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Nutrients Oct 2023Plant sterols are well-known natural lipid-lowering agents. The DESCO (Diet and plant sterols in the control of cholesterolemia) study was a single-center, randomized,... (Randomized Controlled Trial)
Randomized Controlled Trial
The Effect of Dietary Supplementation with Plant Sterols on Total and LDL-Cholesterol in Plasma Is Affected by Adherence to Mediterranean Diet: Insights from the DESCO Randomized Clinical Study.
Plant sterols are well-known natural lipid-lowering agents. The DESCO (Diet and plant sterols in the control of cholesterolemia) study was a single-center, randomized, double-blind, placebo-controlled, two-way crossover clinical trial designed to investigate the effect of a once-a-day ready-to-drink dietary supplement containing 2.5 g of phytosterols on the lipid profile, also in relation to the quality of the diet, in a cohort of 50 Italian individuals with polygenic hypercholesterolemia and low global cardiovascular risk. Eligible individuals were enrolled in a run-in period of 2 weeks. Then, participants who qualified for continuation in the study were randomly allocated (1:1) to a 3-week treatment with either phytosterols or placebo. After a 2-week washout period, enrolled individuals were crossed over to receive the alternative treatment. Dietary supplementation with phytosterols was associated with significant improvement in plasma levels of total cholesterol (TC; -11.8 ± 4.0 mg/dL, = 0.016), low-density lipoprotein cholesterol (LDL-C; -7.8 ± 7.7 mg/dL, = 0.021), and apolipoprotein B-100 (Apo B-100, -3.7 ± 4.1 mg/dL, = 0.048) compared to baseline. The changes in TC and LDL-C were also significant compared to placebo, and greater adherence to the Mediterranean diet was significantly associated with greater reductions in LDL-C. Dietary supplementation with phytosterols was well tolerated and adherence to treatment was high. According to the findings of DESCO, the once-a-day ready-to-drink dietary supplement we tested is able to quickly and significantly decrease plasma levels of TC, LDL-C, and Apo B-100, with a greater effect in individuals more adhering to the Mediterranean dietary pattern.
Topics: Humans; Cholesterol, LDL; Phytosterols; Cholesterol; Apolipoprotein B-100; Diet, Mediterranean; Dietary Supplements; Double-Blind Method
PubMed: 37960208
DOI: 10.3390/nu15214555 -
Nutrients Oct 2023(1) Background: The relationship between lipids, apolipoproteins, and telomere length (TL) has been explored in previous studies; however, the causal relationship...
(1) Background: The relationship between lipids, apolipoproteins, and telomere length (TL) has been explored in previous studies; however, the causal relationship between the two remains unclear. This study aims to assess the causal relationship between lipids, apolipoproteins, and TL using the two-sample Mendelian randomization (MR) approach; (2) Methods: This study comprehensively employed both univariate MR (uvMR) and multivariate MR (mvMR) methods to genetically evaluate the associations between 21 exposures related to lipids and apolipoproteins and the outcome of TL. During the analysis process, we utilized various statistical methods, including Inverse Variance Weighting (IVW), Weighted Median, MR-Egger regression, MR-PRESSO, and outlier tests. Furthermore, to confirm the robustness of the results, we conducted several sensitivity analyses to explore potential heterogeneity; (3) Results: The uvMR analysis indicated that an increase in MUFA, MUFA/FA ratio, LDL-C, VLDL-C, total cholesterol, ApoB, and triglycerides (TG) was associated with an increase in TL. However, this relationship did not manifest in the mvMR analysis, suggesting that this association may be based on preliminary evidence; (4) Conclusions: MR analysis results suggest potential suggestive positive causal relationships between genetically predicted MUFA, MUFA/FA ratio, LDL-C, VLDL-C, total cholesterol, ApoB, and TG with TL.
Topics: Cholesterol, LDL; Mendelian Randomization Analysis; Apolipoproteins; Apolipoproteins B; Triglycerides; Telomere; Genome-Wide Association Study
PubMed: 37960150
DOI: 10.3390/nu15214497 -
Frontiers in Endocrinology 2023Epidemiological evidence for the link of interleukin 1 (IL-1) and its inhibition with cardiovascular diseases (CVDs) remains controversial. We aim to investigate the...
AIMS
Epidemiological evidence for the link of interleukin 1 (IL-1) and its inhibition with cardiovascular diseases (CVDs) remains controversial. We aim to investigate the cardiovascular effects of IL-1 receptor antagonist (IL-1Ra) and underlying mechanisms.
METHODS
Genetic variants identified from a genome-wide association study involving 30,931 individuals were used as instrumental variables for the serum IL-1Ra concentrations. Genetic associations with CVDs and cardiometabolic risk factors were obtained from international genetic consortia. Inverse-variance weighted method was utilized to derive effect estimates, while supplementary analyses employing various statistical approaches.
RESULTS
Genetically determined IL-1Ra level was associated with increased risk of coronary heart disease (CHD; OR, 1.07; 95% CI: 1.03-1.17) and myocardial infarction (OR, 1.13; 95% CI: 1.04-1.21). The main results remained consistent in supplementary analyses. Besides, IL-1Ra was associated with circulating levels of various lipoprotein lipids, apolipoproteins and fasting glucose. Interestingly, observed association pattern with CHD was reversed when adjusting for apolipoprotein B (OR, 0.84; 95%CI: 0.71-0.99) and slightly attenuated on accounting for other cardiometabolic risk factors. Appropriate lifestyle intervention was found to lower IL-1Ra concentration and mitigate the heightened CHD risk it posed.
CONCLUSION
Apolipoprotein B represents the key driver, and a potential target for reversal of the causal link between serum IL-1Ra and increased risk of CHD/MI. The combined therapy involving IL-1 inhibition and lipid-modifying treatment aimed at apolipoprotein B merit further exploration.
Topics: Humans; Interleukin 1 Receptor Antagonist Protein; Genome-Wide Association Study; Coronary Disease; Apolipoproteins B; Myocardial Infarction; Apolipoproteins; Interleukin-1; Receptors, Interleukin-1
PubMed: 37941911
DOI: 10.3389/fendo.2023.1278273 -
Poultry Science Jan 2024Animal growth is closely related to glycolipid metabolism, and the liver is the main organ for glycogen storage and fat synthesis in birds, but whether monochromatic...
Animal growth is closely related to glycolipid metabolism, and the liver is the main organ for glycogen storage and fat synthesis in birds, but whether monochromatic light affects glycogen and lipid synthesis in the liver is unclear. Therefore, in this study, a total of 96 Arbor Acre (AA) broilers at posthatching d 0 (P0) were raised under 4 kinds of light-emitting diode (LED) lights, white light (WL), red light (RL), green light (GL), and blue light (BL), to posthatching d 21 (P21) and 35 (P35). The results showed that the liver, abdominal fat, and abdominal fat indices gradually increased with increasing age under monochromatic light treatments. The liver glycogen and triglyceride (TG) contents also showed an increasing trend. Furthermore, compared with those at P21, the mRNA levels of glycogen synthase (GS), glycogen synthase kinase-3β (GSK-3β), and protein kinase B (AKT1) in the liver were increased in the WL and RL groups at P35, and the mRNA levels of acetyl-CoA carboxylase (ACC) and apolipoprotein B (APOB) increased in all groups at P35. At the same time, the total antioxidant capacity (T-AOC) and liver superoxide dismutase (SOD) contents increased in all groups at P35 compared with those at P21. In addition, at P21, compared with WL, GL and BL promoted the serum glucose (GLU) and TG contents by increasing the mRNA levels of GS, GSK-3β, glucose-6-phosphatase (G6PC), ACC, and fatty acid synthase (FAS), but no effect on the proliferative ability and damage of hepatocytes. At P35, RL promoted the hepatic glycogen and TG contents by increasing GSK-3β, AKT1, ACC, and APOB mRNA levels, and the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were increased than in the WL group. These results suggest that the effects of light color on liver glycogen and lipid synthesis in broilers changed with age, and also provide a theoretical guidance for scientific use of color of light information to improve productive performance in broilers.
Topics: Animals; Liver Glycogen; Chickens; Glycogen Synthase Kinase 3 beta; Lipid Metabolism; RNA, Messenger; Apolipoproteins B; Lipids; Liver
PubMed: 37931402
DOI: 10.1016/j.psj.2023.103193 -
BMC Musculoskeletal Disorders Nov 2023Lipids are critical in bone metabolism, and several studies have highlighted their importance. This study aimed to investigate the relationship between apolipoprotein B...
BACKGROUND
Lipids are critical in bone metabolism, and several studies have highlighted their importance. This study aimed to investigate the relationship between apolipoprotein B (apo B) and bone mineral density (BMD) at different skeletal sites (lumbar spine, femoral neck, and total femur) and to compare the influence of apo B with other traditional lipid markers.
METHODS
The study included participants from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2016 who had complete data for apo B and BMD at the three skeletal sites. We used weighted multivariate regression analysis, subgroup analysis, and interaction tests to examine associations. Restricted cubic spline (RCS) was used to examine the non-linear relationship.
RESULTS
A total of 4,258 adults were included in the study. Multivariate linear regression analysis showed that the relationship between apo B and BMD varied by skeletal site: a negative association was found with lumbar spine BMD [β = -0.054, 95%CI: (-0.073, -0.035)]. In contrast, a positive association was found with femoral neck BMD [β = 0.031, 95%CI: (0.011, 0.051)] and no significant association between apo B and total femur BMD.
CONCLUSIONS
Our findings suggest that apo B is associated with BMD in a site-specific manner.
Topics: Adult; Humans; Absorptiometry, Photon; Apolipoproteins B; Bone Density; Femur Neck; Lumbar Vertebrae; Nutrition Surveys
PubMed: 37919727
DOI: 10.1186/s12891-023-06990-x -
Scientific Reports Nov 2023Elevated plasma numbers of atherogenic apoB-lipoproteins (apoB), mostly as low-density lipoproteins (LDL), predict diabetes risk by unclear mechanisms. Upregulation of...
Elevated plasma numbers of atherogenic apoB-lipoproteins (apoB), mostly as low-density lipoproteins (LDL), predict diabetes risk by unclear mechanisms. Upregulation of the NLRP3 inflammasome/interleukin-1 beta (IL-1β) system in white adipose tissue (WAT) is implicated in type 2 diabetes (T2D); however, metabolic signals that stimulate it remain unexplored. We hypothesized that (1) subjects with high-apoB have higher WAT IL-1β-secretion than subjects with low-apoB, (2) WAT IL-1β-secretion is associated with T2D risk factors, and (3) LDL prime and/or activate the WAT NLRP3 inflammasome. Forty non-diabetic subjects were assessed for T2D risk factors related to systemic and WAT glucose and fat metabolism. Regulation of the NLRP3 inflammasome was explored using LDL without/with the inflammasome's priming and activation controls (LPS and ATP). LDL induced IL1B-expression and IL-1β-secretion in the presence of ATP in WAT and macrophages. Subjects with high-apoB had higher WAT IL-1β-secretion independently of covariates. The direction of association of LDL-induced WAT IL-1β-secretion to T2D risk factors was consistently pathological in high-apoB subjects only. Adjustment for IL-1β-secretion eliminated the association of plasma apoB with T2D risk factors. In conclusion, subjects with high-apoB have higher WAT IL-1β-secretion that may explain their risk for T2D and may be related to LDL-induced priming of the NLRP3 inflammasome.ClinicalTrials.gov (NCT04496154): Omega-3 to Reduce Diabetes Risk in Subjects With High Number of Particles That Carry "Bad Cholesterol" in the Blood-Full Text View-ClinicalTrials.gov.
Topics: Humans; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Lipoproteins, LDL; Interleukin-1beta; Diabetes Mellitus, Type 2; Macrophages; Apolipoproteins B; Adipose Tissue, White; Adenosine Triphosphate
PubMed: 37914804
DOI: 10.1038/s41598-023-45870-1 -
Cancer Medicine Nov 2023Plasma cell neoplasms are a group of hematologic neoplasms that often develop in the elderly population. The relationship between cholesterol levels and hematologic...
BACKGROUND
Plasma cell neoplasms are a group of hematologic neoplasms that often develop in the elderly population. The relationship between cholesterol levels and hematologic malignancy has been identified in population studies. However, it is still unclear if there is a relationship between cholesterol levels and plasma cell neoplasm in European ancestry.
METHODS
Prospective cohorts included 502,507 individuals from the UK Biobank who were followed up to 2019 and assessed total cholesterol(TC) levels, low-density lipoprotein (LDL) levels, high-density lipoprotein (HDL) levels, apolipoprotein A (ApoA) and apolipoprotein B (ApoB) as risk factors for plasma cell neoplasms with Cox proportional hazard regression and restricted cubic spline model. We also used two-sample Mendelian randomization to determine if the cholesterol level has a causal effect on developing plasma cell neoplasms.
RESULTS
We observed 1819 plasma cell neoplasm cases during 14.2 years of follow-up in the UK Biobank. We found higher blood serum cholesterol levels at baseline were associated with a lower risk of plasma cell neoplasm in our study. All lipid profiles we analyzed in this study were inversely associated with plasma cell neoplasm risk (all p <0.005) but triglycerides did not have such association. However, there was no suggestive association of genetically predicted serum LDL, HDL, and total cholesterol levels with multiple myeloma.
CONCLUSION
Low serum total cholesterol, LDL, HDL, ApoA, and ApoB levels were all associated with increasing the risk of plasma cell neoplasm.
Topics: Humans; Aged; Cohort Studies; Prospective Studies; Multiple Myeloma; Biological Specimen Banks; Cholesterol, HDL; Cholesterol, LDL; Apolipoproteins B; Risk Factors; Triglycerides; Apolipoproteins A
PubMed: 37908181
DOI: 10.1002/cam4.6649 -
Cardiovascular Revascularization... Apr 2024Apolipoprotein (apo) levels are associated with coronary risk. However, the relationship between apo levels after percutaneous coronary intervention (PCI) and long-term...
BACKGROUND/PURPOSE
Apolipoprotein (apo) levels are associated with coronary risk. However, the relationship between apo levels after percutaneous coronary intervention (PCI) and long-term major adverse cardiac events (MACEs) remains unclear. We aimed to investigate the association between lipid levels, including apo, at follow-up, and long-term MACEs in patients undergoing PCI.
METHODS/MATERIALS
In total, 241 patients who underwent PCI between January 2004 and August 2008 were included in this study. MACEs were defined as cardiac death, acute coronary syndrome, or coronary revascularization of new lesions. The primary endpoint was MACE, and the secondary endpoint was a composite of cardiac death and acute coronary syndrome.
RESULTS
During a mean follow-up period of 2079 days, the following cardiovascular events occurred in 78 patients: cardiovascular death (n = 1), non-fatal acute myocardial infarctions (n = 10), and revascularizations of new lesions (n = 67). Multivariate cox's proportional hazards analysis showed that the apo B level was an independent risk factor for MACEs (hazard ratio 1.11, 95 % confidence interval 1.03-1.20; P = 0.009). In the Kaplan-Meier estimation for primary endpoints, significant differences were observed in the apo B level and apo B/apo A1 ratio (P = 0.04 and P = 0.004, respectively). However, there was no difference in the LDL-C level and LDL-C/HDL-C ratio. At the secondary endpoint, only the apo B/apo A1 ratio was a prognostic factor (P = 0.007).
CONCLUSIONS
In the long-term cardiovascular events of patients undergoing PCI, the apo B level and apo B/apo A1 ratio were more valuable prognostic factors for cardiovascular events compared to the LDL-C level and LDL-C/HDL-C ratio.
Topics: Humans; Prognosis; Percutaneous Coronary Intervention; Acute Coronary Syndrome; Cholesterol, LDL; Apolipoprotein A-I; Risk Factors; Apolipoproteins B; Death
PubMed: 37872021
DOI: 10.1016/j.carrev.2023.10.012 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Sep 2023To investigate the apolipoprotein C-3 (APOC3) gene Ⅰ polymorphism and its relationship with changes in serum lipids in patients with gestational diabetes mellitus (GDM).
OBJECTIVE
To investigate the apolipoprotein C-3 (APOC3) gene Ⅰ polymorphism and its relationship with changes in serum lipids in patients with gestational diabetes mellitus (GDM).
METHODS
A total of 630 pregnant women with GDM and 1027 normal pregnant controls were covered in the study. The genotype and allele frequencies of 3 Ⅰ polymorphism were analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glucose (Glu) were measured by enzymatic methods. Plasma insulin (INS) was measured by chemiluminescence. Apolipoproteins A 1 (apoA1) and B (apoB) levels were measured by turbidimetric immunoassay.
RESULTS
The allele frequencies of S1 and S2 of the 3 polymorphism at the Ⅰ locus were 0.704 and 0.296 in the GDM group and 0.721 and 0.279 in the control group, respectively. There was no significant difference in genotype frequency and allele frequency of 3 Ⅰ polymorphism between the GDM and the control groups ( >0.05). In the GDM group, those with S2S2 and S1S2 genotypes had higher plasma HDL-C levels and lower atherogenic index (AI) values than those with S1S1 genotype did, with the differences being statistically significant (all <0.05). GDM patients were then divided into obesity and non-obesity subgroups. Further subgroup analysis showed that the association of 3 genotype with changes in HDL-C levels was observed only in obese GDM patients, while the association of 3 genotype with changes in AI values was observed in both obese and nonobese patients. In addition, in obese GDM patients, those with S2S2 genotype had significantly higher plasma TG levels than those with S1S1 and S1S2 genotypes did ( <0.05 and <0.01, respectively). In non-obese GDM patients, those with S2S2 genotype had significantly lower apoB/apoA1 ratio than S2S2 carriers did ( <0.05). No genotype-related effect on lipid and apolipoprotein variations was evident in the normal controls.
CONCLUSION
3 Ⅰ polymorphism in GDM patients is associated with HDL-C and TG levels as well as AI value and apoB/apoA1 ratio. The changes in lipid levels and apolipoprotein ratio showed BMI-dependent features. However, association between polymorphism at the locus and the development of GDM was not observed.
Topics: Female; Humans; Pregnancy; Apolipoprotein A-I; Apolipoprotein C-III; Apolipoproteins B; Apolipoproteins C; Cholesterol, HDL; Diabetes, Gestational; Gene Frequency; Genotype; Obesity; Triglycerides
PubMed: 37866958
DOI: 10.12182/20230960505 -
Lipids in Health and Disease Oct 2023Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder. The primary objective of this study was to identify the major pathogenic mutations in a...
BACKGROUND
Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder. The primary objective of this study was to identify the major pathogenic mutations in a Chinese family with FH.
METHODS
Whole-genome sequencing (WGS) was used to identify variants of FH-related genes, including low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9). Bioinformatics software was used to predict signal peptides, transmembrane structures, and spatial construction information of the mutated sequences. Western blotting was performed on the mutant protein to determine the presence of the major structural domains of the LDLR. The PCSK9 and APOB genes were screened and analyzed. Moreover, the proband and his brother were treated with a PCSK9 inhibitor for 1 year, and the effect of the treatment on lipid levels was assessed.
RESULTS
WGS revealed two potentially pathogenic mutations in the LDLR gene. One was a novel mutation, c.497delinsGGATCCCCCAGCTGCATCCCCCAG (p. Ala166fs), and the other was a known pathogenic mutation, c.2054C>T (p. Pro685Leu). Bioinformatics prediction and in vitro experiments revealed that the novel mutation could not be expressed on the cell membrane. Numerous gene variants were identified in the APOB gene that may have a significant impact on the family members with FH. Thus, it is suggested that the severe manifestation of FH in the proband primarily resulted from the cumulative genetic effects of variants in both LDLR and APOB. However, a subsequent study indicated that treatment with a PCSK9 inhibitor (Evolocumab) did not significantly reduce the blood lipid levels in the proband or his brother.
CONCLUSIONS
The cumulative effect of LDLR and APOB variants was the primary cause of elevated blood lipid levels in this family. However, PCSK9 inhibitor therapy did not appear to be beneficial for the proband. This study emphasizes the importance of genetic testing in determining the most suitable treatment options for patients with FH.
Topics: Humans; Male; Apolipoproteins B; East Asian People; Hyperlipoproteinemia Type II; Lipids; Mutation; Proprotein Convertase 9; Receptors, LDL; Genetic Testing
PubMed: 37853441
DOI: 10.1186/s12944-023-01935-8