Search Results (50)

Background/Objectives: Vitamin B12 deficiency affects up to 40% of certain populations worldwide and has been associated with cardiometabolic risk. However, its relationship with detailed lipoprotein subfractions remains poorly defined. This study aimed to investigate the association between serum vitamin B12 levels and atherogenic lipid profiles using NMR-based lipoprotein subfraction analysis. Methods: In this retrospective cross-sectional study, data from 20,665 apparently healthy adults undergoing routine health screening were analyzed. Participants were categorized into quartiles based on serum vitamin B12 levels (Q1: ≤328 pg/mL; Q4: ≥540 pg/mL). Lipoprotein subfractions were quantified using Bruker NMR spectroscopy. The Atherogenic Index of Plasma was calculated as log₁₀(triglycerides/HDL-cholesterol). Statistical analyses included ANCOVA adjusted for age, with corrections for multiple comparisons. Results: Higher serum B12 levels were significantly associated with a more favorable lipid profile. Specifically, AIP values decreased progressively across B12 quartiles (Q1: −0.051 ± 0.273; Q4: −0.170 ± 0.294; p < 0.001, partial η² = 0.017). HDL-cholesterol increased (p < 0.001, partial η² = 0.008), while triglycerides and VLDL-TG subfractions (VLDL1-TG: p < 0.001; VLDL5-TG: p = 0.029) declined with higher B12 levels. Among LDL subfractions, small dense LDL (LDL5-TG) exhibited a consistent inverse association with B12 (p = 0.002, partial η² = 0.001). These associations were robust across all age strata, with no significant interaction between B12 levels and age. Conclusions: Serum vitamin B12 levels are inversely associated with atherogenic lipid parameters in a large cohort of asymptomatic individuals. Higher B12 status correlates with lower AIP, reduced triglyceride-rich lipoproteins, and diminished small dense LDL particles across all age groups. These findings suggest that B12 status may serve as a potential biomarker in cardiovascular risk assessment and highlight the need for prospective interventional studies. Full article

Objectives: Emerging evidence suggests that bilirubin, beyond being a metabolic byproduct, may exert protective effects against metabolic and cardiovascular diseases due to its antioxidant properties. However, its relationship with hyperlipidemia remains unclear. This study investigated the relationship between hyperbilirubinemia and hyperlipidemia in a large, community-based cohort. Methods: Data from 8464 participants in the Jidong Community Cohort were analyzed using a cross-sectional design. Hyperbilirubinemia was defined as serum total bilirubin (STB) ≥ 17.1 μmol/L, whereas hyperlipidemia was determined based on a prior diagnosis or elevated lipid profile. Results: Of all participants, 31.6% had hyperbilirubinemia and 51.8% had hyperlipidemia. Multivariable logistic regression revealed a significant inverse association between hyperbilirubinemia and hyperlipidemia [odds ratio (OR) = 0.764, 95% confidence interval (CI) = 0.686–0.851]. This association was significant in participants aged <65 years (OR = 0.762, p < 0.0001) but not in those aged ≥65 years. Stratified analysis by smoking status further revealed a 29% reduced risk of hyperlipidemia among never-smokers (OR = 0.708, p < 0.001), but not among current (OR = 0.831, p = 0.087) or former smokers (OR = 0.685, p = 0.175). Hyperbilirubinemia was also negatively associated with TC (p < 0.0001), TGs (p < 0.0001), LDL-C (p = 0.0061), very LDL-C (VLDL-C; p = 0.0043), and apolipoprotein B (ApoB; p < 0.0001) levels, as well as the ApoB/apolipoprotein A1 (ApoA1) ratio (p = 0.0003). Restricted cubic spline analysis revealed an inverse relationship of high STB levels with the TC, TG, LDL-C, VLDL-C, and ApoB levels, as well as the ApoB/ApoA1 ratio. Moreover, elevated STB levels were inversely linked to obesity (OR = 0.747, p < 0.0001), arterial stenosis (OR = 0.806, p = 0.0462), and metabolic syndrome (OR = 0.784, p = 0.0008). Conclusions: hyperbilirubinemia may be an independent factor protective against hyperlipidemia and related lipid abnormalities; these results provide insights for the prevention and management of lipid-related diseases. Full article

Background/Objectives: Chronic hepatitis B and metabolic dysfunction-associated steatotic liver disease (MASLD) are associated with risk of advanced hepatic fibrosis and cirrhosis. Given the increased risk, the presence of insulin resistance, metabolic syndrome, and hepatic fibrosis should be assessed in individuals with chronic hepatitis B. The Lipoprotein Insulin Resistance Index (LP-IR) is a simple method of assessing insulin resistance in the general population, and lipoprotein profiles have been shown to reflect hepatic steatosis and fibrosis in patients with MASLD. However, LP-IR and lipoprotein profiles have not been evaluated in patients with chronic hepatitis B. Methods: Lipoprotein profiles and LP-IR scores were evaluated in a cohort of patients with chronic hepatitis B using NMR spectroscopy. Results: Serum samples from 50 patients with chronic hepatitis B and 44 with chronic hepatitis B and metabolic syndrome were analyzed. A cut-off value was defined that differentiates patients with and without insulin resistance. Increased large VLDL and reduced small VLDL particles were observed, suggesting the presence of hepatic steatosis and fibrosis. Conclusions: In this largely Asian cohort of chronic hepatitis B patients, where BMI and conventional markers are less reliable, LP-IR scores differentiated patients with and without insulin resistance and metabolic syndrome. In addition, distinctive lipoprotein profiles such as increased large VLDL and reduced small VLDL particles were observed in these chronic hepatitis B patients, suggesting the presence of hepatic steatosis and fibrosis. Future studies with larger sample sizes are necessary to confirm the utility of these NMR-measured lipoprotein parameters in predicting metabolic disease and fibrosis among patients with underlying liver disease. Full article

Cholesterol, triglycerides, high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), and very-low-density lipoproteins (VLDLs) were evaluated in chimpanzees at Tacugama Chimpanzee Sanctuary, Sierra Leone. Blood from 75 visually healthy chimpanzees was collected, centrifuged within one hour of collection, and analyzed at Choithram Hospital within 24 h. Statistical analyses assessed differences and interactions based on age, body condition score (BCS), housing group, and sex. HDLs varied widely by housing group; HDLs and LDLs were higher in males than in females. Cholesterol and LDLs were higher in prepubertal individuals while VLDLs and triglycerides were higher in postpubertal individuals. Lipid biomarker differences by age and age ∗ sex statistical interactions were not observed. These data represent a novel compilation of serum lipid biomarkers from a large population of sanctuary-housed Western chimpanzees (Pan troglodytes verus) within a range country, a population not previously studied with regard to serum lipid biomarkers. This study has documented significant differences compared to known values from managed chimpanzees and human reference ranges. The relationship of serum lipid biomarkers with health and disease in great apes remains understudied, but the present data set provides a basis for future studies to ascertain whether these differences are healthy biomarker variations or represent an elevated risk factor for disease. Full article

Diabetes mellitus is a chronic, degenerative, and multifactorial disease characterized by hyperglycemia, and at least 537 million people suffered from diabetes in 2021. Agave durangensis Gentry, a species of agave native to the state of Durango, reports phenolic compounds, flavonols, flavonoids, and saponins and could be an alternative for the treatment of diabetes. The aim of this work was to identify the compounds in the leaves of Agave durangensis Gentry and their potential activity in diabetes. The leaf extract of Agave durangensis Gentry (EAD) was characterized by ultra-performance liquid chromatography–mass spectrometry (UPLC-MS), and different families of bioactive compounds were quantified by analytical methods. Probable pharmacological targets were identified in silico, and the inhibition of dipeptidyl peptidase-4 (DPP4) was validated in vitro. A model of hyperglycemia was established with streptozotocin in male Wistar rats, and we administered EAD intragastrically at a dose of 300 mg/kg, as well as combinations of the extract with metformin and sitagliptin over 30 days. Biochemical and histological parameters were analyzed. We identified thirty-six major compounds, where triterpenes represented 30% of the extract. Molecular docking showed that the extract could interact with α-glucosidases and DPP4 since a large number of compounds in the extract have a Δ G lower than that reported for the controls, and DPP4 inhibition was confirmed by in vitro assays. In vivo assays demonstrated that the administration of the extract was able to significantly decrease glucose levels by 56.75% and glycosylated hemoglobin by 52.28%, which is higher than that reported for sitagliptin with a decrease of 35.22%. In addition, the extract decreased triglycerides by 59.28% and very-low-density lipoprotein (VLDL) cholesterol by 60.27%, and when administered in combination with metformin, it decreased them more than when metformin was administered alone. For all the above reasons, Agave durangensis Gentry extract could be used for the development of phytomedicine for the treatment of diabetes. Full article

The liver plays a crucial role in maintaining lipid homeostasis by converting toxic free fatty acids into VLDL, which the body uses for energy. Even minor changes in VLDL formation and secretion can result in serious health conditions such as atherosclerosis and non-alcoholic fatty liver disease. Despite the importance of VLDL, the proteins and signaling pathways involved in its regulation remain largely unknown. This study aims to develop a novel methodology to study intracellular VLDL transport events and explore the role of liver fatty acid-binding protein (LFABP) in VLDL transport and secretion. Current methods to study VLDL are often tedious, time-consuming, and expensive, underscoring the need for an alternative approach. We designed a new immunofluorescence-based assay to track the formation and secretion of VLDL in cells over time using fluorescently tagged TopFluor oleic acid. Confocal microscopy confirmed that TopFluor oleic acid enters hepatocytes and colocalizes with the ER, Golgi, and plasma membrane. Additionally, the collection of cell culture media revealed that TopFluor was incorporated into VLDL particles, as confirmed by fluorescence readings and ApoB100 immunoblots. This novel assay provides a valuable tool for further research into the mechanisms of VLDL regulation and the development of potential therapeutic targets for related diseases. Utilizing this assay, we identified LFABP as a key regulatory protein in post-Golgi VLDL trafficking. Our data suggest that LFABP plays a crucial role in this process, and its functional impairment leads to reduced VLDL secretion. Full article

Background: Recently, we reported that longer-term mixed nut intake significantly reduced serum total and low-density lipoprotein (LDL)-cholesterol, but these markers may not fully capture lipoprotein-related cardiovascular disease (CVD) risk. Objectives: This randomized, controlled, single-blinded, crossover trial in older adults with overweight or obesity examined the effects of longer-term mixed nut consumption on lipoprotein particle size, number, and lipid distribution. Methods: Twenty-eight participants (aged 65 ± 3 years; BMI 27.9 ± 2.3 kg/m²) completed two 16-week periods (control [no nuts] vs. mixed nuts (60 g/day: 15 g of walnuts, pistachios, cashews, and hazelnuts), separated by an 8-week washout. Plasma lipoprotein particle numbers, sizes, and lipid distributions across subclasses were analyzed using high-throughput nuclear magnetic resonance (NMR) spectroscopy. Results: Mixed nut consumption significantly reduced Apolipoprotein B (ApoB) concentrations (−0.07 g/L; p = 0.009), total cholesterol (−0.27 mmol/L; p = 0.047), non-HDL cholesterol (−0.28 mmol/L; p = 0.022), and total triacylglycerol (TAG) (−0.27 mmol/L; p = 0.008). Total very large-density lipoprotein (VLDL) particle numbers decreased by 24 nmol/L (p < 0.001), with reductions observed across all VLDL subclasses. Total LDL particle numbers (p = 0.044), specifically intermediate-density lipoprotein (IDL) (p = 0.002) and large LDL particles (p = 0.015), were also reduced, while HDL particle numbers and sizes were unaffected. The mixed nut intervention significantly reduced cholesterol concentrations across all VLDL subclasses and IDL (all p < 0.01), with no changes in LDL or HDL subclasses. TAG concentrations showed reductions across all lipoprotein subclasses (all p < 0.05). Conclusions: Longer-term mixed nut consumption may lower CVD risk in older adults and favorable shifts in apoB-containing lipoprotein subclasses towards a less atherogenic profile. Full article

Clinical trial results indicate that statin therapy aimed at normalising the lipid profile can prevent and reduce the risk of cardiovascular events. Both LDL and HDL consist of several subfractions, with only the smallest and densest subfractions being the most atherogenic. We examine the effect of Atorvastatin treatment not only on basic lipid profile parameters but also atherogenic lipoprotein subfractions and 25(OH)D levels in patients after the first acute myocardial infarction. The study population had not previously received lipid-lowering medications. Serum 25(OH)D concentration was determined by direct competitive immunochemiluminescent assays. Lipoprotein subfractions, including VLDL, IDL-C, IDL-B, and IDL-A, as well as LDL1, LDL2 (large LDL), and LDL3-7 (sdLDL), were measured in serum (Lipoprint^® system). Almost all patients had 25(OH)D deficiency. Atorvastatin primarily reduced strongly atherogenic sdLDL and decreased the less atherogenic large LDL subfractions. A statistically significant reduction in VLDL cholesterol and IDL fractions was also observed. Analysing LDL subfractions provides a more detailed insight into lipid metabolism and enables the identification of patients with a more atherogenic phenotype. LDL subfractions may thus become not only more accurate prognostic biomarkers but also targets for lipid-lowering therapy. Vitamin D deficiency is associated with atherogenic dyslipidaemia, particularly high levels of sdLDL. Full article

Over 50% of patients who take statins are still at risk of developing atherosclerotic cardiovascular disease (ASCVD) and do not achieve their goal LDL-C levels. This residual risk is largely dependent on triglyceride-rich lipoproteins (TRL) and their remnants. In essence, remnant cholesterol-rich chylomicron (CM) and very-low-density lipoprotein (VLDL) particles play a role in atherogenesis. These remnants increase when lipoprotein lipase (LPL) activity is inhibited. ApoCIII has been thoroughly studied as a chief inhibitor and therapeutic options to curb its effect are available. On top of apoCIII regulation of LPL activity, there is a more precise control of LPL in various tissues, which makes it easier to physiologically divide the TRL burden according to the body’s requirements. In general, oxidative tissues such as skeletal and cardiac muscle preferentially take up lipids during fasting. Conversely, LPL activity in adipocytes increases significantly after feeding, while its activity in oxidative tissues decreases concurrently. This perspective addresses the recent improvements in our understanding of circadian LPL regulations and their therapeutic implications. Three major tissue-specific lipolysis regulators have been identified: ANGPTL3, ANGPTL4, and ANGPTL8. Briefly, during the postprandial phase, liver ANGPTL8 acts on ANGPTL3 (which is released continuously from the liver) to inhibit LPL in the heart and muscle through an endocrine mechanism. On the other hand, when fasting, ANGPTL4, which is released by adipocytes, inhibits lipoprotein lipase in adipose tissue in a paracrine manner. ANGPTL3 inhibitors may play a therapeutic role in the treatment of hypertriglyceridemia. Several approaches are under development. We look forward to future studies to clarify (a) the nature of hormonal and nutritional factors that determine ANGPTL3, 4, and 8 activities, along with what long-term impacts may be expected if their regulation is impaired pharmacologically; (b) the understanding of the quantitative hierarchy and interaction of the regulatory actions of apoCIII, apoAV, and ANGPTL on LPL activity; (c) strategies for the safe and proper treatment of postprandial lipemia; and (d) the effect of fructose restriction on ANGPTL3, ANGPTL4, and ANGPTL8. Full article

This prospective study in Hong Kong aimed at identifying prognostic metabolomic and immunologic biomarkers for Coronavirus Disease 2019 (COVID-19). We examined 327 patients, mean age 55 (19–89) years, in whom 33.6% were infected with Omicron and 66.4% were infected with earlier variants. The effect size of disease severity on metabolome outweighed others including age, gender, peak C-reactive protein (CRP), vitamin D and peak viral levels. Sixty-five metabolites demonstrated strong associations and the majority (54, 83.1%) were downregulated in severe disease (z score: −3.30 to −8.61). Ten cytokines/chemokines demonstrated strong associations (p < 0.001), and all were upregulated in severe disease. Multiple pairs of metabolomic/immunologic biomarkers showed significant correlations. Fourteen metabolites had the area under the receiver operating characteristic curve (AUC) > 0.8, suggesting a high predictive value. Three metabolites carried high sensitivity for severe disease: triglycerides in medium high-density lipoprotein (MHDL) (sensitivity: 0.94), free cholesterol-to-total lipids ratio in very small very-low-density lipoprotein (VLDL) (0.93), cholesteryl esters-to-total lipids ratio in chylomicrons and extremely large VLDL (0.92);whereas metabolites with the highest specificity were creatinine (specificity: 0.94), phospholipids in large VLDL (0.94) and triglycerides-to-total lipids ratio in large VLDL (0.93). Five cytokines/chemokines, namely, interleukin (IL)-6, IL-18, IL-10, macrophage inflammatory protein (MIP)-1b and tumour necrosis factor (TNF)-a, had AUC > 0.8. In conclusion, we demonstrated a tight interaction and prognostic potential of metabolomic and immunologic biomarkers enabling an outcome-based patient stratification. Full article

Kallistatin is an endogenous serine proteinase inhibitor with various functions, including antioxidative, anti-inflammatory, and anti-atherosclerotic properties. To date, associations between kallistatin and lipoprotein subfractions are poorly investigated. In this study, we enrolled 62 obese patients with type 2 diabetes (T2D), 106 nondiabetic obese (NDO) subjects matched in gender, age, and body mass index, as well as 49 gender- and age-matched healthy, normal-weight controls. Serum kallistatin levels were measured with ELISA, and lipoprotein subfractions were analyzed using Lipoprint^® (Quantimetrix Corp., Redondo Beach, CA, USA) gel electrophoresis. Kallistatin concentrations were significantly higher in T2D patients compared to NDO and control groups. We found significant positive correlations between very-low-density lipoprotein (VLDL), small high-density lipoprotein (HDL) subfractions, glucose, hemoglobin A_1c (HbA_1c), betatrophin, and kallistatin, while negative correlations were detected between mean low-density lipoprotein (LDL) size, large and intermediate HDL subfractions, and kallistatin in the whole study population. The best predictor of kallistatin was HbA_1c in T2D patients, high-sensitivity C-reactive protein (hsCRP) and betatrophin in NDO patients, and hsCRP in controls. Our results indicate that kallistatin expression might be induced by persistent hyperglycemia in T2D, while in nondiabetic subjects, its production might be associated with systemic inflammation. The correlation of kallistatin with lipid subfractions may suggest its putative role in atherogenesis. Full article

This study aimed to evaluate the efficacy of Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) in improving body weight, obesity-related outcomes, and lipid profiles of overweight people. Thirty-six overweight participants were randomly assigned to either a probiotic or a placebo group. A placebo powder or L. bulgaricus powder (containing 1 × 10⁸ colony-forming unit (CFU) of the probiotic) was administered daily for 12 weeks. Body composition was determined, and blood tests were performed before and after the intervention. L. bulgaricus supplementation under the present condition did not affect the body weight, fat percentage, or body mass index (BMI) of the participants, while it resulted in a notable decrease in blood triglyceride (TG) levels, which corresponded to a lowering of the TG proportion in the composition of large VLDL (L–XXL sized fractions) and HDL (M and L fractions) in the probiotic-treated group. These results suggest that L. bulgaricus supplementation under the current conditions may not be helpful for losing weight, but it has the potential to decrease blood TG levels by modulating TG accumulation in or transport by VLDL/HDL in obese patients. L. bulgaricus supplements may have health-promoting properties in preventing TG-related diseases in overweight people. Full article

Rapidly proliferating cancer cells have a greater requirement for cholesterol than normal cells. Tumor cells are largely dependent on exogenous lipids given that their growth requirements are not fully met by endogenous pathways. Our current study shows that ccRCC cells have redundant mechanisms of cholesterol acquisition. We demonstrate that all major lipoproteins (i.e., LDL, HDL, and VLDL) have a comparable ability to support the growth of ccRCC cells and are equally effective in counteracting the antitumor activities of TKIs. The intracellular trafficking of exogenous lipoprotein-derived cholesterol appears to be distinct from the movement of endogenously synthesized cholesterol. De novo synthetized cholesterol is transported from the endoplasmic reticulum directly to the plasma membrane and to the acyl-CoA: cholesterol acyltransferase, whereas lipoprotein-derived cholesterol is distributed through the NPC1-dependent endosomal trafficking system. Expression of NPC1 is increased in ccRCC at mRNA and protein levels, and high expression of NPC1 is associated with poor prognosis. Our current findings show that ccRCC cells are particularly sensitive to the inhibition of endolysosomal cholesterol export and underline the therapeutic potential of targeting NPC1 in ccRCC. Full article

Metabolic syndrome (MetS) is associated with alterations of lipoprotein structure and function that can be characterized with advanced lipoprotein testing (ADLT). The effect of the Mediterranean diet (MedDiet) and weight loss on the lipoprotein subclass profile has been scarcely studied. Within the PREDIMED-Plus randomized controlled trial, a sub-study conducted at Bellvitge Hospital recruiting center evaluated the effects of a weight loss program based on an energy-reduced MedDiet (er-MedDiet) and physical activity (PA) promotion (intervention group) compared with energy-unrestricted MedDiet recommendations (control group) on ADLT-assessed lipoprotein subclasses. 202 patients with MetS (n = 107, intervention; n = 95, control) were included. Lipid profiles were determined, and ADLT was performed at baseline, 6, and 12 months. Linear mixed models were used to assess the effects of intervention on lipoprotein profiles. Compared to the control diet, at 12 months, the er-MedDiet+PA resulted in a significant additional 4.2 kg of body weight loss, a decrease in body mass index by 1.4 kg/m², reduction in waist circumference by 2.2 cm, decreased triglycerides, LDL-cholesterol and non-HDL-cholesterol, and increased HDL-cholesterol. In er-MedDiet+PA participants, ADLT revealed a decrease in small dense-LDL-cholesterol (sd-LDL-C), intermediate-density lipoproteins, VLDL-triglyceride, and HDL-Triglyceride, and an increase in large LDL and large VLDL particles. In conclusion, compared to an ad libitum MedDiet (control group), er-MedDiet+PA decreased plasma triglycerides and the triglyceride content in HDL and VLDL particles, decreased sd-LDL-C, and increased large LDL particles, indicating beneficial changes against cardiovascular disease. Full article

Betatrophin, also known as angiopoietin-like protein 8 (ANGPTL8), mainly plays a role in lipid metabolism. To date, associations between betatrophin and lipoprotein subfractions are poorly investigated. For this study, 50 obese patients with type 2 diabetes (T2D) and 70 nondiabetic obese (NDO) subjects matched in gender, age, and body mass index (BMI) as well as 49 gender- and age-matched healthy, normal-weight controls were enrolled. Serum betatrophin levels were measured with ELISA, and lipoprotein subfractions were analyzed using Lipoprint gel electrophoresis. Betatrophin concentrations were found to be significantly higher in the T2D and NDO groups compared to the controls in all subjects and in females, but not in males. We found significant positive correlations between triglyceride, very low density lipoprotein (VLDL), large LDL (low density lipoprotein), small LDL, high density lipoprotein (HDL) -6-10 subfractions, and betatrophin, while negative correlations were detected between betatrophin and IDL, mean LDL size, and HDL-1-5. Proportion of small HDL was the best predictor of betatrophin in all subjects. Small LDL and large HDL subfractions were found to be the best predictors in females, while in males, VLDL was found to be the best predictor of betatrophin. Our results underline the significance of serum betatrophin measurement in the cardiovascular risk assessment of obese patients with and without T2D, but gender differences might be taken into consideration. Full article