Lipids and Lipoproteins in Health and Disease

This Special Issue, “Lipids and Lipoproteins in Health and Disease: Focus on Targeting Atherosclerosis”, contains research articles and reviews devoted to the study of lipids in different processes, with a focus on the pathological changes that happen during atherosclerosis [...]

The Effects of Exclusive Walking on Lipids and Lipoproteins in Women with Overweight and Obesity: A Systematic Review and Meta-Analysis

Objective To evaluate the effects of walking, independent of diet and weight-loss, on lipids and lipoproteins in women with overweight and obesity. Data Source Academic Search Complete, Alternative Health Watch, Global Health, Health Source, CINAHL, MEDLINE, EMBASE, SportDiscus, and ProQuest. Study Inclusion and Exclusion Criteria (1) experiment-control design; (2) women with overweight or obesity; (3) walking as the experiment’s independent variable; (4) four or more weeks; and (5) pre- to post-assessment of lipids and/or lipoproteins. Excluded studies reported use of lipid-lowering medication, diet or other modes of physical activity, and alternative interventions as the control. Data Extraction Data extraction and study quality were completed by the first 2 authors using the Cochrane review protocol and risk of bias assessment. Data Synthesis Raw mean difference between the experiment and control groups using a random effects model. Results Meta-analyses of 21 interventions (N = 1129) demonstrated exclusive walking improves total cholesterol (raw mean difference = 6.67 mg/dL, P = .04) and low-density lipoproteins (raw mean difference = 7.38 mg/dL, P = .04). Greater improvement in total cholesterol, triglycerides, high-density lipoproteins, and low-density lipoproteins existed in women with obesity. Conclusions Exclusive walking aids in normalizing total cholesterol and LDLs in women with overweight and obesity. Exclusive walking can be used as a non-pharmacologic therapy, which may have positive clinical outcomes for individuals who especially struggle with diet and weight-reduction.

Prognostic significance of preoperative serum triglycerides and high-density lipoproteins cholesterol in patients with non-small cell lung cancer: a retrospective study

Background Abnormalities in serum lipids and lipoproteins have been documented to link to the risk of cancers in recent years, but its prognostic value for cancer is not known. This study retrospectively evaluated the significance of preoperative serum lipids and lipoproteins for NSCLC’s prognosis. Methods A retrospective review was implemented of 551 patients succumbed to NSCLC. A ROC curve was utilized to determine the best cut-off value and area under the ROC curve. Kaplan-Meier and a Cox proportional hazards model were utilized to perform survival analysis. Results With a median follow-up of 42 months, the NSCLC patients in the high TG (> 1.21 mmol/L) and low HDL-C (≤ 1.26 mmol/L) two groups exhibited shorter OS and DFS. In multivariable analysis, preoperative HDL-C and TG can work as independent prognosis factors for OS (P<0.001 for both) and DFS (P<0.05 for both) in patients succumbed to NSCLC. Conclusion Abnormalities of serum lipids and lipoproteins metabolism linked to the survival outcomes of NSCLC. Preoperative serum HDL-C and TG may be promising biomarkers to predict the NSCLC patients’ prognosis.

Reduced sensitivity to thyroid hormone is associated with diabetes and hypertension

Background Recently, reduced sensitivity to thyroid hormone as a more common finding in the general population and its possible association with metabolic parameters has been the focus of attention. We evaluated the cross-sectional association of thyroid hormone sensitivity with diabetes, metabolic syndrome (MetS), and its components. Methods The study included a Tehranian representative sample of 5124 subjects aged ≥20 years participating in the Tehran Thyroid Study (2008-2011). Body weight, waist circumference and blood pressure were measured, and serum concentrations of lipids and lipoproteins, fasting blood glucose (FBG), insulin, free T4 (fT4) and TSH were assayed. Thyroid hormone resistance was calculated by thyroid feedback quantile-based index (TFQI) and Iranian-referenced parametric TFQI (PTFQI) and compared with two other indices of TT4RI and TSHI. Results TFQI was significantly associated with high BP metabolic syndrome criterion (OR=1.14, 95% CI: 1.06, 1.23) and DM (OR=1.16, 95% CI: 1.04, 1. 30, p=0.009) in euthyroid subjects after adjusting for age, sex, smoking, physical activity, BMI, and HOMA-IR. TFQI was not associated with new-onset diabetes contrary to known diabetes in subgroup analysis. The results were similar for PTFQI. TSHI (OR=1.22, 95% CI: 1.08, 1.38, P=0.001) and TT4RI (OR=1.08, 95% CI: 1.01, 1.16, P&lt;0.001) were associated only with high BP in euthyroid subjects. Conclusion The new TFQI index seems to be the indicator of reduced sensitivity to thyroid hormone most suitable to associate its population variations with diabetes and hypertension in euthyroid subjects; however, interpretation for diabetes should be concerned with cautions, necessitating future studies.

Sudden Fall in the Lipid-Lowering Effect of Evolocumab: The Butler Is Not Always Guilty

A 78-year-old man came to our attention after undergoing coronary computed tomography angiography documenting multivessel coronary artery disease. He was started on treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab 140 mg subcutaneously every 2 weeks. Treatment-emergent changes in lipids and lipoproteins were long-lasting, and the medication was well tolerated by the patient in the long-term. Unexpectedly, after 2 years of continuous treatment with evolocumab, serum lipids increased, apparently without any reasonable explanation. During the follow-up visit, the patient was found to have habitually injected evolocumab into his right thumb instead of into the appropriate injection sites (i.e., abdomen, thighs or upper arms) after turning the injector upside down.

Sudden Fall in the Lipid-Lowering Effect of Evolocumab: The Butler Is Not Always Guilty

A 78-year-old man came to our attention after undergoing coronary computed tomography angiography documenting multivessel coronary artery disease. He was started on treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab 140 mg subcutaneously every 2 weeks. Treatment-emergent changes in lipids and lipoproteins were long-lasting, and the medication was well tolerated by the patient in the long-term. Unexpectedly, after 2 years of continuous treatment with evolocumab, serum lipids increased, apparently without any reasonable explanation. During the follow-up visit, the patient was found to have habitually injected evolocumab into his right thumb instead of into the appropriate injection sites (i.e., abdomen, thighs or upper arms) after turning the injector upside down.

Lipids and Lipoproteins in Health and Disease: Focus on Targeting Atherosclerosis

Despite advances in pharmacotherapy, intervention devices and techniques, residual cardiovascular risks still cause a large burden on public health. Whilst most guidelines encourage achieving target levels of specific lipids and lipoproteins to reduce these risks, increasing evidence has shown that molecular modification of these lipoproteins also has a critical impact on their atherogenicity. Modification of low-density lipoprotein (LDL) by oxidation, glycation, peroxidation, apolipoprotein C-III adhesion, and the small dense subtype largely augment its atherogenicity. Post-translational modification by oxidation, carbamylation, glycation, and imbalance of molecular components can reduce the capacity of high-density lipoprotein (HDL) for reverse cholesterol transport. Elevated levels of triglycerides (TGs), apolipoprotein C-III and lipoprotein(a), and a decreased level of apolipoprotein A-I are closely associated with atherosclerotic cardiovascular disease. Pharmacotherapies aimed at reducing TGs, lipoprotein(a), and apolipoprotein C-III, and enhancing apolipoprotein A-1 are undergoing trials, and promising preliminary results have been reported. In this review, we aim to update the evidence on modifications of major lipid and lipoprotein components, including LDL, HDL, TG, apolipoprotein, and lipoprotein(a). We also discuss examples of translating findings from basic research to potential therapeutic targets for drug development.

The influence of adiponectin on carbohydrates, lipids, and lipoproteins metabolism: analysis of signaling mechanisms

Dysregulation of adipose tissue functions makes a significant contribution to the pathogenesis of metabolic syndrome, one of the most common diseases in recent years. Adipose tissue is an organ that secretes at least several dozen signaling molecules, adipokines. One of the most studied and at the same time mysterious adipokines is adiponectin. The latter is due to the lack of clear ideas about the biological role of this adipokine, the presence of its several molecular forms with different activity and several types of receptors to this adipokine localized in almost all cells of the body. The purpose of this review is to summarize and analyze the available information about the molecular mechanisms of the effect of adiponectin on metabolism of carbohydrates, lipids and lipoproteins. The literature search was conducted by the keywords "adiponectin" and "metabolic syndrome" in the Pubmed and Elibrary.ru databases for the period from 1995 to 2021.According to the results of the literature analysis, it is assumed that adiponectin is involved in energy metabolism as a «satiety» hormone that promotes the utilization and storage of energy-rich substrates, fatty acids and glucose, which prevents the development or mitigates the already developed insulin resistance. This reduces the amount of plasma triglycerides and increases the level of high-density lipoproteins in the plasma. Adiponectin affects metabolic processes by activating the AdipoR1-APPL1-LKB1-AMPK, AdipoR1-APPL1-p38, AdipoR2-PPARa cascades, and possibly by activating the ceramidase and phosphoinositide pathways and insulin signaling. In addition to the AdipoR1/2 receptors, the adhesion molecule T-cadherin may be involved in the transduction of the adiponectin signal in endothelial and muscle cells. The mechanisms of signal transduction from T-cadherin, as well as from AdipoR2, remain unclear. Studies on the mechanisms of the action of individual molecular forms of adiponectin are extremely rare. The analysis shows the complex nature of adiponectin signaling, many of the mechanisms of which remain undiscovered, and it is possible that the near future will bring us significant progress in this area.

Serum levels of small HDL particles are negatively correlated with death or lung transplantation in an observational study of idiopathic pulmonary fibrosis

BackgroundSerum lipoproteins, such as high density lipoproteins (HDL), may influence disease severity in idiopathic pulmonary fibrosis (IPF). Here, we investigated associations between serum lipids and lipoproteins and clinical endpoints in IPF.MethodsClinical data and serum lipids were analyzed from a discovery cohort (59 IPF subjects, 56 healthy volunteers) and validated using an independent, multicenter cohort (207 IPF subjects) from the Pulmonary Fibrosis Foundation registry. Associations between lipids and clinical endpoints (FVC, forced vital capacity; 6MWD, 6 min walk distance; GAP (Gender Age Physiology) index; death or lung transplantation) were examined using Pearson's correlation and multivariable analyses.ResultsSerum concentrations of small HDL particles (S-HDLPNMR), measured by nuclear magnetic resonance (NMR) spectroscopy, correlated negatively with the GAP index in the discovery cohort of IPF subjects. The negative correlation of S-HDLPNMR with GAP index was confirmed in the validation cohort of IPF subjects. Higher levels of S-HDLPNMR were associated with lower odds of death or its competing outcome, lung transplantation (OR of 0.9 for each 1 μmol·L−1 increase in S-HDLPNMR, p<0.05), at 1, 2, and 3 years from study entry in a combined cohort of all IPF subjects.ConclusionsHigher serum levels of S-HDLPNMR are negatively correlated with the GAP index, as well as with lower observed mortality or lung transplantation in IPF subjects. These findings support the hypothesis that S-HDLPNMR may modify mortality risk in patients with IPF.