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17 pages, 1866 KB  
Article
Changes in Apolipoprotein A1-Associated Proteomic Composition After Pioglitazone Treatment Versus Weight Loss
by Shyon Parsa, Timothy S. Collier, Michael J. McPhaul, Olle Melander, Joshua W. Knowles, Anand Rohatgi and Fahim Abbasi
Int. J. Mol. Sci. 2025, 26(21), 10690; https://doi.org/10.3390/ijms262110690 - 3 Nov 2025
Viewed by 952
Abstract
Insulin resistance (IR) contributes to atherogenic dyslipidemia and elevated ASCVD risk. Apolipoprotein A1 (ApoA1)-associated lipoproteins have diverse anti-atherogenic functions, but it is unclear whether IR drives adverse changes in their proteomic composition. We hypothesized that IR is associated with an atherogenic ApoA1 proteome [...] Read more.
Insulin resistance (IR) contributes to atherogenic dyslipidemia and elevated ASCVD risk. Apolipoprotein A1 (ApoA1)-associated lipoproteins have diverse anti-atherogenic functions, but it is unclear whether IR drives adverse changes in their proteomic composition. We hypothesized that IR is associated with an atherogenic ApoA1 proteome and that insulin-sensitizing interventions would improve its composition. We studied 861 participants without diabetes (age 47 ± 12 years, 65.5% female). IR was directly measured using the steady-state plasma glucose (SSPG) concentration via the insulin suppression test. ApoA1-associated proteins were quantified by mass spectrometry. A subset underwent interventions for 3 months (N total 108): pioglitazone, PIO n = 38 or weight loss, WL n = 70). Paired t-tests assessed pre- and post-intervention changes. At baseline, several ApoA1-associated proteins significantly correlated with SSPG. Both interventions improved IR (p < 0.01). PIO led to significant increases in 14 ApoA1-associated proteins, including ApoC1–C4, ApoA2, ApoA4, ApoD, ApoE, LCAT, and PON1/3. WL increased several ApoA1-associated proteins, including ApoA4, ApoD, ApoM, and PON1/3. In conclusion, IR is associated with a pro-atherogenic ApoA1 proteome, and both interventions improve this profile. However, PIO has a broader proteomic impact. These findings highlight the potential of targeting the ApoA1 proteome to reduce residual ASCVD risk. Full article
(This article belongs to the Special Issue High-Density Lipoproteins in Health and Disease)
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25 pages, 4126 KB  
Article
Structural Characterization of Polysaccharide from Flammulina velutipes and Its Impact on Hyperlipidemia Through Modulation of Hepatic Cholesterol Metabolism and Gut Microbiota
by Wei Jia, Huimin Wang, Ting Feng, Xiaoxiao Liu, Zhendong Liu, Zhengpeng Li, Wenhan Wang and Jingsong Zhang
Foods 2025, 14(19), 3452; https://doi.org/10.3390/foods14193452 - 9 Oct 2025
Cited by 1 | Viewed by 961
Abstract
FVPB1, a novel heteropolysaccharide, was extracted from the Flammulina velutipes fruiting body, and its structure was determined by methylation analysis, nuclear magnetic resonance (NMR) spectroscopy. FVPB1 demonstrated efficacy in inhibiting lipid accumulation in Raw264.7 cells and zebrafish, as well as in reducing weight [...] Read more.
FVPB1, a novel heteropolysaccharide, was extracted from the Flammulina velutipes fruiting body, and its structure was determined by methylation analysis, nuclear magnetic resonance (NMR) spectroscopy. FVPB1 demonstrated efficacy in inhibiting lipid accumulation in Raw264.7 cells and zebrafish, as well as in reducing weight gain and ameliorating liver injury in high-fat diet-induced mice. High concentration of FVPB1 significantly increased serum ApoA1 levels, while all tested doses (low, medium, and high) reduced serum ApoB levels in mice. Intervention with FVPB1 significantly increased the mRNA expression of Lcat and Cyp7a1 enzymes while markedly reducing the transcriptional level of Hmgcr reductase. Additionally, low concentration of FVPB1 enhanced CYP7A1 protein expression, whereas medium and high concentrations of FVPB1 promoted LCAT protein expression. Medium and high concentrations of FVPB1 significantly enhanced bile acid excretion in mice, with the high dose additionally promoting fecal sterol output. Alpha and beta diversity analyses demonstrated that a high-fat diet induced substantial dysbiosis in the gut microbiota of mice, characterized by reduced microbial diversity and richness. Intervention with FVPB1 significantly modulated the structural composition of the intestinal microbiota in high-fat diet-fed mice. Therefore, FVPB1 exerts lipid-lowering effect in high-fat diet-fed mice by modulating cholesterol metabolism and ameliorating gut microbiota dysbiosis. Full article
(This article belongs to the Section Nutraceuticals, Functional Foods, and Novel Foods)
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18 pages, 3597 KB  
Article
Continuous Flow-Mode Synthesis of Aromatic Amines in a 3D-Printed Fixed Bed Reactor Loaded with Amino Sugar-Stabilized Re Apparent Nanoparticles
by Patrick Niyirora, Joanna Wolska, Mateusz M. Marzec, Krystian Sokolowski, Anna Leśniewicz, Piotr Jamróz, Anna Dzimitrowicz, Andrzej Bernasik and Piotr Cyganowski
Molecules 2025, 30(18), 3782; https://doi.org/10.3390/molecules30183782 - 17 Sep 2025
Viewed by 1163
Abstract
In industrial processes, catalysts—materials that speed up chemical reactions without being consumed—are essential. The goal of this research was to create two new rhenium-based nanocomposite catalysts that can effectively and sustainably reduce nitroaromatic compounds to aromatic amines in continuous-flow systems. Nitroaromatic hydrocarbons (NACs), [...] Read more.
In industrial processes, catalysts—materials that speed up chemical reactions without being consumed—are essential. The goal of this research was to create two new rhenium-based nanocomposite catalysts that can effectively and sustainably reduce nitroaromatic compounds to aromatic amines in continuous-flow systems. Nitroaromatic hydrocarbons (NACs), widely used in manufacturing pharmaceuticals, insecticides, and herbicides, often contaminate soil and water, posing significant environmental and health risks. However, their reduction to aromatic amines enables potential industrial reuse. In this study, we synthesized two nanocomposite catalysts based on a copolymer functionalized with N-methyl-D-glucamine, embedded with rhenium (Re)-based apparent nanoparticles, and used them to reduce the NACs in continuous-flow mode to their aromatic amines using newly designed and stereolithographic (SLA) 3D-printed reactors. Advanced characterization techniques were employed to evaluate their structure, morphology, and catalytical performance. Catalyst 1, prepared from a self-modified Purolite D4869 resin and characterized by higher Re loading, exhibited superior conversion rates in batch mode (k1 up to 1.406 s−1). In contrast, Catalyst 2, based on a commercial NMDG-functionalized Dowex resin with a mesoporous structure, demonstrated remarkable stability and catalytic capacity under continuous flow (up to 1.383 mmolNAC mLcat−1). Overall, Catalyst 1 was found to be better suited for rapid batch reactions, whereas Catalyst 2 was found to be more appropriate for long-term flow applications, offering a sustainable route for the efficient conversion of nitroaromatic compounds into valuable aromatic amines. The reactors enabled the efficient conversion of NACs into aromatic amines while enhancing process sustainability and efficiency. Full article
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18 pages, 2898 KB  
Article
Exogenous Catalase Supplementation Alleviates Fusarium graminearum Mycotoxins-Induced Oxidative Stress in Weaned Piglets
by Shujie Liang, Yunfei Jiang, Chong Ling, Meitian Xian, Hui Ye, Qingyun Cao, Changming Zhang, Zemin Dong, Weiwei Wang and Jianjun Zuo
Agriculture 2025, 15(17), 1892; https://doi.org/10.3390/agriculture15171892 - 5 Sep 2025
Viewed by 785
Abstract
The objective of this study was to investigate the impact of exogenous catalase (CAT) on antioxidant properties, as well as on hepatic and intestinal health, in piglets exposed to Fusarium graminearum mycotoxins (FGM). Forty female weaned piglets were divided into five groups (eight [...] Read more.
The objective of this study was to investigate the impact of exogenous catalase (CAT) on antioxidant properties, as well as on hepatic and intestinal health, in piglets exposed to Fusarium graminearum mycotoxins (FGM). Forty female weaned piglets were divided into five groups (eight replicates per group). The pre-feeding period was 3 days, followed by a 28-day experimental period. The piglets in the control (CON) group were fed a diet without FGM contamination, while those in the FGM-exposed (TOX) group were fed a diet with FGM contamination. The LCAT, MCAT, and HCAT groups received an FGM-contaminated diet supplemented with 100, 200, and 400 U/kg of CAT, respectively. The results indicated that 400 U/kg CAT supplementation inhibited (p < 0.05, linear p < 0.05, quadratic p < 0.05) the decreases in average daily gain and average daily feed intake of piglets exposed to FGM. Moreover, all doses of supplemental CAT suppressed (p < 0.05) the increases in diarrhea rate and diarrhea index of FGM-exposed piglets. Additionally, supplemental CAT reversed (p < 0.05, linear and quadratic p < 0.05 in ileal tissue, quadratic p < 0.05 in ileal chyme) the decrease in ileal tissue and increase in ileal chyme of reactive oxygen species of piglets exposed to FGM. Supplemental CAT also enhanced the activities of ileal CAT (p < 0.05, quadratic p < 0.05) coupled with hepatic superoxide dismutase and CAT (p < 0.05, linear p < 0.05, quadratic p < 0.05) and elevated (p < 0.05) the expression of ileal and hepatic antioxidation-related genes of FGM-exposed piglets. Furthermore, the CAT supplementation increased (p < 0.05) the expression of Occludin and Claudin-1 in the ileum and colon of piglets exposed to FGM. The FGM-induced increase in the genus Staphylococcus and decrease in the genus Lactobacillus in the ileum of piglets were inhibited (p < 0.05) by supplemental 400 U/kg CAT, which also modulated the metabolite profiles involved in the glycerophospholipid metabolism pathway in hepatic portal vein blood. Exogenous CAT mitigates oxidative stress induced by FGM, along with improving intestinal and hepatic health of piglets, which can be associated with its ability to enhance intestinal microbiota and regulate hepatic glycerophospholipid metabolism, aside from its direct ability to scavenge oxygen radicals. The appropriate amount of supplemental CAT was 400 U/kg. Full article
(This article belongs to the Section Farm Animal Production)
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17 pages, 2521 KB  
Article
Nutrient-Enriched Germinated Brown Rice Alters the Intestinal Ecological Network by Regulating Lipid Metabolism in Rats
by Chuanying Ren, Shuwen Lu, Shan Shan, Shan Zhang, Bin Hong, Di Yuan, Jingyi Zhang, Shiwei Gao, Qing Liu and Xiaobing Fan
Int. J. Mol. Sci. 2025, 26(16), 7693; https://doi.org/10.3390/ijms26167693 - 8 Aug 2025
Viewed by 2241
Abstract
Metabolic diseases such as high blood lipids, high blood sugar, and disrupted gut microbiota pose a serious threat to people’s physical health. The occurrence of these diseases is closely related to the lack of nutrients in daily rice staple foods, but there is [...] Read more.
Metabolic diseases such as high blood lipids, high blood sugar, and disrupted gut microbiota pose a serious threat to people’s physical health. The occurrence of these diseases is closely related to the lack of nutrients in daily rice staple foods, but there is a lack of comprehensive analysis of the underlying mechanisms. This study used fully nutritious brown rice as raw material, and after germination under various stress conditions, it significantly increased the levels of gamma aminobutyric acid (GABA, four carbon non protein amino acid), resistant starch, flavonoids, and other components that regulate metabolic diseases. Using rats as experimental subjects, a model of hyperlipidemia and hyperglycemia was constructed, with rice consumption as the control. The experimental period was 8 weeks. Research has found that feeding sprouted brown rice can significantly improve the accumulation of white fat in the liver caused by a high-fat diet, significantly reduce TC, TG, LDL-C, apoB, HL, LPL, and LCAT, significantly increase HDL-C and apoA1, and significantly reduce the levels of inflammatory factors IL-6 and TNF-α. Therefore, consuming sprouted brown rice can reduce the risk of hyperlipidemia, inflammation, and tumor occurrence by promoting fat breakdown, and can also increase the abundance of metabolic-promoting microorganisms (especially Euryarchaeota and Lactobacillus) in the intestine, improving the entire metabolic ecological network of rats. Full article
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19 pages, 1637 KB  
Article
High-Tyrosol/Hydroxytyrosol Extra Virgin Olive Oil Enhances Antioxidant Activity in Elderly Post-Myocardial Infarction Patients
by Mojgan Morvaridzadeh, Mehdi Alami, Nada Zoubdane, Hawa Sidibé, Hicham Berrougui, Tamàs Fülöp, Michel Nguyen and Abdelouahed Khalil
Antioxidants 2025, 14(7), 867; https://doi.org/10.3390/antiox14070867 - 16 Jul 2025
Cited by 7 | Viewed by 5207
Abstract
Cardiovascular disease (CVD), particularly atherosclerotic cardiovascular disease (ASCVD), is the leading cause of death worldwide, driven by factors like oxidative stress, inflammation, and lipid metabolism disorders. Although phenolic compounds such as Tyrosol (Tyr) and Hydroxytyrosol (HTyr) found in extra virgin olive oil (EVOO) [...] Read more.
Cardiovascular disease (CVD), particularly atherosclerotic cardiovascular disease (ASCVD), is the leading cause of death worldwide, driven by factors like oxidative stress, inflammation, and lipid metabolism disorders. Although phenolic compounds such as Tyrosol (Tyr) and Hydroxytyrosol (HTyr) found in extra virgin olive oil (EVOO) have shown promising antioxidant and anti-inflammatory effects, their specific roles in modulating oxidative stress biomarkers and high-density lipoprotein (HDL) functionality in elderly populations, especially in those with prior myocardial infarction, are not fully understood. This study aimed to investigate the effects of EVOO phenolic compounds on oxidative stress biomarkers and HDL functionality, and related metabolic outcomes in both healthy and post-myocardial infarction (post-MI) elderly individuals. This pilot randomized clinical trial study included healthy and post-MI participants aged 65–85 years. Participants in each group were randomly assigned to consume 25 mL per day of one of three types of olive oils: high phenolic (HTyr/Tyr) extra virgin olive oil (HP-EVOO), extra virgin olive oil (EVOO), or refined olive oil (ROO) for a period of 26 weeks. Blood samples were collected at baseline and post-intervention to assess key biomarkers. Plasma levels of (poly)phenols, malondialdehyde (MDA), total antioxidant capacity (FRAP), lecithin-cholesterol acyltransferase activity (LCAT), and serum paraoxonase-1 (PON-1) activity were measured. A total of 34 individuals completed the study (mean age: 74 years). Baseline characteristics, including sex, age, body mass index (BMI), weight, blood pressure, and inflammatory markers like C-reactive protein (CRP) levels, did not differ significantly between the two groups. A significant increase in both FRAP levels and PON-1 activity was observed in post-MI participants following HP-EVOO consumption compared to baseline (p = 0.014). No significant changes were observed in MDA levels, LCAT activity, or plasma (poly)phenols. These results indicate that HP-EVOO may enhance antioxidant capacity, particularly FRAP and PON-1 activity, in elderly post-MI individuals. The observed differences between groups suggest that underlying cardiometabolic status may influence the response to olive oil phenolic compounds. Further studies are needed to explore the long-term cardiovascular effects. Full article
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25 pages, 1618 KB  
Article
Chinese Farmers’ Low-Carbon Agricultural Technology Adoption Behavior and Its Influencing Factors
by Liqun Zhu, Yutao Wang, Yujia Liu, Zhuqun Tan, Siqi Ke, Naijuan Hu, Shuyang Qu and Guang Han
Agriculture 2025, 15(10), 1055; https://doi.org/10.3390/agriculture15101055 - 13 May 2025
Cited by 1 | Viewed by 2366
Abstract
Low-carbon agricultural technology (LCAT) is essential for China to achieve its carbon emissions peak by 2030 and neutrality by 2060. Farmers’ adoption of LCAT is crucial for adapting to and mitigating climate change risks. This study explores the social-psychological factors shaping farmers’ LCAT [...] Read more.
Low-carbon agricultural technology (LCAT) is essential for China to achieve its carbon emissions peak by 2030 and neutrality by 2060. Farmers’ adoption of LCAT is crucial for adapting to and mitigating climate change risks. This study explores the social-psychological factors shaping farmers’ LCAT adoption behavior, utilizing the Theory of Planned Behavior and the Normative Activation Model. Survey data from 360 farmers in Wuxi, Jiangsu Province, were analyzed using structural equation modeling. Findings show that behavioral attitude, perceived behavioral control, subjective norms, and personal norms have positive and direct effects on farmers’ LCAT adoption. The analyses also discovered four mediation paths that indirectly influence farmers’ LCAT adoption, including Subjective Norms → Personal Norms → Adoption Level; Consequence Awareness → Personal Norms → Adoption Level; Responsibility Attribution → Personal Norms → Adoption Level; and Consequence Awareness → Responsibility Attribution → Personal Norms → Adoption Level. The study deepens our understanding of the social-psychological mechanism underlying farmers’ LCAT adoption behavior. The findings offer valuable insights for promoting low-carbon agricultural technologies and guiding policy development. Recommendations include promoting LCAT by leveraging social influence to enhance social norms, educating farmers on ethical environmental stewardship, raising awareness of farming’s environmental impacts, and providing policy incentives and technical support to reduce adoption barriers. Full article
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25 pages, 9637 KB  
Article
LCAT in Cancer Biology: Embracing Epigenetic Regulation, Immune Interactions, and Therapeutic Implications
by Manzhi Gao, Wentian Zhang, Xinxin Li, Sumin Li, Wenlan Wang and Peijun Han
Int. J. Mol. Sci. 2025, 26(4), 1453; https://doi.org/10.3390/ijms26041453 - 10 Feb 2025
Cited by 3 | Viewed by 2873
Abstract
Lecithin cholesterol acyltransferase (LCAT) is a crucial enzyme in high-density lipoprotein (HDL) metabolism that is often dysregulated in cancers, affecting tumor growth and therapy response. We extensively studied LCAT expression in various malignancies, linking it to clinical outcomes and genetic/epigenetic alterations. We analyzed [...] Read more.
Lecithin cholesterol acyltransferase (LCAT) is a crucial enzyme in high-density lipoprotein (HDL) metabolism that is often dysregulated in cancers, affecting tumor growth and therapy response. We extensively studied LCAT expression in various malignancies, linking it to clinical outcomes and genetic/epigenetic alterations. We analyzed LCAT expression in multiple cancers and used the Cox regression model to correlate it with patient survival metrics, including overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). We also examined the copy number variations (CNVs), single-nucleotide variations (SNVs), DNA methylation, and N6-methyladenosine (m6A) modifications of LCAT and their connections to tumor immune responses and drug sensitivity. LCAT expression varies among cancers and correlates with patient outcomes. Low expression is linked to poor prognosis in low-grade glioma (LGG) and liver hepatocellular carcinoma (LIHC), while high expression is associated with better outcomes in adrenocortical carcinoma (ACC) and colon adenocarcinoma (COAD). In kidney renal papillary cell carcinoma (KIRP) and uterine corpus endometrial carcinoma (UCEC), LCAT CNV and methylation levels are prognostic markers. LCAT interacts with m6A modifiers and immune molecules, suggesting a role in immune evasion and as a biomarker for immunotherapy response. LCAT expression correlates with chemotherapeutic drug IC50 values, indicating potential for predicting treatment response. In ACC and COAD, LCAT may promote tumor growth, while in LGG and LIHC, it may inhibit progression. LCAT expression and activity regulation could be a new cancer therapy target. As a key molecule linking lipid metabolism, immune modulation, and tumor progression, the potential of LCAT in cancer therapy is significant. Our findings provide new insights into the role of LCAT in cancer biology and support the development of personalized treatment strategies. Full article
(This article belongs to the Section Molecular Immunology)
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11 pages, 530 KB  
Article
A Case–Control Study on the Usefulness of Serum Lecithin: Cholesterol Acyltransferase Activity as a Predictor of Retained Placenta in Close-Up Dairy Cows
by Hiroki Satoh, Kyoko Chisato, Rika Fukumori, Mohamed Tharwat and Shin Oikawa
Animals 2024, 14(24), 3640; https://doi.org/10.3390/ani14243640 - 17 Dec 2024
Cited by 3 | Viewed by 1316
Abstract
The purpose of this study was to investigate the usefulness of the activity of lecithin:cholesterol acyltransferase (LCAT), the enzyme responsible for esterification of cholesterol in plasma, as a predictor of retained placenta (RP) in close-up cows, compared with the non-esterified fatty acids (NEFA) [...] Read more.
The purpose of this study was to investigate the usefulness of the activity of lecithin:cholesterol acyltransferase (LCAT), the enzyme responsible for esterification of cholesterol in plasma, as a predictor of retained placenta (RP) in close-up cows, compared with the non-esterified fatty acids (NEFA) concentration. This study was conducted as a case–control study between February 2010 and February 2016, on a single farm with approximately 200 Holstein parous cows in Hokkaido, Japan. Of the 1187 dairy cattle that calved, 835 dairy cattle were enrolled that underwent routine regular health examinations including blood sampling, body condition score (BCS) and the rumen fill score (RFS) at the close-up stage between 2 and 21 days before their expected calving dates. Of these, 27 cows that were multiparous and had RP were designated as the RP group. The controls were 60 clinically healthy cows that did not develop RP and were matched for the sampling period and parity with the RP group. The LCAT activity and NEFA concentration were significantly (p < 0.01) lower and higher, respectively, in the RP group than in controls. There was no significant difference in cholesteryl esters, free cholesterol concentrations and BCS between the two groups. However, RFS was significantly (p < 0.01) lower in the RP group than in the controls. Cows with LCAT activity of <450 U were 3.6 times more likely to develop RP than those with higher values, whereas those with NEFA levels above 0.4 mEq/L were 5.4 times more likely to. The area under the curve of receiver operator characteristic curves showed that LCAT activity was as efficient as the NEFA concentration in the diagnostic prediction of RP, suggesting it to be a useful predictor. Logistic regression analysis with LCAT or NEFA and RFS as explanatory variables resulted in a model with higher predictive accuracy than with each alone, indicating RFS to be a possible factor in predicting RP. Full article
(This article belongs to the Collection Clinical Pathology in Animals)
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13 pages, 2206 KB  
Article
Identification and Molecular Simulation of Genetic Variants in ABCA1 Gene Associated with Susceptibility to Dyslipidemia in Type 2 Diabetes
by Asifa Majeed, Zunaira Ali Baig and Amir Rashid
Int. J. Mol. Sci. 2024, 25(12), 6796; https://doi.org/10.3390/ijms25126796 - 20 Jun 2024
Cited by 2 | Viewed by 2095
Abstract
Genetic insights help us to investigate disease pathogenesis and risk. The ABCA1 protein encoded by ABCA1 is involved in transporting cholesterol across the cell membrane. Genetic variations in the ABCA1 gene are well documented; however, their role in the development of diabetic dyslipidemia [...] Read more.
Genetic insights help us to investigate disease pathogenesis and risk. The ABCA1 protein encoded by ABCA1 is involved in transporting cholesterol across the cell membrane. Genetic variations in the ABCA1 gene are well documented; however, their role in the development of diabetic dyslipidemia still needs to be explored. This study aimed to identify the associations of rs757194699 (K1587Q) and rs2066714 (I883M) with dyslipidemia in type 2 diabetes and performed molecular simulations. In our case–control study, 330 individuals were divided equally into a diabetic dyslipidemia cases and a healthy controls. Allele-specific polymerase chain reaction and restriction fragment length polymorphism were performed to screen selected variants of the ABCA1 gene. Sanger sequencing was also performed to find genetic mutations in exon 5 of the ABCA1 gene. The C allele of rs757194699 was observed at a high frequency in cases compared to controls and followed the overdominant genetic model (p < 0.0001, OR:3.84; CI:1.67–8.82). The frequency of G allele of rs2066714 was significantly higher in cases compared to controls and followed the genetic model of codominant (p< 0.0001, OR: 39.61; CI:9.97–157.32), dominant (p < 0.0001,OR:59.59; CI:15.19–233.81), overdominant (p< 0.0001, OR:9.75; CI:3.16–30.11), and log-additive (p< 0.0001, OR:42.15; CI:11.08–160.40). In silico modeling and docking revealed that rs2066714 and rs757194699 produced deleterious conformational changes in the ABCA1 protein, resulting in alterations in the binding of the apoA1 protein. There were no genetic variations found in exon-5 in Sanger sequencing. The G allele of rs2066714 and C allele of rs757194699 in the ABCA1 gene were found to be risk alleles in the development of dyslipidemia in type 2 diabetes. These polymorphisms could alter the binding site of ABCA1 with apoA1 thus disturbs the reverse cholesterol transport. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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16 pages, 2316 KB  
Article
Lutein and Zeaxanthin Enhance, Whereas Oxidation, Fructosylation, and Low pH Damage High-Density Lipoprotein Biological Functionality
by Jingyuan Zheng, Brian V. Hong, Joanne K. Agus, Xinyu Tang, Nola R. Klebaner, Siyu Chen, Fei Guo, Danielle J. Harvey, Carlito B. Lebrilla and Angela M. Zivkovic
Antioxidants 2024, 13(5), 616; https://doi.org/10.3390/antiox13050616 - 18 May 2024
Cited by 4 | Viewed by 2680
Abstract
High-density lipoproteins (HDLs) are key regulators of cellular cholesterol homeostasis but are functionally altered in many chronic diseases. The factors that cause HDL functional loss in chronic disease are not fully understood. It is also unknown what roles antioxidant carotenoids play in protecting [...] Read more.
High-density lipoproteins (HDLs) are key regulators of cellular cholesterol homeostasis but are functionally altered in many chronic diseases. The factors that cause HDL functional loss in chronic disease are not fully understood. It is also unknown what roles antioxidant carotenoids play in protecting HDL against functional loss. The aim of this study was to measure how various disease-associated chemical factors including exposure to (1) Cu2+ ions, (2) hypochlorous acid (HOCL), (3) hydrogen peroxide (H2O2), (4) sialidase, (5) glycosidase, (6) high glucose, (7) high fructose, and (8) acidic pH, and the carotenoid antioxidants (9) lutein and (10) zeaxanthin affect HDL functionality. We hypothesized that some of the modifications would have stronger impacts on HDL particle structure and function than others and that lutein and zeaxanthin would improve HDL function. HDL samples were isolated from generally healthy human plasma and incubated with the corresponding treatments listed above. Cholesterol efflux capacity (CEC), lecithin–cholesterol acyl transferase (LCAT) activity, and paraoxonase-1 (PON1) activity were measured in order to determine changes in HDL functionality. Median HDL particle diameter was increased by acidic pH treatment and reduced by HOCl, high glucose, high fructose, N-glycosidase, and lutein treatments. Acidic pH, oxidation, and fructosylation all reduced HDL CEC, whereas lutein, zeaxanthin, and sialidase treatment improved HDL CEC. LCAT activity was reduced by acidic pH, oxidation, high fructose treatments, and lutein. PON1 activity was reduced by sialidase, glycosidase, H2O2, and fructose and improved by zeaxanthin and lutein treatment. These results show that exposure to oxidizing agents, high fructose, and low pH directly impairs HDL functionality related to cholesterol efflux and particle maturation, whereas deglycosylation impairs HDL antioxidant capacity. On the other hand, the antioxidants lutein and zeaxanthin improve or preserve both HDL cholesterol efflux and antioxidant activity but have no effect on particle maturation. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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14 pages, 2024 KB  
Article
A High-Throughput NMR Method for Lipoprotein-X Quantification
by Erwin Garcia, Irina Shalaurova, Steven P. Matyus, Lita A. Freeman, Edward B. Neufeld, Maureen L. Sampson, Rafael Zubirán, Anna Wolska, Alan T. Remaley, James D. Otvos and Margery A. Connelly
Molecules 2024, 29(3), 564; https://doi.org/10.3390/molecules29030564 - 23 Jan 2024
Cited by 3 | Viewed by 3297
Abstract
Lipoprotein X (LP-X) is an abnormal cholesterol-rich lipoprotein particle that accumulates in patients with cholestatic liver disease and familial lecithin–cholesterol acyltransferase deficiency (FLD). Because there are no high-throughput diagnostic tests for its detection, a proton nuclear magnetic resonance (NMR) spectroscopy-based method was developed [...] Read more.
Lipoprotein X (LP-X) is an abnormal cholesterol-rich lipoprotein particle that accumulates in patients with cholestatic liver disease and familial lecithin–cholesterol acyltransferase deficiency (FLD). Because there are no high-throughput diagnostic tests for its detection, a proton nuclear magnetic resonance (NMR) spectroscopy-based method was developed for use on a clinical NMR analyzer commonly used for the quantification of lipoproteins and other cardiovascular biomarkers. The LP-X assay was linear from 89 to 1615 mg/dL (cholesterol units) and had a functional sensitivity of 44 mg/dL. The intra-assay coefficient of variation (CV) varied between 1.8 and 11.8%, depending on the value of LP-X, whereas the inter-assay CV varied between 1.5 and 15.4%. The assay showed no interference with bilirubin levels up to 317 mg/dL and was also unaffected by hemolysis for hemoglobin values up to 216 mg/dL. Samples were stable when stored for up to 6 days at 4 °C but were not stable when frozen. In a large general population cohort (n = 277,000), LP-X was detected in only 50 subjects. The majority of LP-X positive cases had liver disease (64%), and in seven cases, had genetic FLD (14%). In summary, we describe a new NMR-based assay for LP-X, which can be readily implemented for routine clinical laboratory testing. Full article
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18 pages, 7449 KB  
Article
Effects of Thyroid Powder on Tadpole (Lithobates catesbeiana) Metamorphosis and Growth: The Role of Lipid Metabolism and Gut Microbiota
by Bo Zhu, Chuang Shao, Wenjie Xu, Jihong Dai, Guihong Fu and Yi Hu
Animals 2024, 14(2), 208; https://doi.org/10.3390/ani14020208 - 8 Jan 2024
Cited by 6 | Viewed by 4446
Abstract
A low metamorphosis rate of amphibian larvae, commonly known as tadpoles, limits the farming production of bullfrogs (Lithobates catesbeiana). This study aimed to examine the effects of processed thyroid powder as a feed additive on tadpole metamorphosis, lipid metabolism, and gut [...] Read more.
A low metamorphosis rate of amphibian larvae, commonly known as tadpoles, limits the farming production of bullfrogs (Lithobates catesbeiana). This study aimed to examine the effects of processed thyroid powder as a feed additive on tadpole metamorphosis, lipid metabolism, and gut microbiota. Five groups of tadpoles were fed with diets containing 0 g/kg (TH0), 1.5 g/kg (TH1.5), 3 g/kg (TH3), 4.5 g/kg (TH4.5), and 6 g/kg (TH6) thyroid powder for 70 days. The results showed that TH increased the average weight of tadpoles during metamorphosis, with the TH6 group having the highest values. The TH4.5 group had the highest metamorphosis rate (p < 0.05). Biochemical tests and Oil Red O staining showed that the lipid (triglyceride) content in the liver decreased after TH supplementation, especially at doses higher than 1.5 g/kg. RT-qPCR revealed that TH at doses higher than 4.5 g/kg significantly up-regulated the transcriptional expression of the pparα, accb, fas, fadd6, acadl, and lcat genes, which are related to lipid metabolism (p < 0.05). These results showed that TH seems to simultaneously promote the synthesis and decomposition of lipid and fatty acids, but ultimately show a decrease in lipids. As for the gut microbiota, it is noteworthy that Verrucomicrobia increased significantly in the TH4.5 and TH6 groups, and the Akkermansia (classified as Verrucomicrobia) was the corresponding genus, which is related to lipid metabolism. Specifically, the metabolic pathways of the gut microbiota were mainly enriched in metabolic-related functions (such as lipid metabolism), and there were significant differences in metabolic and immune pathways between the TH4.5 and TH0 groups (p < 0.05). In summary, TH may enhance lipid metabolism by modulating the gut microbiota (especially Akkermansia), thereby promoting the growth of tadpoles. Consequently, a supplementation of 4.5 g/kg or 6 g/kg of TH is recommended for promoting the metamorphosis and growth of tadpoles. Full article
(This article belongs to the Special Issue Fish Nutrition, Physiology and Management)
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35 pages, 10537 KB  
Article
Metabolomics Analysis and Biochemical Profiling of Arsenic-Induced Metabolic Impairment and Disease Susceptibility
by Syed Muhammad Shoaib, Samina Afzal, Ali Feezan, Muhammad Sajid Hamid Akash, Ahmed Nadeem and Tahir Maqbool Mir
Biomolecules 2023, 13(9), 1424; https://doi.org/10.3390/biom13091424 - 20 Sep 2023
Cited by 9 | Viewed by 3998
Abstract
Our study aimed to conduct a comprehensive biochemical profiling and metabolomics analysis to investigate the effects of arsenic-induced metabolic disorders, with a specific focus on disruptions in lipid metabolism, amino acid metabolism, and carbohydrate metabolism. Additionally, we sought to assess the therapeutic potential [...] Read more.
Our study aimed to conduct a comprehensive biochemical profiling and metabolomics analysis to investigate the effects of arsenic-induced metabolic disorders, with a specific focus on disruptions in lipid metabolism, amino acid metabolism, and carbohydrate metabolism. Additionally, we sought to assess the therapeutic potential of resveratrol (RSV) as a remedy for arsenic-induced diabetes, using metformin (MF) as a standard drug for comparison. We measured the total arsenic content in mouse serum by employing inductively coupled plasma mass spectrometry (ICP-MS) after administering a 50-ppm solution of sodium arsenate (50 mg/L) in purified water. Our findings revealed a substantial increase in total arsenic content in the exposed group, with a mean value of 166.80 ± 8.52 ppb (p < 0.05). Furthermore, we investigated the impact of arsenic exposure on various biomarkers using enzyme-linked immunosorbent assay (ELISA) methods. Arsenic exposed mice exhibited significant hyperglycemia (p < 0.001) and elevated levels of homeostatic model assessment of insulin resistance (HOMA-IR), hemoglobin A1c (Hb1Ac), Inflammatory biomarkers as well as liver and kidney function biomarkers (p < 0.05). Additionally, the levels of crucial enzymes linked to carbohydrate metabolism, including α-glucosidase, hexokinase, and glucose-6-phosphatase (G6PS), and oxidative stress biomarkers, such as levels of glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD), were significantly reduced in the arsenic-exposed group compared to the control group (p < 0.05). However, the level of MDA was significantly increased. Molecular analysis of gene expression indicated significant upregulation of key enzymes involved in lipid metabolism, such as carnitine palmitoyl-transferase-I (CPT-I), carnitine palmitoyl-transferase-II (CPT-II), lecithin–cholesterol acyltransferase (LCAT), and others. Additionally, alterations in gene expression related to glucose transporter-2 (GLUT-2), glucose-6-phosphatase (G6PC), and glucokinase (GK), associated with carbohydrate metabolism, were observed. Amino acid analysis revealed significant decreases in nine amino acids in arsenic-exposed mice. Metabolomics analysis identified disruptions in lipid metabolomes, amino acids, and arsenic metabolites, highlighting their involvement in essential metabolic pathways. Histopathological observations revealed significant changes in liver architecture, hepatocyte degeneration, and increased Kupffer cells in the livers of arsenic-exposed mice. In conclusion, these findings enhance our comprehension of the impact of environmental toxins on metabolic health and offer potential avenues for remedies against such disruptions. Full article
(This article belongs to the Special Issue Lipid Metabolism in Health and Disease 2023)
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19 pages, 2355 KB  
Article
Differential Expression of Subsets of Genes Related to HDL Metabolism and Atherogenesis in the Peripheral Blood in Coronary Artery Disease
by Alexander D. Dergunov, Elena V. Nosova, Alexandra V. Rozhkova, Margarita A. Vinogradina, Veronika B. Baserova, Mikhail A. Popov, Svetlana A. Limborska and Liudmila V. Dergunova
Curr. Issues Mol. Biol. 2023, 45(8), 6823-6841; https://doi.org/10.3390/cimb45080431 - 16 Aug 2023
Cited by 9 | Viewed by 2520
Abstract
Differential expression of genes (DEGs) in coronary artery disease (CAD) and the association between transcript level and high-density lipoprotein cholesterol (HDL-C) were studied with 76 male patients with CAD and 63 control patients. The transcript level of genes related to HDL metabolism (24 [...] Read more.
Differential expression of genes (DEGs) in coronary artery disease (CAD) and the association between transcript level and high-density lipoprotein cholesterol (HDL-C) were studied with 76 male patients with CAD and 63 control patients. The transcript level of genes related to HDL metabolism (24 genes) and atherosclerosis-prone (41 genes) in RNA isolated from peripheral blood mononuclear cells was measured by real-time RT-PCR. Twenty-eight DEGs were identified. The expression of cholesterol transporters, ALB, APOA1, and LCAT was down-regulated, while the expression of AMN, APOE, LDLR, LPL, PLTP, PRKACA, and CETP was up-regulated. The systemic inflammation in CAD is evidenced by the up-regulation of IL1B, TLR8, CXCL5, and TNFRSF1A. For the controls, TLR8 and SOAT1 were negative predictors of the HDL-C level. For CAD patients, PRKACG, PRKCQ, and SREBF1 were positive predictors, while PRKACB, LCAT, and S100A8 were negative predictors. For CAD patients, the efficiency of reverse cholesterol transport is 73–79%, and intracellular free cholesterol seems to accumulate at hyperalphalipoproteinemia. Both atheroprotective (via S100A8) and proatherogenic (via SREBF1, LCAT, PRKACG, PRKACB, and PRKCQ) associations of gene expression with HDL-C determine HDL functionality in CAD patients. The selected key genes and involved pathways may represent HDL-specific targets for the diagnosis and treatment of CAD and atherosclerosis. Full article
(This article belongs to the Special Issue A Focus on Molecular Basis in Cardiac Diseases)
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