-
Journal of Diabetes Investigation Oct 2023In diabetes, the impairment of insulin secretion and insulin resistance contribute to hypertriglyceridemia, as the enzymatic activity of lipoprotein lipase (LPL) depends... (Review)
Review
In diabetes, the impairment of insulin secretion and insulin resistance contribute to hypertriglyceridemia, as the enzymatic activity of lipoprotein lipase (LPL) depends on insulin action. The transport of LPL to endothelial cells and its enzymatic activity are maintained by the formation of lipolytic complex depending on the multiple positive (glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 [GPIHBP1], apolipoprotein C-II [APOC2], APOA5, heparan sulfate proteoglycan [HSPG], lipase maturation factor 1 [LFM1] and sel-1 suppressor of lin-12-like [SEL1L]) and negative regulators (APOC1, APOC3, angiopoietin-like proteins [ANGPTL]3, ANGPTL4 and ANGPTL8). Among the regulators, GPIHBP1 is a crucial molecule for the translocation of LPL from parenchymal cells to the luminal surface of capillary endothelial cells, and maintenance of lipolytic activity; that is, hydrolyzation of triglyceride into free fatty acids and monoglyceride, and conversion from chylomicron to chylomicron remnant in the exogenous pathway and from very low-density lipoprotein to low-density lipoprotein in the endogenous pathway. The null mutation of GPIHBP1 causes severe hypertriglyceridemia and pancreatitis, and GPIGBP1 autoantibody syndrome also causes severe hypertriglyceridemia and recurrent episodes of acute pancreatitis. In patients with type 2 diabetes, the elevated serum triglyceride levels negatively correlate with circulating LPL levels, and positively with circulating APOC1, APOC3, ANGPTL3, ANGPTL4 and ANGPTL8 levels. In contrast, circulating GPIHBP1 levels are not altered in type 2 diabetes patients with higher serum triglyceride levels, whereas they are elevated in type 2 diabetes patients with diabetic retinopathy and nephropathy. The circulating regulators of lipolytic complex might be new biomarkers for lipid and glucose metabolism, and diabetic vascular complications.
Topics: Humans; Glycosylphosphatidylinositols; Diabetes Mellitus, Type 2; Endothelial Cells; Acute Disease; Pancreatitis; Hypertriglyceridemia; Carrier Proteins; Triglycerides; Lipoproteins, LDL; Lipoproteins, HDL; Angiopoietin-Like Protein 3; Proteins
PubMed: 37448184
DOI: 10.1111/jdi.14056 -
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 -
Cancer Research Sep 2023The secreted lipid transporter apolipoprotein E (APOE) plays important roles in atherosclerosis and Alzheimer's disease and has been implicated as a suppressor of...
UNLABELLED
The secreted lipid transporter apolipoprotein E (APOE) plays important roles in atherosclerosis and Alzheimer's disease and has been implicated as a suppressor of melanoma progression. The APOE germline genotype predicts human melanoma outcomes, with APOE4 and APOE2 allele carriers exhibiting prolonged and reduced survival, respectively, relative to APOE3 homozygotes. While the APOE4 variant was recently shown to suppress melanoma progression by enhancing antitumor immunity, further work is needed to fully characterize the melanoma cell-intrinsic effects of APOE variants on cancer progression. Using a genetically engineered mouse model, we showed that human germline APOE genetic variants differentially modulate melanoma growth and metastasis in an APOE2>APOE3>APOE4 manner. The low-density lipoprotein receptor-related protein 1 (LRP1) receptor mediated the cell-intrinsic effects of APOE variants on melanoma progression. Protein synthesis was a tumor cell-intrinsic process differentially modulated by APOE variants, with APOE2 promoting translation via LRP1. These findings reveal a gain-of-function role for the APOE2 variant in melanoma progression, which may aid in predicting melanoma patient outcomes and understanding the protective effect of APOE2 in Alzheimer's disease.
SIGNIFICANCE
APOE germline variants impact melanoma progression through disparate mechanisms, such as the protein synthesis-promoting function of the APOE2 variant, indicating that germline genetic variants are causal contributors to metastatic outcomes.
Topics: Animals; Humans; Mice; Alzheimer Disease; Apolipoprotein E2; Apolipoprotein E3; Apolipoprotein E4; Apolipoproteins E; Carrier Proteins; Melanoma
PubMed: 37335131
DOI: 10.1158/0008-5472.CAN-23-1252 -
Biomolecules & Biomedicine Jul 2023Atherosclerosis is a chronic process characterized by inflammation and the progressive accumulation of inflammatory cells and lipids in the blood vessel wall, resulting... (Review)
Review
Atherosclerosis is a chronic process characterized by inflammation and the progressive accumulation of inflammatory cells and lipids in the blood vessel wall, resulting in narrowing of the blood vessel's circumference. Treatment of people with dyslipidemia aims to reduce the risk of developing atherosclerotic disease and prevent major adverse cardiovascular events (MACE). The results of previous studies indicated that lipoprotein(a) (Lp(a)) is a critical causal factor in the estimated risk of developing a cardiovascular (CV) incident even after achieving desirable low-density lipoprotein (LDL) cholesterol levels. Lp(a) is a low-density lipoprotein particle, like LDL cholesterol. The levels of Lp(a) in plasma are genetically determined. Lp(a) catabolism is still controversial. The pathogenic potential of Lp(a) can be divided into three categories: promotion of plaque formation, thrombogenicity, and proinflammatory effects. Lp(a) levels above the 75th percentile reduced the risk of aortic valve stenosis and myocardial infarction, whereas higher levels (above 90th percentile) were associated with an increased risk of heart failure. However, no hypolipidemic agents have been approved for targeted use in patients with high Lp(a) levels. There are insufficient randomized controlled trials assessing CV outcomes that would support the evidence that current treatment options, which effectively lower Lp(a) levels, also effectively prevent CV event. However, according to some studies, there is strong evidence that better CV outcome is one of the benefits of such therapy. The results of ongoing clinical trials are eagerly awaited.
Topics: Humans; Lipoprotein(a); Risk Factors; Atherosclerosis; Myocardial Infarction; Cholesterol, LDL
PubMed: 37183706
DOI: 10.17305/bb.2023.8992 -
BMC Public Health Sep 2023Previous studies have investigated the association between cardiometabolic risk factors and cardiovascular disease (CVD), but evidence of the attributable burden of...
BACKGROUND
Previous studies have investigated the association between cardiometabolic risk factors and cardiovascular disease (CVD), but evidence of the attributable burden of individual and combined cardiometabolic risk factors for CVD and mortality is limited. We aimed to investigate and quantify the associations and population attributable fraction (PAF) of cardiometabolic risk factors on CVD and all-cause mortality, and calculate the loss of CVD-free years and years of life lost in relation to the presence of cardiometabolic risk factors.
METHODS
Twenty-two thousand five hundred ninety-six participants aged ≥ 35 without CVD at baseline were included between October 2012 and December 2015. The outcomes were the composite of fatal and nonfatal CVD events and all-cause mortality, which were followed up in 2018 and 2019 and ascertained by hospital records and death certificates. Cox regression was applied to evaluate the association of individual and combined cardiometabolic risk factors (including hypertension, diabetes and high low-density lipoprotein cholesterol (LDL-C)) with CVD risk and all-cause mortality. We also described the PAF for CVD and reductions in CVD-free years and life expectancy associated with different combination of cardiometabolic conditions.
RESULTS
During the 4.92 years of follow-up, we detected 991 CVD events and 1126 deaths. Hazard ratio were 1.59 (95% confidential interval (CI) 1.37-1.85), 1.82 (95%CI 1.49-2.24) and 2.97 (95%CI 1.85-4.75) for CVD and 1.38 (95%CI 1.20-1.58), 1.66 (95%CI 1.37-2.02) and 2.97 (95%CI 1.88-4.69) for all-cause mortality, respectively, in participants with one, two or three cardiometabolic risk factors compared with participants without diabetes, hypertension, and high LDL-C. 21.48% of CVD and 15.38% of all-cause mortality were attributable to the combined effect of diabetes and hypertension. Participants aged between 40 and 60 years old, with three cardiometabolic disorders, had approximately 4.3-year reductions life expectancy compared with participants without any abnormalities of cardiometabolic disorders.
CONCLUSIONS
Cardiometabolic risk factors were associated with a multiplicative risk of CVD incidence and all-cause mortality, highlighting the importance of comprehensive management for hypertension, diabetes and dyslipidemia in the prevention of CVD.
Topics: Humans; Adult; Middle Aged; Cardiovascular Diseases; Cardiometabolic Risk Factors; Cholesterol, LDL; Hypertension; Cholesterol, HDL
PubMed: 37670287
DOI: 10.1186/s12889-023-16659-8 -
Journal of Extracellular Vesicles Jan 2024Bacterial extracellular vesicles (BEVs) contribute to stress responses, quorum sensing, biofilm formation and interspecies and interkingdom communication. However, the...
Bacterial extracellular vesicles (BEVs) contribute to stress responses, quorum sensing, biofilm formation and interspecies and interkingdom communication. However, the factors that regulate their release and heterogeneity are not well understood. We set out to investigate these factors in the common gut commensal Bacteroides thetaiotaomicron by studying BEV release throughout their growth cycle. Utilising a range of methods, we demonstrate that vesicles released at different stages of growth have significantly different composition, with early vesicles enriched in specifically released outer membrane vesicles (OMVs) containing a larger proportion of lipoproteins, while late phase BEVs primarily contain lytic vesicles with enrichment of cytoplasmic proteins. Furthermore, we demonstrate that lipoproteins containing a negatively charged signal peptide are preferentially incorporated in OMVs. We use this observation to predict all Bacteroides thetaiotaomicron OMV enriched lipoproteins and analyse their function. Overall, our findings highlight the need to understand media composition and BEV release dynamics prior to functional characterisation and define the theoretical functional capacity of Bacteroides thetaiotaomicron OMVs.
Topics: Extracellular Vesicles; Bacteroides thetaiotaomicron; Lipoproteins
PubMed: 38240185
DOI: 10.1002/jev2.12406 -
Venous blood parameters in determination of respiratory impairment in amyotrophic lateral sclerosis.Scientific Reports Sep 2023This study aimed to investigate the relationship between venous blood parameters and respiratory functions in patients with amyotrophic lateral sclerosis (ALS) and...
This study aimed to investigate the relationship between venous blood parameters and respiratory functions in patients with amyotrophic lateral sclerosis (ALS) and develop a model to predict respiratory impairment for individual patients with ALS. A total of 416 ALS patients were included in the study, and various hematologic and biochemical laboratory parameters as well as demographic and clinical factors were collected and compared. A multivariable logistic regression model was constructed to assess the association between FVC and venous blood biomarkers and clinical factors. The results showed that along with onset age, bulbar-onset, disease duration, BMI, eosinophil count (EO#), basophil count (BASO#), creatinine (CREA), uric acid (URCI) and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL/HDL) ratio were associated with reduced FVC. The area under the ROC curve is 0.735 for the test set and 0.721 for the validation set. The study also developed a relatively acceptable model for predicting respiratory impairment in ALS patients. These findings suggest that EO#, BASO#, CREA, URIC and LDL/HDL ratio can be useful in assessing FVC in ALS and can be easily accessible, accurate, and low-cost parameters.
Topics: Humans; Amyotrophic Lateral Sclerosis; Respiratory Insufficiency; Leukocyte Count; Cholesterol, HDL; Cholesterol, LDL; Creatinine
PubMed: 37735229
DOI: 10.1038/s41598-023-42075-4 -
Nutrients Jul 2023The current study aimed to examine the association between serum selenium levels and lipids and explore whether the association was modified by diabetic status. A total...
The current study aimed to examine the association between serum selenium levels and lipids and explore whether the association was modified by diabetic status. A total of 4132 adults from the National Health and Nutrition Examination Survey (2011-2016) were included in this study. Multiple linear regression models were used to estimate the association between serum selenium and lipids. Higher serum selenium levels were significantly associated with increased total cholesterol (TC) ( < 0.001), triglyceride (TG) ( = 0.003), and low-density lipoprotein cholesterol (LDL-C) ( = 0.003) in the overall population. Diabetic status interacted with serum selenium for TC and LDL-C ( for interaction = 0.007 and <0.001). Comparing the highest with the lowest tertiles of serum selenium, the multivariate-adjusted β coefficients (95% CIs) were 17.88 (10.89, 24.87) for TC, 13.43 (7.68, 19.18) for LDL-C among subjects without diabetes, but nonsignificant among those with diabetes. In US adults, the serum selenium was positively associated with lipids and the association was modified by diabetic status. Higher serum selenium levels were significantly associated with increased TC and LDL-C among participants without diabetes, but not among participants with diabetes.
Topics: Adult; Humans; Selenium; Cholesterol, LDL; Nutrition Surveys; Lipids; Triglycerides; Diabetes Mellitus; Hypercholesterolemia; Cholesterol, HDL
PubMed: 37513608
DOI: 10.3390/nu15143190 -
Journal of Diabetes and Its... Oct 2023Isthmin-1 (Ism-1) is a newly identified insulin-like adipokine that increases glucose uptake by adipocytes and inhibits hepatic lipid synthesis. Recent studies have...
BACKGROUND
Isthmin-1 (Ism-1) is a newly identified insulin-like adipokine that increases glucose uptake by adipocytes and inhibits hepatic lipid synthesis. Recent studies have shown that Ism-1 can improve the metabolic disorders associated with type 2 diabetes mellitus (T2DM) and improve lipid metabolism. The classic function of high-density lipoprotein cholesterol (HDL-C) is to transport cholesterol from extra-hepatic tissues to the liver for metabolism. In contrast, disorders of lipid metabolism and inflammation are the leading causes of atherosclerosis (As). Atherosclerosis often manifests as loss of elasticity, lipid accumulation, fibrous tissue proliferation and calcium deposits in the affected arteries, eventually forming plaques.
AIM
To illustrate the correlation between HDL-C and Ism-1 in T2DM, and the relationship between lipoprotein cholesterol and carotid plaque.
METHODS
A total of 128 patients with T2DM were enrolled in the study and basic information was collected. HDL-C levels were measured chemically. Serum Ism-1 levels were measured using an enzyme-linked immunosorbent assay (ELISA). Linear regression analysis was used to assess the correlation between serum Ism-1 levels and HDL-C in patients with T2DM. Basic information was again collected from 226 patients with T2DM. Independent sample t-tests were performed to explore the relationship between carotid plaque formation and lipids.
RESULTS
HDL-C was divided into four groups according to quartiles and there was a between-group difference in Ism-1 (p = 0.040). Multivariable linear regression showed a negative association between Ism-1 and HDL-C in T2DM (β = -0.235, p < 0.001), even after adjusting for related factors (β = -0.165, p = 0.009). Low-density lipoprotein cholesterol (LDL-C) and HDL-C showed significant differences between the carotid plaque group and the non-carotid plaque group (p = 0.007, p = 0.003).
CONCLUSION
Serum Ism-1 and HDL-C are negatively correlated in T2DM. LDL-C is significantly higher in carotid plaque group than non-carotid plaque group, while HDL-C is significantly lower than in the non-carotid plaque group.
Topics: Humans; Cholesterol, HDL; Diabetes Mellitus, Type 2; Cholesterol, LDL; Carotid Intima-Media Thickness; Cholesterol; Plaque, Atherosclerotic; Atherosclerosis; Risk Factors
PubMed: 37647712
DOI: 10.1016/j.jdiacomp.2023.108567 -
Journal of Lipid Research Feb 2024Dietary supplements augment the nutritional value of everyday food intake and originate from the historical practices of ancient Egyptian (Ebers papyrus), Chinese (Pen... (Review)
Review
Dietary supplements augment the nutritional value of everyday food intake and originate from the historical practices of ancient Egyptian (Ebers papyrus), Chinese (Pen Ts'ao by Shen Nung), Indian (Ayurveda), Greek (Hippocrates), and Arabic herbalists. In modern-day medicine, the use of dietary supplements continues to increase in popularity with greater than 50% of the US population reporting taking supplements. To further compound this trend, many patients believe that dietary supplements are equally or more effective than evidence-based therapies for lipoprotein and lipid-lowering. Supplements such as red yeast rice, omega-3 fatty acids, garlic, cinnamon, plant sterols, and turmeric are marketed to and believed by consumers to promote "cholesterol health." However, these supplements are not subjected to the same manufacturing scrutiny by the Food and Drug Administration as pharmaceutical drugs and as such, the exact contents and level of ingredients in each of these may vary. Furthermore, supplements do not have to demonstrate efficacy or safety before being marketed. The holistic approach to lowering atherosclerotic cardiovascular disease risk makes dietary supplements an attractive option to many patients; however, their use should not come at the expense of established therapies with proven benefits. In this narrative review, we provide a historical and evidence-based approach to the use of some dietary supplements in lipoprotein and lipid-lowering and provide a framework for managing patient expectations.
Topics: Humans; Dietary Supplements; Fatty Acids, Omega-3; Antioxidants; Cholesterol; Lipoproteins
PubMed: 38145747
DOI: 10.1016/j.jlr.2023.100493