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Metabolic health is highly dependent on intestinal and hepatic handling of dietary and endogenous lipids and lipoproteins. Disorders of lipid and lipoprotein metabolism are commonly observed in patients with insulin resistant states such as obesity, metabolic syndrome, and type 2 diabetes. Evidence from both animal models and human studies indicates that a major underlying factor in metabolic or diabetic dyslipidemia is the overproduction of hepatic and intestinal apolipoprotein (apo)B-containing lipoprotein particles. These particles are catabolized down into highly proatherogenic remnants, which can be taken up into the arterial intima and promote plaque development. Several gut-derived peptides have been identified as key regulators of energy metabolism; one such peptide is the incretin hormone glucagon-like peptide (GLP)-1. Our laboratory has previously demonstrated that GLP-1 can signal both centrally and peripherally to reduce postprandial and fasting lipoprotein secretion. Moreover, we have demonstrated that GLP-1 receptor (GLP-1R) agonists can ameliorate diet-induced dyslipidemia. Recently, we published evidence for a novel vagal neuroendocrine signalling pathway by which native GLP-1 may exert its anti-lipemic effects. Furthermore, we demonstrated a novel role for other gut-derived peptides in regulating intestinal lipoprotein production. Overall, ample evidence supports a key role for GLP-1R on the portal vein afferent neurons and nodose ganglion in modulating intestinal fat absorption and lipoprotein production and identifies other gut-derived peptides as novel regulators of postprandial lipemia. Insights from these data may support identification of potential drug targets and the development of new therapeutics targeting treatment of diabetic dyslipidemia.

Objective·To analyze and explore the influencing factors that lead to cognitive deterioration in individuals with elevated fasting blood glucose (FBG) and the metabolic clues associated with changes in the risk of cognitive deterioration.Methods·Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were downloaded, and the samples with FBG and follow-up data were selected from the database. Clinical information, including age, gender, body mass index, education years, apolipoprotein E4 (APOE4) genotype and race, and corresponding metabolic indicator data, including amino acids, fatty acids, proteins and others were obtained. Based on the FBG levels and diagnosis of cognitive impairment stages in Alzheimer's disease, the subjects were categorized into four groups: normal FBG without/with cognitive deterioration, and elevated FBG without/with cognitive deterioration. The univariate analysis method, the Cox proportional hazards model, orthogonal projections to latent structures discriminant analysis (OPLSDA), and Spearman correlation analysis were employed for data analysis.Results·A total of 1 317 subjects were included, among which 1 153 had normal FBG level (>3.9 mmol/L and

Objective: To determine the frequency of dyslipidaemia in acute non-cardio embolic ischemic stroke patients at a tertiary care centre in Rawalpindi. Study Design: Cross-sectional study Place and Duration of Study: Neurology Department, Pak Emirates Military Hospital (PEMH), Rawalpindi Pakistan, Jul 2022 to Feb 2023. Methodology: Patients with acute non-cardio embolic ischemic stroke were included. Data was collected from the patient files and hospital records including a thorough history, physical examination information, CT/MRI brain, fasting lipid profiles with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Results: The study included 196 patients, of which dyslipidaemia was seen with a major share of high TG in 44(22.44%), followed by high LDL cholesterol in 38(19.38%), and high TC was found in 28(14.28%). Conclusion: More than 1/3rd of patients with acute non-cardioembolic ischemic stroke have dyslipidaemia.

Objective·Previous studies showed that hepatitis B virus (HBV) infection caused outstanding changes in host lipoproteins. However, there are no reports on such component changes of lipoprotein subfractions. This study aimed to quantify the HBV-caused changes in the serum lipoprotein subfractions and their components.Methods·Hepatitis B surface antigen-positive [HBsAg (+)] patients at Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from March to June 2017 were included (n=40), and 40 HBsAg-negative [HBsAg (-)] population were matched as controls. Serum lipoprotein subfractions and their components were quantified by using 1H-NMR. Orthogonal partial least-squares discriminant analysis (OPLS-DA), variance analysis between the two groups, logistic regression analysis and Spearman correlation analysis were conducted to reveal the lipoprotein changes in chronic HBV patients against controls.Results·HBsAg (+) population had significantly lower levels in most lipoprotein subfractions than HBsAg (-) population. After adjustments for age, gender, hypertension, diabetes mellitus and coronary heart disease, the levels of total VLDL, VLDL1-VLDL3, IDL, HDL4, non-HDL and their components were protective factors for HBV infection (OR < 1, P < 0.01). In contrast, VLDL5-(TAG/LP) was a risk factor for HBV infection (OR > 1, P < 0.01). In addition, the severity of inflammation in the HBsAg (+) population was negatively correlated with the levels of lipids in HDL4 with correlation coefficient ranging from -0.71 to -0.51 (P≤ 0.002). Six lipoprotein subfractions were obtained through feature screening, and the AUC of HBV infection diagnosis model was 0.861.Conclusion·HBV infection causes significant changes in liver-excretion of lipoproteins and their circulation metabolism; the lipoprotein phenotypes can differentiate HBV-infected patients from controls.

Methicillin-resistant Staphylococcus aureus (MRSA) has been classified as a high priority pathogen by the World Health Organization underlining the high demand for new therapeutics to treat infections. Human group IIA-secreted phospholipase A2 (hGIIA) is among the most potent bactericidal proteins against Gram-positive bacteria, including S. aureus. To determine hGIIA-resistance mechanisms of MRSA, we screened the Nebraska Transposon Mutant Library using a sublethal concentration of recombinant hGIIA. We identified and confirmed the role of lspA, encoding the lipoprotein signal peptidase LspA, as a new hGIIA resistance gene in both in vitro assays and an infection model in hGIIA-transgenic mice. Increased susceptibility of the lspA mutant was associated with enhanced activity of hGIIA on the cell membrane. Moreover, lspA deletion increased susceptibility to daptomycin, a last-resort antibiotic to treat MRSA infections. MRSA wild type could be sensitized to hGIIA and daptomycin killing through exposure to LspA-specific inhibitors globomycin and myxovirescin A1. Analysis of >26,000 S. aureus genomes showed that LspA is highly sequence-conserved, suggesting universal application of LspA inhibition. The role of LspA in hGIIA resistance was not restricted to MRSA since Streptococcus mutans and Enterococcus faecalis were also more hGIIA-susceptible after lspA deletion or LspA inhibition, respectively. Overall, our data suggest that pharmacological interference with LspA may disarm Gram-positive pathogens, including MRSA, to enhance clearance by innate host defense molecules and clinically applied antibiotics.

Defective nutrient storage and adipocyte enlargement (hypertrophy) are emerging features of metabolic syndrome and type 2 diabetes. Within adipose tissues, how the cytoskeletal network contributes to adipose cell size, nutrient uptake, fat storage, and signaling remain poorly understood. Utilizing the Drosophila larval fat body (FB) as a model adipose tissue, we show that a specific actin isoform—Act5C—forms the cortical actin network necessary to expand adipocyte cell size for biomass storage in development. Additionally, we uncover a non-canonical role for the cortical actin cytoskeleton in inter-organ lipid trafficking. We find Act5C localizes to the FB cell surface and cell-cell boundaries, where it intimately contacts peripheral LDs (pLDs), forming a cortical actin network for cell architectural support. FB-specific loss of Act5C perturbs FB triglyceride (TG) storage and LD morphology, resulting in developmentally delayed larvae that fail to develop into flies. Utilizing temporal RNAi-depletion approaches, we reveal that Act5C is indispensable post-embryogenesis during larval feeding as FB cells expand and store fat. Act5C-deficient FBs fail to grow, leading to lipodystrophic larvae unable to accrue sufficient biomass for complete metamorphosis. In line with this, Act5C-deficient larvae display blunted insulin signaling and reduced feeding. Mechanistically, we also show this diminished signaling correlates with decreased lipophorin (Lpp) lipoprotein-mediated lipid trafficking, and find Act5C is required for Lpp secretion from the FB for lipid transport. Collectively, we propose that the Act5C-dependent cortical actin network of Drosophila adipose tissue is required for adipose tissue size-expansion and organismal energy homeostasis in development, and plays an essential role in inter-organ nutrient transport and signaling.

GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) within the subendothelial spaces and shuttles it to the capillary lumen. GPIHBP1-bound LPL is essential for the margination of triglyceride-rich lipoproteins (TRLs) along capillaries, allowing the lipolytic processing of TRLs to proceed. In peripheral tissues, the intravascular processing of TRLs by the GPIHBP1-LPL complex is crucial for the generation of lipid nutrients for adjacent parenchymal cells. GPIHBP1 is absent from the capillaries of the brain, which uses glucose for fuel; however, GPIHBP1 is expressed in the capillaries of mouse and human gliomas. Importantly, the GPIHBP1 in glioma capillaries captures locally produced LPL. We use NanoSIMS imaging to show that TRLs marginate along glioma capillaries and that there is uptake of TRL-derived lipid nutrients by surrounding glioma cells. Thus, GPIHBP1 expression in gliomas facilitates TRL processing and provides a source of lipid nutrients for glioma cells.

Background: Splenectomy impacts hematological, immunological, and metabolic functions of the patient. Since our understanding of its metabolic effects, in particular effects on lipid metabolism, is limited, this study aims to investigate the effects of splenectomy on lipid metabolism. Methods: The data from 316 patients undergoing splenectomy between 2009 and 2019 were retrospectively analyzed. Thirty-eight patients whose serum lipid values were measured both preoperatively and 1 year after surgery were included in this study. Results: Significantly higher levels of total cholesterol, low-density lipoprotein (LDL), and non-high-density lipoprotein (HDL) lipid profile were found in the postsplenectomy measurements. However, no significant differences were recorded in levels of triglyceride, HDL, or very-LDL. Conclusion: We determined that splenectomy does impact lipid metabolism, and that the metabolic effects of splenectomy should further be investigated.

Objective: Erythrocyte sedimentation rate (ESR) is a cheap, fast and readily available test and its still being used for many medical conditions in order to help diagnosis and evaluation of diseases. In this study, association of ESR, cholesterol levels and monocyte to high density lipoprotein ratio (MHR) with body mass index were inspected in healthy population. Material and Method: This study is an observational, retrospective study. It has been conducted in a university hospital with people admitting to internal medicine outpatient clinics between January 2020 and December 2020. Demographic characteristics, body mass indexes and laboratory parameters of 689 patients were evaluated. Participants were divided into three groups according to body mass indexes; Group 1 (normal weight), Group 2 (overweight), Group 3 (obese). Data obtained from three groups were compared. Results: There were significant associations between body mass index and height, weight, ESR, glucose, monocyte counts, total cholesterol, low density lipoprotein, Non-HDL cholesterol and MHR among groups. ESR was significantly higher in women compared to men. There were significant correlations between body mass index and ESR (r=0.346, p=0.001), glucose (r=0.239, p=0.001) and monocyte count (r=0.096, p=0.013). Conclusion: According to the results of this study, ESR is a parameter associated with BMI and it may reflect the magnitude of inflammation taking place in obesity. ESR was used for more than a century in evaluation of diseases and it still has a place in different medical disorders.

Lipoprotein lipase (LPL) undergoes spontaneous inactivation via global unfolding and this unfolding is prevented by GPIHBP1 (Mysling et al., 2016). We now show: (1) that ANGPTL4 inactivates LPL by catalyzing the unfolding of its hydrolase domain; (2) that binding to GPIHBP1 renders LPL largely refractory to this inhibition; and (3) that both the LU domain and the intrinsically disordered acidic domain of GPIHBP1 are required for this protective effect. Genetic studies have found that a common polymorphic variant in ANGPTL4 results in lower plasma triglyceride levels. We now report: (1) that this ANGPTL4 variant is less efficient in catalyzing the unfolding of LPL; and (2) that its Glu-to-Lys substitution destabilizes its N-terminal α-helix. Our work elucidates the molecular basis for regulation of LPL activity by ANGPTL4, highlights the physiological relevance of the inherent instability of LPL, and sheds light on the molecular defects in a clinically relevant variant of ANGPTL4.

Introduction: Breast cancer accounts for 25% of all female cancer cases in India. Although, lipids and free radicals like Nitric Oxide (NO) have been related to breast cancer, but its pathogenesis remains controversial. Aim: To estimate NO, endothelial NO Synthase (eNOS) and lipid profile in serum of breast cancer patients and also to determine their possible role in patients of breast cancer in Indian women. Materials and Methods: This was a hospital-based case-control study conducted for a period of 24 months from July 2012 to June 2014 in Dr. V.M. Government Medical College, Solapur, with a total of 100 women (50 breast cancer cases and 50 healthy age-matched controls) of age group 35-65 years. Fasting venous blood samples were collected. Biochemical parameters analysed in the study were serum NO, serum eNOS, serum Total Cholesterol (TC), serum Triglycerides (TG), serum High Density Lipoprotein (HDL) and serum Low Density Lipoprotein (LDL). Results were expressed as mean±Standard Deviation (SD) and Student’s unpaired t-test was used to compare the pairs of means. Results: There was no significant difference in mean age between cases (49.73±8.16 years) and controls (48.23±8 years). Serum levels of NO, eNOS, TC, TG and LDL were significantly higher in cases than in controls (55.92±6.54 μmol/L vs 49.58±6.74 μmol/L for NO; 175.4±22.92 U/mL vs 148.6±9.77 U/mL for eNOS; 271±9.16 mg/dL vs 177.58±6.41 mg/dL for TC; 180.70±8.48 mg/dL vs 107.57±8.98 mg/dL for TG; 177.39±6.21 mg/dL vs 98.16±8.90 mg/dL for LDL). However, serum HDL levels did not showed significant difference in case group (57.55±6.40 mg/dL) when compared with control group (57.15±5.35 mg/dL). Conclusion: The present study demonstrated that high serum levels of NO, eNOS and lipids are associated with breast cancer and thereby, suggests that increased NO, eNOS and abnormal lipid profile may have a role in pathogenesis of breast cancer.

Increasing evidence from experimental research suggests that exposure to microcystins (MCs) may induce lipid metabolism disorder. However, population-based epidemiological studies of the association between MCs exposure and the risk of dyslipidemia are lacking. Therefore, we conducted a population-based cross-sectional study involving 720 participants in Hunan Province, China, and evaluated the effects of MCs on blood lipids. After adjusting the lipid related metals, we used binary logistic regression and multiple linear regression models to examine the associations among serum MCs concentration, the risk of dyslipidemia and blood lipids (triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)). Moreover, the additive model was used to explore the interaction effects on dyslipidemia between MCs and metals. Compared to the lowest quartile of MCs exposure, the risk of dyslipidemia [odds ratios (OR) = 2.27, 95% confidence interval (CI): 1.46, 3.53] and hyperTG (OR = 3.01, 95% CI: 1.79, 5.05) in the highest quartile was significantly increased, and showed dose–response relationships. MCs were positively associated with TG level (percent change, 9.43%; 95% CI: 3.53%, 15.67%) and negatively associated with HDL-C level (percent change, −3.53%; 95% CI: −5.70%, −2.10%). In addition, an additive antagonistic effect of MCs and Zn on dyslipidemia was also reported [relative excess risk due to interaction (RERI) = −1.81 (95% CI: −3.56, −0.05)], and the attributable proportion of the reduced risk of dyslipidemia due to the antagonism of these two exposures was 83% (95% CI: −1.66, −0.005). Our study first indicated that MCs exposure is an independent risk factor for dyslipidemia in a dose–response manner.

Apolipoprotein E (APOE) plays an important role in lipid metabolism and is a proven risk factor for development of dementia and other neurodegenerative diseases. The aim of the study was to determine the possible connection between particular APOE alleles, blood lipid profile and different types of epilepsy in children. Alleles of the APOE gene, blood cholesterol (total, highdensity lipoprotein and low-density lipoprotein (LDL) cholesterol, and triglyceride levels were analyzed in blood samples of 111 children with epilepsy and 118 age- and sex-matched children without epilepsy. Distribution of APOE genotypes was the same in children of both groups. Significantly increased levels of total cholesterol and LDL cholesterol were found in control group (Z=3.49 and 3.52 respectively, p0.05). There were statistically significant differences in the levels of total cholesterol (Z=2.09; p

Abstract Background Familial chylomicronemia is an extremely rare disease. Lipoprotein lipase deficiency, lipoprotein defect or lipoprotein receptor defect are the main genetic causes of familial chylomicronemia. Case presentation We report a rare case of hypertriglyceridemia which was diagnosed at 24 days after birth. A newborn south east Asian baby born for G3P2A1 mother was presented with hematuria at 24 days at the hospital. The patient's family history is significant for pink blood in an elder sibling who died within a few months of birth without a proper diagnosis. Physical examination was not significant for any findings. Urinalysis revealed numerous RBC in the urine. Blood draw to perform renal function test revealed a characteristic pink blood. Baby’s blood was normal and red in color at the time of birth. During the present visit, although most of the blood test were not able to be carried out by the regular laboratory instruments, the patient’s lipid profile was alarmingly high with triglyceride levels over 4000 mg/dL. Due to a very high triglyceride level in a neonate and a significant familial history, a genetic cause of hypertriglyceridemia is suspected. Upon diagnosis, baby was discontinued of breast feeding completely and was given a special diet devoid of triglyceride and containing medium chain fatty acid diet and was also started with fenofibrate. After a month and a half, follow up tests were conducted which showed the triglyceride level was reduced to 1300 and a reversal of the blood color from pink to red. Since the imported diet was extremely expensive for the family, the patient was put on skimmed milk with medium-chain triglyceride (MCT) oil. With 6 weeks of treatment, baby’s condition has improved and is thriving well. Conclusions Our case reports an extremely rare and fatal condition and illustrated the significance of timely diagnosis and intervention for saving the life of the baby.

GPIHBP1 is a glycolipid-anchored membrane protein of capillary endothelial cells that binds lipoprotein lipase (LPL) within the interstitial space and shuttles it to the capillary lumen. The LPL•GPIHBP1 complex is responsible for margination of triglyceride-rich lipoproteins along capillaries and their lipolytic processing. The current work conceptualizes a model for the GPIHBP1•LPL interaction based on biophysical measurements with hydrogen-deuterium exchange/mass spectrometry, surface plasmon resonance, and zero-length cross-linking. According to this model, GPIHBP1 comprises two functionally distinct domains: (1) an intrinsically disordered acidic N-terminal domain; and (2) a folded C-terminal domain that tethers GPIHBP1 to the cell membrane by glycosylphosphatidylinositol. We demonstrate that these domains serve different roles in regulating the kinetics of LPL binding. Importantly, the acidic domain stabilizes LPL catalytic activity by mitigating the global unfolding of LPL's catalytic domain. This study provides a conceptual framework for understanding intravascular lipolysis and GPIHBP1 and LPL mutations causing familial chylomicronemia.

Abstract Background Advances in antiretroviral therapies have greatly improved the survival of people living with human immunodeficiency virus (HIV) infection (PLWH); yet, PLWH have a higher risk of cardiovascular disease than those without HIV. While numerous genetic loci have been linked to cardiometabolic risk in the general population, genetic predictors of the excessive risk in PLWH are largely unknown. Methods We screened for common and HIV-specific genetic variants associated with variation in lipid levels in 6284 PLWH (3095 European Americans [EA] and 3189 African Americans [AA]), from the Centers for AIDS Research Network of Integrated Clinical Systems cohort. Genetic hits found exclusively in the PLWH cohort were tested for association with other traits. We then assessed the predictive value of a series of polygenic risk scores (PRS) recapitulating the genetic burden for lipid levels, type 2 diabetes (T2D), and myocardial infarction (MI) in EA and AA PLWH. Results We confirmed the impact of previously reported lipid-related susceptibility loci in PLWH. Furthermore, we identified PLWH-specific variants in genes involved in immune cell regulation and previously linked to HIV control, body composition, smoking, and alcohol consumption. Moreover, PLWH at the top of European-based PRS for T2D distribution demonstrated a > 2-fold increased risk of T2D compared to the remaining 95% in EA PLWH but to a much lesser degree in AA. Importantly, while PRS for MI was not predictive of MI risk in AA PLWH, multiethnic PRS significantly improved risk stratification for T2D and MI. Conclusions Our findings suggest that genetic loci involved in the regulation of the immune system and predisposition to risky behaviors contribute to dyslipidemia in the presence of HIV infection. Moreover, we demonstrate the utility of the European-based and multiethnic PRS for stratification of PLWH at a high risk of cardiometabolic diseases who may benefit from preventive therapies.

High-density lipoprotein (HDL) is a set of particles with heterogeneous structures that have different functions due to various compounds including surface charge, size, lipid, and protein compounds. Several prospective epidemiological studies have demonstrated that there is a clear inverse relationship between serum HDL concentration and risk of coronary heart disease, despite this relationship, clinical evidence has only challenged the usefulness of higher levels of HDL-C in predicting the risk of cardiovascular diseases (CVD) and have proven that the structure of HDL is altered and loosed function. Therefore, extensive research is needed to identify new agents and biomarkers to improve HDL function and reduce the risk of cardiovascular disease. Given that the most important function of HDL is to transfer excess cholesterol from peripheral tissues and macrophage cells through a receptor called ABCA1 and direct it to the liver, plays an important role in protecting the formation of atherosclerotic plaque. This molecule can provide a strong protective effect against oxidative damage caused by free radicals with intermittent inhibition of the production of pro-inflammatory oxidized lipids in the intima layer of arteries. There is an inverse relationship between the ability to efflux cholesterol and the prevalence of CVD. The ability to remove cholesterol from macrophages by HDL, it is a crucial criterion for determining HDL performance, and it has a strong inverse relationship with carotid intima-media thickness and coronary artery stenosis in angiography independent of HDL level

Lipid variations have been frequently observed in global populations that can affect health status. Mainly studies have been conducted on the type 2 diabetic population, but limited data is available on newly diagnosed ones to unravel complications and risk predictors independent of disease progression. This study comprising 244 individuals was carried out to assess the lipid abnormalities in newly diagnosed diabetics and non-diabetics. The clinical and socio-demographic data were collected and analyzed using independent samples t-test and linear regression. Serum lipid variations were observed individually and in combination. The individuals in group I (diabetics with dyslipidemia) revealed elevated levels of low-density lipoprotein and serum triglycerides higher than in group II (non-diabetics with dyslipidemia). The frequency of deranged total cholesterol in group I was observed to be higher than in group II. Independent samples t-test showed a significant mean difference in variables between the two groups. Linear regression analysis showed a significant variable outcome for predictors between high-density lipoprotein (HDL) and physical activity (B= −0.043, 95% CI: −0.80, −0.006) and total cholesterol (TC) with family history (B= −0.062, 95% CI: −0.123, −0.001). The findings conclude that lipid levels deranged independently regardless of type 2 diabetes mellitus and present as an early onset in type 2 diabetes instead of later stage complication. These derangements of lipid levels are an independent risk factor for future cardiovascular pathology.

The role of specific phospholipids (PLs) in lipid transport has been difficult to assess due to an inability to selectively manipulate membrane composition in vivo. Here we show that the phospholipid remodeling enzyme lysophosphatidylcholine acyltransferase 3 (Lpcat3) is a critical determinant of triglyceride (TG) secretion due to its unique ability to catalyze the incorporation of arachidonate into membranes. Mice lacking Lpcat3 in the intestine fail to thrive during weaning and exhibit enterocyte lipid accumulation and reduced plasma TGs. Mice lacking Lpcat3 in the liver show reduced plasma TGs, hepatosteatosis, and secrete lipid-poor very low-density lipoprotein (VLDL) lacking arachidonoyl PLs. Mechanistic studies indicate that Lpcat3 activity impacts membrane lipid mobility in living cells, suggesting a biophysical basis for the requirement of arachidonoyl PLs in lipidating lipoprotein particles. These data identify Lpcat3 as a key factor in lipoprotein production and illustrate how manipulation of membrane composition can be used as a regulatory mechanism to control metabolic pathways.

NmMetQ is a substrate-binding protein (SBP) from Neisseria meningitidis that has been identified as a surface-exposed candidate antigen for meningococcal vaccines. However, this location for NmMetQ challenges the prevailing view that SBPs in Gram-negative bacteria are localized to the periplasmic space to promote interaction with their cognate ABC transporter embedded in the bacterial inner membrane. To elucidate the roles of NmMetQ, we characterized NmMetQ with and without its cognate ABC transporter (NmMetNI). Here, we show that NmMetQ is a lipoprotein (lipo-NmMetQ) that binds multiple methionine analogs and stimulates the ATPase activity of NmMetNI. Using single-particle electron cryo-microscopy, we determined the structures of NmMetNI in the presence and absence of lipo-NmMetQ. Based on our data, we propose that NmMetQ tethers to membranes via a lipid anchor and has dual function and localization, playing a role in NmMetNI-mediated transport at the inner membrane and moonlighting on the bacterial surface.

Introduction: Abnormalities in serum lipid and lipoprotein levels are recognized as major modifiable risk factors for cardiovascular disease and essential hypertension and retinopathy. So this study was conducted to evaluate the role of dyslipidemia on development of retinopathy in hypertensive patients and to establish the association of parameters of serum lipid profile with hypertensive retinopathy. Materials and Methods: A cross-sectional study was conducted in Ophthalmology Department among 135 patients in Nobel Medical College and Teaching Hospital (NoMCTH), Biratnagar who were diagnosed with essential hypertension. Patients having diabetes mellitus, myopia, hazy ocular media and other posterior segment disorders were excluded from the study. The detailed ophthalmic examination was carried out in department of ophthalmology, NoMCTH, Biratnagar and all the study population were investigated for fasting serum lipid profile. Result: Out of 135 patients with essential hypertension, 65.44% had retinopathy and remaining had no signs of retinopathy. Mean age of patients were 60.24 (±15.14) years. Although no gender preponderance was found with retinopathy but this study showed that hypertensive retinopathy increases significantly with increase in age and its incidence increases after the age of 60 years. Conclusion: The duration of hypertension was found to be strongly associated with development of hypertensive retinopathy. The increase in all the lipid profile parameters (Serum TG, TC, and LDL and LDL:HDL) and the obesity were found to be strongly associated with retinopathy in hypertensive patients.

Protein acylation is critical for many cellular functions across all domains of life. In bacteria, lipoproteins have important roles in virulence and are targets for the development of antimicrobials and vaccines. Bacterial lipoproteins are secreted from the cytosol via the Sec pathway and acylated on an N-terminal cysteine residue through the action of three enzymes. In Gram-negative bacteria, the Lol pathway transports lipoproteins to the outer membrane. Here, we demonstrate that the Aat secretion system is a composite system sharing similarity with elements of a type I secretion systems and the Lol pathway. During secretion, the AatD subunit acylates the substrate CexE on a highly conserved N-terminal glycine residue. Mutations disrupting glycine acylation interfere with membrane incorporation and trafficking. Our data reveal CexE as the first member of a new class of glycine-acylated lipoprotein, while Aat represents a new secretion system that displays the substrate lipoprotein on the cell surface.

Objectives: Complement activation product C5a is increased in acute cardiovascular events and infl ammation. However, investigation of C5a in patients with atherosclerotic vascular changes among Mongolian populations is still lacking. Methods: A total of 43 patients were selected using special criteria for this study. Plasma C5a and lipid levels were measured by high-sensitive enzyme-linked immune sorbent assay and colorimetric enzyme assay at the Mongolian National University of Medical Sciences, Core Laboratory and Second General Hospital. All data were analyzed for normality and then parametric or nonparametric tests using GraphPad Prism 6.0 software. The Pearson r correlation analysis was performed using Microsoft Excel. Results: Patients were divided into a healthy group ((n=23, carotid intima-media thickness (cIMT) 1.0 mm by Doppler-ultrasound imaging). The suffi cient number of patients within groups was approved by using column statistical analysis. A signifi cantly elevated plasma C5a protein concentration was found in patients with atherosclerosis compared to healthy controls (276.28±24.82 vs. 61.56±4.35 pg/mL, P

ABSTRACT Background and Objectives: Elevated blood lipid levels are correlated with risk of cardiovascular disease, especially in overweight individuals. The beneficial effect of strength training on lipid profile has been well documented. However, the effect of strength training with flow blood restriction has not been established. The purpose of this study was to compare the effect of eight weeks of strength training with and without blood flow restriction on some of the cardiovascular risk factors in overweight females. Methods: In this study, 28 overweight females aged 18 to 24 years were randomly assigned into three groups of blood flow restriction strength training (BFRT), traditional strength training (TRT) and control. Participants in the BFRT group performed eight weeks of strength training three sessions per week at 30% of 1-repetetion maximum, while participants in the TRT group performed the training at 65-80% of 1-repetetion maximum. Cardiovascular variables, systolic blood pressure and diastolic blood pressure were measured before and after the exercise training. Data was analyzed using descriptive statistics, paired t-test and one-way analysis of variance. Results: Triglyceride level decreased significantly in the BFRT (p=0.022) and TRT (p=0.038) groups compared with the control group. Moreover, there were no significant differences in the body mass, waist-to-hip ratio, body mass index, high-density lipoprotein, low-density lipoprotein, and cholesterol levels between the study groups (P≥0.05). Conclusion: Our findings suggest that the BFRT and TRT may not be suitable for preventing or even reversing the physiological changes induced by obesity. Keywords: Resistance Training, Lipids, lipoprotein, overweight.

Abstract Background Circulating concentrations of lipid biomarkers are associated with risk of cardiovascular diseases (CVD). The evidence for a relationship with cancer risk, however, is not entirely consistent. This study aims to assess the relationships of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein (a) (apo(a)), apoB-100, and lipoprotein(a) (Lp(a)) with risk of common cancer forms and total cancer mortality in comparison to incidence and mortality of CVD. Methods We selected a case-cohort sample out of the prospective EPIC–Heidelberg study, including a random subcohort (n = 2739), and cases of cancer (n = 1632), cancer mortality (n = 761), CVD (n = 1070), and CVD mortality (n = 381). Concentrations of lipid biomarkers were measured in pre-diagnostic blood samples. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Prentice-weighted Cox regression models. Results High levels of circulating apoB-100 and TG were inversely associated and high HDL-C levels were positively associated with breast cancer risk (highest vs. lowest quartile (Q4 vs. Q1), HRapoB 0.71, 95% CI 0.52–0.98; HRTG 0.65, 0.46–0.92; and HRHDL 1.39, 1.01–1.93). Higher levels of Lp(a) were associated with an increase in prostate cancer risk (Q4 vs. Q1, HRLp(a) 1.43, 1.02–2.03) and high levels of apo(a) were associated with a decrease in lung cancer risk (Q4 vs. Q1, HRapo(a) 0.52, 0.30–0.91). High TC, HDL-C, apo(a), and Lp(a) levels were associated with a reduction in total cancer mortality (Q4 vs. Q1, HRTC 0.71, 0.54–0.94; HRHDL 0.67, 0.50–0.91; HRapo(a) 0.71, 0.54–0.93; and HRLp(a) 0.74, 0.57–0.98). All lipid biomarkers were associated with risk of myocardial infarction, whereby TC, apoB-100, TG, and Lp(a) were positively and HLD-C and apo(a) inversely associated with risk. Only high levels of TG were associated with an increased risk of stroke. None of the lipids were associated with risk of colorectal cancer and with risk of CVD mortality after multivariable adjustments. Conclusions This prospective study demonstrates inverse associations of lipid biomarkers with cancer incidence and mortality, with the exception of positive associations of HDL-C and Lp(a) with breast and prostate cancer risk, respectively. Thus, the observed cancer risk pattern clearly differs from the CVD risk pattern.

ABSTRACT Background and Objectives: The aim of the present study was to investigate the effect of six weeks of volleyball training on lipid and lipoprotein profiles of elite high school male volleyball players in the Golestan Province (Iran) during preparation season for an international championship in France. Methods: Training group included 12 elite volleyball players in students’ premier league and control group included 12 healthy non-athlete male students. The training group practiced at 60-85% of maximum heart rate for six weeks, 90 minutes per session, six sessions per week and three sessions a day (first session: technical practice, second session: tactical practice and third session: technical/tactical practice). Blood samples were taken after 12 hours of fasting both before and after the training. Results: Level of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and LDL-C/HDL-C increased in the training group (P> 0.05). However, there was a significant difference between the two groups in TC and LDL-C levels (P 0.05). Conclusion: Our results show that the six-week volleyball training during the preparation season can cause abnormalities in plasma lipid profile. Keywords: Lipid, Lipoprotein, Volleyball Player

Lipoproteins are lipid-protein complexes that are primarily generated and secreted from the intestine, liver, and visceral endoderm and delivered to peripheral tissues. Lipoproteins, which are assembled in the endoplasmic reticulum (ER) membrane, are released into the ER lumen for secretion, but its mechanism remains largely unknown. Here, we show that the release of lipoproteins from the ER membrane requires VMP1, an ER transmembrane protein essential for autophagy and certain types of secretion. Loss of vmp1, but not other autophagy-related genes, in zebrafish causes lipoprotein accumulation in the intestine and liver. Vmp1 deficiency in mice also leads to lipid accumulation in the visceral endoderm and intestine. In VMP1-depleted cells, neutral lipids accumulate within lipid bilayers of the ER membrane, thus affecting lipoprotein secretion. These results suggest that VMP1 is important for the release of lipoproteins from the ER membrane to the ER lumen in addition to its previously known functions.

Introduction: Lichen Planus (LP) is a chronic inflammatory cutaneous disease. Some studies investigated its association with Dyslipidaemia as a main contributing factor for cardiovascular insults. Atherogenic Index of Plasma (AIP) is a strong factor for suspecting that risk. Aim: To investigate lipid profile and calculate AIP in LP patients to early detect atherogenic Dyslipidaemia, if present. Materials and Methods: This case-control study investigated 40 LP patients and 20 age, gender and body mass index (BMI) matched healthy volunteers. Lipid profile of all subjects was evaluated. AIP was estimated as Log {Triglycerides (TGs)/ High Density Lipoprotein-Cholesterol (HDL-C)} and accordingly, patients were categorised into high, medium and low cardiovascular risk patients. Results: Dyslipidaemia was detected in 47.5% of patients, while all control subjects had normal lipid profile (p

Low-density lipoprotein receptor-related protein-1 (LRP1) is a multifunctional uptake receptor for chylomicron remnants in the liver. In vascular smooth muscle cells LRP1 controls reverse cholesterol transport through platelet-derived growth factor receptor β (PDGFR-β) trafficking and tyrosine kinase activity. Here we show that LRP1 regulates hepatic energy homeostasis by integrating insulin signaling with lipid uptake and secretion. Somatic inactivation of LRP1 in the liver (hLRP1KO) predisposes to diet-induced insulin resistance with dyslipidemia and non-alcoholic hepatic steatosis. On a high-fat diet, hLRP1KO mice develop a severe Metabolic Syndrome secondary to hepatic insulin resistance, reduced expression of insulin receptors on the hepatocyte surface and decreased glucose transporter 2 (GLUT2) translocation. While LRP1 is also required for efficient cell surface insulin receptor expression in the absence of exogenous lipids, this latent state of insulin resistance is unmasked by exposure to fatty acids. This further impairs insulin receptor trafficking and results in increased hepatic lipogenesis, impaired fatty acid oxidation and reduced very low density lipoprotein (VLDL) triglyceride secretion.