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Scientific Reports Dec 2023Circadian rhythms, which are governed by a circadian clock, regulate important biological processes associated with obesity. SNPs in circadian clock genes have been...
Circadian rhythms, which are governed by a circadian clock, regulate important biological processes associated with obesity. SNPs in circadian clock genes have been linked to energy and lipid homeostasis. The aim of our study was to evaluate the associations of CLOCK and REV-ERBα SNPs with BMI and plasma lipid levels in pre-pubertal boys and girls. The study sample population comprised 1268 children aged 6-8 years. Information regarding anthropometric parameters and plasma lipid concentrations was available. Genotyping of CLOCK SNPs rs1801260, rs4580704, rs3749474, rs3736544 and rs4864548 and REV-ERBα SNPs rs2017427, rs20711570 and rs2314339 was performed by RT-PCR. The CLOCK SNPs rs3749474 and rs4864548 were significantly associated with BMI in girls but no in boys. Female carriers of the minor alleles for these SNPs presented lower BMI compared to non-carriers. A significant association of the REV-ERBα SNP rs2071570 with plasma total cholesterol, LDL-cholesterol and Apo B in males was also observed. Male AA carriers showed lower plasma levels of total cholesterol, LDL-cholesterol and Apo B levels as compared with carriers of the C allele. No significant associations between any of the studied REV-ERBα SNPs and plasma lipid levels were observed in females. In summary, CLOCK and REV-ERBα SNPs were associated with BMI and plasma lipid levels respectively in a sex-dependent manner. Our findings suggest that sex-related factors may interact with Clock genes SNPs conditioning the effects of these polymorphisms on circadian alterations.
Topics: Child; Female; Humans; Male; Apolipoproteins B; Body Mass Index; Cholesterol, LDL; Circadian Clocks; Circadian Rhythm; Nuclear Receptor Subfamily 1, Group D, Member 1
PubMed: 38092833
DOI: 10.1038/s41598-023-49506-2 -
BMC Medical Genomics Dec 2023In response to the controversy surrounding observational studies of the association between lipid profiles and the risk of insomnia, the aim of this study was to analyze...
OBJECTIVES
In response to the controversy surrounding observational studies of the association between lipid profiles and the risk of insomnia, the aim of this study was to analyze lipid profiles, including triglycerides (TG), apolipoprotein A-1 (ApoA-1), apolipoprotein B (ApoB) and lipoprotein A (LPA), in a European population to further assess the causal relationship between these lipid types and insomnia.
MATERIALS AND METHODS
This study explores the causal effect of lipid profiles on insomnia based on a genome-wide association study (GWAS)-derived public dataset using two-sample and multivariate Mendelian randomization (MVMR) analysis. The main MR analyses used inverse variance weighting (IVW) odds ratio (OR), and the sensitivity analyses included weighted median (WM) and MR‒Egger.
RESULTS
Both MR and MVMR showed that lowering ApoA-1 and LPA levels had causal effects on the risk of insomnia [MR: per 10 units, ApoA-1: OR: 0.7546, 95% CI: 0.6075-0.9372, P = 0.011; LPA: OR: 0.8392, 95% CI: 0.7202-0.9778, P = 0.025; MVMR: per 10 units, ApoA-1: OR: 0.7600, 95% CI: 0.6362-0.9079, P = 0.002; LPA, OR: 0.903, 95% CI: 0.8283-0.9845, P = 0.021]. There were no causal effects of TG or ApoB on insomnia (all P > 0.05). The MR‒Egger intercept test, funnel plot, and IVW methods all suggested an absence of strong directional pleiotropy, and leave-one-out permutation analysis did not detect any single single-nucleotide polymorphism that had a strong influence on the results.
CONCLUSION
Elevated levels of ApoA-1 and LPA were independently and causally associated with the risk of insomnia, suggesting that elevated ApoA-1 and LPA levels may contribute to a reduced risk of insomnia.
Topics: Humans; Apolipoprotein A-I; Apolipoproteins B; Genome-Wide Association Study; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Sleep Initiation and Maintenance Disorders; Triglycerides
PubMed: 38087303
DOI: 10.1186/s12920-023-01761-y -
Lipids in Health and Disease Dec 2023It remains controversial whether the long-term use of statins or newer nonstatin drugs has a positive effect on human longevity. Therefore, this study aimed to...
BACKGROUND
It remains controversial whether the long-term use of statins or newer nonstatin drugs has a positive effect on human longevity. Therefore, this study aimed to investigate the genetic associations between different lipid-lowering therapeutic gene targets and human longevity.
METHODS
Two-sample Mendelian randomization analyses were conducted. The exposures comprised genetic variants that proxy nine drug target genes mimicking lipid-lowering effects (LDLR, HMGCR, PCKS9, NPC1L1, APOB, CETP, LPL, APOC3, and ANGPTL3). Two large-scale genome-wide association study (GWAS) summary datasets of human lifespan, including up to 500,193 European individuals, were used as outcomes. The inverse-variance weighting method was applied as the main approach. Sensitivity tests were conducted to evaluate the robustness, heterogeneity, and pleiotropy of the results. Causal effects were further validated using expression quantitative trait locus (eQTL) data.
RESULTS
Genetically proxied LDLR variants, which mimic the effects of lowering low-density lipoprotein cholesterol (LDL-C), were associated with extended lifespan. This association was replicated in the validation set and was further confirmed in the eQTL summary data of blood and liver tissues. Mediation analysis revealed that the genetic mimicry of LDLR enhancement extended lifespan by reducing the risk of major coronary heart disease, accounting for 22.8% of the mediation effect. The genetically proxied CETP and APOC3 inhibitions also showed causal effects on increased life expectancy in both outcome datasets. The lipid-lowering variants of HMGCR, PCKS9, LPL, and APOB were associated with longer lifespans but did not causally increase extreme longevity. No statistical evidence was detected to support an association between NPC1L1 and lifespan.
CONCLUSION
This study suggests that LDLR is a promising genetic target for human longevity. Lipid-related gene targets, such as PCSK9, CETP, and APOC3, might potentially regulate human lifespan, thus offering promising prospects for developing newer nonstatin therapies.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Proprotein Convertase 9; Longevity; Mendelian Randomization Analysis; Genome-Wide Association Study; Cholesterol, LDL; Apolipoproteins B; Angiopoietin-Like Protein 3
PubMed: 38082436
DOI: 10.1186/s12944-023-01983-0 -
European Journal of Pediatrics Feb 2024To quantify the tracking of apolipoprotein B (apoB) levels from childhood and adolescence and compare the tracking of apoB with low-density lipoprotein (LDL)... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
To quantify the tracking of apolipoprotein B (apoB) levels from childhood and adolescence and compare the tracking of apoB with low-density lipoprotein (LDL) cholesterol, a systematic search of MEDLINE, Embase, Web of Science, and Google Scholar was performed in October 2023 (PROSPERO protocol: CRD42022298663). Cohort studies that measured tracking of apoB from childhood/adolescence (< 19 years) with a minimum follow-up of 1 year, using tracking estimates such as correlation coefficients or tracking coefficients, were eligible. Pooled correlations were estimated using random-effects meta-analysis. Risk of bias was assessed with a review-specific tool. Ten studies of eight unique cohorts involving 4677 participants met the inclusion criteria. Tracking of apoB was observed (pooled r = 0.63; 95% confidence interval [CI] = 0.53-0.71; I = 96%) with no significant sources of heterogeneity identified. Data from five cohorts with tracking data for both lipids showed the degree of tracking was similar for apoB (pooled r = 0.59; 95% CI = 0.55-0.63) and LDL cholesterol (pooled r = 0.58; 95% CI = 0.47-0.68). Study risk of bias was moderate, mostly due to attrition and insufficient reporting.
CONCLUSION
ApoB levels track strongly from childhood, but do not surpass LDL cholesterol in this regard. While there is strong evidence that apoB is more effective at predicting ASCVD risk than LDL cholesterol in adults, there is currently insufficient evidence to support its increased utility in pediatric settings. This also applies to tracking data, where more comprehensive data are required.
WHAT IS KNOWN
• Apolipoprotein B is a known cause of atherosclerotic cardiovascular disease. • Apolipoprotein B levels are not typically measured in pediatric settings, where low-density lipoprotein cholesterol remains the primary lipid screening measure.
WHAT IS NEW
• This meta-analysis of 10 studies showed apolipoprotein B levels tracked strongly from childhood but did not exceed low-density lipoprotein cholesterol in this regard. • More comprehensive tracking data are needed to provide sufficient evidence for increased utility of apolipoprotein B in pediatric settings.
Topics: Adult; Humans; Adolescent; Child; Cholesterol, LDL; Apolipoproteins B; Cholesterol; Atherosclerosis; Cohort Studies; Cholesterol, HDL
PubMed: 38051379
DOI: 10.1007/s00431-023-05350-0 -
Molecular Metabolism Jan 2024Lipoprotein assembly and secretion in the small intestine are critical for dietary fat absorption. Surfeit locus protein 4 (SURF4) serves as a cargo receptor,...
OBJECTIVE
Lipoprotein assembly and secretion in the small intestine are critical for dietary fat absorption. Surfeit locus protein 4 (SURF4) serves as a cargo receptor, facilitating the cellular transport of multiple proteins and mediating hepatic lipid secretion in vivo. However, its involvement in intestinal lipid secretion is not fully understood. In this study, we investigated the role of SURF4 in intestinal lipid absorption.
METHODS
We generated intestine-specific Surf4 knockout mice and characterized the phenotypes. Additionally, we investigated the underlying mechanisms of SURF4 in intestinal lipid secretion using proteomics and cellular models.
RESULTS
We unveiled that SURF4 is indispensable for apolipoprotein transport and lipoprotein secretion. Intestine-specific Surf4 knockout mice exhibited ectopic lipid deposition in the small intestine and hypolipidemia. Deletion of SURF4 impeded the transport of apolipoprotein A1 (ApoA1), proline-rich acidic protein 1 (PRAP1), and apolipoprotein B48 (ApoB48) and hindered the assembly and secretion of chylomicrons and high-density lipoproteins.
CONCLUSIONS
SURF4 emerges as a pivotal regulator of intestinal lipid absorption via mediating the secretion of ApoA1, PRAP1 and ApoB48.
Topics: Mice; Animals; Apolipoprotein B-48; Lipoproteins; Intestines; Chylomicrons; Mice, Knockout; Membrane Proteins
PubMed: 38042368
DOI: 10.1016/j.molmet.2023.101847 -
Clinical Interventions in Aging 2023The measurement of serum biomarkers is a promising decision aid in the assessment of atherosclerosis. However, data on the levels and epidemiological distribution of...
BACKGROUND
The measurement of serum biomarkers is a promising decision aid in the assessment of atherosclerosis. However, data on the levels and epidemiological distribution of serum biomarkers of carotid atherosclerosis (CAS) in the oldest-old are limited. This study aimed to investigate the characteristics of CAS serum biomarkers in the oldest-old over 80 and explore their predictive value for CAS.
METHODS
As part of the China Hainan Centenarian Cohort Study, a total of 1565 individuals over 80 years old were included. Atherosclerosis was assessed by carotid plaque and carotid intima-media thickness. Serum biomarker levels, demographic indicators, and physical examination indicators were detected. Prediction factors correlated to the CAS were explored by logistic regression and verified by receiver operating characteristic curve analysis. Multivariate regression models were fitted, along with subgroup analysis and robustness tests.
RESULTS
Among the oldest-old population, 83.5% (1306) had CAS. In a fully adjusted multivariate logistic regression model, systolic blood pressure (SBP), heart rhythm (HR), serum homocysteine (Hcy), and apolipoprotein B (ApoB) levels were significantly and positively associated with CAS in the oldest-old (P < 0.001). ROC analysis indicated that the combination of serum Hcy, ApoB, SBP, and HR increased the predictive value for CAS in the oldest-old (area under the curve: 0.856, 95% CI: 0.803-0.879; sensitivity: 81.8%; specificity: 85.9%).
CONCLUSION
SBP, HR, Hcy and ApoB are independent risk factors for CAS in the oldest-old. The specific set of biomarkers and their combination with other risk markers may be a promising strategy for assessing CAS in the elderly, especially in global aging.
Topics: Aged, 80 and over; Humans; Aged; Carotid Intima-Media Thickness; Cohort Studies; Carotid Artery Diseases; Atherosclerosis; Biomarkers; Risk Factors; Apolipoproteins B; Homocysteine
PubMed: 38033754
DOI: 10.2147/CIA.S428776 -
Pediatric Endocrinology, Diabetes, and... 2023Atherosclerosis, a precursor to cardiovascular disease (CVD), is deeply intertwined with lipid metabolism. The metabolic process in the Down syndrome (DS) population...
INTRODUCTION
Atherosclerosis, a precursor to cardiovascular disease (CVD), is deeply intertwined with lipid metabolism. The metabolic process in the Down syndrome (DS) population remain less explored. Aim of the study: This study examines the lipid profiles of DS in comparison to their siblings (CG), aiming to uncover potential atherosclerotic and CVD risks.
MATERIAL AND METHODS
The study included 42 people with DS (mean age 14.17 years) and the CG - 20 individuals (mean age 15.92 years). Anthropometric measurements: BMI, BMI SDS, and TMI were calculated. Lipid profile (LP) and metabolomics were determined.
RESULTS
LP: DS display significantly reduced HDL (DS vs. CG: 47±10 vs. 59 ±12 mg/dl; p = 0.0001) and elevated LDL (104 ±25 vs. 90 ±22 mg/dl; p = 0.0331). Triglycerides, APO A1, and APO B/APO A1 ratio corroborate with the elevated risk of CVD in DS. Despite no marked differences in: TCH and APO B, the DS group demonstrated a concerning BMI trend. Of 31 identified metabolites, 12 showed statistical significance (acetate, choline, creatinine, formate, glutamine, histidine, lysine, proline, pyroglutamate, threonine, tyrosine, and xanthine). However, only 8 metabolites passed the FDR validation (acetate, creatinine, formate, glutamine, lysine, proline, pyroglutamate, xanthine).
CONCLUSIONS
Down syndrome individuals show distinct cardiovascular risks, with decreased HDL and increased LDL levels. Combined with metabolomic disparities and higher BMI and TMI, this suggests an increased atherosclerosis risk compared to controls.
Topics: Humans; Child; Adult; Adolescent; Down Syndrome; Apolipoprotein A-I; Risk Factors; Creatinine; Glutamine; Lysine; Pyrrolidonecarboxylic Acid; Cardiovascular Diseases; Atherosclerosis; Apolipoproteins B; Xanthines; Acetates; Formates; Proline
PubMed: 38031830
DOI: 10.5114/pedm.2023.131162 -
Ecotoxicology and Environmental Safety Dec 2023Neonicotinoid insecticides (NNIs) are widely used in agriculture, horticulture, forestry, and household environment, but their potential impact on human health remains a...
Neonicotinoid insecticides (NNIs) are widely used in agriculture, horticulture, forestry, and household environment, but their potential impact on human health remains a subject of concern. This study aimed to investigate the relationship between NNIs and their metabolites in urine with serum lipid profiles in adults using data from the National Health and Nutrition Examination Survey (NHANES) 2015-2016. The study included 1192 participants aged over 20 years with urinary NNIs levels, serum lipid parameter levels and potential confounders. Urinary concentrations of NNIs, including imidacloprid, acetamiprid, clothianidin, thiacloprid, N-desmethyl-acetamiprid, and 5-hydroxy-imidacloprid, were quantified. Serum lipids profiles, such as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (Apo-B), were assessed. Considering the effects of lipid-lowering medications, the censored normal regression model was used to explore the associations between urinary NNIs and TC, TG, HDL-C, LDL-C and Apo-B levels. The results revealed a significant increase of 9.0 mg/dL (95%CI: 2.0, 16.1) in TC levels among participants with detectable N-desmethyl-acetamiprid compared to those with undetectable levels. Stratified analysis indicated that the association between N-desmethyl-acetamiprid and HDL-C levels was more pronounced among participants aged ≥ 46 years compared to those aged between 20 and 45 years with undetectable N-desmethyl-acetamiprid (p=0.044). Additionally, there were marginal effect modification of BMI on the association between N-desmethyl-acetamiprid and LDL-C (p=0.097) and Apo-B (p=0.052) levels. Specifically, participants with BMI ≥ 25 kg/m² and detectable N-desmethyl-acetamiprid tended to have higher LDL-C and Apo-B levels compared to those with BMI < 25 kg/m² and undetectable N-desmethyl-acetamiprid. However, no significant associations were observed between other NNIs and lipid profiles in the present study. To validate these findings, further longitudinal studies with larger sample sizes should be conducted, particularly within populations characterized by a high detection rate of NNIs.
Topics: Adult; Humans; Young Adult; Middle Aged; Insecticides; Nutrition Surveys; Cholesterol, LDL; Cross-Sectional Studies; Neonicotinoids; Triglycerides; Cholesterol, HDL; Apolipoproteins B
PubMed: 37992647
DOI: 10.1016/j.ecoenv.2023.115724 -
Poultry Science Jan 2024Heterosis is the major benefit of crossbreeding and has been exploited in laying hens breeding for a long time. This genetic phenomenon has been linked to various modes...
Transcriptome analysis of ovarian tissues highlights genes controlling energy homeostasis and oxidative stress as potential drivers of heterosis for egg number and clutch size in crossbred laying hens.
Heterosis is the major benefit of crossbreeding and has been exploited in laying hens breeding for a long time. This genetic phenomenon has been linked to various modes of nonadditive gene action. However, the molecular mechanism of heterosis for egg production in laying hens has not been fully elucidated. To fill this research gap, we sequenced mRNAs and lncRNAs of the ovary stroma containing prehierarchical follicles in White Leghorn, Rhode Island Red chickens as well as their reciprocal crossbreds that demonstrated heterosis for egg number and clutch size. We further delineated the modes of mRNAs and lncRNAs expression to identify their potential functions in the observed heterosis. Results showed that dominance was the principal mode of nonadditive expression exhibited by mRNAs and lncRNAs in the prehierarchical follicles of crossbred hens. Specifically, low-parent dominance was the main mode of mRNA expression, while high-parent dominance was the predominant mode of lncRNA expression. Important pathways enriched by genes that showed higher expression in crossbreds compared to either one or both parental lines were cell adhesion molecules, tyrosine and purine metabolism. In contrast, ECM-receptor interaction, focal adhesion, PPAR signaling, and ferroptosis were enriched in genes with lower expression in the crossbred. Protein network interaction identified nonadditively expressed genes including apolipoprotein B (APOB), transferrin, acyl-CoA synthetase medium-chain family member (APOBEC) 3, APOBEC1 complementation factor, and cathepsin S as hub genes. Among these potential hub genes, APOB was the only gene with underdominance expression common to the 2 reciprocal crossbred lines, and has been linked to oxidative stress. LncRNAs with nonadditive expression in the crossbred hens targeted natriuretic peptide receptor 1, epidermal differentiation protein beta, spermatogenesis-associated gene 22, sperm-associated antigen 16, melanocortin 2 receptor, dolichol kinase, glycine amiinotransferase, and prolactin releasing hormone receptor. In conclusion, genes with nonadditive expression in the crossbred may play crucial roles in follicle growth and atresia by improving follicle competence and increasing oxidative stress, respectively. These 2 phenomena could underpin heterosis for egg production in crossbred laying hens.
Topics: Male; Animals; Female; Chickens; Clutch Size; Hybrid Vigor; RNA, Long Noncoding; Plant Breeding; Gene Expression Profiling; Homeostasis; Oxidative Stress; Apolipoproteins B
PubMed: 37980751
DOI: 10.1016/j.psj.2023.103163 -
Journal of Natural Medicines Jan 2024An acylated flavonol glycoside, trans-tiliroside (1), is found in certain parts of different herbs, including the seeds of Rosa canina (Rosaceae). Previous studies on...
An acylated flavonol glycoside, trans-tiliroside (1), is found in certain parts of different herbs, including the seeds of Rosa canina (Rosaceae). Previous studies on compound 1 have focused on triglyceride (TG) metabolism, including its anti-obesity and intracellular TG reduction effects. In the present study, the effects of compound 1 on cholesterol (CHO) metabolism were investigated using human hepatocellular carcinoma-derived HepG2 cells and mice. Compound 1 decreased CHO secretion in HepG2 cells, which was enhanced by mevalonate in a concentration-dependent manner and decreased the secretion of apoprotein B (apoB)-100, a marker of very low-density lipoprotein (VLDL). Compound 1 also inhibited the activity of microsomal triglyceride transfer proteins, which mediate VLDL formation from cholesterol and triglycerides in the liver. In vivo, compound 1 inhibited the accumulation of Triton WR-1339-induced TG in the blood of fasted mice and maintained low levels of apoB-100. These results suggest that compound 1 inhibits the secretion of CHO as VLDL from the liver and has the potential for use for the prevention of dyslipidemia.
Topics: Mice; Humans; Animals; Lipoproteins, VLDL; Apolipoproteins B; Hep G2 Cells; Liver; Triglycerides; Cholesterol; Liver Neoplasms; Lipoproteins, LDL
PubMed: 37973705
DOI: 10.1007/s11418-023-01756-0