Low-density Lipoprotein Lipid Research Articles

Discordance Between Very Low-Density Lipoprotein Cholesterol and Low-Density Lipoprotein Cholesterol Increases Cardiovascular Disease Risk in a Geographically Defined Cohort.

Clinical risk scores are used to identify those at high risk of atherosclerotic cardiovascular disease (ASCVD). Despite preventative efforts, residual risk remains for many individuals. Very low-density lipoprotein cholesterol (VLDL-C) and lipid discordance could be contributors to the residual risk of ASCVD. Cardiovascular disease-free residents, aged ≥40 years, living in Olmsted County, Minnesota, were identified through the Rochester Epidemiology Project. Low-density lipoprotein cholesterol (LDL-C) and VLDL-C were estimated from clinically ordered lipid panels using the Sampson equation. Participants were categorized into concordant and discordant lipid pairings based on clinical cut points. Rates of incident ASCVD, including percutaneous coronary intervention, coronary artery bypass grafting, stroke, or myocardial infarction, were calculated during follow-up. The association of LDL-C and VLDL-C with ASCVD was assessed using Cox proportional hazards regression. Interaction between LDL-C and VLDL-C was assessed. The study population (n=39 098) was primarily White race (94%) and female sex (57%), with a mean age of 54 years. VLDL-C (per 10-mg/dL increase) was significantly associated with an increased risk of incident ASCVD (hazard ratio, 1.07 [95% CI, 1.05-1.09]; P<0.001]) after adjustment for traditional risk factors. The interaction between LDL-C and VLDL-C was not statistically significant (P=0.11). Discordant individuals with high VLDL-C and low LDL-C experienced the highest rate of incident ASCVD events, 16.9 per 1000 person-years, during follow-up. VLDL-C and lipid discordance are associated with a greater risk of ASCVD and can be estimated from clinically ordered lipid panels to improve ASCVD risk assessment.

Recapitulating familial hypercholesterolemia in a mouse model by knock-in patient-specific LDLR mutation.

Familial hypercholesterolemia (FH) is one of the most prevalent monogenetic disorders leading to cardiovascular disease (CVD) worldwide. Mutations in Ldlr, encoding a membrane-spanning protein, account for the majority of FH cases. No effective and safe clinical treatments are available for FH. Adenine base editor (ABE)-mediated molecular therapy is a promising therapeutic strategy to treat genetic diseases caused by point mutations, with evidence of successful treatment in mouse disease models. However, due to the differences in the genomes between mice and humans, ABE with specific sgRNA, a key gene correction component, cannot be directly used to treat FH patients. Thus, we generated a knock-in mouse model harboring the partial patient-specific fragment and including the Ldlr W490X mutation. LdlrW490X/W490X mice recapitulated cholesterol metabolic disorder and clinical manifestations of atherosclerosis associated with FH patients, including high plasma low-density lipoprotein cholesterol levels and lipid deposition in aortic vessels. Additionally, we showed that the mutant Ldlr gene could be repaired using ABE with the cellular model. Taken together, these results pave the way for ABE-mediated molecular therapy for FH.

Changes in bile acid subtypes and improvements in lipid metabolism and atherosclerotic cardiovascular disease risk: the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial

BackgroundDistinct circulating bile acid (BA) subtypes may play roles in regulating lipid homeostasis and atherosclerosis. ObjectivesWe investigated whether changes in circulating BA subtypes induced by weight-loss dietary interventions were associated with improved lipid profiles and atherosclerotic cardiovascular disease (ASCVD) risk estimates. MethodsThis study included adults with overweight or obesity (n = 536) who participated in a randomized weight-loss dietary intervention trial. Circulating primary and secondary unconjugated BAs and their taurine-/glycine-conjugates were measured at baseline and 6 mo after the weight-loss diet intervention. The ASCVD risk estimates were calculated using the validated equations. ResultsAt baseline, higher concentrations of specific BA subtypes were related to higher concentrations of atherogenic very low-density lipoprotein lipid subtypes and ASCVD risk estimates. Weight-loss diet-induced decreases in primary BAs were related to larger reductions in triglycerides and total cholesterol [every 1 standard deviation (SD) decrease of glycocholate, glycochenodeoxycholate, or taurochenodeoxycholate was related to β (standard error) –3.3 (1.3), –3.4 (1.3), or –3.8 (1.3) mg/dL, respectively; PFDR < 0.05 for all]. Greater decreases in specific secondary BA subtypes were also associated with improved lipid metabolism at 6 mo; there was β –4.0 (1.1) mg/dL per 1-SD decrease of glycoursodeoxycholate (PFDR =0.003) for changes in low-density lipoprotein cholesterol. We found significant interactions (P-interaction < 0.05) between dietary fat intake and changes in BA subtypes on changes in ASCVD risk estimates; decreases in primary and secondary BAs (such as conjugated cholate or deoxycholate) were significantly associated with improved ASCVD risk after consuming a high-fat diet, but not after consuming a low-fat diet. ConclusionsDecreases in distinct BA subtypes were associated with improved lipid profiles and ASCVD risk estimates, highlighting the importance of changes in circulating BA subtypes as significant factors linked to improved lipid metabolism and ASCVD risk estimates in response to weight-loss dietary interventions. Habitual dietary fat intake may modify the associations of changes in BAs with ASCVD risk.This trial was registered at clinicaltrials.gov as NCT00072995

Low-density Lipoprotein Receptor Activities, Lipids, Apolipoprotein, and Clinical Course of Patients with Steroid-resistant Nephrotic Syndrome Treated with Low-density Lipoprotein Apheresis: A Case Series.

We herein report three cases of steroid-resistant nephrotic syndrome successfully treated with low-density lipoprotein apheresis (LDL-A). All patients were treated with a combination of steroids, cyclosporine, and LDL-A. In all cases, the serum concentrations of LDL, total and high-density lipoprotein cholesterol, and triglycerides were significantly lowered following LDL-A administration. Furthermore, the estimated LDL receptor activity increased, while both serum LDL and total cholesterol levels decreased, suggesting that LDL-A increases LDL receptor activity by driving changes in serum cholesterol concentration. This case series suggests that LDL-A increases LDL receptor activity, which may improve the intracellular uptake of cyclosporine.

Polydatin ameliorates low-density lipoprotein cholesterol and lipid metabolism by downregulating proprotein convertase subtilisin/kexin type 9 (PCSK9) in triple-negative breast cancer with hyperlipidemia

Polydatin ameliorates low-density lipoprotein cholesterol and lipid metabolism by downregulating proprotein convertase subtilisin/kexin type 9 (PCSK9) in triple-negative breast cancer with hyperlipidemia

Age and the Residual Risk of Cardiovascular Disease following Low Density Lipoprotein-Cholesterol Exposure.

We believe that there is sufficient evidence from basic science, longitudinal cohort studies and randomised controlled trials which validates the low-density lipoprotein cholesterol (LDL-C) or lipid hypothesis. It is important that we can communicate details of the cardiovascular disease (CVD) risk reduction that the average patient could expect depending on the scale of LDL-C decrease following lipid lowering therapy. It is also essential that residual risk (ResR) of CVD be highlighted. To achieve this aim by using existing trial evidence, we developed mathematical models initially for relative risk reduction (RRR) and absolute risk (AR) reduction and then showed that despite optimising LDL-C levels, a considerable degree of ResR remains that is dependent on AR. Age is significantly associated with AR (odds ratio: 1.02, 95% confidence intervals: 1.01-1.04) as was previously demonstrated by analysing the Whickham study cohort using a logistic regression model (age remaining significant even when all the other significant risk factors such as sex, smoking, systolic blood pressure, diabetes and family history were included in the regression model). A discussion of a paper by Ference et al. provided detailed evidence of the relationship between age and AR, based on lifetime LDL-C exposure. Finally, we discussed non-traditional CVD risk factors that may contribute to ResR based on randomised controlled trials investigating drugs improving inflammation, thrombosis, metabolic and endothelial status.

Tianhuang formula ameliorates non-alcoholic fatty liver diseases in type 2 diabetic mice through CRLS1-ATF3/ChREBP pathway

ObjectiveTianhuang Formula (THF) is a hospital formula summarized by Professor Jiao Guo's 30 years of clinical experience. Some studies have shown that it can alleviate dyslipidemia in the body. The purpose of this study is to confirm whether THF can improve non-alcoholic fatty liver diseases (NAFLD) in type 2 diabetic mice induced by high-fat diet (HFD)/streptomycin (STZ) and to clarify its potential mechanism. MethodsAfter induction of diabetes, mice were administrated with THF (60 ​mg/kg or 120 ​mg/kg) once daily for 10 weeks. Blood glucose (FBG), glucose tolerance, and insulin resistance (IR) were assayed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Blood lipids, alanine transaminase (ALT), and aspartate transaminases (AST) were detected. Serum fasting insulin (INS) and adiponectin (APN) levels were measured using ELISA. Histological changes in liver and pancreatic islets were observed by H&E staining, followed by Oil Red O staining for liver lipid quantification and periodic acid-Schiff (PAS) staining to detect glycogen accumulation. Western blotting detected the levels of fatty cardiolipin synthase 1 (CRLS1), transcription factor activator 3 (ATF3), and carbohydrate-responsive element binding protein (ChREBP) in the liver. The mRNA transcripts of hepatic inflammatory factors, lipogenesis and lipolysis-related genes, and gluconeogenic enzyme-phosphoenolpyruvate carboxykinase (PEPCK), CRLS1, ATF3, and ChREBP mRNA levels were evaluated by RT-qPCR. ResultsTHF restored impaired glucose tolerance and insulin resistance, respectively. There was an improvement in HFD/STZ-induced liver and islet damage, high serum HDL-C and ANP levels, and a significant decrease in FBG, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), FFA, INS, ALT, and AST, and lipid droplet counts in the T2DM mice treated with THF. CREBBP binding protein ATF3 mediated the insulin resistance signaling pathway, which regulated glucose and lipid metabolism in the liver. THF upregulated CRLS1, and ChREBP downregulated the expression of downstream ATF3 in the liver. RT-qPCR analysis also systemically indicated that THF suppressed the pathway and key regulators related to inflammation, lipid accumulation, and gluconeogenesis. ConclusionOur findings demonstrated that THF ameliorated lipid profile and attenuated liver steatosis in T2DM mice through CRLS1-ATF3/ChREBP pathway activation.

In vitro evaluation of antiatherogenic potential of Origanum × paniculatum, Lippia alba, Clinopodium nepeta, and Eucalyptus globulus essential oils

IntroductionEssential oils (EOs) are mixtures of secondary plant metabolism compounds with potential lipid-lowering activity and antioxidant properties. They may therefore be considered as add-on therapy for the prevention and treatment of cardiovascular diseases. MethodsEOs of Origanum × paniculatum (OpEO), Lippia alba (chemotype linalool) (LaLEO), Clinopodium nepeta (CnEO) and Eucalyptus globulus (EgEO), were evaluated on THP-1 foam cell macrophages as a cellular model of atherogenesis. Cell viability was determined by the MTT assay, lipid content by thin-layer chromatography, and Oil Red O staining. Antioxidant activity was evaluated by TBARS on low-density lipoprotein lipid peroxidation, and by ABTS•+, DPPH•, and FRAP assays. EOs were characterised by gas chromatography–mass spectrometry and a predictive multivariate data analysis was performed by partial least square regression (PLS) to identify the components related to antiatherogenic potential. ResultsOpEO reduced foam cell viability (IC50 = 45 µl/l) and cholesterol and triacylglycerol content and demonstrated antioxidant activity. In contrast, LaLEO increased lipid content and showed a prooxidant capacity with low reduction of cell viability (IC50 = 340 µl/l). CnEO showed prooxidant activity and reduction of cell viability (IC50 = 130 µl/l) without changes in lipid content. EgEO showed antioxidant activity, lipid increase, and low cytotoxicity (IC50 = 770 µl/l). PLS analysis suggests that cis-sabinene hydrate is responsible for cell viability inhibition, thymol and β-cis-terpineol decrease lipid content and possess antioxidant activity, and linalool increases lipid levels and has prooxidant capacity. ConclusionsOpEO is a promising natural product for therapy against atherosclerosis, with cis-sabinene hydrate, thymol, and β-cis-terpineol as potential active principles.

Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke: A Scientific Statement From the American Heart Association.

The objective of this scientific statement is to evaluate contemporary evidence that either supports or refutes the conclusion that aggressive low-density lipoprotein cholesterol lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment or dementia or hemorrhagic stroke. The writing group used literature reviews, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize existing evidence and to identify gaps in current knowledge. Although some retrospective, case control, and prospective longitudinal studies suggest that statins and low-density lipoprotein cholesterol lowering are associated with cognitive impairment or dementia, the preponderance of observational studies and data from randomized trials do not support this conclusion. The risk of a hemorrhagic stroke associated with statin therapy in patients without a history of cerebrovascular disease is nonsignificant, and achieving very low levels of low-density lipoprotein cholesterol does not increase that risk. Data reflecting the risk of hemorrhagic stroke with lipid-lowering treatment among patients with a history of hemorrhagic stroke are not robust and require additional focused study.

Lipid profiles and their relation to glycemic control in Saudi Arabia: The role of altitudes and environmental factor.

The height from sea levels, environmental factors, human-environment interactions, and lifestyle significantly influence the lipid profile and glycemic control of a population. This study aims to explore the influence of altitude on lipid profiles and glycemic control among the Saudi population at sea level and high altitude. In this retrospective cross-sectional study, a large dataset of patients of both gender and over 30 years old attending internal medicine clinics from two different regions at different heights from sea level, Jeddah (sea level) and Asir region (high altitudes) and referred to commercial laboratories for glycated haemoglobin (HbA1c) and lipids profile. Compared to the Asir region, the Jeddah region had significantly higher mean values for fasting blood sugar (FBG), total cholesterol (TC), low-density lipoprotein (LDL-C), and triglycerides (TG) (P < 0.05). Every 1 mg/dL increase in FBG results in a 0.662 mg/dL increase in TG from the Jeddah region. However, it was a 0.318 mg/dL increase in TG from the Asir region. HbA1c demonstrated a significant (P < 0.05) strong positive correlation with TC, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and lipid ratio. FBG levels were also associated with a high level of TC/HDL-C (β = 0.137 95% confidence interval [CI]: 0.11-0.21; P < 0.05), LDL-C/high-density lipoprotein cholesterol (HDL-C) (β = 0.50; 95% CI: 0.31-1.49; P < 0.05), and TG/HDL-C (β = 0.14; 95% CI = 0.12-0.15; P < 0.05) in Jeddah region. However, significantly high blood pressure was observed in the population from high altitudes. Our results demonstrated a significant positive correlation between lipid profile and glycemic control with high prevalence at sea level.

Comparison of low-density lipoprotein cholesterol estimation methods in individuals with insulin resistance: A cross-sectional study

Background and aimsThe Friedewald, Sampson, and Martin equations were developed to estimate low-density lipoprotein cholesterol levels; however, the validation data of these equations with and without insulin resistance are insufficient. Materials and methodsWe collected data on low-density lipoprotein cholesterol and lipid profiles from the Korea National Health and Nutrition Examination Survey. Using the data on insulin requirement, insulin resistance was calculated for 4,351 participants (median age, 48 [36–59] years; 49.9% male) using the homeostatic model assessment for insulin resistance (n = 2,713) and quantitative insulin-sensitivity check index (n = 2,400). ResultsAccording to the mean and median absolute deviation, the Martin equation yielded more accurate estimates than other equations when the triglyceride level was < 400 mg/dL with insulin resistance; the Sampson equation yielded lower estimates when the direct low-density lipoprotein cholesterol level was < 70 mg/dL and triglyceride level was < 400 mg/dL without insulin resistance. However, the three equations yielded similar estimates when the triglyceride level was < 150 mg/dL with and without insulin resistance. ConclusionThe Martin equation yielded more appropriate estimates than the Friedewald and Sampson equations for triglyceride levels < 400 mg/dL with and without insulin resistance. If the triglyceride level was < 150 mg, the Friedewald equation could also be considered.

Suboptimal lipid management in patients with acute ischemic stroke

ObjectiveLipid-lowering drugs are among the most widely used drugs in cardiovascular prevention. Statins are often abandoned due to side effects, or under dosed, leading to unreached LDL-cholesterol goals and increased occurrence of cardiovascular events. MethodsWe included hospitalized patients with an ischemic stroke or transient ischemic attack. Of 92 patients, low density lipoprotein cholesterol (LDL-C) levels and lipid lowering therapy at admission and discharge were assessed. Based on their cardiovascular risk before the current event according to the most recent European guidelines, LDL-C targets were determined. Low, moderate, high and very high risk corresponded with LDL-C targets below 116, 100, 70 and 55 mg/dL respectively. ResultsBefore current event, 59 (64%) were very high, 21 (23%) high, 11 (12%) moderate and 1 low risk patients and eight patients were treated with low, 23 moderate, and 21 high intensity lipid-lowering therapy. Upon admission, 75 patients had insufficiently managed LDL-cholesterol levels, yet 39 of them were taking lipid lowering therapy. Only eight of the 21 patients on high intensity lipid lowering therapy reached their LDL-C target. During hospitalization 40 patients were switched to a high-intensity statin. Thirty-three patients switched from no treatment or a lower-intensity to a moderate-intensity lipid lowering therapy. Three were dismissed with low-intensity lipid lowering therapy, and five in association with Ezetimibe. Three patients had documented statin-intolerance. ConclusionIn this study, LDL-cholesterol was insufficiently managed according to international guidelines for prevention of ischemic stroke. Further optimization of lipid management in primary and secondary prevention and the use of higher intensity lipid lowering therapy in clinical practice is mandatory.

Liver lipidomics analysis reveals the anti-obesity and lipid-lowering effects of gypnosides from heat-processed Gynostemma pentaphyllum in high-fat diet fed mice

BackgroundIn traditional Chinese medicine, Gynostemma pentaphyllum (G. pentaphyllum) is widely used to treat conditions associated with hyperlipidemia, and its therapeutic potential has been demonstrated in numerous studies. However, the mechanism of lipid metabolism in hyperlipidemic by G. pentaphyllum, especially heat-processed G. pentaphyllum is not yet clear. PurposeThe aim of this study was to investigate the therapeutic mechanism of gypenosides from heat-processed G. pentaphyllum (HGyp) in hyperlipidemic mice by means of a lipidomics. MethodsThe content of the major components of HGyp was determined by ultra-performance liquid chromatography-electrospray ionization ion trap mass spectrometry (UPLC-ESI-MS). An animal model of hyperlipidaemia was constructed using C57BL/6J mice fed with high-fat diet. HGyp was also administered at doses of 50, 100 and 200 mg/kg, all for 12 weeks. Serum parameters were measured, histological sections were prepared and liver lipidome analysis using UPLC-MS coupled with multivariate statistical analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to analyze the genes and proteins associated with lipid lowering in HGyp. ResultsHGyp reduced body weight, serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) and hepatic lipid accumulation in hyperlipidemic obese mice. To explore specific changes in lipid metabolism in relation to HGyp administration, lipid analysis of the liver was performed. Orthogonal partial least squares discriminant analysis (OPLS-DA) score plots showed that HGyp altered lipid metabolism in HFD mice. In particular, fatty acids (FA), triglycerides (DG), TG and ceramides (CER) were significantly altered. Eleven lipids were identified as potential lipid biomarkers, namely TG (18:2/20:5/18:2), TG (18:2/18:3/20:4), DG (18:3/20:0/0:0), Cer (d18:1/19:0), Cer (d16:1/23:0), Ceramide (d18:1/9Z-18:1), PS (19:0/18:3), PS (20:2/0:0), LysoPC (22:5), LysoPE (0:0/18:0), PE (24:0/16:1). Western blot and qRT-PCR analysis showed that these metabolic improvements played a role by down-regulating genes and proteins related to fat production (SREBP1, ACC1, SCD1), up-regulating genes and proteins related to lipid oxidation (CPTA1, PPARα) and lipid transport decomposition in the bile acid pathway (LXRα, PPARγ, FXR, BSEP). ConclusionThe lipid-lowering effect of gypenosides from heat-processed G. pentaphyllum is regulate lipid homeostasis and metabolism.

The human liver lipidome is significantly related to the lipid composition and aggregation susceptibility of low-density lipoprotein (LDL) particles

Background and aimsThe susceptibility of low-density lipoprotein (LDL) to aggregation predicts atherosclerotic cardiovascular disease. However, causes of interindividual variation in LDL lipid composition and aggregation susceptibility remain unclear. We examined whether the lipid composition and aggregation susceptibility of LDL reflect the lipid composition of the human liver. MethodsLiver biopsies and blood samples for isolation of LDL particles were obtained from 40 obese subjects (BMI 45.9 ± 6.1 kg/m2, age 43 ± 8 years). LDL was isolated using sequential ultracentrifugation and lipidomic analyses of liver and LDL samples were determined using ultra-high performance liquid chromatography–mass spectrometry. LDL aggregation susceptibility ex vivo was analyzed by inducing aggregation by human recombinant secretory sphingomyelinase and following aggregate formation. ResultsThe composition (acyl carbon number and double bond count) of hepatic triglycerides, phosphatidylcholines, and sphingomyelins (SMs) was closely associated with that of LDL particles. Hepatic dihydroceramides and ceramides were positively correlated with concentrations of the corresponding SM species in LDL as well with LDL aggregation. These relationships remained statistically significant after adjustment for age, sex, and body mass index. ConclusionsLipid composition of LDL reflects that of the human liver in obese patients. Changes in hepatic sphingolipid metabolism may contribute to interindividual variation of LDL lipid composition and susceptibility to aggregation.

Genetic determinants of circulating metabolites and the risk of stroke and its subtypes.

Circulating metabolites have been implicated in stroke pathogenesis, but their genetic determinants are understudied. Using a Mendelian randomization approach, our aim was to provide evidence for the relationship of circulating metabolites and the risk of stroke and its subtypes. Genetic instruments of 102 circulating metabolites were obtained from a genome-wide association study, including 24,925 European individuals. Stroke was extracted from the MEGASTROKE dataset (67,162 cases; 454,450 controls) and a lacunar stroke dataset (7338 cases; 254,798 controls). The magnetic resonance imaging markers of cerebral small vessel disease and microstructural injury were evaluated by a genome-wide association study of white matter hyperintensities (N=18,381), fractional anisotropy (N=17,663), mean diffusivity (N=17,467) and brain microbleeds (N=25,862). The inverse-variance weighted method Mendelian randomization was used as the primary analytical method, and directional pleiotropy and heterogeneity were examined in sensitivity analyses. A genetic predisposition to a higher level of cholesterol in small and low-density lipoprotein (LDL) was associated with risk of stroke (odds ratio [OR] 1.14, 95% confidence interval [CI]1.08-1.21, p=5.98 × 10-7 ), especially for large-artery atherosclerotic stroke (OR 1.34, 95% CI 1.19-1.52, p=1.90 × 10-6 ). Total lipids in LDL particles were also associated with risk of stroke. A genetically determined higher cholesterol level in high-density lipoprotein (HDL-C) was associated with risk of intracerebral haemorrhage (OR 1.74, 95% CI 1.23-2.45, p=1.66 × 10-3 ). No statistically significant association was found between genetic predisposition to circulating metabolites and magnetic resonance imaging markers of cerebral small vessel disease and microstructural injury. Genetically determined levels of lipids in small LDL were associated with the risk of stroke, suggesting that a therapeutic strategy targeting small LDL levels may be crucial for stroke prevention. HDL-C was positively associated with the risk of intracerebral haemorrhage.

Vitamin D3 alleviates high-fat induced hepatopancreas lipid accumulation and inflammation by activating AMPKkα/PINK1/Parkin-mediated mitophagy in Litopenaeus vannamei

A high-fat diet (HFD) model was built to elucidate the regulatory mechanisms of vitamin D on lipid metabolism in shrimp. An 8-week feeding trial was aimed to determine whether dietary vitamin D3 would ameliorate the adverse effects of HFD feeding in Litopenaeus vannamei. A total of 360 shrimp (initial weight of 0.50 ± 0.01 g) were randomly divided into three diets with three replicates, and each replication consisted of 40 shrimp. Three experimental diets included the control diet (NFD, 7.36% fat, 45.71% protein), HFD (11.32% fat, 45.89% protein) and the HFD supplemented with 0.57 mg/kg vitamin D3 (HFD+VD). The results revealed that growth performance was not affected (P > 0.05) by different experimental diets in L. vannamei. Compared with the control group, HFD group significantly increased (P < 0.05) serum low-density lipoprotein, cholesterol, triglyceride and hepatopancreas lipid accumulation (confirmed by genes expression, morphology observation and fatty acid composition) in L. vannamei. Hepatopancreas inflammation related gene (tnf-α, rab6a) levels and damaged mitochondria numbers were significantly increased (P < 0.05), while levels of immune related genes (alp, acp, lzm) and mitophagy related genes (ampkα, pink1, parkin, atg13, atg14, atg16, atg101) were decreased (P < 0.05) in L. vannamei. Compared with the HFD group, HFD+VD group significantly decreased (P < 0.05) hepatopancreas lipid deposition in L. vannamei. Hepatopancreas inflammation related genes (tnf-α, aif, rab6a) levels and damaged mitochondria numbers were significantly decreased (P < 0.05), while mitophagy related genes (ampkα, pink1, parkin, becline, atg13, atg14, atg16, atg101, atg9, atg12, lc3) and immune related genes (alp, acp, lzm) were increased (P < 0.05) in L. vannamei. In conclusion, the results of present study showed that: (1) High fat diet could promote hepatopancreas lipid accumulation, increase inflammation and inhibit mitophagy in L.vannamei; (2) Dietary vitamin D3 supplementation could alleviate high-fat induced hepatopancreas lipid accumulation and inflammation by activating AMPKkα/PINK1/Parkin-mediated mitophagy in L.vannamei.

Development of Fermented Shrimp Shell Product with Hypoglycemic and Hypolipidemic Effects on Diabetic Rats.

In 2020, approximately 9.3 billion tons of crustaceans were consumed, and 45–48% of shrimp shell (SS) by-products were discarded as waste. In this study, the SS of Litopenaeus vannamei was fermented by Lactobacillus plantarum LV33204, Stenotrophomonas maltophilia LV2122 (strong proteolytic activity), and Aeromonas dhakensis LV1111 (chitin-degrading activity), and the optimal fermentation conditions of liquid-fermented SS was established. Contents of total peptide, astaxanthin, and total phenolic content of the fermented SS were significantly higher than that of unfermented SS. In the presence of fermented SS, glucose uptake and insulin resistance of TNF-α-stimulated FL83B hepatocytes were markedly improved. Furthermore, daily oral supplement of fermented SS to streptozotocin (STZ)/nicotinamide (NA)-induced diabetic rats for 7 weeks significantly reduced plasma glucose and insulin resistance. Meanwhile, ingestion of fermented SS might enhance hepatic catabolism of glucose by increasing hexokinase and glucose-6-phosphate dehydrogenase activity and decreasing glucose-6-phosphatase activity. In addition, the fermented SS downregulated plasma total cholesterol (TG), triglycerides (TCs), low-density lipoprotein cholesterol (LDL-C), liver TG, and TC and lipid peroxidation levels in diabetic rats. In conclusion, a biorefinery process for waste SS was established through mixed strain fermentation. The in vitro and in vivo data reveal that the fermented SS is a promising functional food for the management of diabetic hyperglycemia and hyperlipidemia.

LIPID INDICES, ARTERIAL DAMAGE AND ALBUMINURIA IN PEDIATRIC PATIENTS WITH UNTREATED PRIMARY HYPERTENSION

Objective: Adult data proved that dyslipidemia is associated with cardiovascular risk. Our study aimed to analyze the relation between lipid indices, arterial damage and urinary albumin excretion (UAE) in children with primary hypertension (PH). Design and method: In 87 pediatric patients (15.10 ± 2.68 years, 60 boys, 27 girls) with untreated PH, we nalysed total, high-density, and low-density lipoprotein cholesterol (T-C, LDL-C, HDL-C), triglycerides (TG), and lipid indices: TG/HDL-C, Non-HDL-C, T-C/HDL-C, LDL-C/HDL-C, atherogenic index of plasma (AIP), atherogenic index (AI), lipoprotein combine index (LCI), and CHOLIndex (LDL-C - HDL-C). Additionally, we assessed 24 h ABPM, central and peripheral office BP, and arterial damage: aortic PWV, AIx75HR, cIMT, carotid arterial stiffness estimated by ultrasonic wall tracking (E-tracking - ET) and UAE [mg/24 h]. Lipid reference values were taken from the American Academy of Paediatrics 2011 Guidelines. Results: In the study group, borderline/high T-C was found in 22 (25.3%), LDL-C in 10 (11.5%), TG in 45 (51.7%), and borderline/low HDL-C in 28 (32.2%) patients; overall, 60 (69.0%) patients had dyslipidemia. Children with borderline/high LDL-C had significantly higher aPWV (5.83 ± 1.78 vs. 5.26 ± 0.78 [m/s], p = 0.047) and UAE (16 [8–122] vs. 8 [5–22] [mg/24], p = 0.034) compared to patients with normal LDL-C. In 87 studied children, UAE correlated with T-C and LDL-C (R = 0.269, p = 0.017; R = 0.245, p = 0.030) and AIx75HR with T-C (R = 0.228, p = 0.035). Also, ET augmentation index (ET AIx) correlated with HDL-C, T-C/HDL-C and AI (R = -0.245, p = 0.023; R = 0.233, p = 0.031; R = 0.233, p = 0.031), and maximal diameter of common carotid artery (D_max) with HDL-C, TG/HDL-C, T-C/HDL-C, LDL-C/HDL-C, AIP, and AI (R = -0.332, p = 0.002; R = 0.220, p = 0.042; R = 0.255, p = 0.018; R = 0.223, p = 0.039; R = 0.220, p = 0.042; R = 0.255; p = 0.018). Logistic regression revealed that the rise in CHOLIndex increased risk of elevated (&gt;30 mg/24 h) UAE (OR: 1.035 95CI: 1.008–1.070). Conclusions: 1. Lipid disturbances are common in pediatric patients with PH 2. Elevated lipid indices are associated with common carotid artery diameter and stiffness in hypertensive children and adolescents. 3. Pediatric patients with PH and abnormal LDL cholesterol are at risk of increased aortic stiffness. 4. CHOLIndex may serve as a marker of risk of hypertensive nephropathy in pediatric patients with PH.

Multiparametric platform for profiling lipid trafficking in human leukocytes

SummarySystematic insight into cellular dysfunction can improve understanding of disease etiology, risk assessment, and patient stratification. We present a multiparametric high-content imaging platform enabling quantification of low-density lipoprotein (LDL) uptake and lipid storage in cytoplasmic droplets of primary leukocyte subpopulations. We validate this platform with samples from 65 individuals with variable blood LDL-cholesterol (LDL-c) levels, including familial hypercholesterolemia (FH) and non-FH subjects. We integrate lipid storage data into another readout parameter, lipid mobilization, measuring the efficiency with which cells deplete lipid reservoirs. Lipid mobilization correlates positively with LDL uptake and negatively with hypercholesterolemia and age, improving differentiation of individuals with normal and elevated LDL-c. Moreover, combination of cell-based readouts with a polygenic risk score for LDL-c explains hypercholesterolemia better than the genetic risk score alone. This platform provides functional insights into cellular lipid trafficking and has broad possible applications in dissecting the cellular basis of metabolic disorders.

The Difference of Lipid Profile Pre and Post Endurance Exercise in Obese Male Adolescents

Obesity among adolescents has short-term and long-term consequences in terms of physical and psychosocial development. In adolescence obesity often causes serious complications such as hypertension, dyslipidemia, insulin resistance, dysglycemia, fatty liver, psychosocial complications. Dyslipidemia in obesity is closely related to the occurrence of atherosclerosis which often leads to coronary heart disease (CHD) and vascular disorders. Dyslipidemia is indicated by an increase in total cholesterol, low density lipoprotein (LDL), or triglycerides (TG), or a decrease in high density lipoprotein (HDL). Boys have a higher visceral fat ratio than girls. Physical exercise without dietary restrictions has been shown to improve blood lipid profiles and reduce fat mass. Endurance exercise increases fat oxidation during submaximal exercise. Zumba has been shown to reduce fat mass and improve aerobic fitness. To analyze the effect of endurance exercise with Zumba fitness 3x/week for 8 weeks on the lipid profile of obese male adolescents at senior high school Surabaya. This study was conducted from July 2020 to August 2020. The research subjects were 12 teenage boys aged 14-18 years at senior high school Surabaya, with obesity nutritional status p>95 according to CDC 2000. Research subjects were given an endurance exercise intervention with Zumba fitness 3 times a week for 8 weeks, light-moderate intensity 30-60 minutes. The volume of exercise is gradually increased by starting with an increase in duration and then the intensity of the exercise includes whole body movement with a combination of aerobics and dance. This study was conducted without calorie restriction. Pre- and post-exercise assessment of lipid profile (total cholesterol, triglycerides, HDL and LDL). TG, HDL, and total cholesterol before and after exercise had no significant difference which is TG = 0.106, HDL = 0.259 and total cholesterol = 0.188. Pre- and post-exercise LDL data had a significant difference with a significance value of 0.014 for LDL. In this study, there was a 6.8% decrease in TG; decreased LDL 4.9%; increase in HDL 12.49%; and a 3.6% reduction in total cholesterol. Endurance exercise with zumba fitness 3 times in a week for 8 weeks in obese male adolescents without calorie restriction, can improve LDL lipid profile, but does not improve TG, HDL and total cholesterol.