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Background: The association between low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio and the clinical outcomes of acute intracranial hemorrhage (ICH) remains unclear. In this study, we attempt to investigate whether low LDL-C/HDL-C ratio is associated with poor clinical outcomes in patients with ICH. Methods: The database was collected from a multicenter, prospective, observational cohort study, conducted in 13 hospitals in Beijing from January 2014 to September 2016. A total of 1,964 patients with ICH were initially screened in our database. Next, we selected patients with admission serum lipid information for retrospective analysis. Patients were categorized into four groups based on LDL-C/HDL-C ratio quartiles. The main outcomes were 30-day and 90-day poor functional outcome, which is defined as modified Rankin Scale score of 3 to 6, and 90-day all-cause death. Logistic regression was used to assess the association between LDL-C/HDL-C ratio and 30-day or 90-day poor functional outcome. Kaplan–Meier survival analysis and Cox regression were used to assess the association between LDL-C/HDL-C ratio and 90-day all-cause death. Restricted cubic splines were used to explore the nonlinear association between LDL-C/HDL-C ratio and the outcome of patients with ICH. Results: A total of 491 patients with spontaneous ICH were finally enrolled in our study. The mean age was 57.6 years old, and 72.1% (357/491) were men. After adjustment for confounders, patients in the lowest LDL-C/HDL-C quartile (< 1.74) had a significantly higher risk of 30-day and 90-day poor functional outcome compared with those in the highest quartile (> 3.16; 30-day: adjusted odds ratio 3.61, 95% confidence interval 1.68–7.72; 90-day: adjusted odds ratio 2.82, 95% confidence interval 1.33–5.95). Restricted cubic splines depicted a nonlinear association between LDL-C/HDL-C ratio and 90-day poor functional outcomes, indicating LDL-C/HDL-C ratio of 3.1–3.5 was correlated with better 90-day functional outcome. However, no significant correlation was found between low LDL-C/HDL-C ratio and 90-day all-cause death. Conclusions: Lower LDL-C/HDL-C ratio (< 1.74) is independently associated with an increased risk of poor functional outcome in patients with ICH. In the population of patients whom we studied, there is a nonlinear association between LDL-C/HDL-C ratio and 90-day poor functional outcome, and patients with an LDL-C/HDL-C ratio of 3.1 to 3.5 tend to have the lowest risk of 90-day poor functional outcome. [ABSTRACT FROM AUTHOR]

Background: Metabolic and Bariatric surgery (MBS) leads to significant weight loss and improvements in obesity-related comorbidities. However, the impact of MBS on Apolipoprotein B100 (Apo-B100) regulation is unclear. Apo-B100 is essential for the assembly and secretion of serum lipoprotein particles. Elevated levels of these factors can accelerate the development of atherosclerotic plaques in blood vessels. This study aimed to evaluate changes in Apo-B100 levels following MBS. Methods: 121 participants from the Iranian National Obesity and Metabolic Surgery Database (INOSD) underwent Laparoscopic Sleeve Gastrectomy (LSG) (n = 43), One-Anastomosis Gastric Bypass (OAGB) (n = 70) or Roux-en-Y Gastric Bypass (RYGB) (n = 8). Serum Apo-B100, lipid profiles, liver enzymes, and fasting glucose were measured preoperatively and six months postoperatively. Results: Apo-B100 levels significantly decreased from 94.63 ± 14.35 mg/dL preoperatively to 62.97 ± 19.97 mg/dL after six months (p < 0.01), alongside reductions in total cholesterol, triglycerides, LDL, VLDL, AST, and ALT (p < 0.05). Greater Apo-B100 reductions occurred in non-diabetics versus people with diabetes (p = 0.012) and strongly correlated with baseline Apo-B100 (r = 0.455, p < 0.01) and LDL levels (r = 0.413, p < 0.01). However, surgery type did not impact Apo-B100 changes in multivariate analysis (p > 0.05). Conclusion: Bariatric surgery leads to a significant reduction in Apo-B100 levels and improvements in lipid profiles and liver enzymes, indicating a positive impact on dyslipidemia and cardiovascular risk in individuals with high BMI. [ABSTRACT FROM AUTHOR]

Background and Objectives: It is well known that lipid abnormalities exist in the context of non-alcoholic fatty liver disease (NAFLD). The association between lipoprotein(a) [Lp(a)] levels and NAFLD is poorly understood. The main objective of the present study was to assess the association between Lp(a) levels and NAFLD. Methods: This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42023392526). A literature search was performed to detect studies that evaluated the association between Lp(a) levels, NAFLD and steatohepatitis (NASH). Results: Ten observational studies, including 40,045 patients, were identified and considered eligible for this systematic review. There were 9266 subjects in the NAFLD groups and 30,779 individuals in the respective control groups. Five studies evaluated patients with NAFLD (hepatic steatosis was associated with lower Lp(a) levels in four studies, while the remaining showed opposite results). Two studies evaluating NASH patients showed that Lp(a) levels were not different compared to controls. However, the increment of Lp(a) levels was correlated with liver fibrosis in one of them. In addition, one study analyzed simultaneously patients with NAFLD and NASH, showing a neutral result in NAFLD patients and a positive relationship in NASH patients. Two studies that included patients with the new definition of metabolic-associated fatty liver disease (MAFLD) also showed neutral results. Conclusion: Although there could be an association between Lp(a) levels and hepatic steatosis, the results of the studies published to date are contradictory and not definitive. [ABSTRACT FROM AUTHOR]

Bacterial lipoproteins are characterized by the presence of a conserved N-terminal lipid-modified cysteine residue that allows the hydrophilic protein to anchor into bacterial cell membranes. These lipoproteins play essential roles in a wide variety of physiological processes. Based on transcriptome analysis of the verrucomicrobial methanotroph Methylacidiphilum fumariolicum SolV, we identified a highly expressed lipoprotein, WP_009060351 (139 amino acids), in its genome. The first 86 amino acids are specific for the methanotrophic genera Methylacidiphilum and Methylacidmicrobium, while the last 53 amino acids are present only in lipoproteins of members from the phylum Verrucomicrobiota (Hedlund). Heterologous expression of WP_009060351 in Escherichia coli revealed a 25-kDa dimeric protein and a 60-kDa tetrameric protein. Immunoblotting showed that WP_009060351 was present in the total membrane protein and peptidoglycan fractions of M. fumariolicum SolV. The results suggest an involvement of lipoprotein WP_009060351 in the linkage between the outer membrane and the peptidoglycan. [ABSTRACT FROM AUTHOR]

Purpose of Review: Cholesteryl ester transfer proteins (CETP) regulate plasma cholesterol levels by transferring cholesteryl esters (CEs) among lipoproteins. Lipoprotein cholesterol levels correlate with the risk factors for atherosclerotic cardiovascular disease (ASCVD). This article reviews recent research on CETP structure, lipid transfer mechanism, and its inhibition. Recent Findings: Genetic deficiency in CETP is associated with a low plasma level of low-density lipoprotein cholesterol (LDL-C) and a profoundly elevated plasma level of high-density lipoprotein cholesterol (HDL-C), which correlates with a lower risk of atherosclerotic cardiovascular disease (ASCVD). However, a very high concentration of HDL-C also correlates with increased ASCVD mortality. Considering that the elevated CETP activity is a major determinant of the atherogenic dyslipidemia, i.e., pro-atherogenic reductions in HDL and LDL particle size, inhibition of CETP emerged as a promising pharmacological target during the past two decades. CETP inhibitors, including torcetrapib, dalcetrapib, evacetrapib, anacetrapib and obicetrapib, were designed and evaluated in phase III clinical trials for the treatment of ASCVD or dyslipidemia. Although these inhibitors increase in plasma HDL-C levels and/or reduce LDL-C levels, the poor efficacy against ASCVD ended interest in CETP as an anti-ASCVD target. Nevertheless, interest in CETP and the molecular mechanism by which it inhibits CE transfer among lipoproteins persisted. Insights into the structural-based CETP-lipoprotein interactions can unravel CETP inhibition machinery, which can hopefully guide the design of more effective CETP inhibitors that combat ASCVD. Summary: Individual-molecule 3D structures of CETP bound to lipoproteins provide a model for understanding the mechanism by which CETP mediates lipid transfer and which in turn, guide the rational design of new anti-ASCVD therapeutics. [ABSTRACT FROM AUTHOR]

Monoalkyldiacylglycerol (MADG), an ether analog of triacylglycerols, is abundant in some marine animals such as deep-sea sharks and echinoderms. The present study aims to investigate the effects of an MADG-rich neutral lipid derived from Berryteuthis magister (MNB) on the lipid metabolism of diabetic/obese KK-Ay mice. Male mice (5 weeks old) were fed soybean oil (control group), MNB, or fish oil (FO) which contain the same amount of EPA and DHA in the form of triacylglycerols. MNB or FO supplementation resulted in a decrease in adipose tissue weights and blood glucose levels compared to the control mice. Interestingly, serum lipid levels in the MNB group were significantly lower than those of the control and FO groups. Although there was no difference in EPA and DHA levels in the tissues between the FO and MNB groups, a decrease in the number of lipoprotein particles was characteristically observed in the mice fed with MNB. Our results suggest that the MADG structure-dependent effect on lipoprotein synthesis and/or secretion partly accounted for the reduced serum lipids in KK-Ay mice by dietary MNB. This study advances the understanding of MADG as a nutraceutical and provides insights into the role of ether lipids in lipoprotein metabolism that can contribute to the development of prevention and treatment strategies for hyperlipidemia. [ABSTRACT FROM AUTHOR]

Moyamoya disease (MMD) is a chronic cerebrovascular disease with unknown etiology. The pathogenesis of vascular changes remains unclear. Ischemic and hemorrhagic adult MMD patients and healthy volunteers were enrolled to collect serum for data-independent acquisition (DIA)-based proteomic analysis and ELISA validation. DIA serum proteomic revealed that apolipoprotein C-I (APOC1), apolipoprotein D (APOD), and apolipoprotein A-IV (APOA4) were decreased. The reductases glutathione S-transferase omega-1 (GSTO1) and peptidyl-prolyl cis–trans isomerase A (PPIA) were upregulated, and ADAMTS-like protein 4 (ADAMTSL4) was downregulated in both ischemic and hemorrhagic MMD. Afamin (AFM) and transforming growth factor-beta-induced protein ig-h3 (TGFBI) increased in ischemic patients but decreased in hemorrhagic patients. Serum ELISA results confirmed that APOA4, APOC1, and APOD were decreased compared to controls. Then, we retrospectively analyzed biochemical indexes of 200 MMD patients. A total of 54 enrolled MMD patients showed decreased total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-c). APOA4, APOC1, and APOD were vital factors in the HDL decrease in MMD patients. Lipoprotein dysfunction in MMD patients is involved in MMD. Intimal thickening by enhanced adhesion, middle layer vascular smooth muscle cell migration, and decreased lipid antioxidant function represented by HDL are potential pathogeneses of vascular changes in MMD. [ABSTRACT FROM AUTHOR]

The assembly of large, multi-cofactor membrane protein complexes like photosystem II (PSII) requires a high level of coordination. The process is facilitated by a large network of auxiliary proteins that bind transiently to unassembled subunits, preassembled modules or intermediate states of PSII, which are comprised of a subset of subunits. However, analysis of these immature, partially assembled PSII complexes is hampered by their low abundance and intrinsic instability. In this study, PSII was purified from the thermophilic cyanobacterium Thermosynechococcus elongatus via Twin-Strep-tagged CP43 and further separated by ion exchange chromatography into mature and immature complexes. Mass spectrometry analysis of the immature Psb27-PSII intermediate revealed six different Psb27 proteoforms with distinct lipid modifications. The maturation and functional role of thylakoid localized lipoproteins are discussed. [ABSTRACT FROM AUTHOR]

Background and Purpose: The relationship between lipid levels and the prognosis of acute intracerebral hemorrhage (ICH) remains controversial. Thus, we aimed to investigate whether lower low-density lipoprotein cholesterol (LDL-C) levels increased the risk of adverse outcomes, as well as the current situation of statin treatment in acute ICH patients with premorbid lipid-lowering therapy.Methods: From August 1, 2015, to July 31, 2019, a total of 73,098 ICH patients were included in our study from the Chinese Stroke Center Alliance program. Patients were grouped by LDL-C levels of < 1.4 mmol/L, 1.4-1.8 mmol/L, 1.8-2.6 mmol/L, and > 2.6 mmol/L. Logistic regression was used to assess the association between LDL-C levels and the composite risk of hematoma expansion (HE) or in-hospital death. Moreover, statin treatment in ICH patients with cardio-cerebrovascular diseases was analyzed.Results: In total, 6368 (8.7%) patients were identified as a composite of HE or in-hospital death with a mean LDL-C level of 2.9 ± 1.7 mmol/L. In the univariate analysis, patients who achieved lower LDL-C concentrations under 1.4 mmol/L had a 36% higher risk of adverse outcomes compared with the ≥ 2.6 mmol/L group (OR 1.36, 95%CI 1.23-1.51). Similar results were obtained in multivariate analyses, especially for patients with GCS scores of 9-15. For acute ICH patients with concomitant atherosclerotic disease, statin treatment was discontinued in the majority of Chinese population.Conclusions: Lower LDL-C levels (< 1.4 mmol/L) are associated with an increased risk of HE and ensuing mortality in acute ICH patients. Maintaining an optimal LDL-C range may have therapeutic potential against HE which merits further investigation. [ABSTRACT FROM AUTHOR]

Hypercholesterolemia is a well-known etiological feature for cardiovascular diseases and a common indication of maximum categories of metabolic disorders. Para methoxy cinnamic acid is one of the cinnamic acid derivatives as a natural product obtained from the rice bran oil as an active constituent and has the antioxidant property. The present study was designed to evaluate the hypolipidemic activity of P-methoxy cinnamic acid against high fat diet induced hyperlipidemia in experimental rats. Male Wistar albino rats were divided into five groups (n = 6), and high fat diet was used to induce the hyperlipidemia for 28 days. P-methoxy cinnamic acid was used in two different doses (40 and 80 mg/kg body weight), and they were administered orally to the rats for 28 days during high fat diet. Atorvastatin (5 mg/kg) was used as reference standard. A significant elevated level of lipid abnormalities and tissue antioxidant parameters were reversed from normal level by the treatment of P-methoxy cinnamic acid in both the doses. Histopathological evidence further supported the protective action. Based on the initial findings, it was concluded that P-methoxy cinnamic acid was able to offer significant protection against high fat diet induced atherosclerosis. Future studies were recommended to identify the molecular mechanism of P-methoxy cinnamic acid against atherosclerosis protection. [ABSTRACT FROM AUTHOR]

Purpose: Wolfberry is rich in bioactive compounds which may lower cardiovascular disease risk. This meta-analysis aimed to systematically evaluate the effects of wolfberry-based randomized controlled trials (RCTs) on overall cardiovascular health. Methods: Four online databases (PubMed, CINAHL Plus, Medline and Cochrane Library) were searched to shortlist relevant RCTs. Outcomes of interests included blood lipids and lipoproteins, blood pressure, biomarkers of oxidative stress, inflammation and other cardiovascular health-related indicators. Random-effects models were used to provide a weighted mean difference (WMD) and/or Hedges' g for quantitative synthesis. This was coupled with subcategory analyses which stratified RCTs according to the form in which wolfberry was administered (whole wolfberry versus wolfberry extract). Results: From the 785 articles identified, 10 were selected for meta-analysis. Compared to the control, groups which consumed wolfberry showed a reduction in blood triglycerides [WMDpooled (95% confidence interval): − 0.14 (− 0.19, − 0.09) mmol/L] and increased blood high-density lipoprotein cholesterol [WMDpooled: 0.06 (0.02, 0.09) mmol/L]. Notably, effects for both triglycerides [WMDwhole: − 0.14 (− 0.19, − 0.09) mmol/L; WMDextract: − 0.07 (− 0.30, 0.16) mmol/L] and high-density lipoprotein cholesterol [WMDwhole: 0.06 (0.02, 0.09) mmol/L; WMDextract: 0.05 (− 0.02, 0.13) mmol/L] were more prominent after whole wolfberry interventions. Additionally, blood malondialdehyde equivalents were also significantly decreased in wolfberry consuming groups [Hedges' gpooled: − 1.45 (− 2.75, − 0.16)]. No changes were observed for the other lipids and lipoproteins as well as blood pressure. Conclusions: Wolfberry consumption is effective in improving blood lipids and lipoproteins profile and lowering oxidative stress. This supports the incorporation of wolfberry, particularly as whole fruits, into dietary patterns targeted at improving cardiovascular health. [ABSTRACT FROM AUTHOR]

Plants store triacylglycerides in organelles called oil bodies, which are important fuel sources for germination. Oil bodies consist of a lipid core surrounded by an interfacial single layer membrane of phospholipids and proteins. Oleosins are highly conserved plant proteins that are important for oil body formation, solubilising the triacylglycerides, stabilising oil bodies, and playing a role in mobilising the fuel during the germination process. The domain structure of oleosins is well established, with N- and C-terminal domains that are hydrophilic flanking a long hydrophobic domain that is proposed to protrude into the triacylglyceride core of the oil body. However, beyond this general understanding, little molecular level detail on the structure is available and what is known is disputed. This lack of knowledge limits our understanding of oleosin function and concomitantly our ability to engineer them. Here, we review the state of play in the literature regarding oleosin structure and function, and provide some examples of how oleosins can be used in commercial settings. [ABSTRACT FROM AUTHOR]

Marine crude oil spill is the most alarming environmental issue and the dreadful instance of petroleum hydrocarbon pollution around the world. Successful remediation of these toxic pollutants demands for the ample production of biosurfactant and biocatalysts by the native hydrocarbon-degrading microbes. The main focus of this investigation is to determine the potential of a halo-tolerant and biosurfactant-producing hydrocarbonoclastic bacterium, Enterobacter hormaechei, for the effective bioremediation of marine oil spill. The strain had the ability to produce biosurfactant with excellent surface and emulsification activities along with biocatalysts. The activity of the extracellular enzymes such as lipase and laccase was found to be 160 U/ml and 38 U/ml, respectively, whereas the intracellular enzymes like alkane hydroxylase, alcohol dehydrogenase and esterase showed the corresponding activities of 48 U/ml, 86 U/ml and 102 U/ml. Overall, E. hormaechei could be able to degrade nearly 85% of petroleum hydrocarbons present in crude oil within 10 days of incubation. The biosurfactant was characterized to be an anionic, high molecular weight (48 kDa) lipoprotein-type biosurfactant. The biosurfactant was further characterized by Fourier transform infrared spectroscopy. The E. hormaechei was employed for the treatment of simulated marine oil spill and the degradation followed pseudo-second-order kinetics with rate constant k2 0.2775 and R2 0.9923. The crude oil degradation was confirmed by gas chromatography–mass spectrometry. The study suggested that the E. hormaechei is a potential biosurfactant and biocatalysts producer with the effective management of accidental marine oil spills. [ABSTRACT FROM AUTHOR]

Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) belong to the same gene family. Liver-specific expression of CETP improves reverse cholesterol transport (RCT) and PLTP knockout (KO) decreases RCT in mice. In this study, we investigate the effect of CETP transgene (CETP-tg) on RCT and whether CETP-tg can partially restore RCT efficiency in PLTP KO mice. Several rounds of crossing were carried out to produce colonies of wild type (WT), CETP-tg, PLTP KO, and CETP-tg × PLTP KO mice were obtained after several generations of reproduction. The efficiency of RCT was detected using [3H]-cholesterol-laden macrophages, and the underlying mechanisms were investigated by multiple techniques. Our data demonstrated that CETP-tg significantly increased the transport rate of [3H]-cholesterol from macrophages to plasma and liver, and finally the excretion through feces compared to the WT littermates. The RCT improving effect of CETP-tg was similar in PLTPKO mice. Furthermore, CETP-tg did not affect the expression of RCT-related proteins, such as low-density lipoprotein receptor. The mechanisms of improving RCT may be attributed to the low level of oxidized lipids in CETP-tg mouse and CETP-mediated lipid transport. Collectively, CETP-tg improves RCT in mice, and CETP can not compensate for PLTP deficiency. [ABSTRACT FROM AUTHOR]

Purpose of Review: The term high density lipoproteins (HDL) refers to an eclectic collection of subparticles that play diverse roles in physiology. Here, we define the term "HDL subspecies" and review recent work on their molecular characterization and relation to disease, focusing on cardiovascular disease and diabetes. Recent Findings: The HDL family contains over 200 proteins and nearly 200 lipids that partition into different particles in plasma. Simple subfractionation of HDL based on a particular physicochemical property has not risen to the challenge of revealing the roles of specific particles in disease. However, by targeting minor protein or lipid components, a handful of compositionally defined HDL subspecies have been described and characterized. Summary: By combining targeted particle isolation techniques with the power of large human studies, progress is being made in understanding HDL subspecies functions and implications for disease. However, much work remains before these advancements can be translated into disease mitigation strategies. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of coronary artery disease (CAD) is high among patients with cirrhosis; however, the impact of it on cardiovascular disease (CVD) is not known. The aim of the current study was to evaluate CVD events in patients with cirrhosis and impact of cirrhosis on biomarkers of atherogenesis. Methods: The study included 682 patients with decompensated cirrhosis referred for liver transplantation (LT) evaluation between 2010 and 2017. All patients were followed until they experienced a CVD event, non-cardiac death, liver transplantation or last follow-up. To evaluate mechanistic link, patients with NASH cirrhosis were propensity matched 1:2 to non-cirrhosis NASH patients and biomarkers of atherogenic risk were compared. Results: The composite CVD outcome occurred in 23(3.4%) patients after a median follow-up period of 585 days (IQR 139, 747). A strong association between presence of any CAD and CVD event was noted (HR = 6.8, 95% CI 2.9, 15.9) that was independent of age, gender, BMI, and MELD score. In competing risk model, the combined rate of LT and non-cardiac was significantly higher when compared to the rate of CVD events. Marker of insulin resistance and inflammation-related markers were similar in patients with and without cirrhosis. Patients with cirrhosis were more likely to have reduced VLDL, sdLDL-C, LDL-C, and triglycerides. Interestingly, patients with cirrhosis had an increase in serum HDL-2, the anti-atherogenic lipoprotein, and adiponectin, a protective serum adipokine. Conclusion: The risk of CVD events in patients with cirrhosis is low and may potentially be due to improvement in markers of atherogenic risk. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) is associated with an increased risk of developing atherosclerotic cardiovascular disease (ASCVD). Patients with OSA have increased levels of oxidative stress and several studies have shown higher levels of oxidative stress markers. Oxidized-LDL (Ox-LDL) is an important risk factor for ASCVD and a number of studies have measured its levels in patients with OSA, though results from these studies are conflicting. This meta-analysis aimed to reassess circulating levels of Ox-LDL in patients with OSA in comparison with controls. Methods: Studies evaluating Ox-LDL levels in patients with OSA and controls were explored in databases of PubMed, EMBASE, Scopus, and Web of Science. Two authors independently performed the search from January 1990 to February 2019. Two authors independently screened the studies according to title, abstract, and full text. In addition, the Newcastle-Ottawa Quality Assessment Scale was utilized to evaluate the quality of the studies. The impact of OSA on Ox-LDL levels was determined using the random effects model. Results: Of 195 articles retrieved, 98 were duplicates, 49 were excluded by title, 20 excluded by abstract, and 22 by full texts. Six eligible studies were included in the meta-analysis. Pooled analysis demonstrated that Ox-LDL increased in patients with OSA compared with controls. In addition, subgroup analysis revealed that studies matching age or BMI between OSA patients and controls showed no significant difference between patients with OSA and healthy controls, while unmatched studies had higher levels of Ox-LDL in patients with OSA in comparison with controls. Conclusion: This study demonstrated higher circulating concentrations of Ox-LDL in patients with OSA. However, no significant difference was found in studies in which patients and controls were matched for age and BMI, suggesting the involvement of these two confounding factors as a cause for elevated concentrations of circulating Ox-LDL in patients with OSA. [ABSTRACT FROM AUTHOR]

Purpose: The benefit of exercise training on lipid profile in bariatric surgery patients is scarce. We assess the effect of a supervised exercise-training program on lipid profile following bariatric surgery. Materials and Methods: A total of 60 patients were prospectively recruited, of those 49 completed the study (age 41 ± 11 years; body mass index 45.9 ± 6.1 kg/m2, 75% women). The bariatric surgery procedures performed were sleeve gastrectomy (SG) (n = 24) and biliopancreatic diversion with duodenal switch (BPD-DS) (n = 25). Of the 49 patients who completed the study, 34 had been randomized to a 12-week supervised exercise training program (exercise group) between the 3rd and the 6th month following bariatric surgery (SG = 17 and BPD-DS = 17). Fasting blood samples and anthropometric measurements were performed preoperatively and at 3, 6, and 12 months after bariatric surgery. Results: At 6 months and 12 months, percentage of weight loss was similar between groups (6 months: − 29.6 ± 5.5 vs. − 27.8 ± 7.7%; P = 0.371; 12 months: − 38.4 ± 10.4 vs. − 37.9 ± 9.5%; P = 0.876 exercise vs. control). Both groups had an increase in HDL values between the 3nd and the 6th month following bariatric surgery. There was a significantly greater increment in HDL values in the exercise group (0.18 ± 0.14 vs. 0.07 ± 0.12 mmol/L, P = 0.014; exercise vs. control). Conclusion: Our results showed a beneficial effect of a 12-week supervised exercise-training program in bariatric surgery patients showing similar weight loss on HDL-cholesterol levels without additional effect on LDL-cholesterol levels. [ABSTRACT FROM AUTHOR]

Background: Arterial stiffness is an independent predictor of cardiovascular disease (CVD) morbidity and mortality. A risk factor-independent association of arterial stiffness with traditional lipids has been described extensively, but it is still unclear whether an independent relationship exists between arterial stiffness and particles of lipoprotein subclasses. Methods: The Baptist Employee Healthy Heart Study (BEHHS) is a lifestyle intervention study examining the effects of web-based programs on reducing CVD risk in high-risk persons. Participants had their brachial arterial augmentation index (AI, a measure arterial stiffness) assessed using the EndoPAT 2000 device. Cardio IQ™ ion mobility lipoprotein fractionation was utilized for measurement of particles of lipoprotein subclasses. Results: The population consisted of 182 participants, (74% women, 49% Hispanic) with a mean age of 52 ± 9 years. There was a significant trend association between quartiles of AI and total cholesterol, HDL-c, large LDL-p, small IDL-p, large IDL-p, and all subclasses of HDL particles (total HDL-p, small HDL-p, and large HDL-p). In logistic regression analysis, only HDL-c, total LDL-p, large LDL-p, small IDL-p, large IDL-p, total HDL-p, small HDL-p, and large HDL-p demonstrated significant independent association with AI. Conclusion: Several lipoprotein subclasses demonstrate independent significant associations with arterial stiffness. A safe and relatively inexpensive blood test may be useful in identifying subclinical atherosclerosis process in a relatively young high CVD risk population. Trial registration: ClinicalTrials.gov, NCT01912209. Registered July 31, 2013 [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Prediabetes is associated with postprandial hypertriacylglycerolaemia. Resistance exercise acutely lowers postprandial plasma triacylglycerol (TG); however, the changes in lipid metabolism that mediate this reduction are poorly understood. The aim of this study was to identify the constitutive metabolic mechanisms underlying the changes in postprandial lipid metabolism after resistance exercise in obese men with prediabetes. Methods: We evaluated the effect of a single bout of whole-body resistance exercise (seven exercises, three sets, 10–12 repetitions at 80% of one-repetition maximum) on postprandial lipid metabolism in ten middle-aged (50 ± 9 years), overweight/obese (BMI: 33 ± 3 kg/m2), sedentary men with prediabetes (HbA1c >38 but <48 mmol/mol [>5.7% but <6.5%]), or fasting plasma glucose >5.6 mmol/l but <7.0 mmol/l or 2 h OGTT glucose >7.8 mmol/l but <11.1 mmol/l). We used a randomised, crossover design with a triple-tracer mixed meal test (ingested [(13C4)3]tripalmitin, i.v. [U-13C16]palmitate and [2H5]glycerol) to evaluate chylomicron-TG and total triacylglycerol-rich lipoprotein (TRL)-TG kinetics. We used adipose tissue and skeletal muscle biopsies to evaluate the expression of genes regulating lipolysis and lipid oxidation, skeletal muscle respirometry to evaluate oxidative capacity, and indirect calorimetry to assess whole-body lipid oxidation. Results: The single bout of resistance exercise reduced the lipaemic response to a mixed meal in obese men with prediabetes without changing chylomicron-TG or TRL-TG fractional clearance rates. However, resistance exercise reduced endogenous and meal-derived fatty acid incorporation into chylomicron-TG and TRL-TG. Resistance exercise also increased whole-body lipid oxidation, skeletal muscle mitochondrial respiration, oxidative gene expression in skeletal muscle, and the expression of key lipolysis genes in adipose tissue. Conclusions/interpretation: A single bout of resistance exercise improves postprandial lipid metabolism in obese men with prediabetes, which may mitigate the risk for cardiovascular disease and type 2 diabetes. [ABSTRACT FROM AUTHOR]

The unique and ubiquitous bacterial lipoprotein biosynthesis pathway is an attractive new antibiotic target. Crystal structures of its three biosynthetic enzymes have been solved recently. The first enzyme, Phosphatidylglycerol:proLipoprotein diacylglyceryl Transferase (Lgt), which initiates the post-translational modification at the metabolic interface of protein biosynthesis, phospholipid biosynthesis, protein secretion and lipid modification was reported to be a seven-transmembrane helical structure with a catalytic periplasmic head. Its complete solubilization in water or mild detergent in a fully active state, its chromatographic behaviour as an active monomer in the absence of detergent and recovery of active whole-length protein after proteolytic treatment of spheroplasts cast serious doubts about its proposed membrane association and orientation. Rather, it could be a seven-helical bundle partially embedded in the inner membrane's inner leaflet aided by hydrophobic interaction. In fact, there are examples where originally reported seven-transmembrane proteins were later shown to be seven-helical peripheral membrane proteins based on solubilization criterion and re-analysis. Validated computational tool, Membrane Optimal Docking Area (MODA), also predicted a weaker association of Lgt's helices with the membrane compared to typical transmembrane proteins. This insight is crucial to Lgt-based antibiotic design. [ABSTRACT FROM AUTHOR]

Apolipophorin III (apoLp-III) is an insect apolipoprotein that is predominantly present in a lipid-free state in the hemolymph. ApoLp-III from Galleria mellonella is able to interact with membrane components of Gram-negative bacteria, as part of an innate immune response to infection. The protein also exists in a lipoprotein-associated state when large amounts of lipids are mobilized. Therefore, lipid-bound apoLp-III was generated to analyze the binding interaction with lipopolysaccharides and phosphatidylglycerol, both abundantly present in membranes of Gram-negative bacteria. G. mellonella apoLp-III was lipidated with palmitoyl-2-oleoyl-glycero-3-phosphocholine to form lipid-protein complexes. The particle shape was discoidal with a 16.4 nm diameter, a molecular mass of 460 kDa, and contained 4 apoLp-III molecules. These discoidal lipoproteins were used to compare the lipopolysaccharide and phosphatidylglycerol binding activity with lipid-free apoLp-III. Lipopolysaccharide binding interaction was analyzed by non-denaturing PAGE, showing reduced ability of the lipid-bound protein to form lipopolysaccharide-protein complexes and to disaggregate lipopolysaccharide micelles. The apoLp-III-induced release of calcein from phosphatidylglycerol vesicles was decreased approximately fivefold when the protein was in the lipid-bound form, indicating reduced binding interaction with the phosphatidylglycerol membrane surface. These results show that when apoLp-III adopts a lipid-bound conformation, it is markedly less effective in interacting with lipopolysaccharides and phosphatidylglycerol vesicles. Thus, in order to be an effective antimicrobial protein, apoLp-III needs to be in a lipid-free state. [ABSTRACT FROM AUTHOR]

Bacteremia is a major clinical challenge requiring early treatment. Metabolic alterations occur during bacteremia, and accordingly plasma concentrations of lipoproteins LDL-C and HDL-C are substantially changed. We questioned whether bacteremia with Gram-negative versus Gram-positive bacteria causes contrasting changes of lipoprotein levels in order to differentiate between the 2-g stain types and if there is a relation with outcome parameters namely ICU-admission, 30-day mortality, duration of hospitalization. This is a retrospective dual-center cross-sectional study, including 258 patients with bacteremia. Plasma lipid levels were analyzed within 48 h to positive blood culture. Upon admission, HDL-C, LDL-C, and total cholesterol (p = 0.99) in plasma did not significantly differ between patients with Gram-negative and Gram-positive bacteremia, while significantly higher triglyceride concentrations were found in Gram-negative bacteremia (p < 0.05). 30-day mortality and ICU admission were associated with lower LDL-C and HDL-C concentrations as compared to survivors and non-ICU patients, and patients with HDL-C < 20 mg dl−1 and LDL-C < 55 mg dl−1 had a relative risk (RR) of 2.85 for ICU therapy requirement and RR = 2 of death within 30 days. Reduced HDL-C and LDL-C concentrations were associated with adverse patient's outcome in bacteremia. Discrimination between Gram-negative and Gram-positive pathogens upon lipoprotein patterns is unlikely. [ABSTRACT FROM AUTHOR]

Structure-function studies of the cytochrome b6f complex, the central hetero-oligomeric membrane protein complex in the electron transport chain of oxygenic photosynthesis, which formed the basis for a high-resolution (2.5 Å) crystallographic solution of the complex, are described. Structure-function differences between the structure of subunits of the bc complexes, b6f, and bc1 from mitochondria and photosynthetic bacteria, which are often assumed to function identically, are discussed. Major differences which suggest that quinone-dependent electron transport pathways can vary in b6f and bc1 complexes are as follows: (a) an additional c-type heme, cn, and bound single copies of chlorophyll a and β-carotene in the b6f complex; and (b) a cyclic electron transport pathway that encompasses the b6f and PSI reaction center complexes. The importance of including lipid in crystallization of the cytochrome complex, or with any hetero-oligomeric membrane protein complex, is emphasized, and consequences to structure-function of b6f being a lipoprotein complex discussed, including intra-protein dielectric heterogeneity and resultant pathways of trans-membrane electron transport. The role of the b6f complex in trans-membrane signal transduction from reductant generated on the p-side of the electron transport chain to the regulation of light energy to the two photosystems by trans-side phosphorylation of the light-harvesting chlorophyll protein is presented. Regarding structure aspects relevant to plastoquinol-quinone entrance-egress: (i) modification of the p-side channel for plastoquinone access to the iron-sulfur protein would change the rate-limiting step in electron transport; (ii) the narrow niche for entry of plastoquinol into b6f from the PSII reaction center complex would seem to require close proximity between the complexes. [ABSTRACT FROM AUTHOR]

We propose a multiphysical mathematical model by fully coupling lipid deposition, monocytes/macrophages recruitment and angiogenesis to investigate the pathophysiological responses of an atherosclerotic plaque to the dynamic changes in the microenvironment. The time evolutions of cellular (endothelial cells, macrophages, smooth muscle cells, etc.) and acellular components (low density lipoprotein, proinflammatory cytokines, extravascular plasma concentration, etc.) within the plaque microenvironment are assessed quantitatively. The thickening of the intima, the distributions of the lipid and inflammatory factors, and the intraplaque hemorrhage show a qualitative consistency with the MRI and histology data. Models with and without angiogenesis are compared to demonstrate the important role of neovasculature in the accumulation of blood-borne components in the atherosclerotic lesion by extravasation from the leaky vessel wall, leading to the formation of a lipid core and an inflammatory microenvironment, which eventually promotes plaque destabilization. This model can serve as a theoretical platform for the investigation of the pathological mechanisms of plaque progression and may contribute to the optimal design of atherosclerosis treatment strategies, such as lipid-lowering or anti-angiogenetic therapies. [ABSTRACT FROM AUTHOR]

Vibrio vulnificus, a Gram-negative halophilic bacterium, is an opportunistic human pathogen that is responsible for the majority of seafood-associated deaths worldwide. Lipoproteins are important components of the bacterial cell envelope and have been shown to be involved in a wide variety of cellular processes. Little is known about the localisation or transport mechanism of lipoproteins in V. vulnificus. To assess the localisation of lipoproteins in V. vulnificus, we tested two established techniques for the rapid separation of membrane-associated proteins: detergent extraction with Sarkosyl and outer membrane vesicles (OMVs) preparation. The results showed that Sarkosyl extraction was not useful for the separation of lipoproteins from the different membranes of V. vulnificus. On the other hand, we confirmed that OMVs produced by V. vulnificus contained lipoproteins from the outer but not the inner membrane. Analysis of the OMVs components confirmed the localisation of several well-known lipoproteins to membranes that were different from expected, based on their predicted functions. Using this technique, we found that Asp at position +2 of mature lipoproteins can function as an inner membrane retention signal in V. vulnificus. Interestingly, the Escherichia coli “+2 rule” does not apply to the V. vulnificus lipoprotein IlpA (G2D) mutant, as a Ser to Asp mutation at position +2 of IlpA did not affect its outer membrane localisation. Furthermore, an IlpA tether-mRFP chimeric lipoprotein and its G2D mutant also behaved like IlpA. Together, these results suggest that the sorting rule of lipoproteins in V. vulnificus might be different from that in E. coli. [ABSTRACT FROM AUTHOR]

The association of brain-derived neurotrophic factor (BDNF) as a member of neurotrophin family and metabolic syndrome (MetS) has been proposed, however basic evidence necessary to prove (or disprove) this association in non-genetic animal model is rare. Therefore, we investigated the alteration of encephalic BDNF gene expression in a mouse model of high-fat diet (HFD) induced MetS. To translate MetS, male NMRI mice (9 weeks old; N = 13) fed on a HFD including suet powder (37.50%) and granulated sugar (19.85%) while control mice were fed a diet contained suet powder (6.25%) and granulated sugar (49.09%). We monitored the development of MetS by measuring fasting blood sugar (FBS) and lipid (total cholesterol (TC) and triacylglycerol (TGs)) and lipoprotein (high-density lipoprotein cholesterol (HDL-C), very low-density lipoprotein cholesterol (VLDL-C)) profiles, atherogenic index (AI), and somatic indices after 1 and 3 months of dietary interventions. The HFD intake led to increased body weight, liver weight, FBS, TC, and decreased HDL-C as compared to chow diet in mice after first month of dietary intervention. The increased FBS, body weight, abdominal fat mass, TGs, TC, and VLDL-C and decreased HDL-C were observed in HFD-fed mice as compared to those of chow-fed mice at 3th month. The statistical comparison of two HFD groups in two time intervals of 1st and 3th month confirmed that our HFD-induced MetS model was reliable because FBS, TGs and VLDL-C, TC, and AI have been increased significantly during selected time intervals. The AI increased significantly in HFD-fed mice compared to chow-fed mice after 3 months. The AI in HFD-fed mice treated with HFD for 3 months was increased significantly as compared to mice fed HFD for 1 month. Our diet-induced model more closely mimics the changes observed in human MetS and showed that encephalic BDNF gene in mice fed HFD was under-expressed by 0.30 fold with respect to chow-fed mice after 3 months of dietary intervention. [ABSTRACT FROM AUTHOR]

Lipoproteins (LPs) are a set of naturally occurring bio-nanoparticles consisting of Apo-LPs, phospholipids, a highly hydrophobic core of cholesteryl esters and triglycerides that participate mainly in the targeted transport of cholesteryl esters and other hydrophobic molecules through the bloodstream. They also are able to recognize specific receptors on normal and abnormal cells. Therefore, LPs represent a relevant tool for targeted delivery of cancer diagnostics and therapeutics due to their native biocompatibility, biodegradability, nano-scale size and receptor-mediated uptake. The circulating LPs are categorized into five classes, each with its own characteristic protein and lipid composition. Low-density LPs (LDL) and high-density LPs (HDL) are two major subclasses of LPs which were extensively subjected to attractive and versatile vehicles for targeted delivery of anticancer drugs. This study focus to highlight the potential applications of LDL and HDL bio-nanocarriers in the field of specific target drug delivery to cancer cells. [ABSTRACT FROM AUTHOR]

Background/Purpose: Dyslipidemia is common in liver transplant recipients. This retrospective study investigates whether donors play a role. Methods: Prospectively collected data of donors and recipients of deceased-donor liver transplantation (DDLT) and living-donor liver transplantation (LDLT) were reviewed. Total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein (HDL) and fasting glucose were compared between groups. HDL ≥1.6 mmol/L at 2 years after transplant was considered the marker of a favorable post-transplant lipid profile in recipients. Univariate and multivariate analyses were performed to identify predictive factors for this marker. Results: There were 85 DDLTs and 80 LDLTs. LDLT donors were younger (30 vs. 50 years, p < 0.001) and lighter (58.2 vs. 63.4 kg, p = 0.008) and had a lower body mass index (21.2 vs. 23.7, p < 0.001). The DDLT group had more fatty grafts ( p = 0.001) and longer cold (375 vs. 103.5 min, p < 0.001) and warm (50.5 vs. 46 min, p = 0.034) ischemia. LDLT donors had lower fasting glucose (4.85 vs. 7.21 mmol/L, p < 0.001) and triglyceride (0.87 vs. 1.22 mmol/L, p = 0.016) but higher HDL (1.58 vs. 1.39 mmol/L, p = 0.022). LDLT recipients also had higher HDL at 1 year (1.48 vs. 1.28 mmol/L, p = 0.026) and 2 years (1.43 vs. 1.21 mmol/L, p = 0.008). Fourteen (16.5%) DDLT recipients and 27 (33.8%) LDLT recipients had HDL ≥1.6 mmol/L at 2 years. On multivariate analysis, donor HDL ≥1.6 mmol/L (RR 4.311, 95% CI 1.666-11.158, p = 0.003) and recipient body mass index <24 (RR 2.753, 95% CI 1.064-7.127, p = 0.037) were the two independent predictive factors. Conclusion: LDLT recipients had better lipid profiles than DDLT recipients. The feature of high HDL level in donors was transferred to recipients. [ABSTRACT FROM AUTHOR]

Purpose: To compare the effects of the order of concurrent exercise (endurance plus strength or strength plus endurance) on lipoprotein profiles in men. Methods: After the evaluation of maximum strength (one repetition maximum-1RM) in the half-squat and of aerobic fitness (maximal velocity in treadmill incremental test), 11 physically active male subjects underwent two randomized sessions composed of four sets of half-squat strength exercises until exhaustion (at 80 % of 1RM) and a 5-km run high-intensity intermittent exercise (1:1 min at V ), performed in different orders: (1) strength plus run (S-A) and inverse order, and run plus strength (A-S). Blood samples were collected before and immediately after the first exercise (Post-1) and after the second exercise (Post-2) in the intra-session sequence. Serum was analyzed for total cholesterol (TC) and its ratio, HDL-c and LDL-c, and triacylglycerol (TAG). Results: There were effects of condition for TC, LDL-c, and TC/HDL, with greater values in the AS than SA ( p < 0.001 for all). For the delta analysis, there was an interaction effect for TAG, with greater delta-1 S-A than delta-1 A-S ( p = 0.035), and higher delta-1 S-A than delta-2 S-A ( p = 0.001); for LDL-c, with higher delta-1 S-A values than delta-2 S-A ( p = 0.010); and for TC, with higher delta-1 S-A values than delta-2 S-A ( p = 0.038). Conclusion: We conclude that there are no differences between the order of acute high-intensity intermittent run plus strength exercises regarding modulation of the lipoprotein profile in healthy, physically active men. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: We aimed to determine whether plasma lipoproteins, after leakage into the retina and modification by glycation and oxidation, contribute to the development of diabetic retinopathy in a mouse model of type 1 diabetes. Methods: To simulate permeation of plasma lipoproteins into retinal tissues, streptozotocin-induced mouse models of diabetes and non-diabetic mice were challenged with intravitreal injection of human 'highly-oxidised glycated' low-density lipoprotein (HOG-LDL), native- (N-) LDL, or the vehicle PBS. Retinal histology, electroretinography (ERG) and biochemical markers were assessed over the subsequent 14 days. Results: Intravitreal administration of N-LDL and PBS had no effect on retinal structure or function in either diabetic or non-diabetic animals. In non-diabetic mice, HOG-LDL elicited a transient inflammatory response without altering retinal function, but in diabetic mice it caused severe, progressive retinal injury, with abnormal morphology, ERG changes, vascular leakage, vascular endothelial growth factor overexpression, gliosis, endoplasmic reticulum stress, and propensity to apoptosis. Conclusions/interpretation: Diabetes confers susceptibility to retinal injury imposed by intravitreal injection of modified LDL. The data add to the existing evidence that extravasated, modified plasma lipoproteins contribute to the propagation of diabetic retinopathy. Intravitreal delivery of HOG-LDL simulates a stress known to be present, in addition to hyperglycaemia, in human diabetic retinopathy once blood-retinal barriers are compromised. [ABSTRACT FROM AUTHOR]

A decrease in high-density lipoprotein (HDL) level and an increase in atherogenic low-density lipoprotein (LDL) concentration in plasma are involved in the progress of atherosclerosis and incidence of cardiovascular diseases. Cholesteryl ester transfer protein (CETP) passes cholesteryl ester and triglyceride molecules through a hydrophobic tunnel between lipoproteins and via that decreases the HDL/LDL ratio in plasma. Thus, inhibition of CETP activity by specific inhibitors could diminish atherosclerosis occurrence. Anacetrapib as a specific reversible inhibitor of CETP by stabilizing CETP-HDL complex significantly increases the HDL/LDL ratio in plasma. For better understanding the mechanism of CETP inhibition by Anacetrapib, after docking Anacetrapib against a CETP structure, molecular dynamics simulation of CETP and CETP-Anacetrapib in an explicit water cage was performed. Analyses of acquired trajectories show that Anacetrapib increases fluctuation of residues 421-442 of CETP through hydrophobic interactions and thus disrupts the integrity of an α-helix (helix B) structure in the C-terminal concave surface. Creation of a hinge by defeat of the helix B in the C-terminal of CETP, where CETP interacts with LDL, results in missing of an α-helix (residues 436-440) and conversion of banana-shaped CETP to a hemisphere conformation. According to the obtained results, bending of the CETP structure and conversion of the secondary structure in the C-terminal domain in the presence of Anacetrapib may destabilize CETP-VLDL complex and through that shift the dynamics of CETP to the formation of the CETP-HDL complex. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Until recently, type 2 diabetes was seen as a disease caused by an impaired ability of insulin to promote the uptake and utilisation of glucose. Work on forkhead box protein O (FOXO) transcription factors revealed new aspects of insulin action that have led us to articulate a liver- and beta cell-centric narrative of diabetes pathophysiology and treatment. FOXO integrate a surprisingly diverse subset of biological functions to promote metabolic flexibility. In the liver, they controls the glucokinase/glucose-6-phosphatase switch and bile acid pool composition, directing carbons to glucose or lipid utilisation, thus providing a unifying mechanism for the two abnormalities of the diabetic liver: excessive glucose production and increased lipid synthesis and secretion. Moreover, FOXO are necessary to maintain beta cell differentiation, and diabetes development is associated with a gradual loss of FOXO function that brings about beta cell dedifferentiation. We proposed that dedifferentiation is the main cause of beta cell failure and conversion into non-beta endocrine cells, and that treatment should restore beta cell differentiation. Our studies investigating these proposals have revealed new dimensions to the pathophysiology of diabetes that can be leveraged to design new therapies. [ABSTRACT FROM AUTHOR]

Dopamine receptor genes are known to be candidate genes, mutations of which may be involved in the development of cardiovascular diseases. The human D4 receptor gene ( DRD4) contains a variable number (two to ten copies) of tandem 48-bp repeats in exon 3. The goal of the study was to analyze the association of DRD4 gene polymorphism with cardiovascular disease risk factors in the Russian population: blood pressure (BP), high-density (HDL) and low-density (LDL) lipoprotein cholesterol levels, and the triglyceride level. We genotyped 257 women and 425 men for variable number tandem repeat polymorphism in DRD4. The subjects were Novosibirsk residents of Slavic ethnicity. They were divided either into 7+ (those having the allele of seven or eight repeats) and 7-(two to six repeats) groups or into 2+5+ (two or five repeats) and 2-5-(three, four, six, seven, or eight repeats) groups. We found associations between the 7+ allele and elevated systolic and diastolic BP in women but not in men. Neither sex showed associations between the long variants of the DRD4 gene and pulse blood pressure. The presence of the 2-or 5-allele of the DRD4 polymorphism was associated with low HDL cholesterol levels in women and low total cholesterol levels in men. The polymorphism exerted no significant effects on LDL, HDL, or triglyceride levels in men. [ABSTRACT FROM AUTHOR]

Acrylamide is a well-known potent carcinogen and neurotoxin that, until now, has not been sufficiently investigated with regard to its effects on lipid metabolism. We investigated physiological effects of acrylamide (AA) on lipoprotein metabolism using human macrophages, dermal cells, and zebrafish models. Functional and structural properties of lipoproteins were modified by AA (final concentration of 5-100 mM) with loss of antioxidant ability and multimerization of apoA-I in vitro. AA exacerbated LDL oxidation, degradation, and LDL uptake into macrophages with increased ROS production. In human cells, treatment of AA (1-100 μM) caused cellular senescence of dermal cells with severe cytotoxicity. Waterborne exposure of zebrafish in cage water containing AA (300 ppm) resulted in acute death within 26 h along with elevation of body weight, blood glucose, triglyceride, and hepatic inflammation. AA exposure caused fat accumulation in liver in a dose-dependent manner. In conclusion, AA affected lipoprotein metabolism to result exacerbation of atherosclerosis. Exposure of zebrafish to AA resulted in acute inflammatory death with hyperlipidemia. [ABSTRACT FROM AUTHOR]

Four decades ago, it was observed that stimulation of T cells induces rapid changes in cellular cholesterol that are required before proliferation can commence. Investigators returning to this phenomenon have finally revealed its molecular underpinnings. Cholesterol trafficking and its dysregulation are now also recognized to strongly influence dendritic cell function, T cell polarization, and antibody responses. In this review, the state of the literature is reviewed on how cholesterol and its trafficking regulate the cells of the adaptive immune response and in vivo disease phenotypes of dysregulated adaptive immunity, including allergy, asthma, and autoimmune disease. Emerging evidence supporting a potential role for statins and other lipid-targeted therapies in the treatment of these diseases is presented. Just as vascular biologists have embraced immunity in the pathogenesis and treatment of atherosclerosis, so should basic and clinical immunologists in allergy, pulmonology, and other disciplines seek to encompass a basic understanding of lipid science. [ABSTRACT FROM AUTHOR]

The efficacy of diallyl trisulfide (DATS) against arsenic (As) induced dyslipidemia in the plasma and livers of rats was studied. Oral administration of As [5 mg/kg of body weight (BW)/day] for 4 weeks showed significant ( p<0.05) increases in TC, LDL-C, VLDL-C, FFA, PL, and TG levels and the activity of HMG-CoA reductase in the plasma and liver, with significant ( p<0.05) reductions in levels of HDL-C hepatic ubiquinones and activities of LCAT and LPL in the plasma and liver. Oral administration of DATS (80 mg/kg of BW) for 4 weeks in As intoxicated rats significantly ( p<0.05) reduced plasma and liver TC, FFA, TGs, VLDL-C, and LDL-C levels, and the activity of HMG-CoA reductase, and significantly ( p<0.05) increased the activities of LCAT and LPL and the levels of HDL-C and ubiquinone in the livers of rats. DATS protects against As-induced dyslipidemia in rats. [ABSTRACT FROM AUTHOR]

Although genome-wide association (GWA) studies have provided valuable insights into the genetic architecture of human disease, they have elucidated relatively little of the heritability of complex traits. A significant part of the missing heritability might be explained by rare combinations of common SNPs. We hypothesized that epistasis among 15 genes (148 SNPs) involved in lipoprotein metabolism would influence HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels. Using SNPwinter software with the various epistatic models, we identified 58 association signals with HDL-C levels for SNPs in eleven genes and 118 associations with LDL-C for SNPs in fourteen genes. These associations were discovered in the urban Ansan cohort ( n = 4,102) and replicated in a rural cohort ( n = 3,434), the Ansung. We found replicated associations with new genes ( SOAT1, APOB, HMGCR, and FDFT1 for HDL-C, and SOAT1, FDFT1, LPL, SQLE, ABCA1, LRP1, SCARB1, and PLTP for LDL-C), in addition to those ( CETP, LIPC, LPL, ABCA1, PLTP, SCARB1, and LRP1 for HDL-C, and CETP, LIPC, LDLR, APOB, CYP7A1, and HMGCR for LDL-C) identified by GWA studies, through investigating pairwise interactions between candidate genes of biological and clinical importance. Interestingly, we found that some genes were more likely to be involved in epistatic interactions ( ABCA1 and LIPC for HDL-C, and ABCA1, SCARB1, and LIPC for LDL-C). [ABSTRACT FROM AUTHOR]

Atherosclerosis remains the leading cause of severe cardiovascular complications such as cardio- and cerebrovascular events. Given that prevention and early intervention play important roles in the reduction of cardiovascular complications associated with atherosclerosis, it is critical to better understand how to target the modifiable risk factors, such as diet, in order to best minimize their contributions to the development of the disease. Studies have shown that various dietary sources of protein can affect blood lipid levels, a modifiable risk factor for atherosclerosis, either positively or negatively. This clearly highlights that not all proteins are 'created equal.' For example, consumption of diets high in either animal- or vegetable-based sources of protein have resulted in varied and inconsistent effects on blood cholesterol levels, often depending on the amino acid composition of the protein and the species investigated. Careful consideration of the source of dietary protein may play an important role in the prevention of atherosclerosis and subsequent cardiovascular complications. Given the recent focus on high protein diets, an emphasis on controlled studies in the area is warranted. The goal of this review is to present the current state of the literature that examines the effects of casein, a commonly utilized animal-based protein, on blood cholesterol levels and the varying effects noted in both animals and humans. [ABSTRACT FROM AUTHOR]

The imbalance of CD4CD25 regulatory T (Treg) cells and Th17 cells has shown to be involved in pathogenesis of atherosclerosis and acute coronary syndrome [ACS, including unstable angina (UA) and acute myocardial infarction (AMI)]. The purpose of this study is to explore the significance of Treg/Th17 ratio in early diagnosis for ACS. We detected expression of Treg and Th17 in patients with AMI, UA, stable angina, and subjects with normal coronary arteries at the time of admission. Our results showed that ACS patients have a significant increase of Th17 number, but a marked decline of Treg/Th17 ratio, Treg number, and Treg function. Significant positive correlations in Th17 frequency and negative correlation in Treg frequency, Treg/Th17 ratio were found to levels of oxidized low-density lipoprotein (Ox-LDL), high sensitive C-reactive protein (hsCRP), Lipoprotein (a) [Lp(a)], and Creatine kinase-MB(mass) (CK-MBmass) in serum. Receiver-operating characteristic curves shown that the predictive specificity and sensitivity of Treg/Th17 ratio for ACS and AMI was the highest among all the five markers: Ox-LDL, hsCRP, Lp(a), CK-MBmass, and Treg/Th17 ratio. In conclusion, Treg/Th17 ratio appeared to be a novel indicator for early diagnosis of ACS. [ABSTRACT FROM AUTHOR]

We studied the lipoprotein profiles of human hepatic cells at various stages of differentiation. The production of three major classes of lipoproteins, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), was detected in three well-differentiated human hepatoma cell lines and primary human hepatocytes; however, these lipoproteins were not detected in the culture medium in which undifferentiated hepatoma cell lines were grown. Reverse transcription polymerase chain reaction analysis demonstrated that the expression levels of apolipoprotein A1 (ApoA1), ApoB100, and microsomal triglyceride transfer protein (MTP) were markedly lower in the undifferentiated hepatoma cell lines than in the well-differentiated hepatoma cell lines and primary hepatocytes. These results indicate that apolipoprotein synthesis, and triglyceride-transport by MTP might be rate-limiting steps in lipoprotein production in mature hepatic cells. [ABSTRACT FROM AUTHOR]

A variety of Gram-negative pathogens possess host-specific lactoferrin (Lf) receptors that mediate the acquisition of iron from host Lf. The integral membrane protein component of the receptor, lactoferrin binding protein A specifically binds host Lf and is required for acquisition of iron from Lf. In contrast, the role of the bi-lobed surface lipoprotein, lactoferrin binding protein B (LbpB), in Lf binding and iron acquisition is uncertain. A common feature of LbpBs from most species is the presence of clusters of negatively charged amino acids in the protein's C-terminal lobe. Recently it has been shown that the negatively charged regions from the Neisseria meningitidis LbpB are responsible for protecting against an 11 amino acid cationic antimicrobial peptide (CAP), lactoferricin (Lfcin), derived from human Lf. In this study we investigated whether the LbpB confers resistance to other CAPs since N. meningitidis is likely to encounter other CAPs from the host. LbpB provided protection against the cathelicidin derived peptide, cathelicidin related antimicrobial peptide (mCRAMP), but did not confer protection against Tritrp 1 or LL37 under our experimental conditions. When tested against a range of rationally designed synthetic peptides, LbpB was shown to protect against IDR-1002 and IDR-0018 but not against HH-2 or HHC10. [ABSTRACT FROM AUTHOR]

The intestinal production of lipoproteins is one of the key processes by which the body prepares dietary lipid for dissemination to locations throughout the body where they are required. Paramount to this is the relationship between dietary lipid and the enterocytes that line the gut, along with the processes which prepare this lipid for efficient uptake by these cells. These include those which occur in the mouth and stomach along with those which occur within the intestinal lumen itself. Additionally, the interplay between digested lipid, dual avenues for lipid uptake by enterocytes (passive and lipid transporter proteins), a system of intercellular lipid resynthesis and transport, and a complex system of lipoprotein synthesis yield a system open to significant modulation. In this review, we will attempt to outline the processes of lipid digestion, lipoprotein synthesis and the exogenous and endogenous factors which exert their influence. [ABSTRACT FROM AUTHOR]

Lipid measurement is one of the cornerstones of cardiovascular risk assessment and treatment. It is widely accepted that reduction of atherogenic lipids reduces risk of atherosclerotic cardiovascular disease. As the study of lipids has yielded deeper understanding of the pathophysiology of lipid metabolism, it has become clear that different techniques to quantify atherogenic lipids and lipoproteins could be complementary. For example, low-density lipoprotein cholesterol can exist in a range of forms from small, dense to large, buoyant, and therefore, discordance may arise between measures of its cholesterol content and particle concentration. In this article, we review the most recent literature on discordance in lipid measurements. We emphasize interesting and important new findings, and aim to bring the reader up-to-date on the topic. We submit that lipid discordances create an opportunity to better personalize the risk assessed for atherogenic cardiovascular disease and the care we give patients with dyslipidemia. We note that while prior research has often examined one lipid measure vs another in their abilities to predict the average risk in a population, recent studies are increasingly asking what lipid discordance in individual patients can tell us about risk. We propose that this latter approach asks the more clinically important question. The message from these studies is consistent: discordance matters. As the field moves forward, we propose standardization of methods for discordance research. In our view, this will best enable us to further clarify the clinical implications of the principle of discordance and best inform personalized cardiovascular care. [ABSTRACT FROM AUTHOR]

Clinical studies have established the important impact of atherosclerotic disease in Western societies. This disease is characterized by the accumulation of lipids and the migration of various cell types in the sub-endothelial space of blood vessels. As demonstrated by many studies, endothelial cells play an essential role in the development of this disease. The endothelium acts as a gatekeeper of blood vessel integrity and cardiovascular health status. For instance, the transfer of lipids via the transport of lipoproteins in the arterial intima is believed to be mediated by endothelial cells through a process termed transcytosis. In addition, lipoproteins that accumulate in the sub-endothelial space may also be modified, in a process that can direct the activation of endothelial cells. These steps are essential for the initiation of an atherosclerotic plaque and may be mediated, at least in part, by caveolae and their associated protein caveolin-1. In the present study, we evaluate the role of caveolin-1/caveolae in the regulation of these two steps in endothelial cells. Our data clearly demonstrate that caveolin-1 is involved in the regulation of lipoprotein transcytosis across endothelial cells and in the regulation of vascular inflammation. [ABSTRACT FROM AUTHOR]

Advanced lipid testing has been suggested by some experts to identify patients with substantial residual risk for more aggressive targeting of lifestyle and pharmacologic therapies. It measures the subpopulation of lipoproteins and apolipoproteins, which include lipoprotein (a), apolipoprotein A-I, and apolipoprotein B, and measures of lipoprotein particle composition such as LDL particle (LPL-P) and HDL particle (HDL-P) number and size. Obesity is associated with smaller LDL-P and HDL-P sizes. Moderate weight loss via fasting/calorie restriction is associated with LDL-P size increase, whereas moderate weight loss via endurance exercise is associated with HDL-P size increase. Diets high in carbohydrates are associated with a more atherogenic advanced lipoprotein profile characterized by smaller LDL-P and HDL-P sizes. In summary, lifestyle changes such as weight loss, exercise, and dietary modification correlate with improvement in the profile of advanced lipoproteins. Regrettably, therapies targeting HDL and HDL composition have been disappointing to date. [ABSTRACT FROM AUTHOR]