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Lipid Synthesis (lipid + synthesis)
Selected AbstractsS -Adenosylmethionine Attenuates Hepatic Lipid Synthesis in Micropigs Fed Ethanol With a Folate-Deficient DietALCOHOLISM, Issue 7 2007Farah Esfandiari Background: To demonstrate a causative role of abnormal methionine metabolism in the pathogenesis of alcoholic steatosis, we measured the effects on hepatic lipid synthesis of supplementing ethanol and folate-deficient diets with S -adenosylmethionine (SAM), a metabolite that regulates methionine metabolism. Methods: Yucatan micropigs were fed folate-deficient diets as control, with ethanol at 40% of kcal, and with ethanol supplemented with SAM at 0.4 g/1,000 kcal for 14 weeks. Histopathology, triglyceride levels and transcripts, and protein levels of the regulatory signals of hepatic lipid synthesis were measured in terminal omental adipose and liver samples. Results: Feeding ethanol at 40% of kcal with folate-deficient diets for 14 weeks increased and supplemental SAM maintained control levels of liver and plasma triglyceride. Serum adiponectin, liver transcripts of adiponectin receptor-1 (AdipoR1), and phosphorylated adenosine monophosphate kinase- , (p-AMPK,) were each reduced by ethanol feeding and were sustained at normal levels by SAM supplementation of the ethanol diets. Ethanol feeding activated and SAM supplementation maintained control levels of ER stress-induced transcription factor sterol regulatory element-binding protein-1c (SREBP-1c) and its targeted transcripts of lipid synthesizing enzymes acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and glycerol-3-phosphate acyltransferase (GPAT). Conclusions: Ethanol feeding with a folate-deficient diet stimulates hepatic lipid synthesis by down-regulating adiponectin-mediated pathways of p-AMPK to increase the expression of nSREBP-1c and its targeted lipogenic enzymes. Preventing abnormal hepatic methionine metabolism by supplementing ethanol diets with SAM reduces liver triglyceride levels by up-regulation of adiponectin-mediated pathways to decrease fatty acid and triglyceride synthesis. This study demonstrates that ethanol-induced hepatic lipid synthesis is mediated in part by abnormal methionine metabolism, and strengthens the concept that altered methionine metabolism plays an integral role in the pathogenesis of steatosis. [source] Insulino-mimetic and anti-diabetic effects of vanadium compoundsDIABETIC MEDICINE, Issue 1 2005A. K. Srivastava Abstract Compounds of the trace element vanadium exert various insulin-like effects in in vitro and in vivo systems. These include their ability to improve glucose homeostasis and insulin resistance in animal models of Type 1 and Type 2 diabetes mellitus. In addition to animal studies, several reports have documented improvements in liver and muscle insulin sensitivity in a limited number of patients with Type 2 diabetes. These effects are, however, not as dramatic as those observed in animal experiments, probably because lower doses of vanadium were used and the duration of therapy was short in human studies as compared with animal work. The ability of these compounds to stimulate glucose uptake, glycogen and lipid synthesis in muscle, adipose and hepatic tissues and to inhibit gluconeogenesis, and the activities of the gluconeogenic enzymes: phosphoenol pyruvate carboxykinase and glucose-6-phosphatase in the liver and kidney as well as lipolysis in fat cells contributes as potential mechanisms to their anti-diabetic insulin-like effects. At the cellular level, vanadium activates several key elements of the insulin signal transduction pathway, such as the tyrosine phosphorylation of insulin receptor substrate-1, and extracellular signal-regulated kinase 1 and 2, phosphatidylinositol 3-kinase and protein kinase B activation. These pathways are believed to mediate the metabolic actions of insulin. Because protein tyrosine phosphatases (PTPases) are considered to be negative regulators of the insulin-signalling pathway, it is suggested that vanadium can enhance insulin signalling and action by virtue of its capacity to inhibit PTPase activity and increase tyrosine phosphorylation of substrate proteins. There are some concerns about the potential toxicity of available inorganic vanadium salts at higher doses and during long-term therapy. Therefore, new organo-vanadium compounds with higher potency and less toxicity need to be evaluated for their efficacy as potential treatment of human diabetes. [source] Stearoyl-CoA desaturase: a new therapeutic target of liver steatosisDRUG DEVELOPMENT RESEARCH, Issue 8 2006Pawel Dobrzyn Abstract Stearoyl-CoA desaturase (SCD) is the rate limiting enzyme catalyzing the biosynthesis of monounsaturated fatty acids, mainly oleate and palmitoleoate, which are used as substrates for the synthesis of triglycerides, wax esters, cholesterol esters, and phospholipids. Recent studies have shown that SCD1, the main SCD isoform expressed in liver, is a key player in the regulation of lipid metabolism. SCD1 deficient mice have increased energy expenditure, reduced body adiposity, increased insulin sensitivity and are resistant to diet-induced obesity and liver steatosis. SCD1 was found to be specifically repressed during leptin-mediated weight loss and leptin-deficient ob/ob mice lacking SCD1 showed markedly reduced adiposity, despite higher food intake. In addition, SCD1 deficiency completely corrects the hypometabolic phenotype and hepatic steatosis of ob/ob mice, and attenuates fasting-induced liver steatosis in peroxisome proliferator-activated receptor-, , deficient mice. Consequently, increased SCD activity has been found in humans and animals which accumulate significant amounts of lipids in liver, whereas SCD1 deficiency ameliorates both high-fat diet induced and genetically induced hepatic steatosis. Much evidence indicates that the direct anti-steatotic effect of SCD1 deficiency stems from increased fatty acid oxidation and reduced lipid synthesis. In this review we discuss our current understanding of the role of SCD1 in regulation of hepatic lipid partitioning and test the hypothesis that pharmacological manipulation of SCD might be of benefit in the treatment of non-alcoholic fatty liver disease. Drug Dev. Res. 67:643,650, 2006. © 2006 Wiley-Liss, Inc. [source] Phospholipase stimulates lipogenesis in SZ95 sebocytesEXPERIMENTAL DERMATOLOGY, Issue 7 2008S. Schagen Introduction:, With progressing ageing human sebocytes reduce lipid production. However, the influence of certain aging mechanisms on sebaceous lipid synthesis as well as ways to influence the latter is not fully identified. Certain lipids act as ligands of nuclear receptors such as PPAR. Phospholipase (PLA2) catalyzes the hydrolysis of the sn-2 fatty acyl bond of phospholipids to yield free fatty acid and lysophospholipid. It has been hypothesized that PPAR may be activated by hydrolysis products of phospholipids and also by eicosanoids obtained through PLA2 activity. Materials and Methods:, A method to quantify sebaceous lipid synthesis of SZ95 sebocytes in vitro was established and the cells were treated by snake venom Bothrops moojeni gel filtration fractions (Botmo GF). Botmo GF fractions were further purified by RP-HPLC, and a fraction with PLA2 activity (Botmo GF11-117) and a fraction without enzymatic activity (Botmo GF11-101) were identified and additionally tested. Results:, Botmo GF fractions increased lipogenesis in SZ95 sebocytes without inducing apparent toxic or apoptotic effects. Botmo GF11-101 (1 ,g/ml) enhanced neutral lipid synthesis by up to 170% and polar lipid synthesis by up to 120%. The enzymatically active PLA2 Botmo GF11-117 (1 ,g/ml) increased synthesis of neutral lipids by up to 200%, and polar lipids by up to 120% compared to untreated SZ95 sebocytes. Conclusion:, PLA2 activation or suppression could be important for human sebaceous lipogenesis. PLA2 modifiers may be attractive for skin lipid research and pharmacological/cosmetic products. [source] Quantitative modeling of triacylglycerol homeostasis in yeast , metabolic requirement for lipolysis to promote membrane lipid synthesis and cellular growthFEBS JOURNAL, Issue 22 2008Jürgen Zanghellini Triacylglycerol metabolism in Saccharomyces cerevisiae was analyzed quantitatively using a systems biological approach. Cellular growth, glucose uptake and ethanol secretion were measured as a function of time and used as input for a dynamic flux-balance model. By combining dynamic mass balances for key metabolites with a detailed steady-state analysis, we trained a model network and simulated the time-dependent degradation of cellular triacylglycerol and its interaction with fatty acid and membrane lipid synthesis. This approach described precisely, both qualitatively and quantitatively, the time evolution of various key metabolites in a consistent and self-contained manner, and the predictions were found to be in excellent agreement with experimental data. We showed that, during pre-logarithmic growth, lipolysis of triacylglycerol allows for the rapid synthesis of membrane lipids, whereas de novo fatty acid synthesis plays only a minor role during this growth phase. Progress in triacylglycerol hydrolysis directly correlates with an increase in cell size, demonstrating the importance of lipolysis for supporting efficient growth initiation. [source] Leptin stimulates uncoupling protein-2 mRNA expression and Krebs cycle activity and inhibits lipid synthesis in isolated rat white adipocytesFEBS JOURNAL, Issue 19 2000Rolando B. Ceddia The treatment of rats and mice with leptin causes dramatic body fat reduction and in some cases even disappearance of fat tissue. Here, we report the effects of leptin (10 and 100 ng·mL,1) on isolated rat adipocytes maintained for 15 h in culture. Leptin decreased the incorporation of acetate into total lipids by 30%. A reduction in this incorporation (42%) was still observed after the leptin-cultivated adipocytes were exposed to a supra-physiological insulin concentration (10 000 µU·mL,1). On the other hand, leptin increased acetate degradation by 69% and the maximal activity of citrate synthase by 50% in isolated adipocytes. It also increased oleate degradation by 35 and 50% at concentrations of 10 and 100 ng·mL,1, respectively. Eventually, leptin upregulated the uncoupling protein-2 (UCP2) mRNA level by 63% and had no effect on uncoupling protein-3 (UCP3) mRNA in isolated adipocytes. The upregulation of UCP2 mRNA might have contributed to the stimulation of acetate and fatty acid degradation by leptin. The peripheral effects of leptin observed in this study are in line with the general energy dissipating role postulated for this hormone and for UCP2. They suggest mechanisms by which adipocytes regulate their fat content by an autocrine pathway without the participation of the central nervous system. [source] LPL polymorphism predicts stroke risk in menGENETIC EPIDEMIOLOGY, Issue 3 2002Alanna C. Morrison Abstract Variation in lipid levels has been associated with atherosclerotic vascular disease, including stroke. Genes contributing to interindividual variation in lipid levels may play a role in the etiology of stroke, either through their effects on lipid synthesis and metabolism or through separate pathways. For this reason, we sought to examine the association between polymorphisms in the lipoprotein lipase (LPL) and apolipoprotein E (APOE) genes and subclinical and clinical stroke in the Atherosclerosis Risk in Communities (ARIC) Study. Subclinical stroke was determined by cerebral magnetic resonance imaging (MRI). Subclinical cerebral infarct cases (n = 197) were compared to a stratified random sample identified from individuals participating in the MRI examination (n = 200). Incidence of clinical ischemic stroke was determined by following the ARIC cohort for an average of 7.5 years for potential cerebrovascular events; 218 validated clinical ischemic strokes were identified. A stratified random sample of the ARIC cohort (CRS, n = 964) was used as the comparison group for clinical cases. The LPL S291-carrying genotypes and APOE ,2- and ,4-carrying genotypes were not significantly associated with subclinical or clinical stroke. The LPL X447-containing genotypes were significantly associated with subclinical (odds ratio [OR], 4.32; 95% confidence interval [CI], 1.23,15.15; P = 0.020) and clinical stroke (hazard rate ratio [HRR], 2.57; 95% CI, 1.24,5.34; P = 0.01) in men, both by themselves and after adjustment for multiple stroke risk factors. The LPL S447X polymorphism is significantly associated with subclinical cerebral infarction and incident clinical ischemic stroke in men from a middle-aged American population. This association does not appear to be mediated by triglyceride, high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol levels, or additional stroke risk factors. Genet. Epidemiol. 22:233,242, 2002. © 2002 Wiley-Liss, Inc. [source] 6-O glucose linoleate supports in vitro human hair growth and lipid synthesisINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 2 2007P. Vingler Synopsis The hair follicle is a very active organ with a complex structure, which produces a hair fibre at a rate of 0.3 mm a day. Accordingly, the hair follicle is highly demanding in energy source, as the hair bulb matrix cells are endowed with one of the highest rates of proliferation in the human body. Moreover, recent data have shown the involvement of lipids in hair follicle function. As in vitro -grown hair follicle keeps producing a hair fibre that closely resembles the natural hair fibre, we decided to use this model to investigate the role of a new of glucose linoleate derivative (6-O-linoleyl- d -glucose: 6-O-GL) as a lipid precursor and energy provider. Our results demonstrated that 6-O-GL was (i) quite stable and surprisingly resistant to oxidative degradation, and (ii) readily taken up and metabolized by the hair follicle into various lipids, namely neutral lipids, ceramides and polar lipids. Moreover, it supported hair follicle growth and survival in a glucose- and linoleic-acid free medium. 6-O-GL thus appeared to be a bi-functional nutrient, ensuring both proper fibre quality and production by the hair follicle. Résumé Le follicule pileux est un organe très actif et d'une structure très complexe, qui produit la tige pilaire au rythme de 0.3 mm par jour. En conséquence, le follicule pileux est très demandeur en ressources énergétiques, les cellules de la matrice bulbaire ayant un des taux de prolifération les plus élevé de l'organisme. De plus des études récentes ont mis en évidence le rôle de lipides dans le fonctionnement du follicule pileux. Puisque le follicule pileux in vitro continue à produire une fibre de qualité identique à celle d'une fibre naturelle, nous avons décidé d'utiliser ce modèle pour étudier le rôle d'un nouveau linoléate de glucose (6-O-linoleyl- d -glucose: 6-O-GL) en tant que précurseur lipidique et source d'énergie. Nos résultats démontrent que le 6-O-GL est très stable et étonnamment résistant à l'auto oxydation, qu'il est capté et métabolisé par le follicule pileux en divers lipides, neutres, polaires et céramides. De plus, le 6-O-GL soutient la croissance et la survie du follicule dans un milieu dépourvu de glucose et d'acide linoléique. Le 6-O-GL apparaît donc comme un agent bi-fonctionnel, permettant au follicule pileux de maintenir in vitro la production de la tige pilaire. [source] Different apoptosis ratios and gene expressions in two human cell lines after sevoflurane anaesthesiaACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2009S. KVOLIK Background: The aim of this study was to determine the effect of a single exposure of carcinoma cells (Caco-2 and HEp-2) to an anaesthetic gas mixture containing sevoflurane 3%, applied for a period of either 1 or 2 h, on the induction of apoptosis, propapototic gene expression and sphingomyelinase activity. Methods: Apoptosis was determined by flow cytometry. p53, caspase 3 and CYP2E1 gene expression was determined using reverse transcriptase polymerase chain reaction. Activities of acid (aSMase) and neutral sphingomyelinases (nSMase) were measured using methyl- 14C sphingomyeline, and for de novo ceramide and lipid synthesis [3H] palmitic acid was used. All results were compared with controls and analysed by Mann,Whitney and Kruskal,Wallis tests. Results: In the treated Caco-2 cells, the apoptotic ratio increased 24 h after anaesthesia (16.9%; P=0.04). The expression of both p53 and caspase-3 genes increased in Caco-2 and decreased in HEp-2 cells. The CYP2E1 gene expression was observed only in the Caco-2 cells. In control cells, the catalytic activity of aSMase was 2.3 times higher than that of nSMase activity. Decreased aSMase and nSMase activities were observed in Caco-2 cells 24 h after exposition. aSMase activity was halved (54.2%; P=0.06) in HEp-2 cells 24 h after anaesthesia. De novo ceramide synthesis correlated with SMase activity in Caco-2 cells. Conclusion: Sevoflurane anaesthesia induces late apoptosis in the colonic and laryngeal cancer cells investigated. Although the results obtained may indicate that an anaesthetic gas mixture containing sevoflurane induces p53-dependent apoptosis in the Caco-2 cells, the mechanism of apoptosis induction is unclear and remains to be elucidated. [source] Quantitative Lipid Metabolomic Changes in Alcoholic Micropigs With Fatty Liver DiseaseALCOHOLISM, Issue 4 2009Angela M. Zivkovic Background:, Chronic ethanol consumption coupled with folate deficiency leads to rapid liver fat accumulation and progression to alcoholic steatohepatitis (ASH). However, the specific effects of alcohol on key liver lipid metabolic pathways involved in fat accumulation are unknown. It is unclear whether lipid synthesis, lipid export, or a combination of both is contributing to hepatic steatosis in ASH. Methods:, In this study we estimated the flux of fatty acids (FA) through the stearoyl-CoA desaturase (SCD), phosphatidylethanolamine- N -methyltransferase (PEMT), and FA elongation pathways in relation to liver triacylglycerol (TG) content in Yucatan micropigs fed a 40% ethanol folate-deficient diet with or without supplementation with S -adenosyl methionine (SAM) compared with controls. Flux through the SCD and PEMT pathways was used to assess the contribution of lipid synthesis and lipid export respectively on the accumulation of fat in the liver. Liver FA composition within TG, cholesterol ester (CE), phosphatidylethanolamine, and phosphatidylcholine classes was quantified by gas chromatography. Results:, Alcoholic pigs had increased liver TG content relative to controls, accompanied by increased flux through the SCD pathway as indicated by increases in the ratios of 16:1n7 to 16:0 and 18:1n9 to 18:0. Conversely, flux through the elongation and PEMT pathways was suppressed by alcohol, as indicated by multiple metabolite ratios. SAM supplementation attenuated the TG accumulation associated with alcohol. Conclusions:, These data provide an in vivo examination of liver lipid metabolic pathways confirming that both increased de novo lipogenesis (e.g., lipid synthesis) and altered phospholipid metabolism (e.g., lipid export) contribute to the excessive accumulation of lipids in liver affected by ASH. [source] S -Adenosylmethionine Attenuates Hepatic Lipid Synthesis in Micropigs Fed Ethanol With a Folate-Deficient DietALCOHOLISM, Issue 7 2007Farah Esfandiari Background: To demonstrate a causative role of abnormal methionine metabolism in the pathogenesis of alcoholic steatosis, we measured the effects on hepatic lipid synthesis of supplementing ethanol and folate-deficient diets with S -adenosylmethionine (SAM), a metabolite that regulates methionine metabolism. Methods: Yucatan micropigs were fed folate-deficient diets as control, with ethanol at 40% of kcal, and with ethanol supplemented with SAM at 0.4 g/1,000 kcal for 14 weeks. Histopathology, triglyceride levels and transcripts, and protein levels of the regulatory signals of hepatic lipid synthesis were measured in terminal omental adipose and liver samples. Results: Feeding ethanol at 40% of kcal with folate-deficient diets for 14 weeks increased and supplemental SAM maintained control levels of liver and plasma triglyceride. Serum adiponectin, liver transcripts of adiponectin receptor-1 (AdipoR1), and phosphorylated adenosine monophosphate kinase- , (p-AMPK,) were each reduced by ethanol feeding and were sustained at normal levels by SAM supplementation of the ethanol diets. Ethanol feeding activated and SAM supplementation maintained control levels of ER stress-induced transcription factor sterol regulatory element-binding protein-1c (SREBP-1c) and its targeted transcripts of lipid synthesizing enzymes acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and glycerol-3-phosphate acyltransferase (GPAT). Conclusions: Ethanol feeding with a folate-deficient diet stimulates hepatic lipid synthesis by down-regulating adiponectin-mediated pathways of p-AMPK to increase the expression of nSREBP-1c and its targeted lipogenic enzymes. Preventing abnormal hepatic methionine metabolism by supplementing ethanol diets with SAM reduces liver triglyceride levels by up-regulation of adiponectin-mediated pathways to decrease fatty acid and triglyceride synthesis. This study demonstrates that ethanol-induced hepatic lipid synthesis is mediated in part by abnormal methionine metabolism, and strengthens the concept that altered methionine metabolism plays an integral role in the pathogenesis of steatosis. [source] Mechanisms of action of isoniazidMOLECULAR MICROBIOLOGY, Issue 5 2006Graham S. Timmins Summary For decades after its introduction, the mechanisms of action of the front-line antituberculosis therapeutic agent isoniazid (INH) remained unclear. Recent developments have shown that peroxidative activation of isoniazid by the mycobacterial enzyme KatG generates reactive species that form adducts with NAD+ and NADP+ that are potent inhibitors of lipid and nucleic acid biosynthetic enzymes. A direct role for some isoniazid-derived reactive species, such as nitric oxide, in inhibiting mycobacterial metabolic enzymes has also been shown. The concerted effects of these activities , inhibition of cell wall lipid synthesis, depletion of nucleic acid pools and metabolic depression , drive the exquisite potency and selectivity of this agent. To understand INH action and resistance fully, a synthesis of knowledge is required from multiple separate lines of research , including molecular genetic approaches, in vitro biochemical studies and free radical chemistry , which is the intent of this review. [source] Lipid trafficking to the outer membrane of Gram-negative bacteriaMOLECULAR MICROBIOLOGY, Issue 3 2006William T. Doerrler Summary The envelope of Gram-negative bacteria is composed of two distinct lipid membranes: an inner membrane and outer membrane. The outer membrane is an asymmetric bilayer with an inner leaflet of phospholipids and an outer leaflet of lipopolysaccharide. Most of the steps of lipid synthesis occur within the cytoplasmic compartment of the cell. Lipids must then be transported across the inner membrane and delivered to the outer membrane. These topological features combined with the ability to apply the tools of biochemistry and genetics make the Gram-negative envelope a fascinating model for the study of lipid trafficking. In addition, as lipopolysaccharide is essential for growth of most strains and is a potent inducer of the mammalian innate immune response via activation of Toll-like receptors, Gram-negative lipid transport is also a promising target for the development of novel antibacterial and anti-inflammatory compounds. This review focuses on recent developments in our understanding of lipid transport across the inner membrane and to the outer membrane of Gram-negative bacteria. [source] Impact of maternal circulating cholesterol and gestational diabetes mellitus on lipid metabolism in human term placentaMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 6 2008Charles Marseille-Tremblay Abstract Maternal hypercholesterolemia (HC) during pregnancy and gestational diabetes mellitus (GDM) are associated with disturbance of fetal development which may also modify key features of placental functions. In this study, we evaluated the impact of maternal hypercholesterolemia on placental cholesterol and lipid metabolism in 59 women classified in two groups according to the median concentration of plasma total cholesterol (6.42 mM). The impact of GDM was also evaluated on the metabolism of placentas obtained from 7 insulin-treated GDM and 7 non-GDM women. We showed that high maternal circulating cholesterol is associated with a significant increase in the LDL-cholesterol, ApoB-100 and triglyceride concentrations in the maternal blood. However the level of cholesterol in the venous cord blood and placenta remains unchanged in response to modification in maternal cholesterol profile. The levels of Fatty acid synthase (FAS) and SREBP-2 expressions in placenta are significantly increased in the HC group while expression of both sterol regulatory element-binding proteins-1 (SREBP-1) and HMG-CoA reductase (HMGR) are not modified. GDM is not associated with modification in the maternal lipid profile but it increases the concentration of inflammatory cytokines (IL-1, and TNF-,) in placenta which correlates with a dramatic induction of FAS expression without affecting the expression of mature SREBPs proteins. In conclusion, our study suggests that in placenta, expressions of key proteins involved in de novo lipid synthesis are affected by changes in maternal metabolism (HC and GDM) that may subsequently affect fetal development. Mol. Reprod. Dev. 75: 1054,1062, 2007. © 2007 Wiley-Liss, Inc. [source] Stearoyl-CoA desaturase as a new drug target for obesity treatmentOBESITY REVIEWS, Issue 2 2005A. Dobrzyn Summary Stearoyl-CoA desaturase (SCD), the rate-limiting enzyme in monounsaturated fatty acid synthesis, has recently been shown to be the critical control point regulating hepatic lipogenesis and lipid oxidation. As several manifestations of the metabolic syndrome and type 2 diabetes mellitus are associated with alterations in intracellular lipid partitioning, we propose that SCD1 may be a potential therapeutic target in the treatment of obesity and the metabolic syndrome. In support of this notion, we have shown that SCD1-deficient mice have increased energy expenditure, reduced body adiposity, increased insulin sensitivity and are resistant to diet-induced obesity and liver steatosis. Furthermore, SCD1 was found to be specifically repressed during leptin-mediated weight loss, and leptin-deficient ob/ob mice lacking SCD1 showed marked correction of the hypometabolic phenotype and hepatic steatosis. Much evidence indicates that the direct anti-steatotic effect of SCD1 deficiency stems from increased fatty acid oxidation and decreased lipid synthesis. All of these findings reveal that pharmacological manipulation of SCD activity might be of benefit in the treatment of obesity, diabetes, liver steatosis and other diseases of the metabolic syndrome. [source] The Benefits of Sunflower Oleodistillate (SOD) in Pediatric DermatologyPEDIATRIC DERMATOLOGY, Issue 6 2009Lawrence F. Eichenfield M.D. In its natural state, the oil contains high levels of essential fatty acids, particularly linoleic acid, which has skin barrier-enhancing properties. A sunflower oleodistillate (SOD), which is produced through a molecular distillation process without the use of solvents, has been shown to increase the epidermal key lipid synthesis and to reduce inflammation in vitro and in animal models. It has also been shown to activate peroxisome proliferative-activated receptor-, (PPAR-,) in vitro. As PPAR-, agonists have been shown to stimulate keratinocyte differentiation, improve barrier function, and enhance lipid metabolism in the skin, it has been suggested that SOD might also be efficacious in atopic dermatitis (AD). An initial clinical evaluation of the care effect of a 2% SOD emulsion in 20 adult volunteers with atopic skin revealed the moisturizing properties of SOD. Finally, a strong steroid-sparing effect and a positive effect on quality-of-life parameters were clearly demonstrated for the 2% SOD cream in studies in infants and babies with AD. [source] Quantitative proteome analysis of HCC cell lines with different metastatic potentials by SILACPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 23-24 2008Ning Chen Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and metastasis is the main cause for treatment failure and high fatality of HCC. In order to make further exploration into the mechanism of HCC metastasis and to search for the candidates of diagnostic marker and therapeutic target, stable-isotope labeling by amino acids in cell culture (SILAC) technique was employed to conduct differential proteome analysis on HCC cell lines , MHCC97L and HCCLM6 with low and high metastatic potentials. In total, 2335 reliable proteins were identified using LTQ-FT mass spectrum, among which 91 proteins were upregulated and 61 proteins were downregulated in HCCLM6. Most of the upregulated proteins were involved in adherence, morphogenesis, and lipid synthesis, while lots of the downregulated proteins were involved in electron transport, which might be crucial for HCC metastasis. Six dysregulated proteins were validated by Western blotting in the cell lines. Interestingly, the upregulation of solute carrier family 12 member 2 (SLC 12A2) and protein disulfide-isomerase A4 (PDIA4) were further confirmed in the culture supernatants by Western blotting and in the sera of HCC patients with different metastatic potentials by ELISA. Our study provided not only the valuable insights into the HCC metastasis mechanisms but also the potential candidate biomarkers for prediction of HCC metastasis. [source] Real-time detection of single-living pancreatic ,-cell by laser tweezers Raman spectroscopy: High glucose stimulationBIOPOLYMERS, Issue 7 2010Xi Rong Abstract Glucose acts as a ,-cell stimulus factor and leads to cellular responses that involve a large amount of biomolecule formation, relocation, and transformation. We hypothesize that information about these changes can be obtained in real-time by laser tweezers Raman spectroscopy. To test this hypothesis, repeated measurements designs in accordance with the application of Raman spectroscopy detection were used in the current experiment. Single rat ,-cells were measured by Raman spectroscopy in 2.8 mmol/l glucose culture medium as a basal condition. After stimulation with high glucose (20 mmol/l), the same cells were measured continuously. Each cell was monitored over a total time span of 25 min, in 5 min intervals. During this period of time, cells were maintained at an appropriate temperature controlled by an automatic heater, to provide near-physiological conditions. It was found that some significant spectral changes induced by glucose were taking place during the stimulation time course. The most noticeable changes were the increase of spectral intensity at the 1002, 1085, 1445, and 1655 cm,1 peaks, mainly corresponding to protein and lipid. We speculate that these changes might have to do with ,-cell protein and lipid synthesis. Using laser tweezers Raman spectroscopy in combination with glucose stimulation, optical spectral information from rat ,-cells was received and analyzed. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 587,594, 2010. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] Inhibition of starch synthesis results in overproduction of lipids in Chlamydomonas reinhardtiiBIOTECHNOLOGY & BIOENGINEERING, Issue 2 2010Yantao Li Abstract Starch and neutral lipids are two major carbon storage compounds in many microalgae and plants. Lipids are more energy rich and have often been used as food and fuel feedstocks. Genetic engineering of the lipid biosynthesis pathway to overproduce lipid has achieved only limited success. We hypothesize that through blocking the competing pathway to produce starch, overproduction of neutral lipid may be achieved. This hypothesis was tested using the green microalga Chlamydomonas reinhardtii and its low starch and starchless mutants. We discovered that a dramatic increase in neutral lipid content and the neutral lipid/total lipid ratio occurred among the mutants under high light and nitrogen starvation. BAFJ5, one of the mutants defective in the small subunit of ADP-glucose pyrophosphorylase, accumulated neutral and total lipid of up to 32.6% and 46.4% of dry weight (DW) or 8- and 3.5-fold higher, respectively, than the wild-type. These results confirmed the feasibility of increasing lipid production through redirecting photosynthetically assimilated carbon away from starch synthesis to neutral lipid synthesis. However, some growth impairment was observed in the low starch and starchless mutants, possibly due to altered energy partitioning in PSII, with more excitation energy dissipated as heat and less to photochemical conversion. This study demonstrated that biomass and lipid production by the selected mutants can be improved by physiological manipulation. Biotechnol. Bioeng. 2010;107: 258,268. © 2010 Wiley Periodicals, Inc. [source] Microalgae for oil: Strain selection, induction of lipid synthesis and outdoor mass cultivation in a low-cost photobioreactorBIOTECHNOLOGY & BIOENGINEERING, Issue 1 2009Liliana Rodolfi Abstract Thirty microalgal strains were screened in the laboratory for their biomass productivity and lipid content. Four strains (two marine and two freshwater), selected because robust, highly productive and with a relatively high lipid content, were cultivated under nitrogen deprivation in 0.6-L bubbled tubes. Only the two marine microalgae accumulated lipid under such conditions. One of them, the eustigmatophyte Nannochloropsis sp. F&M-M24, which attained 60% lipid content after nitrogen starvation, was grown in a 20-L Flat Alveolar Panel photobioreactor to study the influence of irradiance and nutrient (nitrogen or phosphorus) deprivation on fatty acid accumulation. Fatty acid content increased with high irradiances (up to 32.5% of dry biomass) and following both nitrogen and phosphorus deprivation (up to about 50%). To evaluate its lipid production potential under natural sunlight, the strain was grown outdoors in 110-L Green Wall Panel photobioreactors under nutrient sufficient and deficient conditions. Lipid productivity increased from 117 mg/L/day in nutrient sufficient media (with an average biomass productivity of 0.36 g/L/day and 32% lipid content) to 204 mg/L/day (with an average biomass productivity of 0.30 g/L/day and more than 60% final lipid content) in nitrogen deprived media. In a two-phase cultivation process (a nutrient sufficient phase to produce the inoculum followed by a nitrogen deprived phase to boost lipid synthesis) the oil production potential could be projected to be more than 90 kg per hectare per day. This is the first report of an increase of both lipid content and areal lipid productivity attained through nutrient deprivation in an outdoor algal culture. The experiments showed that this marine eustigmatophyte has the potential for an annual production of 20 tons of lipid per hectare in the Mediterranean climate and of more than 30 tons of lipid per hectare in sunny tropical areas. Biotechnol. Bioeng. 2009;102: 100,112. © 2008 Wiley Periodicals, Inc. [source] Insulin resistance at the crossroads of metabolic syndrome: Systemic analysis using microarraysBIOTECHNOLOGY JOURNAL, Issue 9 2010Dr. Eunjung Kim Abstract Recently, it has been suggested that insulin resistance is a better predictor of metabolic syndrome than obesity. Numerous studies have been conducted to identify insulin resistance susceptibility genes in various model systems. This review focuses on recent findings in microarray analyses, which have indicated that (i) in the liver, genes involved in lipid synthesis and gluconeogenesis are increased in an animal model of insulin resistance that leads into liver steatosis and hyperglycemia; (ii) in adipose tissues, genes involved in fatty acid synthesis and adipogenesis are down-regulated both in insulin-resistant humans and in animals; and (iii) in muscle, overall gene expression, including genes involved in fatty acid oxidation and biosynthesis, is either decreased or unresponsive compared to that of insulin-sensitive control human subjects or animals. Considering the multifaceted effects of insulin resistance in various tissues, aiming at multi-targets rather than a single target will be a more promising strategy for the prevention or treatment of insulin resistance. [source] Host cell lipids control cholesteryl ester synthesis and storage in intracellular ToxoplasmaCELLULAR MICROBIOLOGY, Issue 6 2005Yoshifumi Nishikawa Summary The intracellular protozoan Toxoplasma gondii lacks a de novo mechanism for cholesterol synthesis and therefore must scavenge this essential lipid from the host environment. In this study, we demonstrated that T. gondii diverts cholesterol from low-density lipoproteins for cholesteryl ester synthesis and storage in lipid bodies. We identified and characterized two isoforms of acyl-CoA:cholesterol acyltransferase (ACAT)-related enzymes, designated TgACAT1, and TgACAT1, in T. gondii. Both proteins are coexpressed in the parasite, localized to the endoplasmic reticulum and participate in cholesteryl ester synthesis. In contrast to mammalian ACAT, TgACAT1, and TgACAT1, preferentially incorporate palmitate into cholesteryl esters and present a broad sterol substrate affinity. Mammalian ACAT-deficient cells transfected with either TgACAT1, or TgACAT1, are restored in their capability of cholesterol esterification. TgACAT1, produces steryl esters and forms lipid bodies after transformation in a Saccharomyces cerevisiae mutant strain lacking neutral lipids. In addition to their role as ACAT substrates, host fatty acids and low-density lipoproteins directly serve as Toxoplasma ACAT activators by stimulating cholesteryl ester synthesis and lipid droplet biogenesis. Free fatty acids significantly increase TgACAT1, mRNA levels. Selected cholesterol esterification inhibitors impair parasite growth by rapid disruption of plasma membrane. Altogether, these studies indicate that host lipids govern neutral lipid synthesis in Toxoplasma and that interference with mechanisms of host lipid storage is detrimental to parasite survival in mammalian cells. [source] 2435: Control of the Meibomian gland in health and diseaseACTA OPHTHALMOLOGICA, Issue 2010DA SULLIVAN Purpose The meibomian gland is extremely important in maintaining the health and integrity of the ocular surface. This gland, through its lipid synthesis and secretion, promotes the stability and prevents the evaporation of the tear film. Conversely, meibomian gland dysfunction (MGD) leads to a decreased stability and increased evaporation of the tear film. Indeed, meibomian gland dysfunction is thought to be the major cause of dry eye syndromes throughout the world. Our goal is to advance understanding of the regulation of meibomian gland function and the mechanisms underlying MGD. Methods Procedures included the immortalization of human meibomian gland epithelial cells with human telomerase reverse transcriptase, the evaluation of cellular responsiveness, and the identification of glandular gene expression changes in MGD. Gene analyses were conducted with Illumina HumanHT-12 v3 Expression BeadChips and Geospiza bioinformatics software. Results To date we have [a] immortalized human meibomian gland epithelial cells that respond to secretagogue, growth factor, neurotransmitter and hormone exposure with alterations in proliferation, differentiation, signaling, gene expression and/or lipogenesis; [b] discovered human meibomian gland genes that may facilitate the development and/or progression of MGD. These genes encode proteins that promote keratinization and amplify inflammation. Conclusion Our findings advance our understanding of the control of the meibomian gland in both health and disease. [Acknowledgments: S.M. Richards, M. Hatton, A.M. Fay and K. Lo; Supported by grants from NIH (R01EY05612) and Alcon] Commercial interest [source] 4133: Dry eye and human tear lipid compositional, conformational and functional relationships using spectroscopyACTA OPHTHALMOLOGICA, Issue 2010D BORCHMAN Purpose Knowledge of the relationships among composition, conformation and function of tear film lipids could facilitate the development of therapies to alleviate symptoms related to meibomian gland dysfunction (MGD) and to diagnose the disease. Toward this goal, we used spectroscopic approaches to assess tear lipid composition and conformation relationships with age, sex and meibomian gland dysfunction. Methods Spectra of meibum from 41 patients diagnosed with MGD (Md) and 27 normal donors (Mn) were acquired. Results 1H-NMR spectra showed cholesterol esters were found to decrease by 21% with MGD. The number of double bonds/ester increased with age and MGD which indirectly relates to tear film stability. With age, the amount of CH2 groups increased twice as much as the C=C moieties and the C=C/CH2 and CH3/CH2 ratios were related to lipid order and indirectly related to meibum delivery. With the use of MALDI-TOF MS, we quantified and identified lipid components in Mn and Md such as cholesterol, hydrocarbons and wax esters with a sensitivity of 9 pmoles for each analyte. Sixty-nine of the 189 resolved peaks were unique to Md spectra compared to Mn spectra and were not due to waxes. Extra peaks in Md spectra may arise from increased lipid synthesis, bacteria or cellular debris. Conclusion It is reasonable that as the lipids become more ordered and more viscous with Md, less lipid flows out of the meibomian gland orifice and more casual lipid is present on the lid margin. The age- and disease-related changes in the physical and chemical characteristics of meibum lipids suggest that the C=C/CH2 and CH3/CH2 ratios may be more important than quantity in relation to tear film stability. [source] Sodium lauryl sulphate alters the mRNA expression of lipid-metabolizing enzymes and PPAR signalling in normal human skin in vivoEXPERIMENTAL DERMATOLOGY, Issue 12 2009Hans Törmä Abstract:, Detergents irritate skin and affect skin barrier homeostasis. In this study, healthy skin was exposed to 1% sodium lauryl sulphate (SLS) in water for 24 h. Biopsies were taken 6 h to 8 days post exposure. Lipid patterns were stained in situ and real-time polymerase chain reaction (PCR) was used to examine mRNA expression of enzymes synthesizing barrier lipids, peroxisome proliferator-activated receptors (PPAR) and lipoxygenases. The lipid pattern was disorganized from 6 h to 3 days after SLS exposure. Concomitant changes in mRNA expression included: (i) reduction, followed by induction, of ceramide-generating ,-glucocerebrosidase, (ii) increase on day 1 of two other enzymes for ceramide biosynthesis and (iii) persistent reduction of acetyl-CoA carboxylase-B, a key enzyme in fatty acid synthesis. Surprisingly, the rate-limiting enzyme in cholesterol synthesis, HMG-CoA reductase, was unaltered. Among putative regulators of barrier lipids synthesis, PPAR, and PPAR, exhibited reduced mRNA expression, while PPAR,/, and LXR, were unaltered. Epidermal lipoxygenase-3, which may generate PPAR, agonists, exhibited reduced expression. In conclusion, SLS induces reorganization of lipids in the stratum corneum, which play a role in detergents' destruction of the barrier. The changes in mRNA expression of enzymes involved in synthesizing barrier lipids are probably important for the restoration of the barrier. [source] | ||||||||||||||||