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Journal of Lipid Research Jul 2018A better understanding of intracellular lipoprotein assembly may help identify proteins with important roles in lipid disorders. apoB-containing lipoproteins (B-lps) are... (Review)
Review
A better understanding of intracellular lipoprotein assembly may help identify proteins with important roles in lipid disorders. apoB-containing lipoproteins (B-lps) are macromolecular lipid and protein micelles that act as specialized transport vehicles for hydrophobic lipids. They are assembled predominantly in enterocytes and hepatocytes to transport dietary and endogenous fat, respectively, to different tissues. Assembly occurs in the endoplasmic reticulum (ER) and is dependent on lipid resynthesis in the ER and on a chaperone, namely, microsomal triglyceride transfer protein (MTTP). Precursors for lipid synthesis are obtained from extracellular sources and from cytoplasmic lipid droplets. MTTP is the major and essential lipid transfer protein that transfers phospholipids and triacylglycerols to nascent apoB for the assembly of lipoproteins. Assembly is aided by cell death-inducing DFF45-like effector B and by phospholipid transfer protein, which may facilitate additional deposition of triacylglycerols and phospholipids, respectively, to apoB. Here, we summarize the current understanding of the different steps in the assembly of B-lps and discuss the role of lipid transfer proteins in these steps to help identify new clinical targets for lipid-associated disorders, such as heart disease.
Topics: Animals; Apolipoproteins B; Carrier Proteins; Humans
PubMed: 29650752
DOI: 10.1194/jlr.R083451 -
Current Opinion in Endocrinology,... Apr 2021This review summarizes the evidence that apolipoprotein B (apoB) integrates the conventional lipid markers - total cholesterol, triglycerides, LDL-cholesterol, and... (Review)
Review
PURPOSE OF REVIEW
This review summarizes the evidence that apolipoprotein B (apoB) integrates the conventional lipid markers - total cholesterol, triglycerides, LDL-cholesterol, and non-HDL-cholesterol - into a single index that accurately and simply quantitates the atherogenic risk due to the apoB lipoprotein particles.
RECENT FINDINGS
Marked hypertriglyceridemia remains the essential signal for hyperchylomicronemia and potential pancreatitis. However, with the exception of Lp(a) and the abnormal cholesterol-enriched remnant particles that are the hallmark of type III hyperlipoproteinemia, recent evidence from discordance analyses and Mendelian randomization indicate that apoB integrates the risk due to the atherogenic lipoprotein particles because all LDL particles are, within the limits of our ability to measure any differences, equally atherogenic and all, except the largest VLDL particles are, within the limits of our ability to measure any differences, equally atherogenic.
SUMMARY
Measuring apoB as well as the conventional lipids is essential for accurate diagnosis. For almost all follow-up, however, apoB is all that need be measured. ApoB is the Rosetta Stone of lipidology because dyslipoproteinemia cannot be understood unless apoB is measured.
Topics: Apolipoproteins B; Cholesterol, LDL; Dyslipidemias; Humans; Hypertriglyceridemia; Lipoproteins; Triglycerides
PubMed: 33229928
DOI: 10.1097/MED.0000000000000596 -
Circulation Research Nov 2015
Topics: Animals; Aorta; Aortic Diseases; Apolipoproteins B; Atherosclerosis; Female; Humans; Lipoproteins, LDL; Male; Oligonucleotides, Antisense
PubMed: 26541678
DOI: 10.1161/CIRCRESAHA.115.307609 -
Environmental Science and Pollution... Mar 2021Previous population investigation of perfluoroalkyl substances (PFAS) features associations with lipids in a number of populations; these investigations have seldom...
Previous population investigation of perfluoroalkyl substances (PFAS) features associations with lipids in a number of populations; these investigations have seldom included consideration of apolipoproteins. Apolipoprotein B (Apo B) fractions were considered in this descriptive analysis because they are essential to the assembly, transport, and cellular uptake of lipid classes associated with poorer health outcomes, and they are associated with incident and prevalent disease. Regression models stratified by diabetes and lipid lowering medication (LLM) status for data from National Health and Nutrition Examination Survey for 2007-2014 were fitted to interrogate associations between selected PFAS and Apo B for US adults aged ≥ 20 years. Adjusted concentrations of Apo B were positively associated with perfluorooctanoic acid (PFOA β = 0.03878, p < 0.01), perfluorooctane sulfonic acid (PFOS β = .02029, p = 0.02), and perfluorononanoic acid (PFNA β = .01968, p = .03) for nondiabetics who were not taking lipid lowering medications. These associations were not seen among diabetic participants, except for perfluorodecanoic acid (PFDA) in those taking LLMs (β = 0.03831, p = 0.02). We also note that LLMs have an inferred greater impact on Apo B in the diabetics compared to the nondiabetic populations. We have considered several sources of confounding and think the data are most consistent with a weak causal association that PFAS exposure increases Apo B. The rodent toxicology literature also contains evidence that PFAS disrupt fatty acid trafficking including Apo B, although how the specific findings may relate to circulating human Apo B concentrations is unclear. We therefore advocate for attempts to replicate the findings in other populations and to consider additional types of mechanistic studies.
Topics: Adult; Aged; Alkanesulfonic Acids; Apolipoproteins; Apolipoproteins B; Caprylates; Diabetes Mellitus; Environmental Pollutants; Fluorocarbons; Humans; Nutrition Surveys
PubMed: 33196992
DOI: 10.1007/s11356-020-11593-3 -
Journal of Hypertension Jan 2021The current study examines the placental and maternal lipid profile and expression of genes involved in placental lipid metabolism in women with preeclampsia.
OBJECTIVES
The current study examines the placental and maternal lipid profile and expression of genes involved in placental lipid metabolism in women with preeclampsia.
METHODS
The current study includes normotensive control women (n = 40) and women with preeclampsia (n = 39). Preeclampsia women were further classified into women delivering at term preeclampsia (T-PE; n = 15) and preterm preeclampsia (PT-PE; n = 24).
RESULTS
There were no significant differences in maternal lipid profile between the T-PE and normotensive control groups. Maternal plasma VLDL (P < 0.05) and ratios of total cholesterol : HDL (P < 0.05), atherogenic index [log (triglycerides/HDL)] (P < 0.01) and apolipoprotein B : apolipoprotein A (P < 0.05) were higher in the PT-PE group as compared with the normotensive control group. Placental total cholesterol and HDL levels were higher (P < 0.05) in the T-PE as compared with the normotensive control group. Higher placental triglycerides (P < 0.05) were observed in PT-PE group compared with T-PE group. Placental mRNA levels of peroxisome proliferator activated receptor α, carnitine palmitoyl transferase-1, cluster of differentiation 36 and lipoprotein lipases were lower (P < 0.05) in the PT-PE than normotensive control group. A negative association of mRNA levels of peroxisome proliferator activated receptor α (r = -0.246, P = 0.032; r = -0.308, P = 0.007, respectively), carnitine palmitoyl transferase-1 (r = -0.292, P = 0.011; r = -0.366, P = 0.001), lipoprotein lipases (r = -0.296, P = 0.010; r = -0.254, P = 0.028) with SBP and DBP was observed. There was a positive association of placental triglycerides (r = 0.244, P = 0.031) with DBP.
CONCLUSION
Women with preeclampsia exhibit higher lipid : lipoprotein ratios suggesting an atherogenic state particularly in women delivering preterm. Lower expression of genes involved in placental fatty acid oxidation and transport was also observed in preeclampsia.
Topics: Apolipoproteins B; Female; Humans; Infant, Newborn; Lipid Metabolism; Lipids; Placenta; Pre-Eclampsia; Pregnancy
PubMed: 32833919
DOI: 10.1097/HJH.0000000000002596 -
Expert Opinion on Pharmacotherapy Feb 2019Familial Hypercholesterolemia (FH) is an inherited disorder characterized by a defect in the binding and internalization of low-density lipoprotein (LDL) particles,... (Review)
Review
Familial Hypercholesterolemia (FH) is an inherited disorder characterized by a defect in the binding and internalization of low-density lipoprotein (LDL) particles, resulting in markedly elevated LDL levels and premature atherosclerosis. It is one of the most common inherited disorders of lipid metabolism. Many FH patients, especially those with homozygous FH do not reach LDL goals with traditional LDL therapies and may require additional, less often used, therapies. Areas covered: Mipomersen is an anti-sense oligonucleotide that prevents production of apolipoprotein B leading to decreased levels of very low-density lipoprotein (VLDL) and LDL. In this review the authors discuss the pharmacokinetics of the drug, the clinical trials evaluating its efficacy and safety, and risks and challenges associated with its clinical implementation. Its use as therapy for the treatment of FH is also discussed. Expert opinion: Mipomersen is approved for use only in homozygous FH. It has frequent adverse effects, such as injection site reactions, flu-like symptoms, and hepatoxicity. It is useful only in patients who have failed other therapies, and it faces competition from other medications that have more tolerable side effect profiles.
Topics: Animals; Anticholesteremic Agents; Apolipoproteins B; Atherosclerosis; Cholesterol, LDL; Humans; Hyperlipoproteinemia Type II; Oligonucleotides
PubMed: 30526168
DOI: 10.1080/14656566.2018.1550071 -
Nigerian Journal of Clinical Practice Mar 2019Apolipoprotein B (apo B) has been widely reported to be a better predictor of cardiovascular risk than low-density lipoprotein cholesterol (LDL-C). This is the reason...
BACKGROUND
Apolipoprotein B (apo B) has been widely reported to be a better predictor of cardiovascular risk than low-density lipoprotein cholesterol (LDL-C). This is the reason apo B treatment target values based on the equivalence to LDL-C values in healthy population has been advocated using percentiles from population studies. The aim of this study was to determine the apo B values equivalent to currently used medical decision targets for LDL-C concentration in a population of healthy Nigerians and examine for any demographic influence.
MATERIALS AND METHODS
A total of 252 apparently healthy individuals (89 males, 163 females), between the ages of 30 and 65 years were selected from core health workers (medical and nursing staffs) of University College Hospital Ibadan between December 2015 and May 2016. Serum lipids and apo B were measured using enzymatic and immunoturbidimetry method, respectively.
RESULTS
The mean apo B of the study population were 94 and 98 mg/dL in men and women, respectively. Mean apo B concentration was significantly higher in the female participants in the age groups above 55 years. LDL-C concentrations of 100, 130, 160, and 190 mg/dL corresponded to the 15, 55, 87, and 95 percentile, respectively. The corresponding apo B concentrations were 73 mg/dL (15 percentile), 95 mg/dL (55 percentile), 124 mg/dL (87 percentile), and 145 mg/dL (95 percentile). The group of participants with LDL-C of <130 mg/dL and the group with equivalent apo B of <95 mg/dL has the same clinical and biochemical characteristics in both men and women.
CONCLUSION
This study has defined apo B targets that may potentially be used to guide the initiation of therapy in persons with dyslipidemia. It has also demonstrated the population level relationship that exists between apo B and LDL-cholesterol and has shown the gender and age-related influence of apo B distribution in the population.
Topics: Adult; Age Factors; Aged; Apolipoproteins B; Biomarkers; Cholesterol, LDL; Dyslipidemias; Female; Humans; Male; Middle Aged; Nigeria; Risk Factors; Sex Factors
PubMed: 30837423
DOI: 10.4103/njcp.njcp_348_17 -
Biochimica Et Biophysica Acta Dec 2016MicroRNAs (miRs) are small, non-coding RNAs that regulate gene expression and have been implicated in many pathological conditions. Significant progress has been made to... (Review)
Review
MicroRNAs (miRs) are small, non-coding RNAs that regulate gene expression and have been implicated in many pathological conditions. Significant progress has been made to unveil their role in lipid metabolism. This review aims at summarizing the role of different miRs that regulate hepatic assembly and secretion of apolipoprotein B (apoB)-containing lipoproteins. Overproduction and/or impaired clearance of these lipoproteins from circulation increase plasma concentrations of lipids enhancing risk for cardiovascular disease. So far, three miRs, miR-122, miR-34a, and miR-30c have been shown to modulate hepatic production of apoB-containing low density lipoproteins. In this review, we will first provide a brief overview of lipid metabolism and apoB-containing lipoprotein assembly to orient readers to different steps that have been shown to be regulated by miRs. Then, we will discuss the role of each miR on plasma lipids and atherosclerotic burden. Furthermore, we will summarize mechanistic studies explaining how these miRs regulate hepatic lipid synthesis, fatty acid oxidation, and lipoprotein secretion. Finally, we will briefly highlight the potential use of each miR as a therapeutic drug for treating cardiovascular diseases. This article is part of a Special Issue entitled: MicroRNAs and lipid/energy metabolism and related diseases edited by Carlos Fernández-Hernando and Yajaira Suárez.
Topics: Animals; Apolipoproteins B; Atherosclerosis; Fatty Acids; Humans; Lipid Metabolism; Lipids; Lipogenesis; Lipoproteins; MicroRNAs
PubMed: 26923435
DOI: 10.1016/j.bbalip.2016.02.020 -
Journal of the American College of... Jun 2024
Topics: Humans; Apolipoproteins B; Biomarkers; Cardiovascular Diseases; Apolipoprotein B-100
PubMed: 38839201
DOI: 10.1016/j.jacc.2024.04.008 -
Nutrients Mar 2022Osteoarthritis (OA) imposes an increasing social burden due to global activity limitations, especially among the aged. Links between circulating lipids and OA have been...
Osteoarthritis (OA) imposes an increasing social burden due to global activity limitations, especially among the aged. Links between circulating lipids and OA have been reported; however, confounding data from observational studies have hindered causal conclusions. We used Mendelian randomization (MR) approach to evaluate the genetic causal effects of circulating apolipoproteins and lipoprotein lipids on OA risk. Genetic instruments at the genome-wide significance level (p < 5 × 10−8) were selected from genome-wide association studies (n = 393,193−441,016 individuals). Summary-level OA data were obtained from the UK Biobank (39,427 cases, 378,169 controls). Bidirectional two-sample Mendelian randomization (MR) analyses used MR-Egger, weighted median, and MR-PRESSO for sensitivity analysis. Genetic predisposition to 1-SD increments of Apolipoprotein B (APOB), and low-density lipoprotein (LDL) was associated with a decreased risk of knee or hip OA (KHOA) (odds ratio (OR) = 0.925, 95% confidence interval (95% CI): 0.881−0.972, p = 0.002; OR = 0.898, 95% CI: 0.843−0.957, p = 0.001) and hip OA (HOA) (OR = 0.894; 95% CI: 0.832−0.961, p = 0.002; OR = 0.870 95% CI: 0.797−0.949, p = 0.002). Genetically predicted APOB showed an association with knee OA (KOA) (OR per SD increase, 0.930, 95% CI: 0.876−0.987, p = 0.016). The OR of KOA was 0.899 (95% CI: 0.835−0.968, p = 0.005) for a 1-SD increase in LDL. Apolipoprotein A1, high-density lipoprotein, and triglycerides showed no association. Inverse MR showed no causal effect of KOA, HOA, or KHOA on these serum lipids. Distinct protective genetic-influence patterns were observed for APOB and LDL on OA, offering new insights into relationships between lipids and OA risk and a better understanding of OA etiology.
Topics: Aged; Apolipoprotein B-100; Apolipoproteins B; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Osteoarthritis, Hip; Osteoarthritis, Knee; Polymorphism, Single Nucleotide; Triglycerides
PubMed: 35405941
DOI: 10.3390/nu14071327