orally administered drugs and prodrugs in lipidic formulations, even when intestinal lymphatic transport is involved in the absorption pathway. Further studies are needed to clarify the underlying mechanisms of low systemic bioavailability of DTG following oral administration of the prodrug and potential ways to overcome this limitation.

P-347 the causal effects of serum lipids and apolipoproteins on endometriosis: a two-sample mendelian randomization analysis

Abstract Study question Is the risk of endometriosis associated with genetically predicted levels of different blood lipid and apolipoprotein traits? Summary answer Our Mendelian randomization (MR) analysis indicated that causal associations existed between some serum lipid and apolipoprotein levels and endometriosis occurrence in European ancestry. What is known already Endometriosis is a chronic gynecological disease with a high prevalence among reproductive-aged women. Recently, many observational, epidemiological studies have investigated the causal effect of different serum lipid and apolipoprotein parameters on the occurrence and progression of endometriosis. However, the results of these studies remained controversial. Moreover, no different subtypes of endometriosis were investigated in previous observational studies, thus detailed information about the associations was insufficient. Study design, size, duration We performed a two-sample MR analysis in the largest available genetic datasets. To correctly employ the MR method, the following assumptions are required to be met: (a) the genetic variants must be strongly associated with the exposures; (b) the single-nucleotide polymorphisms (SNPs) are not correlated with the confounders that are related to the exposure and the outcome; (c) the SNPs can influence the outcome solely through the exposure and no other biological pathways are concerned. Participants/materials, setting, methods Summary-level data for genetic variants of different serum lipid and apolipoprotein traits were derived from the UK Biobank and EBI database. Instrumental variables (IVs) associated with endometriosis and all the subtypes were acquired from the FinnGen biobank. The MR method is an accurate way to determine the underlying causality between the exposure and the outcome, which can minimize the effect of potential confounders and avoid reverse causality. Main results and the role of chance Our results demonstrated that five serum lipid-related traits were causally linked to lower odds of endometriosis, including very low-density lipoprotein (VLDL) cholesterol (OR: 1.231, 95% CI: 1.035-1.463, p = 0.019), cholesterol in chylomicron (CM) and extremely large VLDL (OR: 1.290, 95% CI: 1.013-1.644, p = 0.039), total cholesterol (TC) (OR: 1.250, 95% CI: 1.001-1.562, p = 0.049), apolipoprotein B (OR: 1.273, 95% CI: 1.022-1.587, p = 0.031), the ratio of apolipoprotein B to apolipoprotein A1 (OR: 1.163, 95% CI: 1.011-1.337, p = 0.035), while high-density lipoprotein cholesterol (HDL) (OR: 0.853, 95% CI: 0.754-0.963, p = 0.011) and apolipoprotein A1 (OR: 0.874, 95% CI: 0.770-0.993, p = 0.038) showed the opposite. Subgroup analyses about subtypes of endometriosis suggested the causal association of several serum lipid and apolipoprotein levels with peritoneal endometriosis. Neither pleiotropy nor heterogeneity was found in our study. No evidence was detected on the causal relations of low-density lipoprotein cholesterol (LDL) (OR: 1.014, 95% CI: 0.859-1.197, p = 0.868 and OR: 1.029, 95% CI: 0.906-1.169, p = 0.659, respectively) and triglyceride (TG) (OR: 1.138, 95% CI: 0.978-1.324, p = 0.095) with endometriosis. Limitations, reasons for caution Several limitations do exist in this study. We could not control the uniformity of sex between the exposure and the outcome, due to a lack of suitable summary-level data. Furthermore, it is possible that some of the null findings were due to limited statistical power from current genome-wide association study. Wider implications of the findings Our study found strong evidence for the possibility that aberrant lipid metabolism is causally involved in the pathogenesis of endometriosis, especially for endometriosis of pelvic peritoneum, and shed new insights on targeting serum lipid and apolipoprotein levels as a potential novel strategy for the prevention and treatment of endometriosis. Trial registration number not applicable

Ultraviolet light scattering scanning flow cytometry in the characterization of submicron microparticles.

Ultraviolet lasers are commonly used in flow cytometry to excite fluorochrome molecules with subsequent measurement of the specific fluorescence of individual cells. In this study, the performance of the ultraviolet light scattering (UVLS) in the analysis of individual particles with flow cytometry has been demonstrated for the first time. The main advantage of the UVLS relates to the improvement of the analysis of submicron particles due to the strong dependence of the scattering efficiency on the wavelength of the incident light. In this work, submicron particles were analyzed using a scanning flow cytometer (SFC) that allows measurements of light scattering in an angle-resolved regime. The measured light-scattering profiles of individual particles were utilized in solution of the inverse light-scattering problem to retrieve the particle characteristics using a global optimization. The standard polystyrene microspheres were successfully characterized from the analysis of UVLS which provided the size and refractive index (RI) of individual beads. We believe that the main application of UVLS relates to the analysis of microparticles in a serum, in particular in the analysis of chylomicrons (CMs). We have demonstrated the performance of the UVLS SFC in the analysis of CMs of a donor. The RI versus size scatterplot of CMs was successfully retrieved from the analysis. The current set-up of the SFC has allowed us to characterize individual CMs starting from the size of 160 nm that provides determination of the CM concentration in a serum with flow cytometry. This feature of the UVLS should help with the analysis of lipid metabolism measuring RI and size map evolution after lipase action.

The Relationship Between the Three Genes of Apolipoprotein E and the Hippocampus and Interference with Alzheimer's Disease

Glycoproteins in the Apolipoprotein E (APOE) class have a role in controlling lipid metabolism. In astrocytes, microglia, vascular wall cells, and choroid plexus cells of the central nervous system, it is abundantly expressed. According to the rapid advancement of contemporary medicine, numerous investigations have demonstrated the existence of ApoE in chylomicron (CM), very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and certain high-density lipoprotein (HDL). ApoE has also been demonstrated to have a substantial impact on Alzheimer's disease (AD). To enhance the investigation of innovative medications and give researchers a theoretical foundation, research on ApoE is required in this area. Because damage to the hippocampus is a significant concern for the population in Alzheimer's research, we need to study the effects of ApoE on the hippocampus. This paper will discuss the relationship between age and sex of hippocampal atrophy after the ApoE gene has caused AD. The paper through a method of literature review and the analysis of some clinical cases explores the impact of the ApoE gene on health, followed by a comparison of the disease state before and after, as well as the clinical pattern of hippocampal atrophy, including a description of clinical symptoms. The paper finds that ApoE significantly impacts AD and that the hippocampus is significantly atrophied after the onset of Alzheimer's disease.

Glucagon-like Peptide-2 Acutely Enhances Chylomicron Secretion in Humans Without Mobilizing Cytoplasmic Lipid Droplets.

A portion of ingested fats are retained in the intestine for many hours before they are mobilized and secreted in chylomicron (CM) particles. Factors such as glucagon-like peptide-2 (GLP-2) and glucose can mobilize these stored intestinal lipids and enhance CM secretion. We have recently demonstrated in rodents that GLP-2 acutely enhances CM secretion by mechanisms that do not involve the canonical CM synthetic assembly and secretory pathways. To further investigate the mechanism of GLP-2's potent intestinal lipid mobilizing effect, we examined intracellular cytoplasmic lipid droplets (CLDs) in intestinal biopsies of humans administered GLP-2 or placebo. A single dose of placebo or GLP-2 was administered subcutaneously 5 hours after ingesting a high-fat bolus. In 1 subset of participants, plasma samples were collected to quantify lipid and lipoprotein concentrations for 3 hours after placebo or GLP-2. In another subset, a duodenal biopsy was obtained 1-hour after placebo or GLP-2 administration for transmission electron microscopy and proteomic analysis. GLP-2 significantly increased plasma triglycerides by 46% (P = 0.009), mainly in CM-sized particles by 133% (P = 0.003), without reducing duodenal CLD size or number. Several proteins of interest were identified that require further investigation to elucidate their potential role in GLP-2-mediated CM secretion. Unlike glucose that mobilizes enterocyte CLDs and enhances CM secretion, GLP-2 acutely increased plasma CMs without significant mobilization of CLDs, supporting our previous findings that GLP-2 does not act directly on enterocytes to enhance CM secretion and most likely mobilizes secreted CMs in the lamina propria and lymphatics.

Lipoprotein particles exhibit distinct mechanical properties

AbstractLipoproteins (LPs) are micelle‐like structures with a similar size to extracellular vesicles (EVs) and are therefore often co‐isolated, as intensively discussed within the EV community. LPs from human blood plasma are of particular interest as they are responsible for the deposition of cholesterol ester and other fats in the artery, causing lesions, and eventually atherosclerosis. Plasma lipoproteins can be divided according to their size, density and composition into chylomicrons (CM), very‐low‐density lipoproteins (VLDL), low‐density lipoproteins (LDL) and high‐density lipoproteins (HDL). Here, we use atomic force microscopy for mechanical characterization of LPs. We show that the nanoindentation approach used for EV analysis can also be used to characterize LPs, revealing specific differences between some of the particles. Comparing LPs with each other, LDL exhibit a higher bending modulus as compared to CM and VLDL, which is likely related to differences in cholesterol and apolipoproteins. Furthermore, CM typically collapse on the surface after indentation and HDL exhibit a very low height after surface adhesion both being indications for the presence of LPs in an EV sample. Our analysis provides new systematic insights into the mechanical characteristics of LPs.

Dietary Choline Mitigates High-Fat Diet-Impaired Chylomicrons Assembly via UPRer Modulated by perk DNA Methylation

High-fat diets (HFD) lead to impairment of chylomicrons (CMs) assembly and adversely influence intestinal lipid homeostasis. However, the mechanisms of HFD impairing CMs assembly have yet to be fully understood. Additionally, although choline, as a lipid-lowering agent, has been widely used and its deficiency has been closely linked to non-alcoholic steatohepatitis (NASH), the contribution of choline by functioning as a methyl donor in alleviating HFD-induced intestinal lipid deposition is unknown. Thus, this study was conducted to determine the mechanism of HFD impairing CMs assembly and also tested the effect of choline acting as a methyl donor in this process. To this end, in this study, four diets (control, HFD, choline and HFD + choline diet) were fed to yellow catfish for 10 weeks in vivo and their intestinal epithelial cells were isolated and incubated for 36 h in fatty acids (FA) with or without choline solution combining si-perk transfection in vitro. The key findings from this study as follows: (1) HFD caused impairment of CMs assembly main by unfolded protein response (UPRer). HFD activated perk and then induced UPRer, which led to endoplasmic reticulum dysfunction and further impaired CMs assembly via protein-protein interactions between Perk and Apob48. (2) Choline inhibited the transcriptional expression level of perk via activating the -211 CpG methylation site, which initiated the subsequent ameliorating effect on HFD-impaired CMs assembly and intestinal lipid dysfunction. These results provide a new insight into direct crosstalk between UPRer and CMs assembly, and also emphasize the critical contribution of choline acting as a methyl donor and shed new light on choline-deficient diet-induced NASH.

Particle Size Distribution of Plasma Lipoproteins in Donkeys from Death Valley Compared to a Sampling of Horses.

Simple SummaryDonkeys, like horses, belong to the Equidae family. Though they share some physical attributes, much of their physiology is quite different from horses. Both horses and donkeys can develop clinical issues associated with obesity; insulin dysregulation; and altered lipid metabolism, often termed equine metabolic syndrome or donkey metabolic syndrome, respectively. Unlike large breed horses, however, donkeys, ponies, and miniature horses are more susceptible to developing dyslipidemias. This study aimed to use a novel Lipoprint® assay to compare the lipid profiles of apparently healthy donkeys and large-breed horses to establish a baseline for future work that may lead to the use of this test methodology for the evaluation and monitoring of equids with endocrine disorders.The clinical evaluation of lipid metabolism in equids is often limited to the measurement of total cholesterol and triglyceride concentrations. This provides a limited picture of metabolic state and general health, given the continuous exchange of lipid species between various lipoproteins. Major lipoprotein classes in equids include high-density lipoprotein (HDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and chylomicrons (CM). Unlike large breed horses, donkeys are highly susceptible to hepatic lipidosis. Currently, serum triglyceride concentrations serve as a surrogate marker of hepatic lipid exportation. Both VLDL, indicative of hepatic exportation, and its metabolic end-product, LDL, are rich in triglycerides, and contribute to this value. Diagnostic assays that distinguish VLDL from LDL could be useful in better recognizing the hepatic pathology in donkeys. The compositional differences of lipoproteins across species limit the use of commercially available assays developed for the measurement of human lipoproteins in domestic animals. In this study, we evaluated a high-resolution polyacrylamide gel electrophoresis method (Lipoprint®) for separating major lipoprotein classes and sub-fractionating LDL and HDL based on particle size in a large group of donkeys, and compared the pattern to a representative set of horses. Donkeys proved an HDL-rich species, with HDL accounting for the bulk of all lipoproteins (average 78.45%, SD 6.6%, range 92.2–55%). VLDL accounted for a large portion of the total (average 21.6%, SD 6.6%, range 37.1–7.8%), with minimal amounts of LDL detected. The horses tested had higher proportions of VLDL as compared to donkeys (31.7% and 21.6%, respectively p = 0.00008). The later finding draws into question the purported relationship between VLDL, high triglycerides, and hepatic lipidosis, given the incidence of the disease in donkeys is far higher than in horses.

Purifying chylous plasma by precluding triglyceride via carboxylated polyethersulfone microfiltration membrane

Precluding the excessive lipoproteins from plasma rapidly and effectively is highly needed for biomedical detection and reducing plasma product scrap in blood donation stations. The current centrifugation procedure is high-cost and time-consuming. Herein, we fabricated an anionic microfiltration polyethersulfone (PES) membrane modified by interface swelling and implanting of acrylic acid (AA) for screening out large particle lipoprotein chylomicron (CM) and adsorbing cationic very low-density lipoproteins (VLDL). To improve the separation efficiency, a two-stage filtration through carboxylated polyethersulfone microfiltration membranes with the mean pore size of 0.45 and 0.22 μm respectively were conducted. Attenuated total reflection Fourier transform infrared technique (ATR-FTIR), water contact angle (WCA), Zeta potential and scanning electron microscope (SEM) were employed to characterize the modified membrane. To test the effectiveness of this membrane, plasma flux and concentration variation of plasma components were examined to study the purification effectiveness. Furthermore, the hemocompatibility of modified membranes was tested to confirm its practicability on blood-contacting materials. The carboxylated polyethersulfone microfiltration membrane shows its promising potential application to purify chylous plasma.

Post prandial metabolism of lipoproteins in familial chylomicronemia patients treated with lomitapide and tiparvovec

Background and Aims : Familial chylomicronemia syndrome (FCS) is a rare recessive monogenic disease characterized by triglycerides (TG) levels >10 mmol/L. FCS is causally associated with mutations in candidate genes but most patients have mutations in lipoprotein lipase (LPL). Defects in LPL result in reduced clearance of chylomicrons (CM) and development of acute pancreatitis. Treatment of FSC patients is based on combined action of a lipid- and carbohydrate-reduced diet in addition to available hypolipidemic therapies that often fails to achieve a desired TG levels.

Associations of maternal lipoprotein particle distribution in mid-pregnancy with birth outcomes: a pilot study

BackgroundAn excessive rise in maternal lipids during pregnancy may have detrimental impacts on maternal and fetal health leading to adverse pregnancy outcomes. However, knowledge gaps exist with respect to the association between lipid biomarkers and birth outcomes.MethodsWe conducted a secondary data analysis of healthy pregnant women (N = 25) with mid-pregnancy fasting serum samples collected at 22–28 weeks of gestation and birth outcome data. Serum was analyzed for conventional lipid profile (total-C, HDL-C, LDL-C, and triglycerides) and lipoprotein subclass distribution, including particle number (nM) and size (nm), for very low-density lipoprotein (VLDL)/chylomicron (CM), low density lipoprotein (LDL), and high-density lipoprotein (HDL), by nuclear magnetic resonance spectroscopy.Associations between maternal lipids and birth outcomes, including birth weight (g) and gestational age (weeks), were assessed using multivariable linear regression, adjusted for pre-pregnancy BMI.ResultsAlthough conventional lipids were not associated (p > 0.05) with birth outcomes, every 1-unit increment in large VLDL/CM particles (nM) and VLDL/CM size (nm) was associated with an increase in birth weight (confounder-adjusted β-coefficient, 45.80 g [5.30, 86.20, p = 0.003] and 24.90 g [8.80, 40.90, p = 0.002], respectively). Among the HDL subclass parameters, a 1-unit (nM) increase in the concentration of total HDL-particles was associated with a reduced birth weight (confounder adjusted β-coefficient, -19.40 g [95% confidence interval, -36.70, -2.20]; p = 0.03) after adjustment for maternal pre-pregnancy BMI.ConclusionThe preliminary results of this pilot study suggest that total particle concentrations of VLDL/CM and HDL in mid-pregnancy have divergent associations with birth weight, potentially reflecting the specific roles of these lipoprotein particles with respect to placental function and fetal growth.

Inclusion of a Phytomedicinal Flavonoid in Biocompatible Surface-Modified Chylomicron Mimic Nanovesicles with Improved Oral Bioavailability and Virucidal Activity: Molecular Modeling and Pharmacodynamic Studies.

Morin hydrate (MH) is a widely-used Asian phytomedicinal flavonoid with a wide range of reported therapeutic activities. However, MH has limited oral bioavailability due to its low aqueous solubility and intestinal permeability, which in turn hinders its potential antiviral activity. The study reported herein was designed to encapsulate MH in polyethyleneglycolated (PEGylated) chylomicrons (PCMs) and to boost its antiviral activity and biological availability for oral administration using a rat experimental model. The PEGylated edge activator combined with the conventional components of chylomicrons (CMs) amplify the transport of the drug across the intestine and its circulation period, hence its therapeutic impact. The implementation of variables in the in vitro characterization of the vesicles was investigated. Using Design Expert® software, a 24 factorial design was conducted, and the resulting PCM formulations were fabricated utilizing a thin-film hydration technique. The efficacy of the formulations was assessed according to their zeta potential (ZP), entrapment efficiency percentage (EE%), amount of drug released after 8 h (Q8h), and particle size (PS) data. Formulation F9, which was deemed to be the optimal formula, used compritol as the lipidic core together in defined amounts with phosphatidylcholine (PC) and Brij52. Computer-aided studies revealed that MH alone in a suspension had both diminished intestinal permeability and absorption, but was enhanced when loaded in PCMs. This was affirmed by the superiority of formulation F9 results in ex vivo permeation and pharmacokinetic studies. Furthermore, formulation F9 had a superior safety profile and antiviral activity over a pure MH suspension. Molecular-docking studies revealed the capability of MH to inhibit MERS-CoV 3CLpro, the enzyme shown to exhibit a crucial role in viral replication. Additionally, F9 suppressed both MERS-CoV-induced histopathological alteration in lung tissue and resulting oxidative and inflammatory biomarkers. Collectively, the results reported herein affirmed the potential of PCMs as nanocarriers for the effective oral administration of MH as an antiviral.

Lymphatics - not just a chylomicron conduit.

Lymphatics are known to have active, regulated pumping by smooth muscle cells that enhance lymph flow, but whether active regulation of lymphatic pumping contributes significantly to the rate of appearance of chylomicrons (CMs) in the blood circulation (i.e., CM production rate) is not currently known. In this review, we highlight some of the potential mechanisms by which lymphatics may regulate CM production. Recent data from our lab and others are beginning to provide clues that suggest a more active role of lymphatics in regulating CM appearance in the circulation through various mechanisms. Potential contributors include apolipoproteins, glucose, glucagon-like peptide-2, and vascular endothelial growth factor-C, but there are likely to be many more. The digested products of dietary fats absorbed by the small intestine are re-esterified and packaged by enterocytes into large, triglyceride-rich CM particles or stored temporarily in intracellular cytoplasmic lipid droplets. Secreted CMs traverse the lamina propria and are transported via lymphatics and then the blood circulation to liver and extrahepatic tissues, where they are stored or metabolized as a rich energy source. Although indirect data suggest a relationship between lymphatic pumping and CM production, this concept requires more experimental evidence before we can be sure that lymphatic pumping contributes significantly to the rate of CM appearance in the blood circulation.

Mechanisms Underlying the Impacts of Lipids on the Diverse Bioavailability of Per- and Polyfluoroalkyl Substances in Foods.

Food is a major source of human exposure to per- and polyfluoroalkyl substances (PFASs), yet little is known about their bioavailability in food matrices. Here, the relative bioavailability (RBA) of PFASs in foods was determined using an in vivo mouse model. Pork, which had the highest lipid content, exhibited the greatest effect on bioavailability by increasing the RBAs of perfluoroalkyl acids (PFAAs) while reducing those of fluorotelomer phosphate diesters (diPAPs). During intestinal digestion of lipids, the bioaccessibility of PFAAs increased due to their greater partition into the stable mixed micelles. However, diPAPs were more likely to partition into the undigested oil phase due to their strong hydrophobicity. Both in vitro incubation and molecular docking results indicated that the PFAAs exhibited stronger binding affinities with mouse blood chylomicrons (CMs) than with diPAPs. Collectively, both lipid digestion in the intestine and the carrier effect of CMs played important roles in modulating the bioavailability of PFASs in food. More attention should be given to further evaluating the health risks of PFASs associated with the intake of high-lipid foods.

Changes in the lipid profile of neutered cats’ blood in cases of obesity and diabetes

The aim of the present study was to examine the lipid profile, lipid fractions and the lipid peroxidation state in the blood of neutered cats with obesity and diabetes. Three groups of neutered cats (males and females) were formed for the study. We compared cats with obesity (7-9 points on a 9-point BCS scale), with obesity complicated by diabetes, and clinically healthy animals with normal body condition scores (4-5 BCS points). Lipidogram parameters, fractions of high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL), chylomicrons (CM), lipid peroxidation products (POL) - lipid hydroperoxides (GPL) and malondialdehyde (MDA) were analysed. In obese cats, a decrease in HDL and phospholipids was observed, and an increase in LDL, VLDL, CM, triglycerides, and cholesterol. No significant differences in lipid and lipoprotein metabolism between neutered females and males were found. A tendency towards increasing concentrations of lipoproteins, triglycerides and cholesterol in males, as well as an increase in phospholipids in females was found. In cats with obesity and associated diabetes, the ratio of phospholipids: cholesterol was less than one, while in healthy cats - more than one. Obesity and diabetes initiate POL and increased concentrations of GPL and MDA, which were the highest in the blood of females with associated pathology.