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Lipids in Health and Disease

  1476-511X

 

 

Cơ quản chủ quản:  BioMed Central Ltd. , BMC

Lĩnh vực:
Clinical BiochemistryBiochemistry (medical)Endocrinology, Diabetes and MetabolismEndocrinology

Các bài báo tiêu biểu

Multiple roles of dihomo-γ-linolenic acid against proliferation diseases
Tập 11 - Trang 1-9 - 2012
Xiaoping Wang, Huanping Lin, Yan Gu
Considerable arguments remain regarding the diverse biological activities of polyunsaturated fatty acids (PUFA). One of the most interesting but controversial dietary approaches focused on the diverse function of dihomo-dietary γ-linolenic acid (DGLA) in anti-inflammation and anti-proliferation diseases, especially for cancers. This strategy is based on the ability of DGLA to interfere in cellular lipid metabolism and eicosanoid (cyclooxygenase and lipoxygenase) biosynthesis. Subsequently, DGLA can be further converted by inflammatory cells to 15-(S)-hydroxy-8,11,13-eicosatrienoic acid and prostaglandin E1 (PGE1). This is noteworthy because these compounds possess both anti-inflammatory and anti-proliferative properties. PGE1 could also induce growth inhibition and differentiation of cancer cells. Although the mechanism of DGLA has not yet been elucidated, it is significant to anticipate the antitumor potential benefits from DGLA.
The extended lipid panel assay: a clinically-deployed high-throughput nuclear magnetic resonance method for the simultaneous measurement of lipids and Apolipoprotein B
Tập 19 - Trang 1-11 - 2020
Erwin Garcia, Dennis W. Bennett, Margery A. Connelly, Elias J. Jeyarajah, Franklin C. Warf, Irina Shalaurova, Steven P. Matyus, Justyna Wolak-Dinsmore, David N. Oskardmay, Randolph M. Young, Maureen Sampson, Alan T. Remaley, James D. Otvos
Standard lipid panel assays employing chemical/enzymatic methods measure total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C), from which are calculated estimates of low-density lipoprotein cholesterol (LDL-C). These lipid measures are used universally to guide management of atherosclerotic cardiovascular disease risk. Apolipoprotein B (apoB) is generally acknowledged to be superior to LDL-C for lipid-lowering therapeutic decision-making, but apoB immunoassays are performed relatively infrequently due to the added analytic cost. The aim of this study was to develop and validate the performance of a rapid, high-throughput, reagent-less assay producing an “Extended Lipid Panel” (ELP) that includes apoB, using the Vantera® nuclear magnetic resonance (NMR) analyzer platform already deployed clinically for lipoprotein particle and other testing. Partial least squares regression models, using as input a defined region of proton NMR spectra of plasma or serum, were created to simultaneously quantify TC, TG, HDL-C, and apoB. Large training sets (n > ~ 1000) of patient sera analyzed independently for lipids and apoB by chemical methods were employed to ensure prediction models reflect the wide lipid compositional diversity of the population. The analytical performance of the NMR ELP assay was comprehensively evaluated. Excellent agreement was demonstrated between chemically-measured and ELP assay values of TC, TG, HDL-C and apoB with correlation coefficients ranging from 0.980 to 0.997. Within-run precision studies measured using low, medium, and high level serum pools gave coefficients of variation for the 4 analytes ranging from 1.0 to 3.8% for the low, 1.0 to 1.7% for the medium, and 0.9 to 1.3% for the high pools. Corresponding values for within-lab precision over 20 days were 1.4 to 3.6%, 1.2 to 2.3%, and 1.0 to 1.9%, respectively. Independent testing at three sites over 5 days produced highly consistent assay results. No major interference was observed from 38 endogenous or exogenous substances tested. Extensive assay performance evaluations validate that the NMR ELP assay is efficient, robust, and substantially equivalent to standard chemistry assays for the clinical measurement of lipids and apoB. Routine reporting of apoB alongside standard lipid measures could facilitate more widespread utilization of apoB for clinical decision-making.
Long-chain fatty acid activates hepatocytes through CD36 mediated oxidative stress
Tập 17 - Trang 1-9 - 2018
Jun Liu, Ping Yang, Guoqing Zuo, Song He, Wei Tan, Xiaoyu Zhang, Chunxiao Su, Lei Zhao, Li Wei, Yao Chen, Xiongzhong Ruan, Yaxi Chen
Accumulating evidence suggests that activated hepatocytes are involved in the deposition of the excess extracellular matrix during liver fibrosis via the epithelial to mesenchymal transition. Lipid accumulation in hepatocytes are implicated in the pathogenesis of chronic liver injury. CD36 is known to mediate long-chain fatty acid (LCFA) uptake and lipid metabolism. However, it is unclear whether LCFA directly promotes hepatocyte activation and the involved mechanisms have not been fully clarified. Mice were fed with a high fat diet (HFD) and normal hepatocyte cells (Chang liver cells) were treated with palmitic acid (PA) in vivo and in vitro. Real-time polymerase chain reaction (RT-PCR) and western blotting were used to examine the gene and protein expression of molecules involved in hepatic fibrogenesis and hepatocyte activation. CD36 was knocked down by transfecting CD36 siRNA into hepatocyte cells. Hydrogen peroxide (H2O2) and reactive oxygen species (ROS) levels were detected using commercial kits. HFD induced a profibrogenic response and up-regulated CD36 expression in vivo. Analogously, PA increased lipid accumulation and induced human hepatocyte activation in vitro, which was also accompanied by increased CD36 expression. Interestingly, knockdown of CD36 resulted in a reduction of hepatocyte lipid deposition and decreased expression of Acta2 (34% decrease), Vimentin (29% decrease), Desmin (60% decrease), and TGF-β signaling pathway related genes. In addition, HFD and PA increased the production of H2O2 in vivo (48% increase) and in vitro (385% increase), and the antioxidant, NAC, ameliorated PA-induced hepatocyte activation. Furthermore, silencing of CD36 in vitro markedly attenuated PA-induced oxidative stress (H2O2: 41% decrease; ROS: 39% decrease), and the anti-activation effects of CD36 knockdown could be abolished by pretreatment with H2O2. Our study demonstrated that LCFA facilitates hepatocyte activation by up-regulating oxidative stress through CD36, which could be an important mechanism in the development of hepatic fibrosis.
Arachidonic acid induces macrophage cell cycle arrest through the JNK signaling pathway
Tập 17 Số 1 - Trang 1-9 - 2018
Shen, Ziying, Ma, Yunqing, Ji, Zhonghao, Hao, Yang, Yan, Xuan, Zhong, Yuan, Tang, Xiaochun, Ren, Wenzhi
Arachidonic acid (AA) has potent pro-apoptotic effects on cancer cells at a low concentration and on macrophages at a very high concentration. However, the effects of AA on the macrophage cell cycle and related signaling pathways have not been fully investigated. Herein we aim to observe the effect of AA on macrophages cell cycle. AA exposure reduced the viability and number of macrophages in a dose- and time-dependent manner. The reduction in RAW264.7 cell viability was not caused by apoptosis, as indicated by caspase-3 and activated caspase-3 detection. Further research illustrated that AA exposure induced RAW264.7 cell cycle arrested at S phase, and some cell cycle-regulated proteins were altered accordingly. Moreover, JNK signaling was stimulated by AA, and the stimulation was partially reversed by a JNK signaling inhibitor in accordance with cell cycle-related factors. In addition, nuclear and total Foxo1/3a and phosphorylated Foxo1/3a were elevated by AA in a dose- and time-dependent manner, and this elevation was suppressed by the JNK signaling inhibitor. Our study demonstrated that AA inhibits macrophage viability by inducing S phase cell cycle arrest. The JNK signaling pathway and the downstream FoxO transcription factors are involved in AA-induced RAW264.7 cell cycle arrest.
Early postoperative changes of sphingomyelins and ceramides after laparoscopic sleeve gastrectomy
Tập 17 Số 1 - 2018
Hakan Özer, İbrahim Aslan, Mehmet Tahi̇r Oruç, Yaşar Çöpelci, Ebru Afşar, Sabriye Kaya, Mutay Aslan
Factors influencing drug switching and changes in low-density lipoprotein-cholesterol levels with atorvastatin: a real-world observational study
Tập 22 Số 1
Yu-Cheol Lim, Eui-Kyung Lee, Mi-Hai Park
Abstract Background Although generic drugs have been approved with the assurance of interchangeable applications with original drugs, some physicians, and patients still view their efficacy and interchangeability negatively. Using real-world data, we aimed to determine factors that impact switching between drugs that contain the same active ingredient, i.e., atorvastatin, and, in turn, whether this ‘switch’ could alter clinical outcomes. Methods Using the National Health Insurance Service senior cohort, a retrospective cohort study was conducted to assess patients who had newly started atorvastatin 10 mg and had at least two records of national health examinations from 2010 to 2014. Drug switching, which was defined as a change in the atorvastatin product administered 90 days before the first and second examinations, was assessed. Greedy propensity score matching (1:2) was performed between switchers and non-switchers to control for potential confounders. Factors influencing switching were analyzed using multivariate logistic regression to estimate odds ratios and 95% confidence intervals (CIs). Changes in low-density lipoprotein-cholesterol (LDL-C) levels attributable to drug switching were evaluated using difference-in-differences regression. Results A total of 1,588 patients were included, of whom 25.3% switched drugs (1,187 non-switchers and 401 switchers). Compared to patients taking generics before the first examination, those taking the original drugs had a lower odds ratio (0.31; 95% CI [0.21, 0.46]) for subsequent drug switching. A change in medical institution was associated with a significantly higher odds ratio (6.83; 95% CI [4.66, 10.02]). There were no significant differences in LDL-C alterations between switchers and non-switchers (0.42 mg/dL; 95% CI [-2.29, 3.13]). Conclusion The type of first-time drug administered and changes in medical institution can influence drug switching. No significant changes in LDL-C values were observed in the various switching scenarios between the original and generic drugs, suggesting their interchangeable application in real-world clinical practice.
Effects of extended-release niacin/laropiprant on correlations between apolipoprotein B, LDL-cholesterol and non-HDL-cholesterol in patients with type 2 diabetes
Tập 15 - Trang 1-10 - 2016
Eliot A. Brinton, Joseph Triscari, Philippe Brudi, Erluo Chen, Amy O. Johnson-Levonas, Christine McCrary Sisk, Rae Ann Ruck, Alexandra A. MacLean, Darbie Maccubbin, Yale B. Mitchel
LDL-C, non-HDL-C and ApoB levels are inter-correlated and all predict risk of atherosclerotic cardiovascular disease (ASCVD) in patients with type 2 diabetes mellitus (T2DM) and/or high TG. These levels are lowered by extended-release niacin (ERN), and changes in the ratios of these levels may affect ASCVD risk. This analysis examined the effects of extended-release niacin/laropiprant (ERN/LRPT) on the relationships between apoB:LDL-C and apoB:non-HDL-C in patients with T2DM. T2DM patients (n = 796) had LDL-C ≥1.55 and <2.97 mmol/L and TG <5.65 mmol/L following a 4-week, lipid-modifying run-in (~78 % taking statins). ApoB:LDL-C and apoB:non-HDL-C correlations were assessed after randomized (4:3), double-blind ERN/LRPT or placebo for 12 weeks. Pearson correlation coefficients between apoB:LDL-C and apoB:non-HDL-C were computed and simple linear regression models were fitted for apoB:LDL-C and apoB:non-HDL-C at baseline and Week 12, and the correlations between measured apoB and measured vs predicted values of LDL-C and non-HDL-C were studied. LDL-C and especially non-HDL-C were well correlated with apoB at baseline, and treatment with ERN/LRPT increased these correlations, especially between LDL-C and apoB. Despite the tighter correlations, many patients who achieved non-HDL-C goal, and especially LDL-C goal, remained above apoB goal. There was a trend towards greater increases in these correlations in the higher TG subgroup, non-significant possibly due to the small number of subjects. ERN/LRPT treatment increased association of apoB with LDL-C and non-HDL-C in patients with T2DM. Lowering LDL-C, non-HDL-C and apoB with niacin has the potential to reduce coronary risk in patients with T2DM.
Age and gender-specific distribution of metabolic syndrome components in East China: role of hypertriglyceridemia in the SPECT-China study
Tập 17 - Trang 1-11 - 2018
Boren Jiang, Yanjun Zheng, Yingchao Chen, Yi Chen, Qin Li, Chunfang Zhu, Ningjian Wang, Bing Han, Hualing Zhai, Dongping Lin, Yingli Lu
Chinese population are experiencing remarkably changes of economic and cultural environments. The present study was to examine the prevalence of metabolic syndrome (MetS) by age between genders and to investigate the current characteristics of MetS and its components in China. SPECT-China is a population-based cross-sectional survey on Chinese adults aged ≥18 years in East China. A total of 10,441 Chinese residents participated in anthropometric and laboratory measurements. Of these, 9969 subjects (females, 5868) were eligible for the data analysis reported here. Estimates of the prevalence of MetS and its components were calculated. Presence of MetS was defined based on the IDF/AHA harmonized criteria. MetS z-score was calculated to evaluate the degree of total metabolic disorder. The age-standardized prevalence of the metabolic syndrome was 22.0% (21.9% in men and 22.0% in women). Unlike the continuous MetS rise with age in females, the MetS prevalence in males remained stable among 46–55, 56–65 and > 65 yrs. age groups (31.2%, 31.4%, 32.5%, p = 0.538). In the five components of MetS, contrary to the elevated BP and BG disorders, the frequency of TG disorders decreased with age in males (46.6%(46–55 yrs), 37.2% (56–65 yrs), 27.7%(> 65 yrs), p < 0.001). Multivariable logistic regression showed that in males, more TG disorders were associated with higher BMI, higher educational level and current nonsmoker. In the MetS subjects, the 3-factor combinations which included TG disorders decreased with age in both genders. The whole metabolic profile became better in older male MetS subjects, which was opposite to the female. Our results showed a distinct age-related prevalence of MetS between genders in dramatically changed China, in which the TG disorders played an important role. More targeted measures need to be taken to meet the serious challenges of metabolic diseases. ChiCTR-ECS- 14005052 , Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China).
Adiponectin improves NF-κB-mediated inflammation and abates atherosclerosis progression in apolipoprotein E-deficient mice
Tập 15 - Trang 1-14 - 2016
Xuemei Wang, Qingjie Chen, Hongwei Pu, Qin Wei, Mingjun Duan, Chun Zhang, Tao Jiang, Xi Shou, Jianlong Zhang, Yining Yang
Atherosclerosis is a common pathological basis of cardiovascular disease. Adiponectin (APN) has been shown to have an anti-atherosclerosis effect, and the underlying mechanisms, however, are largely unknown. Nuclear factor κB (NF-κB) has also been regarded as a proatherogenic factor, mainly because of its regulation of a variety of the proinflammatory genes linked to atherosclerosis. It was hypothesized that the inhibitory effects of adiponectin on the atherosclerosis is through the inhibition of NF-κB signaling pathway. We injected adenovirus of Ad-eGFP virus (control group) or the same amount of Ad-APN-eGFP virus (APN group) in ApoE-/- mice tail-intravenously. Blood samples and aorta were executed at 0 day, 4, and 8 week of high-fat diet feeding. Histopathological changes of aortic arch root were detected. Levels of TC, TG, HDL-C, LDL-C were measured. Adiponectin and Matrix metalloproteinases-9 (MMP-9) concentration were detected by enzyme-linked immunosorbent assay. Gene and protein levels of adiponectin, eNOS, IL-6, MCP-1,VCAM-1, and other inflammatory factors were determined. Adiponectin, NF-κB p65 in aortic arch root were determined by immunofluorescence and western blot. Transduction of Ad-APN inhibited the formation of atherosclerotic plaque in aorta when compared with control group. The lesion formation in aortic arch root was inhibited significantly (P < 0.01). Lesion lumen ratio decreased significantly (P < 0.001). The expression of adiponectin attenuated the increases of serum TC (P < 0.001), TG (P < 0.001), and LDL-C (P < 0.001) induced by the high-fat diet, and the increase in body weight (P < 0.05). As increasing serum adiponectin, the levels of MMP-9 were significantly decreased (P < 0.05). The exogenous adiponectin increased the gene expression of the anti-inflammatory factors eNOS (P < 0.05) and IL-10 (P < 0.001), and reduced the gene expression of inflammatory factors tumor necrosis factor-α (TNF-α) (P < 0.001), IL-6 (P < 0.001), VCAM-1 (P < 0.05), respectively. Adiponectin effectively inhibited the activation of NF-κB pathway and the expression of NF-κB nuclear protein p65. Adiponectin may protect the aorta from atherosclerotic injury by reducing inflammation. The molecular mechanism may involve inhibited the expression of downstream components of NF-κB and its transcription factors.
In vitro biological properties and health benefits of a novel sulfated polysaccharide isolated from Cymodocea nodosa
Tập 16 - Trang 1-11 - 2017
Rihab Ben Abdallah Kolsi, Bochra Gargouri, Sameh Sassi, Donyez Frikha, Saloua Lassoued, Karima Belghith
During the last few decades, there has been a growing interest in the search for novel bioactive compounds from marine origins. The present study is the first to determine the molecular characterization which it was deposited in the genebank database, to investigate and evaluate the biological properties of sulfated polysaccharide from Cymodocea nodosa (CNSP) seagrass. The results revealed that CNSP had high activity in total antioxidant assay (59.03 mg ascorbic acid equivalents/g extract), reducing power (OD = 0.3), DPPH radical scavenging (IC50 = 1.22 mg/ml) and ABTS radical scavenging (IC50 = 1.14 mg/ml). It was also noted to exhibit antimicrobial activity against a wide range of microorganisms, with important inhibition zones. The results revealed that CNSP was able to inhibit the proliferation of Hela cell lines with a dose-dependent manner. Overall, the results presented in this study demonstrate that CNSP has several attractive antioxidant, antimicrobial and antiproliferative properties with potential benefits towards health.