Biochemie der Lipide - Aktuelle Forschungsartikel renommierter Fachzeitschriften
Aktuelle Fachartikel zur Chemie und Biochemie der Lipide, sortiert nach Erscheinungsdatum.
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Purpose of review: The phospholipase A2 (PLA2) family of proteins includes lipolytic enzymes that liberate the sn-2 fatty acyl chains from phospholipids to yield nonesterified fatty acids and lysophospholipids. The purpose of this review is to discuss recent findings showing distinct roles of several of these PLA2 enzymes in inflammatory metabolic diseases such as diabetes and atherosclerosis.
Recent findings: The group 1B PLA2 digestion of phospholipids in the intestinal lumen facilitates postprandial lysophospholipid absorption, which suppresses hepatic fatty acid oxidation leading to increased VLDL synthesis, decreased glucose tolerance, and promotion of tissue lipid deposition to accentuate diet-induced hyperlipidemia, diabetes, and obesity. Other secretory PLA2s promote inflammatory metabolic diseases by generating bioactive lipid metabolites to induce inflammatory cytokine production, whereas the major intracellular PLA2s, cPLA2α, and iPLA2, generate arachidonic acid and lysophosphatic acid in response to extracellular stimuli to activate leukocyte chemotactic response.
Summary: Each member of the PLA2 family of enzymes serves a distinct role in generating active lipid metabolites that promote inflammatory metabolic diseases including atherosclerosis, hyperlipidemia, obesity, and diabetes. The development of specific drugs that target one or more of these PLA2 enzymes may be novel strategies for treatment of these chronic inflammatory metabolic disorders.
Purpose of review: To review the aberrations of insulin signaling to atypical protein kinase C (aPKC) in muscle and liver that generate cardiovascular risk factors, including obesity, hypertriglyceridemia, hypercholesterolemia, insulin resistance and glucose intolerance in type 2 diabetes mellitus (T2DM), and obesity-associated metabolic syndrome (MetSyn).
Recent findings: aPKC and Akt mediate the insulin effects on glucose transport in muscle and synthesis of lipids, cytokines and glucose in liver. In T2DM, whereas Akt and aPKC activation are diminished in muscle, and hepatic Akt activation is diminished, hepatic aPKC activation is conserved. Imbalance between muscle and hepatic aPKC activation (and expression of PKC-ι in humans) by insulin results from differential downregulation of insulin receptor substrates that control phosphatidylinositol-3-kinase. Conserved activation of hepatic aPKC in hyperinsulinemic states of T2DM, obesity and MetSyn is problematic, as excessive activation of aPKC-dependent lipogenic, gluconeogenic and proinflammatory pathways increases the cardiovascular risk factors. Indeed, selective inhibition of hepatic aPKC by adenoviral-mediated expression of kinase-inactive aPKC, or newly developed small-molecule biochemicals, dramatically improves abdominal obesity, hepatosteatosis, hypertriglyceridemia, hypercholesterolemia, insulin resistance and glucose intolerance in murine models of obesity and T2DM.
Summary: Hepatic aPKC is a unifying target for treating multiple clinical abnormalities that increase the cardiovascular risk in insulin-resistant states of obesity, MetSyn and T2DM.
Purpose of review: Noncholesterol sterols (NCSs) in plasma encompass endogenous cholesterol precursors and exogenous phytosterols and cholesterol metabolites, which are used as surrogate measures of cholesterol synthesis and cholesterol absorption, respectively. The ratios of cholesterol synthesis to cholesterol absorption surrogates are also utilized to assess the overall balance of cholesterol metabolism, with higher values representing more synthesis and lower values more absorption. The objective of this review is to focus on recent findings using plasma NCSs and their potential in customizing dietary and pharmacological hypolipidemic therapies.
Recent findings: NCSs are often used to assess the impact of pharmacological and dietary interventions on cholesterol metabolism. Various forms of dyslipidemia have been characterized using NCSs, and NCSs may be a valuable tool in selecting appropriate treatment therapies. NCSs levels are affected by genetic, dietary and physiological factors and have been related to cardiovascular disease risk.
Summary: The expanded use of plasma NCSs is currently limited by the lack of standardized methodology. However, noncholesterol sterols are still a valuable research tool for the overall assessment of cholesterol metabolism and may have clinical potential in the personalization of diet and medicine.
Purpose of review: HDL and their main apolipoprotein (apo) constituent apoA-I are antiatherogenic. This has been predominantly attributed to the ability of apoA-I/HDL to efflux cholesterol from macrophages within atherosclerotic plaques. It is now emerging that a number of the protective properties of HDL may be due to their effects on the endothelium.
Recent findings: In addition to their well characterized anti-inflammatory and antioxidant effects, apoA-I and HDL regulate several other key biological pathways known to preserve endothelial function and promote vascular repair. The ATP-binding cassette (ABC) transporters ABCA1 and ABCG1, and the scavenger receptor B type 1 mediate multiple intracellular signaling pathways as well as the efflux of cholesterol and/or oxysterols in response to apoA-I/HDL. Although cholesterol efflux triggers a host of signaling events in endothelial cells, there is evidence that some of the beneficial actions of HDL may occur independently of efflux.
Summary: Current data suggest that in endothelial cells ABCA1 and ABCG1 mediate the activation of intracellular signaling pathways primarily through the efflux of cholesterol and oxysterols to apoA-I/HDL. Interaction between HDL and scavenger receptor B type 1 initiates the greatest number of known signaling pathways and there is evidence that some of these are activated independent of efflux.
Purpose of review: The implication of the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) in promoting protein synthesis has been well described. Over the past years, several studies revealed that mTORC1 also plays a crucial role in promoting lipid biosynthesis and that such connection could be linked to diseases including obesity, nonalcoholic fatty liver disease (NAFLD), and cancer. Here, we review the mechanisms by which mTORC1 regulates lipid synthesis by focusing on the key signaling events that trigger hepatic de-novo lipogenesis in response to nutrients and insulin.
Recent findings: mTORC1 promotes lipid synthesis by activating the transcription factor sterol regulatory element binding protein 1 (SREBP-1). Recent studies indicate that mTORC1 regulates SREBP-1 activation at multiple levels. Although mTORC1 was originally shown to be necessary and sufficient to activate SREBP-1 in vitro, new studies indicate that hyperactivation of mTORC1 is insufficient to trigger SREBP-1 activation and lipid biogenesis in vivo. These findings reveal that the molecular connection between mTORC1 and SREBP-1 is more complex than originally envisioned.
Summary: The discovery of a connection between mTORC1 and SREBP-1 opens a new chapter in our understanding of the molecular mechanisms regulating de-novo lipogenesis. A better comprehension of these mechanisms is key for the development of new tools to treat NAFLD and its complications.
Purpose of review: Perturbations in fatty acid levels and in regulatory proteins linked to fat and mitochondrial homeostasis are associated with modifying the risk of Parkinson's disease . Findings, that are not surprising, based on the high fat content of the brain, the myriad of neurological functions dependent on polyunsaturated fatty acids and the role of mitochondria in energy supply and stress amelioration. Nevertheless, dissecting out the molecular links between lipid biology, mitochondrial regulation and Parkinson's disease is complicated by the divergent causes underpinning Parkinson's disease pathophysiology. Here, we summarize aspects of fatty acid biology relevant to Parkinson's disease; the known links between the modulation of fat and Parkinson's disease and introduce mechanisms whereby the E3-ubiquitin ligase, Parkin known to be mutated as a genetic predisposing factor in Parkinson's disease, modulates fat uptake and mitochondrial control.
Recent findings: Prior evidence supports that Parkin, under mitochondrial stress conditions, plays a pivotal role in the mitophagy mitochondrial housekeeping program. Recent evidence now demonstrates a broader role of Parkin in controlling fat uptake and mitochondrial regulatory programs.
Summary: The identification that Parkin has a multifunctional role in modulating cellular fatty acid uptake and mitochondrial biology further strengthens the pathophysiologic link between fat metabolism, mitochondria and Parkinson's disease.
Purpose of review: The finding that brown adipose tissue (BAT) is present in adults brought BAT physiology into the focus of many researchers interested in energy metabolism. Here, we review recent insight into how BAT develops, functions and might help to treat metabolic disorders in humans.
Recent findings: BAT is under control of the nervous system, and several pathways have been identified that allow direct manipulation of BAT biology. In addition, some brown adipocytes arise from a distinct subset of white adipocyte precursors and studies were performed that characterize the development of these ‘brite’ adipocytes. Importantly, progress has been made in understanding how BAT takes up and dissipates nutrients that in metabolic disorders are present in excess. Finally, as it seems that BAT activity declines with age and obesity, we review findings that might shed light on how humans could sustain or increase BAT activity, thus preventing or treating obesity, hyperlipidemia and type 2 diabetes.
Summary: BAT is a powerful organ that controls the development of metabolic disease. These powers are boosted by mechanisms that turn white into brown fat and enhance lipid flux into BAT. However, in humans, it remains unclear what was the first: metabolic disease or decreased BAT activity.
Purpose of review: A strong positive correlation between plasma apolipoprotein (apo) C-III and triglyceride concentrations has been invariably observed in human and animal studies. The hypertriglyceridemic effect of apo C-III has been conventionally explained by its extracellular roles in inhibiting lipolysis catalysed by lipoprotein lipase and attenuating triglyceride-rich lipoprotein clearance through receptor-dependent and/or independent mechanisms. However, recent experimental evidence suggests that apo C-III may also play an intracellular role in promoting hepatic triglyceride-rich lipoprotein production.
Recent findings: Kinetic studies with humans and genetically modified mice have shown that apo C-III is linked with increased production of triglyceride-rich lipoproteins, such as very-low-density lipoprotein 1 (VLDL1). Mutational studies on human apo C-III variants (originally identified in humans with hypotriglyceridemia or hyperalphalipoproteinemia) provide the structure–function analysis of human apo C-III, demonstrating that loss-of-function mutations within human apo C-III impair the assembly and secretion of triglyceride-rich VLDL1 under lipid-rich conditions.
Summary: The current review summarizes recent experimental evidence for an intrahepatic role of human apo C-III in promoting mobilization and utilization of triglyceride during VLDL1 assembly/secretion. Understanding mechanisms by which hepatic apo C-III expression is regulated under insulin resistance and diabetic conditions will lead to better and more rational strategies for the prevention and treatment of diabetic hypertriglyceridemia that is closely related to premature atherosclerosis.
Purpose of review: The hepatic low-density lipoprotein receptor (LDLR) pathway is essential for clearing circulating LDL and is an important therapeutic target for treating cardiovascular disease. Abundance of the LDLR is subject to both transcriptional and nontranscriptional control. Here, we highlight a new post-transcriptional mechanism for controlling LDLR function via ubiquitination of the receptor by the E3-ubiquitin ligase inducible degrader of the LDLR (IDOL).
Recent findings: IDOL is a recently identified transcriptional target of the liver X receptors. Acting as an E3-ubiquitin ligase IDOL promotes ubiquitination of the LDLR, thereby marking it for lysosomal degradation. The determinants required for degradation of the LDLR by IDOL have been largely identified. IDOL also targets two related lipoprotein receptors, the very low-density lipoprotein receptor and apolipoprotein E receptor 2. Despite several similarities, the IDOL, and PCSK9 pathways for controlling LDLR abundance seem independent of each other. Genome-wide association studies have recently identified IDOL as a locus influencing variability in circulating levels of LDL, thereby highlighting the possible role of IDOL in human lipoprotein metabolism.
Summary: Transcriptional induction of IDOL by liver X receptor defines a new post-transcriptional pathway for controlling LDLR abundance and LDL uptake independent of sterol regulatory element binding proteins. Targeting IDOL activity may offer a novel therapeutic approach complementary to statins for treating cardiovascular disease.
Purpose of review: Elevated plasma triglyceride and reduced HDL concentrations are prominent features of metabolic syndrome and type 2 diabetes. Individuals with Tangier disease also have elevated plasma triglyceride concentrations and very low HDL, resulting from mutations in ATP-binding cassette transporter A1 (ABCA1), an integral membrane protein that facilitates nascent HDL particle assembly. Past studies attributed the inverse relationship between plasma HDL and triglyceride to intravascular lipid exchange and catabolic events. However, recent studies also suggest that hepatic signaling and lipid mobilization and secretion may explain how HDL affects plasma triglyceride concentrations.
Recent findings: Hepatocyte-specific ABCA1 knockout mice have markedly reduced plasma HDL and a two-fold increase in triglyceride due to failure to assemble nascent HDL particles by hepatocytes, causing increased catabolism of HDL apolipoprotein A-I and increased hepatic production of triglyceride-enriched VLDL. In-vitro studies suggest that nascent HDL particles may induce signaling to decrease triglyceride secretion. Inhibition of microRNA 33 expression in nonhuman primates augments hepatic ABCA1, genes involved in fatty acid oxidation, and decreases expression of lipogenic genes, causing increased plasma HDL and decreased triglyceride levels.
Summary: New evidence suggests potential mechanisms by which hepatic ABCA1-mediated nascent HDL formation regulates VLDL–triglyceride production and contributes to the inverse relationship between plasma HDL and triglyceride.
Purpose of review: MicroRNAs (miRNAs) regulate gene expression by binding to target mRNAs and control a wide range of biological functions. Recent reports have identified specific miRNAs as major regulators of fatty acid and cholesterol homeostasis. This review examines the biological function of various miRNAs and the emerging evidence linking specific miRNAs to critical pathways in lipid metabolism.
Recent findings: Disruption of lipid balance can lead to metabolic disturbances and thus tight regulation is required to maintain lipid homeostasis. Recent studies have shown key roles for miR-33 and miR-122 in regulation of lipid metabolism, and further evidence implicates miR-370 in regulation of miR-122. In addition, miRNAs involved in adipogenesis (miR-378/378* and miR-27) as well as newly discovered miRNAs such as miR-613, miR-302a, and miR-168 have now been implicated in regulation of lipid metabolism.
Summary: Growing evidence support key roles for miRNAs in regulating both cholesterol and fatty acid metabolism, leading to considerable interest in miRNAs as potential drug targets to modulate lipid and lipoprotein metabolism. MiRNA-based therapeutics hold considerable promise in the fight to curtail the growing epidemic of obesity and type 2 diabetes and the associated risk of atherosclerosis.
Background:
Resveratrol (RSV), a naturally occurring polyphenolic stilbenoid, is known to possess potent anti-atherogenic properties; however, the effect of RSV on hypercholesterolemia is not fully understood. We hypothesized that RSV decreases blood cholesterol levels through the activation of cholesterol 7alpha-hydroxylase (CYP7A1)-mediated bile acid synthetic pathway pathways in vitro and in vivo.
Methods:
In this study, we evaluated body weight, serum lipid concentrations, hepatic lipid content and the size of the bile acid pool in high-fat diet (HFD)-fed C57BL/6J mice that were treated with RSV. In addition, we characterized the underlying mechanism of the effects of RSV in HepG2 hepatocytes by Western blot analysis.
Results:
RSV (200 mg/kg per day) reduced body weight and liver weight gains, improved serum lipid parameters, reduced hepatic cholesterol accumulation and increased the bile acid pool size in mice fed an HFD for 8 wks. RSV significantly increased liver expression of CYP7A1 mRNA and protein and CYP7A1 enzyme activity. Furthermore, RSV treatment upregulated CYP7A1 expression and induced liver X receptor alpha (LXRalpha) activation in a time- and dose-dependent manner in HepG2 cells. In addition, the specific liver X receptor alpha (LXRalpha) inhibitor geranylgeranyl pyrophosphate (GGPP) inhibited the RSV-induced expression of CYP7A1 in HepG2 hepatocytes.
Conclusion:
The beneficial effects of RSV on HFD-induced hypercholesterolemia are mediated through LXRalpha signaling pathways, suggesting a potential target for the prevention of dyslipidemia.
Background:
A higher prevalence of coronary heart disease (CHD) in people with diabetes. We investigated the high-density lipoprotein (HDL) subclass profiles and alterations of particle size in CHD patients with diabetes or without diabetes.
Methods:
Plasma HDL subclasses were quantified in CHD by 1-dimensional gel electrophoresis coupled with immunodetection.
Results:
Although the particle size of HDL tend to small, the mean levels of low density lipoprotein cholesterol(LDL-C) and total cholesterol (TC) have achieved normal or desirable for CHD patients with or without diabetes who administered statins therapy. Fasting plasma glucose (FPG), triglyceride (TG), TC, LDL-C concentrations, and HDL3 (HDL3b and 3a) contents along with Gensini Score were significantly higher; but those of HDL-C, HDL2b+prebeta2, and HDL2a were significantly lower in CHD patients with diabetes versus CHD patients without diabetes; The prebeta1-HDL contents did not differ significantly between these groups. Multivariate regression analysis revealed that Gensini Score was significantly and independently predicted by HDL2a, and HDL2b+prebeta2.
Conclusions:
The abnormality of HDL subpopulations distribution and particle size may contribute to CHD risk in diabetes patients. The HDL subclasses distribution may help in severity of coronary artery and risk stratification, especially in CHD patients with therapeutic LDL, TG and HDL levels.
Background:
Hyperlipidemia plays a crucial role in the development and progression of coronary artery disease (CAD). Recent studies have identified that microRNAs (miRNAs) are important regulators of lipid metabolism, but little is known about the circulating levels of lipometabolism-related miRNAs and their relationship with the presence of CAD in patients with hyperlipidemia.
Methods:
In the present study, we enrolled a total of 255 hyperlipidemia patients with or without CAD and 100 controls with normal blood lipids. The plasma levels of four known lipometabolism-related miRNAs, miR-122, miR-370, miR-33a, and miR-33b were quantified by real-time quantitative PCR. Blood levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol were determined. Furthermore, the severity of CAD was assessed with the Gensini score system based on the degree of luminal narrowing and its geographic importance.
Results:
Our results revealed for the first time that plasma levels of miR-122 and miR-370 were significantly increased in hyperlipidemia patients compared with controls, and the levels of miR-122 and miR-370 were positively correlated with TC, TG, and LDL-C levels in both hyperlipidemia patients and controls. Multiple logistic regression analysis demonstrated that the increased levels of miR-122 and miR-370 were associated with CAD presence, even after adjustment for other cardiovascular risk factors. Furthermore, miR-122 and miR-370 levels were positively correlated with the severity of CAD quantified by the Gensini score. However, both miR-33a and miR-33b were undetectable in plasma.
Conclusions:
Our results suggest that increased plasma levels of miR-122 and miR-370 might be associated with the presence as well as the severity of CAD in hyperlipidemia patients.
Background:
Paraoxonase-1 (PON1) is an enzyme with numerous functions and receives an increasing interest in clinical and epidemiological studies. Sometimes samples are stored for longer periods at a certain temperature. Therefore the stability of PON1 activity must be checked and retained upon storage for longer periods.
Results:
In this study the stability of PON1 activity has been tested in human serum samples during storage up to 12 months at 3 commonly used temperatures, -20degreesC, -70degreesC and 196degreesC. It was found that the stability of the PON1 activity is constant during 12 months of storage at 70degreesC and 196degreesC. Storage at 20degreesC resulted in a small but statistically significant decrease after 6 months to about 94% of its original value. Nonetheless, the rank order between the samples at T = 0 and 12 months remained the same. The same temperature dependence was found for the associated high-density lipoprotein.
Conclusions:
It can be concluded that 70degreesC is the right temperature for storage to maintain the PON1 activity for at least one year. Storage at a lower temperature in liquid nitrogen (196degreesC) is not necessary.
Background:
Bai Ku Yao is a special subgroup of the Yao minority in China. The present study was undertaken to detect the association of rs5888 single nucleotide polymorphism (SNP) in the scavenger receptor class B type 1 (SCARB1) gene and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.
Methods:
A total of 598 subjects of Bai Ku Yao and 585 subjects of Han Chinese were randomly selected from our stratified randomized cluster samples. Genotypes of the SCARB1 rs5888 SNP were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.
Results:
The levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI were lower but ApoB was higher in Bai Ku Yao than in Han (P < 0.05-0.001). The frequencies of C and T alleles were 78.3 % and 21.7 % in Bai Ku Yao, and 73.7 % and 26.3 % in Han (P < 0.01); respectively. The frequencies of CC, CT and TT genotypes were 60.0 %, 36.6 % and 3.4 % in Bai Ku Yao, and 54.2 %, 39.0 % and 6.8 % in Han (P < 0.01); respectively. The subjects with TT genotype in both ethnic groups had lower HDL-C and ApoAI levels than the subjects with CC or CT genotype (P < 0.05 for all). Subgroup analyses showed that the subjects with TT genotype in Bai Ku Yao had lower HDL-C and ApoAI levels in males than the subjects with CC or CT genotype (P < 0.05 for all), and the T allele carriers had higher TC, LDL-C and ApoB levels in females than the T allele noncarriers (P < 0.05 for all). The participants with TT genotype in Han also had a lower tendency of HDL-C and ApoAI levels in males than the participants with CC or CT genotype, but the difference did not reach statistically significant (P = 0.063 and P = 0.086; respectively). The association of serum HDL-C and ApoAI levels and genotypes was confirmed by the multiple linear regression analysis in both ethnic groups. Serum lipid parameters were also correlated with several environmental factors.
Conclusions:
The differences in serum lipid levels between the two ethnic groups might partially attribute to the differences in the SCARB1 rs5888 SNP and several environmental factors.
Background:
Serum beta-cryptoxanthin levels are lower in overweight subjects than in normal subjects. Abnormalities of adipocytokine profiles in obesity subjects have been reported. There are several reports that serum beta-cryptoxanthin levels in them were relatively lower than normal subjects.ObjectiveWe hypothesize that supplementation of highly concentrated beta-cryptoxanthin improves serum adipocytokine profiles in obese subjects. This study tested the association between beta-cryptoxanthin intake and serum adipocytokine levels.
Methods:
An intervention study consisted of a 3-week long before-and-after controlled trial, where beta-cryptoxanthin (4.7 mg/day) was given to 17 moderately obese postmenopausal women.
Results:
The results indicated no significant changes in body weight or body mass index (BMI). Serum beta-cryptoxanthin levels increased significantly by 4-fold. Serum high molecular weight (HMW)-adiponectin levels increased significantly, while serum plasminogen activator inhibitor (PAI)-1 levels decreased.
Conclusions:
We concluded that increasing the intake of beta-cryptoxanthin to approximately 4 mg per day for 3 weeks may have beneficial effects on the serum adipocytokine status and consequently alleviate progression of metabolic syndrome.
Background:
Oleamide (ODA) is a fatty acid primary amide first identified in the cerebrospinal fluid of sleep-deprived cats, which exerts effects on vascular and neuronal tissues, with a variety of molecular targets including cannabinoid receptors and gap junctions. It has recently been reported to exert a hypolipidemic effect in hamsters. Here, we have investigated the nuclear receptor family of peroxisome proliferator-activated receptors (PPARs) as potential targets for ODA action.
Results:
Activation of PPARalpha, PPARbeta and PPARgamma was assessed using recombinant expression in Chinese hamster ovary cells with a luciferase reporter gene assay. Direct binding of ODA to the ligand binding domain of each of the three PPARs was monitored in a cell-free fluorescent ligand competition assay. A well-established assay of PPARgamma activity, the differentiation of 3T3-L1 murine fibroblasts into adipocytes, was assessed using an Oil Red O uptake-based assay. ODA, at 10 and 50 muM, was able to transactivate PPARalpha, PPARbeta and PPARgamma receptors. ODA bound to the ligand binding domain of all three PPARs, although complete displacement of fluorescent ligand was only evident for PPARgamma, at which an IC50 value of 38 muM was estimated. In 3T3-L1 cells, ODA, at 10 and 20 muM, induced adipogenesis in an apparently concentration-dependent manner.
Conclusions:
We have, therefore, identified a novel site of action of ODA through PPAR nuclear receptors and shown how ODA should be considered as a weak PPARgamma ligand in vitro.
Background:
Oilseed samples from four Acacia species (A. cyclops, A. ligulata, A. salicina and A. cyanophylla) were analyzed in order to evaluate the potential nutritional value of their unexploited seeds.
Methods:
Samples were collected from different Tunisian geographic locations. Seed oils were extracted and carotenoids, tocopherols and sterols were analyzed using chromatographic methods.
Results:
The studied Acacia seeds seem to be quite rich in lipids (from 6% to 12%). All Acacia species contains mainly the xanthophylls zeaxanthin and lutein compounds: from ca. 38 mg.kg-1 of total lipids (A. cyclops) to ca 113 mg.kg-1 of total lipids (A. cyanophylla). Total tocopherols varied from ca. 221 mg.kg-1 of total lipids (A. cyclops) to ca. 808 mg.kg-1 of total lipids (A. ligulata). Sterols are highly present and their contents ranged between ca. 7 g. kg-1 of total lipids (A. salicina) and 11 g. kg-1 of total lipids (A. cyclops).
Conclusion:
This study highlights that these unexploited seeds might have a potential nutritional value and encourages researchers to more explore and find developments for these plants for healthy purposes.
Background:
Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease in industrialized countries. The present study was undertaken to explore the preventive effect of dietary sea cucumber cerebroside (SCC) extracted from Acaudina molpadioides in fatty liver rats.
Methods:
Male Wistar rats were randomly divided into four groups including normal control group, NAFLD model group, and two SCC-treated groups with SCC at 0.006% and 0.03% respectively. The fatty liver model was established by administration of 1% orotic acid (OA) to the rats. After 10d, serum and hepatic lipid levels were detected. And the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were also determined. Besides, to gain the potential mechanism, the changes of key enzymes and gene expressions related to the hepatic lipid metabolism were measured.
Results:
Dietary SCC at the level of 0.006% and 0.03% ameliorated the hepatic lipid accumulation in fatty liver rats. SCC administration elevated the serum triglyceride (TG) level and the ALT, AST activities in OA-fed rats. The activities of hepatic lipogenic enzymes including fatty acid synthase (FAS), malic enzyme (ME) and glucose-6-phosphatedehydrogenase (G6PDH) were inhibited by SCC treatment. And the gene expressions of FAS, ME, G6PDH and sterol-regulatory element binding protein (SREBP-1c) were also reduced in rats fed SCC. However, dietary SCC didn't affect the activity and mRNA expression of carnitine palmitoyltransferase (CPT) in liver. Besides, suppression of microsomal triglyceride transfer protein (MTP) activity was observed in SCC-feeding rats.
Conclusions:
These results suggested that dietary SCC could attenuate hepatic steatosis due to its inhibition of hepatic lipogenic gene expression and enzyme activity and the enhancement of TG secretion from liver.
Dyslipidemia is common in chronic hemodialysis patients and its underlying mechanism is complex. Hemodialysis causes an imbalance between antioxidants and production of reactive oxygen species, which induces the oxidative stress and thereby may lead to accelerated atherosclerosis. Statins have been found to be little effective in end-stage kidney disease and other lipid-lowering therapies have been only scarcely studied. The study aimed to assess the effect of low-dose fenofibrate therapy on plasma lipids and redox status in long-term hemodialysis patients with mild hypertriglyceridemia.Twenty seven chronic hemodialysis patients without any lipid-lowering therapy were included in a double-blind crossover, placebo-controlled study. The patients were randomized into two groups and were given a sequence of either 100 mg of fenofibrate per each hemodialysis day for 4 weeks or placebo with a week-long wash-out period between treatment periods. Plasma lipids, high sensitive C-reactive protein (CRP), urea, creatinine, electrolytes, phosphocreatine kinase (CK), GOT, GPT and plasma thiols (total and free glutathione, homocysteine, cysteine and cysteinylglycine) were measured at baseline and after each of the study periods. Plasma aminothiols were measured by reversed phase HPLC with thiol derivatization with 2-chloro-1-methylquinolinium tetrafluoroborate.Fenofibrate therapy caused a significant decrease of total serum cholesterol, LDL cholesterol and triglycerides and an increase of HDL cholesterol. The treatment was well tolerated with no side-effects but there was a small but significant increase of CK not exceeding the upper limit of normal range. There were no changes of serum CRP, potassium, urea, and creatinine and liver enzymes during the treatment. Neither total nor total free cysteinylglycine and cysteine changed during the study but both total and free glutathione increased during the therapy with fenofibrate and the same was observed in case of plasma homocysteine.The study shows that a treatment with reduced fenofibrate dose is safe and effective in reducing serum triglycerides and cholesterol in chronic dialysis patients and may shift plasma aminothiol balance towards a more antioxidative pattern.
