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Calcified Tissue International Feb 2024Observational studies have shown a causal association between dyslipidemia and osteoporosis, but the genetic causation and complete mechanism of which are uncertain. The...
BACKGROUND
Observational studies have shown a causal association between dyslipidemia and osteoporosis, but the genetic causation and complete mechanism of which are uncertain. The disadvantage of previous observational studies is that they are susceptible to confounding factors and bias, that makes it difficult to infer a causal link between those two diseases. Abnormal epigenetic modifications, represented by DNA methylation, are important causes of many diseases. However, there are no studies showing a bridging role for methylation modifications in blood lipid metabolism and osteoporosis.
METHODS
SNPs for lipid profile (Blood VLDL cholesterol (VLDL-C), blood LDL cholesterol (LDL-C), blood HDL cholesterol (HDL-C), blood triglycerides (TG), diagnosed pure hypercholesterolaemia, blood apolipoprotein B (Apo B), blood apolipoprotein A1(Apo A1)), and bone mineral density (BMD) in different body parts (Heel BMD, lumbar BMD, whole-body BMD, femoral neck BMD) were obtained from large meta-analyses of genome-wide association studies as instrumental variables for two-sample Mendelian randomization. Assessment of the genetic effects of lipid profile-associated methylation sites and bone mineral density was carried out using the summary-data-based Mendelian randomization (SMR) method.
RESULTS
Two-sample Mendelian randomization showed that there was a negative causal association between hypercholesterolaemia and heel BMD (p = 0.0103, OR = 0.4590), and total body BMD (p = 0.0002, OR = 0.2826). LDL-C had a negative causal association with heel BMD (p = 8.68E-05, OR = 0.9586). VLDL-C had a negative causal association with heel BMD (p = 0.035, OR = 0.9484), lumbar BMD (p = 0.0316, OR = 0.9356), and total body BMD (p = 0.0035, OR = 0.9484). HDL-C had a negative causal association with heel BMD (p = 1.25E-05, OR = 0.9548), lumbar BMD (p = 0.0129, OR = 0.9358), and total body BMD (p = 0.0399, OR = 0.9644). Apo B had a negative causal association with heel BMD (p = 0.0001, OR = 0.9647). Apo A1 had a negative causal association with heel BMD (p = 0.0132, OR = 0.9746) and lumbar BMD (p = 0.0058, OR = 0.9261). The p-values of all positive results corrected by the FDR method remained significant and sensitivity analysis showed that there was no horizontal pleiotropy in the results despite the heterogeneity in some results. SMR identified 3 methylation sites associated with lipid profiles in the presence of genetic effects on BMD: cg15707428(GREB1), cg16000331(SREBF2), cg14364472(NOTCH1).
CONCLUSION
Our study provides insights into the potential causal links and co-pathogenesis between dyslipidemia and osteoporosis. The genetic effects of dyslipidaemia on osteoporosis may be related to certain aberrant methylation genetic modifications.
Topics: Humans; Apolipoprotein A-I; Genome-Wide Association Study; Lipid Metabolism; Mendelian Randomization Analysis; Hypercholesterolemia; Multiomics; Cholesterol, LDL; Osteoporosis; Bone Density; DNA Methylation; Lipids; Apolipoproteins B; Polymorphism, Single Nucleotide
PubMed: 38071623
DOI: 10.1007/s00223-023-01160-6 -
Journal of Lipid Research Aug 2023Hypertriglyceridemic hyperapoB is an adverse lipoprotein phenotype characterized by low high density lipoprotein (HDL) cholesterol, high triglycerides, high...
Hypertriglyceridemic hyperapoB is an adverse lipoprotein phenotype characterized by low high density lipoprotein (HDL) cholesterol, high triglycerides, high apolipoprotein B (ApoB), and low low density lipoprotein (LDL) cholesterol to ApoB ratio. We investigated whether and to what extent hypertriglyceridemic hyperapoB associates with the incidence and resolution of nonalcoholic fatty liver disease (NAFLD). This prospective cohort study included 9,019 Chinese participants 40 years or older, from 2010 to 2015. Logistic regression models were used to examine the odds ratios (ORs) for the incidence and resolution of NAFLD associated with the hypertriglyceridemic hyperapoB lipoprotein phenotype and individual lipid and lipoprotein parameters. During a median 4.3 years of follow-up, compared with participants with optimal phenotype, the fully adjusted ORs (95% CIs) for participants with hypertriglyceridemic hyperapoB were 2.75 (1.91, 3.95) and 0.57 (0.33, 1.00) for incidence and resolution of NAFLD, respectively. These associations were consistent across subgroup participants with varied demographic, lifestyle, and metabolic status. Individually, each unit increase in HDL cholesterol (OR: 0.98; 95% CI: 0.97, 0.99), natural logarithm-transformed triglycerides (1.89; 1.52, 2.36), and ApoB (1.006; 1.002, 1.011) was independently associated with NAFLD incidence, and only triglycerides (0.77; 0.60, 0.99) was independently associated with NAFLD resolution. Our findings suggest that Chinese adults with hypertriglyceridemic hyperapoB have a higher risk of NAFLD incidence and a lower likelihood of NAFLD resolution. These associations were stable among adults with different demographic, lifestyle, and metabolic status, supporting hypertriglyceridemic hyperapoB as a valuable clinical marker for the prevention and control of NAFLD.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Cohort Studies; Prospective Studies; Lipoproteins, LDL; Triglycerides; Cholesterol; Apolipoproteins B; Lipoproteins; Cholesterol, HDL
PubMed: 37481036
DOI: 10.1016/j.jlr.2023.100418 -
Current Medicinal Chemistry 2021Cardiovascular Disease (CVD) is the most important and the number one cause of mortality in both developing and industrialized nations. The co-morbidities associated... (Review)
Review
Cardiovascular Disease (CVD) is the most important and the number one cause of mortality in both developing and industrialized nations. The co-morbidities associated with CVD are observed from infancy to old age. Apolipoprotein B100 (Apo B) is the primary apolipoprotein and structural protein of all major atherogenic particles derived from the liver including Very-Low- Density Lipoproteins (VLDL), Intermediate-density Lipoprotein (IDL), and Low-density Lipoprotein (LDL) particles. It has been suggested that measurement of the Apo B concentration is a superior and more reliable index for the prediction of CVD risk than is the measurement of LDL-C. Nutraceuticals and medicinal plants have attracted significant attention as it pertains to the treatment of non-communicable diseases, particularly CVD, diabetes mellitus, hypertension, and Nonalcoholic Fatty Liver Disease (NAFLD). The effect of nutraceuticals and herbal products on CVD, as well as some of its risk factors such as dyslipidemia, have been investigated previously. However, to the best of our knowledge, the effect of these natural products, including herbal supplements and functional foods (e.g. fruits and vegetables as either dry materials, or their extracts) on Apo B has not yet been investigated. Therefore, the primary objective of this paper was to review the effect of bioactive natural compounds on plasma Apo B concentrations. It is concluded that, in general, medicinal plants and nutraceuticals can be used as complementary medicine to reduce plasma Apo B levels in a safe, accessible, and inexpensive manner in an attempt to prevent and treat CVD.
Topics: Apolipoproteins B; Biological Products; Dietary Supplements; Humans; Lipoproteins, LDL; Lipoproteins, VLDL; Triglycerides
PubMed: 32338202
DOI: 10.2174/0929867327666200427092114 -
Arteriosclerosis, Thrombosis, and... May 2024Zebrafish have become a powerful model of mammalian lipoprotein metabolism and lipid cell biology. Most key proteins involved in lipid metabolism, including cholesteryl... (Review)
Review
Zebrafish have become a powerful model of mammalian lipoprotein metabolism and lipid cell biology. Most key proteins involved in lipid metabolism, including cholesteryl ester transfer protein, are conserved in zebrafish. Consequently, zebrafish exhibit a human-like lipoprotein profile. Zebrafish with mutations in genes linked to human metabolic diseases often mimic the human phenotype. Zebrafish larvae develop rapidly and externally around the maternally deposited yolk. Recent work revealed that any disturbance of lipoprotein formation leads to the accumulation of cytoplasmic lipid droplets and an opaque yolk, providing a visible phenotype to investigate disturbances of the lipoprotein pathway, already leading to discoveries in MTTP (microsomal triglyceride transfer protein) and ApoB (apolipoprotein B). By 5 days of development, the digestive system is functional, making it possible to study fluorescently labeled lipid uptake in the transparent larvae. These and other approaches enabled the first in vivo description of the STAB (stabilin) receptors, showing lipoprotein uptake in endothelial cells. Various zebrafish models have been developed to mimic human diseases by mutating genes known to influence lipoproteins (eg, , ). This review aims to discuss the most recent research in the zebrafish ApoB-containing lipoprotein and lipid metabolism field. We also summarize new insights into lipid processing within the yolk cell and how changes in lipid flux alter yolk opacity. This curious new finding, coupled with the development of several techniques, can be deployed to identify new players in lipoprotein research directly relevant to human disease.
Topics: Zebrafish; Animals; Lipid Metabolism; Apolipoproteins B; Humans; Disease Models, Animal; Phenotype; Zebrafish Proteins; Mutation
PubMed: 38482694
DOI: 10.1161/ATVBAHA.123.318287 -
Communications Biology Feb 2024Apolipoprotein B-100 (APOB) is a component of fat- and cholesterol-transporting molecules in the bloodstream. It is the main lipoprotein in low-density lipoprotein...
Apolipoprotein B-100 (APOB) is a component of fat- and cholesterol-transporting molecules in the bloodstream. It is the main lipoprotein in low-density lipoprotein cholesterol (LDL) and has been implicated in conditions that end healthspan (the interval between birth and onset of chronic disease). However, APOB's direct relationship with healthspan remains uncertain. With Mendelian randomization, we show that higher levels of APOB and LDL shorten healthspan in humans. Multivariable Mendelian randomization of APOB and LDL on healthspan suggests that the predominant trait accounting for the relationship is APOB. In addition, we provide preliminary evidence that APOB increases risk for Alzheimer's disease, a condition that ends healthspan. If these relationships are causal, they suggest that interventions to improve healthspan in aging populations could include strategies targeting APOB. Ultimately, given that more than 44 million people currently suffer from Alzheimer's disease worldwide, such interventions are needed.
Topics: Humans; Alzheimer Disease; Mendelian Randomization Analysis; Apolipoproteins B; Cholesterol, LDL; Phenotype
PubMed: 38402277
DOI: 10.1038/s42003-024-05887-2 -
International Journal of Epidemiology Oct 2019
Topics: Apolipoproteins B; Atherosclerosis; Cholesterol; Coronary Disease; Data Interpretation, Statistical; Humans; Membrane Transport Proteins; Mendelian Randomization Analysis; Proprotein Convertase 9; Proteoglycans; Risk Factors; Triglycerides
PubMed: 30968109
DOI: 10.1093/ije/dyz068 -
Nutrients Jan 2023In the present review, we provide a comprehensive narrative overview of the current knowledge on the effects of total and specific types of nut consumption (excluding... (Review)
Review
In the present review, we provide a comprehensive narrative overview of the current knowledge on the effects of total and specific types of nut consumption (excluding nut oil) on blood lipids and lipoproteins. We identified a total of 19 systematic reviews and meta-analyses of randomized controlled trials (RCTs) that were available in PubMed from the inception date to November 2022. A consistent beneficial effect of most nuts, namely total nuts and tree nuts, including walnuts, almonds, cashews, peanuts, and pistachios, has been reported across meta-analyses in decreasing total cholesterol (mean difference, MD, -0.09 to -0.28 mmol/L), LDL-cholesterol (MD, -0.09 to -0.26 mmol/L), and triglycerides (MD, -0.05 to -0.17 mmol/L). However, no effects on HDL-cholesterol have been uncovered. Preliminary evidence indicates that adding nuts into the regular diet reduces blood levels of apolipoprotein B and improves HDL function. There is also evidence that nuts dose-dependently improve lipids and lipoproteins. Sex, age, or nut processing are not effect modifiers, while a lower BMI and higher baseline lipid concentrations enhance blood lipid/lipoprotein responses. While research is still emerging, the evidence thus far indicates that nut-enriched diets are associated with a reduced number of total LDL particles and small, dense LDL particles. In conclusion, evidence from clinical trials has shown that the consumption of total and specific nuts improves blood lipid profiles by multiple mechanisms. Future directions in this field should include more lipoprotein particle, apolipoprotein B, and HDL function studies.
Topics: Nuts; Lipids; Cholesterol, LDL; Lipoproteins; Apolipoproteins B
PubMed: 36771303
DOI: 10.3390/nu15030596 -
Journal of the American College of... Jan 2024
Topics: Humans; Lipoprotein(a); Apolipoproteins B; Lipoproteins, LDL
PubMed: 38233013
DOI: 10.1016/j.jacc.2023.11.008 -
Arquivos Brasileiros de Cardiologia Jul 2020Excess Weight and Cardiovascular Diseases are health problems with increasing prevalence among children and adolescents, hence the need to investigate the issues related... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Excess Weight and Cardiovascular Diseases are health problems with increasing prevalence among children and adolescents, hence the need to investigate the issues related to them to better deal with the problem.
OBJECTIVE
To investigate the influence of excess adiposity on the levels of apolipoprotein B and A1 in children and adolescents.
METHODS
A systematic search was conducted in the PubMed, Embase, Lilacs, Web of Science, Ovid and Science direct databases, searching for cohort eligible studies and evaluating their results, methodological quality and risk of bias; combinable studies with good quality and low risk of bias were evaluated by meta-analysis. The summary measure used was the weighted mean difference (WMD) with its respective 95% confidence interval.
RESULTS
8 articles attended the eligibility criteria including individuals with age mean varying from 9 to 15.7 years of age. The meta-analysis included 4 articles with a total of 7,974 children and adolescents. It was observed a mean increase of 4,94mg/dL (95%CI: 4,22 to 5,67) in the ApoB levels in individuals with excess of body adiposity. For the ApoA1, we identified a mean reduction of -8,13mg/dL (95%CI: -9,09 to -7,17 mg/dL) in its levels in children and adolescents with higher body adiposity. Beside this, the influence of excess adiposity on the ApoB and ApoA1 levels was higher between adolescents than children.
CONCLUSIONS
The excess of body adiposity influenced both the reduction of ApoA1 values and the increase of ApoB levels, being these changes more relevant among adolescents. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).
Topics: Adiposity; Adolescent; Apolipoproteins B; Child; Humans; Obesity; Prospective Studies
PubMed: 32696854
DOI: 10.36660/abc.20190331 -
Global Heart Jan 2021Apolipoprotein B (apoB) integrates and extends the information from the conventional measures of atherogenic cholesterol and triglyceride. To illustrate how apoB could...
BACKGROUND AND AIMS
Apolipoprotein B (apoB) integrates and extends the information from the conventional measures of atherogenic cholesterol and triglyceride. To illustrate how apoB could simplify and improve the management of dyslipoproteinemia, we compared conventional lipid markers and apoB in a sample of Americans and Asian Indians.
METHODS
Data from the US National Health and Nutrition Examination Survey (NHANES) (11,778 participants, 2009-2010, 2011-2012), and the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) cohort study in Delhi, India (4244 participants), 2011 were evaluated. We compared means and distributions of plasma lipids, and apo B using the Mann-Whitney U test and Fisher's exact test. A p value of < 0.05 was considered significant.
RESULTS
The plasma lipid profile differed between Asian Indians and Americans. Plasma triglycerides were greater, but HDL-C lower in Asian Indians than in Americans. By contrast, total cholesterol, non-HDL-C, and LDL-C were all significantly higher in Americans than Asian Indians. However, apoB was significantly higher in Asian Indians than Americans. The LDL-C/apoB ratio and the non-HDL-C/apoB ratio were both significantly lower in Asian Indians than Americans.
CONCLUSION
Whether Americans or Asian Indians are at higher risk from apoB lipoproteins cannot be determined based on their lipid levels because the information from lipids cannot be integrated. ApoB, however, integrates and extends the information from triglycerides and cholesterol. Replacing the conventional lipid panel with apoB for routine follow ups could simultaneously simplify and improve clinical care.
Topics: Apolipoproteins B; Cholesterol, HDL; Cohort Studies; Humans; Lipids; Nutrition Surveys; Triglycerides
PubMed: 33598387
DOI: 10.5334/gh.882