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  1. Absorption Of Dietary Lipid Components

    OpenAIRE

    Abdulkadir Hurşit

    2015-01-01

    Although the digestion and absorption of lipids that are necessary for the survival of living organisms are well known in general terms, nevertheless how different lipids to be digested, how it is distributed into the bloodstream, and how to be used by the cells, are unknown issues by most non specialist people. In recent years, knowledge of lipid digestion and absorption has expanded considerably. More insight has been gained in the mechanism of action of H + pump as a transport system in fa...

  2. Global deletion of MGL in mice delays lipid absorption and alters energy homeostasis and diet-induced obesity

    Science.gov (United States)

    Douglass, John D.; Zhou, Yin Xiu; Wu, Amy; Zadrogra, John A.; Gajda, Angela M.; Lackey, Atreju I.; Lang, Wensheng; Chevalier, Kristen M.; Sutton, Steven W.; Zhang, Sui-Po; Flores, Christopher M.; Connelly, Margery A.; Storch, Judith

    2015-01-01

    Monoacylglycerol lipase (MGL) is a ubiquitously expressed enzyme that catalyzes the hydrolysis of monoacylglycerols (MGs) to yield FFAs and glycerol. MGL contributes to energy homeostasis through the mobilization of fat stores and also via the degradation of the endocannabinoid 2-arachidonoyl glycerol. To further examine the role of MG metabolism in energy homeostasis, MGL−/− mice were fed either a 10% (kilocalories) low-fat diet (LFD) or a 45% (kilocalories) high-fat diet (HFD) for 12 weeks. Profound increases of MG species in the MGL−/− mice compared with WT control mice were found. Weight gain over the 12 weeks was blunted in both diet groups. MGL−/− mice were leaner than WT mice at both baseline and after 12 weeks of LFD feeding. Circulating lipids were decreased in HFD-fed MGL−/− mice, as were the levels of several plasma peptides involved in glucose homeostasis and energy balance. Interestingly, MGL−/− mice had markedly reduced intestinal TG secretion following an oral fat challenge, suggesting delayed lipid absorption. Overall, the results indicate that global MGL deletion leads to systemic changes that produce a leaner phenotype and an improved serum metabolic profile. PMID:25842377

  3. Alterations of lipid metabolism in Wilson disease

    OpenAIRE

    Stremmel Wolfgang; Eckert Nicola; Pfeiffenberger Jan; Gotthardt Daniel; Gohdes Annina; Seessle Jessica; Reuner Ulrike; Weiss Karl

    2011-01-01

    Abstract Introduction Wilson disease (WD) is an inherited disorder of human copper metabolism, characterised by accumulation of copper predominantly in the liver and brain, leading to severe hepatic and neurological disease. Interesting findings in animal models of WD (Atp7b-/- and LEC rats) showed altered lipid metabolism with a decrease in the amount of triglycerides and cholesterol in the serum. However, serum lipid profile has not been investigated in large human WD patient cohorts to dat...

  4. Intestinal Cgi-58 deficiency reduces postprandial lipid absorption.

    Directory of Open Access Journals (Sweden)

    Ping Xie

    Full Text Available Comparative Gene Identification-58 (CGI-58, a lipid droplet (LD-associated protein, promotes intracellular triglyceride (TG hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty meal does induce temporary cytosolic accumulation of LDs. Accumulated LDs are eventually cleared out, implying existence of TG hydrolytic machinery in enterocytes. However, identities of proteins responsible for LD-TG hydrolysis remain unknown. Here we report that intestine-specific inactivation of CGI-58 in mice significantly reduces postprandial plasma TG concentrations and intestinal TG hydrolase activity, which is associated with a 4-fold increase in intestinal TG content and large cytosolic LD accumulation in absorptive enterocytes during the fasting state. Intestine-specific CGI-58 knockout mice also display mild yet significant decreases in intestinal fatty acid absorption and oxidation. Surprisingly, inactivation of CGI-58 in intestine significantly raises plasma and intestinal cholesterol, and reduces hepatic cholesterol, without altering intestinal cholesterol absorption and fecal neutral sterol excretion. In conclusion, intestinal CGI-58 is required for efficient postprandial lipoprotein-TG secretion and for maintaining hepatic and plasma lipid homeostasis. Our animal model will serve as a valuable tool to further define how intestinal fat metabolism influences the pathogenesis of metabolic disorders, such as obesity and type 2 diabetes.

  5. Dietary Lipid and Carbohydrate Interactions: Implications on Lipid and Glucose Absorption, Transport in Gilthead Sea Bream (Sparus aurata) Juveniles.

    Science.gov (United States)

    Castro, Carolina; Corraze, Geneviève; Basto, Ana; Larroquet, Laurence; Panserat, Stéphane; Oliva-Teles, Aires

    2016-06-01

    A digestibility trial was performed with gilthead sea bream juveniles (IBW = 72 g) fed four diets differing in lipid source (fish oil, FO; or a blend of vegetable oil, VO) and starch content (0 %, CH-; or 20 %, CH+) to evaluate the potential interactive effects between carbohydrates and VO on the processes involved in digestion, absorption and transport of lipids and glucose. In fish fed VO diets a decrease in lipid digestibility and in cholesterol (C), High Density Lipoprotein(HDL)-C and Low Density Lipoprotein (LDL)-C (only in CH+ group) were recorded. Contrarily, dietary starch induced postprandial hyperglycemia and time related alterations on serum triacylglycerol (TAG), phospholipid (PL) and C concentrations. Fish fed a CH+ diet presented lower serum TAG than CH- group at 6 h post-feeding, and the reverse was observed at 12 h post-feeding for TAG and PL. Lower serum C and PL at 6 h post-feeding were recorded only in VOCH+ group. No differences between groups were observed in hepatic and intestinal transcript levels of proteins involved in lipid transport and hydrolysis (FABP, DGAT, GPAT, MTP, LPL, LCAT). Lower transcript levels of proteins related to lipid transport (ApoB, ApoA1, FABP2) were observed in the intestine of fish fed the CH+ diet, but remained unchanged in the liver. Overall, transcriptional mechanisms involved in lipid transport and absorption were not linked to changes in lipid serum and digestibility. Dietary starch affected lipid absorption and transport, probably due to a delay in lipid absorption. This study suggests that a combination of dietary VO and starch may negatively affect cholesterol absorption and transport. PMID:27023202

  6. Identification of novel inhibitors of dietary lipid absorption using zebrafish.

    Directory of Open Access Journals (Sweden)

    Justin D Clifton

    Full Text Available Pharmacological inhibition of dietary lipid absorption induces favorable changes in serum lipoprotein levels in patients that are at risk for cardiovascular disease and is considered an adjuvant or alternative treatment with HMG-CoA reductase inhibitors (statins. Here we demonstrate the feasibility of identifying novel inhibitors of intestinal lipid absorption using the zebrafish system. A pilot screen of an unbiased chemical library identified novel compounds that inhibited processing of fluorescent lipid analogues in live zebrafish larvae. Secondary assays identified those compounds suitable for testing in mammals and provided insight into mechanism of action, which for several compounds could be distinguished from ezetimibe, a drug used to inhibit cholesterol absorption in humans that broadly inhibited lipid absorption in zebrafish larvae. These findings support the utility of zebrafish screening assays to identify novel compounds that target complex physiological processes.

  7. Lipid Raft Alterations in Aged-Associated Neuropathologies.

    Science.gov (United States)

    Marin, Raquel; Fabelo, Noemí; Fernández-Echevarría, Cecilia; Canerina-Amaro, Ana; Rodríguez-Barreto, Deiene; Quinto-Alemany, David; Mesa-Herrera, Fátima; Díaz, Mario

    2016-01-01

    Lipid rafts are membrane microdomains particularly enriched in cholesterol, sphingolipids and saturated fatty acids. These microstructures play a key role in a plethora of mechanisms involved in cell signaling, synapsis, cell-cell communication and cell survival. In the last years, increasing evidence indicate that lipid rafts may be altered in age-related neuropathologies, such as Alzheimer's disease and Parkinson disease even at asymptomatic stages. In particular, important changes in raft lipid composition are observed with the progression of these diseases, then inducing alterations in their physicochemical properties. Furthermore, these phenomena contribute to neuropathological events related to amyloidogenesis, aberrant protein aggregation and toxic cell signalling. In this review, we discuss some relevant data on the age-related molecular changes occurring in lipid rafts since the first stages of these neurodegenerative diseases. Further characterization of specific parameters associated with alterations of these microdomains may provide potential tools of diagnosis and prediction of these neuropathologies.

  8. Lipid-rhodopsin hydrophobic mismatch alters rhodopsin helical content

    OpenAIRE

    Soubias, Olivier; Niu, Shui-Lin; Mitchell, Drake C.; Gawrisch, Klaus

    2008-01-01

    The ability of photo-activated rhodopsin to achieve the enzymatically active metarhodopsin II conformation is exquisitely sensitive to bilayer hydrophobic thickness. The sensitivity of rhodopsin to the lipid matrix has been explained by the hydrophobic matching theory which predicts that lipid bilayers adjust elastically to the hydrophobic length of transmembrane helices. Here, we examined if bilayer thickness adjusts to the length of the protein or if the protein alters its conformation to a...

  9. Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism.

    Science.gov (United States)

    Abruzzese, Giselle Adriana; Heber, Maria Florencia; Ferreira, Silvana Rocio; Velez, Leandro Martin; Reynoso, Roxana; Pignataro, Omar Pedro; Motta, Alicia Beatriz

    2016-07-01

    Prenatal hyperandrogenism is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS patients have high risk of developing fatty liver and steatosis. This study aimed to evaluate the role of prenatal hyperandrogenism in liver lipid metabolism and fatty liver development. Pregnant rats were hyperandrogenized with testosterone. At pubertal age, the prenatally hyperandrogenized (PH) female offspring displayed both ovulatory (PHov) and anovulatory (PHanov) phenotypes that mimic human PCOS features. We evaluated hepatic transferases, liver lipid content, the balance between lipogenesis and fatty acid oxidation pathway, oxidant/antioxidant balance and proinflammatory status. We also evaluated the general metabolic status through growth rate curve, basal glucose and insulin levels, glucose tolerance test, HOMA-IR index and serum lipid profile. Although neither PH group showed signs of liver lipid content, the lipogenesis and fatty oxidation pathways were altered. The PH groups also showed impaired oxidant/antioxidant balance, a decrease in the proinflammatory pathway (measured by prostaglandin E2 and cyclooxygenase-2 levels), decreased glucose tolerance, imbalance of circulating lipids and increased risk of metabolic syndrome. We conclude that prenatal hyperandrogenism generates both PHov and PHanov phenotypes with signs of liver alterations, imbalance in lipid metabolism and increased risk of developing metabolic syndrome. The anovulatory phenotype showed more alterations in liver lipogenesis and a more impaired balance of insulin and glucose metabolism, being more susceptible to the development of steatosis. PMID:27179108

  10. Intragastric layering of lipids delays lipid absorption and increases plasma CCK but has minor effects on gastric emptying and appetite

    NARCIS (Netherlands)

    Foltz, Martin; Maljaars, Jeroen; Schuring, Ewoud A. H.; van der Wal, Robert J. P.; Boer, Theo; Duchateau, Guus S. M.; Peters, Harry P. F.; Stellaard, Frans; Masclee, Ad A.

    2009-01-01

    Foltz M, Maljaars J, Schuring EA, van der Wal RJ, Boer T, Duchateau GS, Peters HP, Stellaard F, Masclee AA. Intragastric layering of lipids delays lipid absorption and increases plasma CCK but has minor effects on gastric emptying and appetite. Am J Physiol Gastrointest Liver Physiol 296: G982-G991,

  11. Ether lipid generating enzyme AGPS alters the balance of structural and signaling lipids to fuel cancer pathogenicity.

    Science.gov (United States)

    Benjamin, Daniel I; Cozzo, Alyssa; Ji, Xiaodan; Roberts, Lindsay S; Louie, Sharon M; Mulvihill, Melinda M; Luo, Kunxin; Nomura, Daniel K

    2013-09-10

    Aberrant lipid metabolism is an established hallmark of cancer cells. In particular, ether lipid levels have been shown to be elevated in tumors, but their specific function in cancer remains elusive. We show here that the metabolic enzyme alkylglyceronephosphate synthase (AGPS), a critical step in the synthesis of ether lipids, is up-regulated across multiple types of aggressive human cancer cells and primary tumors. We demonstrate that ablation of AGPS in cancer cells results in reduced cell survival, cancer aggressiveness, and tumor growth through altering the balance of ether lipid, fatty acid, eicosanoid, and fatty acid-derived glycerophospholipid metabolism, resulting in an overall reduction in the levels of several oncogenic signaling lipids. Taken together, our results reveal that AGPS, in addition to maintaining ether lipids, also controls cellular utilization of fatty acids, favoring the generation of signaling lipids necessary for promoting the aggressive features of cancer. PMID:23980144

  12. The Alteration of Lipid Metabolism in Burkitt Lymphoma Identifies a Novel Marker: Adipophilin

    OpenAIRE

    Ambrosio, Maria R.; Piccaluga, Pier P.; Maurilio Ponzoni; Rocca, Bruno J; Valeria Malagnino; Monica Onorati; Giulia De Falco; Valeria Calbi; Martin Ogwang; Naresh, Kikkeri N.; Pileri, Stefano A.; Claudio Doglioni; Lorenzo Leoncini; Stefano Lazzi

    2012-01-01

    BACKGROUND: Recent evidence suggests that lipid pathway is altered in many human tumours. In Burkitt lymphoma this is reflected by the presence of lipid droplets which are visible in the cytoplasm of neoplastic cells in cytological preparations. These vacuoles are not identifiable in biopsy section as lipids are "lost" during tissue processing. METHODS AND RESULTS: In this study we investigated the expression of genes involved in lipid metabolism, at both RNA and protein level in Burkitt lymp...

  13. Altered lipid metabolism in a Drosophila model of Friedreich's ataxia.

    Science.gov (United States)

    Navarro, Juan A; Ohmann, Elisabeth; Sanchez, Diego; Botella, José A; Liebisch, Gerhard; Moltó, María D; Ganfornina, María D; Schmitz, Gerd; Schneuwly, Stephan

    2010-07-15

    Friedreich's ataxia (FRDA) is the most common form of autosomal recessive ataxia caused by a deficit in the mitochondrial protein frataxin. Although demyelination is a common symptom in FRDA patients, no multicellular model has yet been developed to study the involvement of glial cells in FRDA. Using the recently established RNAi lines for targeted suppression of frataxin in Drosophila, we were able to study the effects of general versus glial-specific frataxin downregulation. In particular, we wanted to study the interplay between lowered frataxin content, lipid accumulation and peroxidation and the consequences of these effects on the sensitivity to oxidative stress and fly fitness. Interestingly, ubiquitous frataxin reduction leads to an increase in fatty acids catalyzing an enhancement of lipid peroxidation levels, elevating the intracellular toxic potential. Specific loss of frataxin in glial cells triggers a similar phenotype which can be visualized by accumulating lipid droplets in glial cells. This phenotype is associated with a reduced lifespan, an increased sensitivity to oxidative insult, neurodegenerative effects and a serious impairment of locomotor activity. These symptoms fit very well with our observation of an increase in intracellular toxicity by lipid peroxides. Interestingly, co-expression of a Drosophila apolipoprotein D ortholog (glial lazarillo) has a strong protective effect in our frataxin models, mainly by controlling the level of lipid peroxidation. Our results clearly support a strong involvement of glial cells and lipid peroxidation in the generation of FRDA-like symptoms.

  14. Infrared reflection-absorption spectroscopy: principles and applications to lipid-protein interaction in Langmuir films.

    Science.gov (United States)

    Mendelsohn, Richard; Mao, Guangru; Flach, Carol R

    2010-04-01

    Infrared reflection-absorption spectroscopy (IRRAS) of lipid/protein monolayer films in situ at the air/water interface provides unique molecular structure and orientation information from the film constituents. The technique is thus well suited for studies of lipid/protein interaction in a physiologically relevant environment. Initially, the nature of the IRRAS experiment is described and the molecular structure information that may be obtained is recapitulated. Subsequently, several types of applications, including the determination of lipid chain conformation and tilt as well as elucidation of protein secondary structure are reviewed. The current article attempts to provide the reader with an understanding of the current capabilities of IRRAS instrumentation and the type of results that have been achieved to date from IRRAS studies of lipids, proteins, and lipid/protein films of progressively increasing complexity. Finally, possible extensions of the technology are briefly considered. PMID:20004639

  15. Dietary manipulation of the sow milk does not influence the lipid absorption capacity of the progeny

    DEFF Research Database (Denmark)

    Lauridsen, Charlotte; Hedemann, Mette Skou; Pierzynowski, Stefan;

    2007-01-01

    A control diet without supplemental fat and four diets containing 8% of coconut oil, rapeseed oil, fish oil or sunflower oil were fed to lactating sows in order to investigate the lipid absorption capacity of their progeny in terms of pancreatic enzyme activity, hormonal regulation, and bile salt...

  16. Regulation of intestinal lipid absorption by clock genes.

    Science.gov (United States)

    Hussain, M Mahmood

    2014-01-01

    Plasma levels of triacylglycerols and diacylglycerols, the lipoproteins that transport them, and proteins involved in their absorption from the intestinal lumen fluctuate in a circadian manner. These changes are likely controlled by clock genes expressed in the intestine that are probably synchronized by neuronal and humoral signals from the suprachiasmatic nuclei, which constitute a master clock entrained by light signals from the eyes and from the environment, e.g., food availability. Acute changes in circadian rhythms--e.g., due to nonsynchronous work schedules or a transcontinental flight--may trigger intestinal discomfort. Chronic disruptions in circadian control mechanisms may predispose the individual to irritable bowel syndrome, gastroesophageal reflux disease, and peptic ulcer disease. A more detailed understanding of the molecular mechanisms underlying temporal changes in intestinal activity might allow us to identify novel targets for developing therapeutic approaches to these disorders.

  17. Alteration of interleaflet coupling due to compounds displaying rapid translocation in lipid membranes

    Science.gov (United States)

    Reigada, Ramon

    2016-09-01

    The spatial coincidence of lipid domains at both layers of the cell membrane is expected to play an important role in many cellular functions. Competition between the surface interleaflet tension and a line hydrophobic mismatch penalty are conjectured to determine the transversal behavior of laterally heterogeneous lipid membranes. Here, by a combination of molecular dynamics simulations, a continuum field theory and kinetic equations, I demonstrate that the presence of small, rapidly translocating molecules residing in the lipid bilayer may alter its transversal behavior by favoring the spatial coincidence of similar lipid phases.

  18. Effect of dietary cellulose on site of lipid absorption

    International Nuclear Information System (INIS)

    The effect of dietary cellulose on the localization within the small intestine of isotopically labeled triglyceride (TG) and cholesterol (CH) from a test meal was investigated. Feeding a 20% cellulose meal resulted in greater quantities of 14C-TG present in both the contents and mucosa of the distal intestine compared with a fiber-free control meal. In contrast, cellulose had no effect on the localization of CH within either the intestinal contents or the mucosa. Accumulation of TG within the intestine was not due to differences in stomach emptying, as the emptying rate was similar for both TG and CH. Within the bulk phase TG must be hydrolyzed by pancreatic lipase before it is available for cellular uptake at the microvillus membrane, whereas CH requires no hydrolysis. The greater amount of TG, but not of CH, within the intestine suggests that cellulose can interfere with lipase activity in vivo. Consequently, cellulose can delay TG hydrolysis and increase the amount of lipid absorbed in the ileum

  19. Altered lipid composition in cortical lipid rafts occurs at early stages of sporadic Alzheimer's disease and facilitates APP/BACE1 interactions.

    Science.gov (United States)

    Fabelo, Noemí; Martín, Virginia; Marín, Raquel; Moreno, Dolores; Ferrer, Isidre; Díaz, Mario

    2014-08-01

    The presence of lipid alterations in lipid rafts from the frontal cortex in late stages of Alzheimer's disease (AD) has been recently demonstrated. Here, we have isolated and analyzed the lipid composition of lipid rafts from different brain areas from control and AD subjects at initial neuropathologic stages. We have observed that frontal cortex lipid rafts are profoundly altered in AD brains from the earliest stages of AD, namely AD I/II. These changes in the lipid matrix of lipid rafts affected both lipid classes and fatty acids and were also detected in the entorhinal cortex, but not in the cerebellum from the same subjects. Paralleling these changes, lipid rafts from AD frontal and entorhinal cortices displayed higher anisotropy for environment-sensitive probes, indicating that lipid changes in AD lipid rafts increased membrane order and viscosity in these domains. The pathophysiological consequences of these alterations in the development and progression of AD were strengthened by the significant, and specific, accumulation of β-secretase within the lipid rafts of AD subjects even at the earliest stages. Our results provide a mechanistic connection between lipid alterations in these microdomains and amyloidogenic processing of amyloid precursor protein.

  20. Wheat leaf lipids during heat stress: I. High day and night temperatures result in major lipid alterations.

    Science.gov (United States)

    Narayanan, Sruthi; Tamura, Pamela J; Roth, Mary R; Prasad, P V Vara; Welti, Ruth

    2016-04-01

    Understanding how wheat (Triticum aestivum L.) plants under high temperature (HT) regulate lipid composition is critical to developing climate-resilient varieties. We measured 165 glycerolipids and sterol derivatives under optimum and high day and night temperatures in wheat leaves using electrospray ionization-tandem mass spectrometry. Levels of polar lipid fatty acyl chain unsaturation were lower in both heat-tolerant genotype Ventnor and susceptible genotype Karl 92 under HT, compared with optimum temperature. The lower unsaturation was predominantly because of lower levels of 18:3 acyl chains and higher levels of 18:1 and 16:0 acyl chains. Levels of 18:3-containing triacylglycerols increased threefold/more under HT, consistent with their possible role in sequestering fatty acids during membrane lipid remodelling. Phospholipids containing odd-numbered or oxidized acyl chains accumulated in leaves under HT. Sterol glycosides (SG) and 16:0-acylated sterol glycosides (ASG) were higher under HT than optimum temperatures. Ventnor had lower amounts of phospholipids with oxidized acyl chains under HT and higher amounts of SG and 16:0-ASG than Karl 92. Taken together, the data demonstrate that wheat leaf lipid composition is altered by HT, in which some lipids are particularly responsive to HT, and that two wheat genotypes, chosen for their differing physiological responses to HT, differ in lipid profile under HT. PMID:26436679

  1. Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition.

    Science.gov (United States)

    Zhu, Zhu; Hua, Bingxuan; Shang, Zhanxian; Yuan, Gongsheng; Xu, Lirong; Li, Ermin; Li, Xiaobo; Sun, Ning; Yan, Zuoqin; Qian, Ruizhe; Lu, Chao

    2016-01-01

    Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice) by altering exposure to light. C57 BL/6J mice (C57 mice) and ApoE-KO mice (ApoE-KO mice) exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1) levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation. PMID:27631008

  2. Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition.

    Science.gov (United States)

    Zhu, Zhu; Hua, Bingxuan; Shang, Zhanxian; Yuan, Gongsheng; Xu, Lirong; Li, Ermin; Li, Xiaobo; Sun, Ning; Yan, Zuoqin; Qian, Ruizhe; Lu, Chao

    2016-01-01

    Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice) by altering exposure to light. C57 BL/6J mice (C57 mice) and ApoE-KO mice (ApoE-KO mice) exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1) levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

  3. Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

    Directory of Open Access Journals (Sweden)

    Zhu Zhu

    2016-01-01

    Full Text Available Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice by altering exposure to light. C57 BL/6J mice (C57 mice and ApoE-KO mice (ApoE-KO mice exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1 levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

  4. Advanced shotgun lipidomics for characterization of altered lipid patterns in neurodegenerative diseases and brain injury

    Science.gov (United States)

    Wang, Miao; Han, Xianlin

    2016-01-01

    Summary Multi-dimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) is a powerful technology platform among current lipidomics practices due to its high efficiency, sensitivity, and reproducibility, as well as its broad coverage. This platform has been broadly used to determine the altered lipid profiles induced by diseases, injury, genetic manipulations, drug treatments, and aging, among others. Herein, we summarized the principles underlying this platform and presented a protocol for analysis of many of the lipid classes and subclasses covered by MDMS-SL directly from lipid extracts of brain samples. We believe that this protocol could aid the researchers in the field to determine the altered lipid patterns in neurodegenerative diseases and brain injury. PMID:26235081

  5. The adrenal specific toxicant mitotane directly interacts with lipid membranes and alters membrane properties depending on lipid composition.

    Science.gov (United States)

    Scheidt, Holger A; Haralampiev, Ivan; Theisgen, Stephan; Schirbel, Andreas; Sbiera, Silviu; Huster, Daniel; Kroiss, Matthias; Müller, Peter

    2016-06-15

    Mitotane (o,p'.-DDD) is an orphan drug approved for the treatment of adrenocortical carcinoma. The mechanisms, which are responsible for this activity of the drug, are not completely understood. It can be hypothesized that an impact of mitotane is mediated by the interaction with cellular membranes. However, an interaction of mitotane with (lipid) membranes has not yet been investigated in detail. Here, we characterized the interaction of mitotane and its main metabolite o,p'-dichlorodiphenyldichloroacetic acid (o,p'-DDA) with lipid membranes by applying a variety of biophysical approaches of nuclear magnetic resonance, electron spin resonance, and fluorescence spectroscopy. We found that mitotane and o,p'-DDA bind to lipid membranes by inserting into the lipid-water interface of the bilayer. Mitotane but not o,p'-DDA directly causes a disturbance of bilayer structure leading to an increased permeability of the membrane for polar molecules. Mitotane induced alterations of the membrane integrity required the presence of phosphatidylethanolamine and/or cholesterol. Collectively, our data for the first time characterize the impact of mitotane on the lipid membrane structure and dynamics, which may contribute to a better understanding of specific mitotane effects and side effects. PMID:27002491

  6. Chloroform alters interleaflet coupling in lipid bilayers: an entropic mechanism

    Science.gov (United States)

    Reigada, Ramon; Sagués, Francesc

    2015-01-01

    The interaction of the two leaflets of the plasmatic cell membrane is conjectured to play an important role in many cell processes. Experimental and computational studies have investigated the mechanisms that modulate the interaction between the two membrane leaflets. Here, by means of coarse-grained molecular dynamics simulations, we show that the addition of a small and polar compound such as chloroform alters interleaflet coupling by promoting domain registration. This is interpreted in terms of an entropic gain that would favour frequent chloroform commuting between the two leaflets. The implication of this effect is discussed in relation to the general anaesthetic action. PMID:25833246

  7. Lipid body accumulation alters calcium signaling dynamics in immune cells.

    Science.gov (United States)

    Greineisen, William E; Speck, Mark; Shimoda, Lori M N; Sung, Carl; Phan, Nolwenn; Maaetoft-Udsen, Kristina; Stokes, Alexander J; Turner, Helen

    2014-09-01

    There is well-established variability in the numbers of lipid bodies (LB) in macrophages, eosinophils, and neutrophils. Similarly to the steatosis observed in adipocytes and hepatocytes during hyperinsulinemia and nutrient overload, immune cell LB hyper-accumulate in response to bacterial and parasitic infection and inflammatory presentations. Recently we described that hyperinsulinemia, both in vitro and in vivo, drives steatosis and phenotypic changes in primary and transformed mast cells and basophils. LB reach high numbers in these steatotic cytosols, and here we propose that they could dramatically impact the transcytoplasmic signaling pathways. We compared calcium release and influx responses at the population and single cell level in normal and steatotic model mast cells. At the population level, all aspects of FcɛRI-dependent calcium mobilization, as well as activation of calcium-dependent downstream signaling targets such as NFATC1 phosphorylation are suppressed. At the single cell level, we demonstrate that LB are both sources and sinks of calcium following FcɛRI cross-linking. Unbiased analysis of the impact of the presence of LB on the rate of trans-cytoplasmic calcium signals suggest that LB enrichment accelerates calcium propagation, which may reflect a Bernoulli effect. LB abundance thus impacts this fundamental signaling pathway and its downstream targets.

  8. Investigating the correlation between in vivo absorption and in vitro release of fenofibrate from lipid matrix particles in biorelevant medium

    DEFF Research Database (Denmark)

    Borkar, Nrupa Nitin; Xia, Dengning; Holm, René;

    2014-01-01

    Lipid matrix particles (LMP) may be used as better carriers for poorly water-soluble drugs than liquid lipid carriers because of reduced drug mobilization in the formulations. However, the digestion process of solid lipid particles and their effect on the absorption of poorly water-soluble drugs...... are not fully understood. This study aimed at investigating the effect of particle size of LMP on drug release in vitro as well as absorption in vivo in order to get a better understanding on the effect of degradation of lipid particles on drug solubilisation and absorption. Fenofibrate, a model...... poorly water-soluble drug, was incorporated into LMP in this study using probe ultrasound sonication. The resultant LMP were characterised in terms of particle size, size distribution, zeta potential, entrapment efficiency, in vitro lipolysis and in vivo absorption in rat model. LMP of three different...

  9. Human Ozone (O3) Exposure Alters Serum Profile of Lipid Metabolites

    Science.gov (United States)

    HUMAN OZONE (O3) EXPOSURE ALTERS SERUM PROFILE OF LIPID METABOLITES Miller, D B.1; Kodavanti, U P.2 Karoly, E D.3; Cascio W.E2, Ghio, A J. 21. UNC-Chapel Hill, Chapel Hill, N.C., United States. 2. NHEERL, U.S. EPA, RTP, N.C., United States. 3. METABOLON INC., Durham, N.C., United...

  10. Altered lipid accumulation in Nannochloropsis salina CCAP849/3 following EMS and UV induced mutagenesis

    Directory of Open Access Journals (Sweden)

    T.A. Beacham

    2015-09-01

    Full Text Available Microalgae have potential as a chemical feed stock in a range of industrial applications. Nannochloropsis salina was subject to EMS mutagenesis and the highest lipid containing cells selected using fluorescence-activated cell sorting. Assessment of growth, lipid content and fatty acid composition identified mutant strains displaying a range of altered traits including changes in the PUFA content and a total FAME increase of up to 156% that of the wild type strain. Combined with a reduction in growth this demonstrated a productivity increase of up to 76%. Following UV mutagenesis, lipid accumulation of the mutant cultures was elevated to more than 3 fold that of the wild type strain, however reduced growth rates resulted in a reduction in overall productivity. Changes observed are indicative of alterations to the regulation of the omega 6 Kennedy pathway. The importance of these variations in physiology for industrial applications such as biofuel production is discussed.

  11. Alterations in Lipid and Inositol Metabolisms in Two Dopaminergic Disorders.

    Directory of Open Access Journals (Sweden)

    Eva C Schulte

    Full Text Available Serum metabolite profiling can be used to identify pathways involved in the pathogenesis of and potential biomarkers for a given disease. Both restless legs syndrome (RLS and Parkinson`s disease (PD represent movement disorders for which currently no blood-based biomarkers are available and whose pathogenesis has not been uncovered conclusively. We performed unbiased serum metabolite profiling in search of signature metabolic changes for both diseases.456 metabolites were quantified in serum samples of 1272 general population controls belonging to the KORA cohort, 82 PD cases and 95 RLS cases by liquid-phase chromatography and gas chromatography separation coupled with tandem mass spectrometry. Genetically determined metabotypes were calculated using genome-wide genotyping data for the 1272 general population controls.After stringent quality control, we identified decreased levels of long-chain (polyunsaturated fatty acids of individuals with PD compared to both RLS (PD vs. RLS: p = 0.0001 to 5.80x10-9 and general population controls (PD vs. KORA: p = 6.09x10-5 to 3.45x10-32. In RLS, inositol metabolites were increased specifically (RLS vs. KORA: p = 1.35x10-6 to 3.96x10-7. The impact of dopaminergic drugs was reflected in changes in the phenylalanine/tyrosine/dopamine metabolism observed in both individuals with RLS and PD.A first discovery approach using serum metabolite profiling in two dopamine-related movement disorders compared to a large general population sample identified significant alterations in the polyunsaturated fatty acid metabolism in PD and implicated the inositol metabolism in RLS. These results provide a starting point for further studies investigating new perspectives on factors involved in the pathogenesis of the two diseases as well as possible points of therapeutic intervention.

  12. Alterations in plasma lipid profile patterns in head and neck cancer and oral precancerous conditions

    Directory of Open Access Journals (Sweden)

    Patel Prabhudas

    2004-01-01

    Full Text Available BACKGROUND : The changes in lipid profile have long been associated with cancer because lipids play a key role in maintenance of cell integrity. AIMS : The present study evaluated alterations in plasma lipid profile in untreated head and neck cancer patients as well as patients with oral precancerous conditions (OPC and its association with habit of tobacco consumption. MATERIAL AND METHODS : This hospital-based case control study included 184 head and neck cancer patients, 153 patients with OPC and 52 controls. Plasma lipids including: (i Total cholesterol, (ii LDL cholesterol (LDLC, (iii HDL cholesterol (HDLC (iv VLDL cholesterol (VLDLC and (v triglycerides were analysed by spectrophotometric kits. STATISTICAL ANALYSIS USED : Student′s t-test was performed to compare mean values of the parameters. RESULTS : A significant decrease in plasma total cholesterol and HDLC was observed in cancer patients (P=0.008 and P=0.000 respectively as well as in patients with OPC (P=0.014 and P=0.000, respectively as compared to the controls. The plasma VLDL and triglycerides levels were significantly lower in cancer patients as compared to the patients with OPC (P=0.04 and controls (P=0.059. The tobacco habituates showed lower plasma lipid levels than the non-habituates. Our data strengthen the evidence of an inverse relationship between plasma lipid levels and head and neck malignancies as well as OPC. CONCLUSION :The lower levels of plasma cholesterol and other lipid constituents in patients might be due to their increased utilization by neoplastic cells for new membrane biogenesis. The findings strongly warrant an in-depth study of alterations in plasma lipid profile in head neck cancer patients.

  13. Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

    Science.gov (United States)

    Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B.; Kallen, Caleb B.; Lang, Charles H.

    2014-01-01

    Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and

  14. Evidence does not support absorption of intact solid lipid nanoparticles via oral delivery

    Science.gov (United States)

    Hu, Xiongwei; Fan, Wufa; Yu, Zhou; Lu, Yi; Qi, Jianping; Zhang, Jian; Dong, Xiaochun; Zhao, Weili; Wu, Wei

    2016-03-01

    Whether and to what extent solid lipid nanoparticles (SLNs) can be absorbed integrally via oral delivery should be clarified because it is the basis for elucidation of absorption mechanisms. To address this topic, the in vivo fate of SLNs as well as their interaction with biomembranes is investigated using water-quenching fluorescent probes that can signal structural variations of lipid-based nanocarriers. Live imaging indicates prolonged retention of SLNs in the stomach, whereas in the intestine, SLNs can be digested quickly. No translocation of intact SLNs to other organs or tissues can be observed. The in situ perfusion study shows bioadhesion of both SLNs and simulated mixed micelles (SMMs) to intestinal mucus, but no evidence of penetration of integral nanocarriers. Both SLNs and SMMs exhibit significant cellular uptake, but fail to penetrate cell monolayers. Confocal laser scanning microscopy reveals that nanocarriers mainly concentrate on the surface of the monolayers, and no evidence of penetration of intact vehicles can be obtained. The mucous layer acts as a barrier to the penetration of both SLNs and SMMs. Both bile salt-decoration and SMM formulation help to strengthen the interaction with biomembranes. It is concluded that evidence does not support absorption of intact SLNs via oral delivery.Whether and to what extent solid lipid nanoparticles (SLNs) can be absorbed integrally via oral delivery should be clarified because it is the basis for elucidation of absorption mechanisms. To address this topic, the in vivo fate of SLNs as well as their interaction with biomembranes is investigated using water-quenching fluorescent probes that can signal structural variations of lipid-based nanocarriers. Live imaging indicates prolonged retention of SLNs in the stomach, whereas in the intestine, SLNs can be digested quickly. No translocation of intact SLNs to other organs or tissues can be observed. The in situ perfusion study shows bioadhesion of both SLNs and

  15. Inflammation-related alterations of lipids after spinal cord injury revealed by Raman spectroscopy

    Science.gov (United States)

    Tamosaityte, Sandra; Galli, Roberta; Uckermann, Ortrud; Sitoci-Ficici, Kerim H.; Koch, Maria; Later, Robert; Schackert, Gabriele; Koch, Edmund; Steiner, Gerald; Kirsch, Matthias

    2016-06-01

    Spinal cord injury (SCI) triggers several lipid alterations in nervous tissue. It is characterized by extensive demyelination and the inflammatory response leads to accumulation of activated microglia/macrophages, which often transform into foam cells by accumulation of lipid droplets after engulfment of the damaged myelin sheaths. Using an experimental rat model, Raman microspectroscopy was applied to retrieve the modifications of the lipid distribution following SCI. Coherent anti-Stokes Raman scattering (CARS) and endogenous two-photon fluorescence (TPEF) microscopies were used for the detection of lipid-laden inflammatory cells. The Raman mapping of CH2 deformation mode intensity at 1440 cm-1 retrieved the lipid-depleted injury core. Preserved white matter and inflammatory regions with myelin fragmentation and foam cells were localized by specifically addressing the distribution of esterified lipids, i.e., by mapping the intensity of the carbonyl Raman band at 1743 cm-1, and were in agreement with CARS/TPEF microscopy. Principal component analysis revealed that the inflammatory regions are notably rich in saturated fatty acids. Therefore, Raman spectroscopy enabled to specifically detect inflammation after SCI and myelin degradation products.

  16. Distal small bowel motility and lipid absorption in patients following abdominal aortic aneurysm repair surgery

    Institute of Scientific and Technical Information of China (English)

    Robert J Fraser; Paul Jury; John Dent; Marc Ritz; Addolorata C Di Matteo; Rosalie Vozzo; Monika Kwiatek; Robert Foreman; Brendan Stanley; Jack Walsh; Jim Burnett

    2006-01-01

    AIM: To investigate distal small bowel motility and lipid absorption in patients following elective abdominal aortic aneurysm (AAA) repair surgery.METHODS: Nine patients (aged 35-78 years; body mass index (BMI) range: 23-36 kg/m2) post-surgery for AAA repair, and seven healthy control subjects (20-50 years;BMI range: 21-29 kg/m2) were studied. Continuous distal small bowel manometry was performed for up to 72 h, during periods of fasting and enteral feeding (Nutrison(R)). Recordings were analyzed for the frequency,origin, length of migration, and direction of small intestinal burst activity. Lipid absorption was assessed on the first day and the third day post surgery in a subset of patients using the 13C-triolein-breath test, and compared with healthy controls. Subjects received a 20-min intraduodenal infusion of 50 mL liquid feed mixed with 200 μL 13C-triolein. End-expiratory breath samples were collected for 6 h and analyzed for 13CO2 concentration.RESULTS: The frequency of burst activity in the proximal and distal small intestine was higher in patients than in healthy subjects, under both fasting and fed conditions (P<0.005). In patients there was a higher proportion of abnormally propagated bursts (71% abnormal), which began to normalize by d 3 (25% abnormal) post-surgery.Lipid absorption data was available for seven patients on d 1 and four patients on d 3 post surgery. In patients,absorption on d 1 post-surgery was half that of healthy control subjects (AUC 13CO2 1323 ± 244 vs 2 646 ±365;P< 0.05, respectively), and was reduced to the one-fifth that of healthy controls by d 3 (AUC 13CO2 470 ± 832 vs 2646 ± 365; P< 0.05, respectively).CONCLUSION: Both proximal and distal small intestinal motor activity are transiently disrupted in critically ill patients immediately after major surgery,with abnormal motility patterns extending as far as the ileum. These motor disturbances may contribute to impaired absorption of enteral nutrition, especially when

  17. Alterations of metabolic activity in human osteoarthritic osteoblasts by lipid peroxidation end product 4-hydroxynonenal

    OpenAIRE

    Shi, Qin; Vaillancourt, France; Côté, Véronique; Fahmi, Hassan; Lavigne, Patrick; Afif, Hassan; Di Battista, John A.; Fernandes, Julio C; Benderdour, Mohamed

    2006-01-01

    4-Hydroxynonenal (HNE), a lipid peroxidation end product, is produced abundantly in osteoarthritic (OA) articular tissues, but its role in bone metabolism is ill-defined. In this study, we tested the hypothesis that alterations in OA osteoblast metabolism are attributed, in part, to increased levels of HNE. Our data showed that HNE/protein adduct levels were higher in OA osteoblasts compared to normal and when OA osteoblasts were treated with H2O2. Investigating osteoblast markers, we found t...

  18. Hypoxia reduces the efficiency of elisidepsin by inhibiting hydroxylation and altering the structure of lipid rafts.

    Science.gov (United States)

    Király, Anna; Váradi, Tímea; Hajdu, Tímea; Rühl, Ralph; Galmarini, Carlos M; Szöllősi, János; Nagy, Peter

    2013-12-02

    The mechanism of action of elisidepsin (PM02734, Irvalec®) is assumed to involve membrane permeabilization via attacking lipid rafts and hydroxylated lipids. Here we investigate the role of hypoxia in the mechanism of action of elisidepsin. Culturing under hypoxic conditions increased the half-maximal inhibitory concentration and decreased the drug's binding to almost all cell lines which was reversed by incubation of cells with 2-hydroxy palmitic acid. The expression of fatty acid 2-hydroxylase was strongly correlated with the efficiency of the drug and inversely correlated with the effect of hypoxia. Number and brightness analysis and fluorescence anisotropy experiments showed that hypoxia decreased the clustering of lipid rafts and altered the structure of the plasma membrane. Although the binding of elisidepsin to the membrane is non-cooperative, its membrane permeabilizing effect is characterized by a Hill coefficient of ~3.3. The latter finding is in agreement with elisidepsin-induced clusters of lipid raft-anchored GFP visualized by confocal microscopy. We propose that the concentration of elisidepsin needs to reach a critical level in the membrane above which elisidepsin induces the disruption of the cell membrane. Testing for tumor hypoxia or the density of hydroxylated lipids could be an interesting strategy to increase the efficiency of elisidepsin.

  19. Triphenyltin alters lipid homeostasis in females of the ramshorn snail Marisa cornuarietis

    Energy Technology Data Exchange (ETDEWEB)

    Lyssimachou, Angeliki [Environmental Chemistry Department, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Navarro, Juan Carlos [Institute of Aquaculture of Torre de la Sal, CSIC, 12595 Ribera de Cabanes, Castellon (Spain); Bachmann, Jean [Department of Ecology and Evolution-Ecotoxicology, Johann Wolfgang Goethe-University Frankfurt, D-60054 Frankfurt am Main (Germany); Porte, Cinta, E-mail: cinta.porte@cid.csic.e [Environmental Chemistry Department, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain)

    2009-05-15

    Molluscs are sensitive species to the toxic effects of organotin compounds, particularly to masculinisation. Both tributyltin (TBT) and triphenyltin (TPT) have been recently shown to bind to mollusc retinoid X receptor (RXR). If RXR is involved in lipid homeostasis, exposure to TPT would have an immediate effect on endogenous lipids. To test this hypothesis, the ramshorn snail Marisa cornuarietis was exposed to environmentally relevant concentrations of TPT (30, 125, 500 ng/L as Sn) in a semi-static water regime for 7 days. Percentage of lipids and total fatty acid content decreased significantly in TPT-exposed females while the activity of peroxisomal acyl-CoA oxidase, involved in fatty acid catabolism, increased. In addition, fatty acid profiles (carbon chain length and unsaturation degree) were significantly altered in exposed females but not in males. This work highlights the ability of TPT to disrupt lipid metabolism in M. cornuarietis at environmentally realistic concentrations and the higher susceptibility of females in comparison to males. - Short-term exposure to the fungicide TPT disrupts lipid metabolism in M. cornuarietis at environmentally realistic concentrations.

  20. Dietary sphingomyelin lowers hepatic lipid levels and inhibits intestinal cholesterol absorption in high-fat-fed mice.

    Directory of Open Access Journals (Sweden)

    Rosanna W S Chung

    Full Text Available Controlling intestinal lipid absorption is an important strategy for maintaining lipid homeostasis. Accumulation of lipids in the liver is a major risk factor for metabolic syndrome and nonalcoholic fatty liver disease. It is well-known that sphingomyelin (SM can inhibit intestinal cholesterol absorption. It is, however, unclear if dietary SM also lowers liver lipid levels. In the present study (i the effect of pure dietary egg SM on hepatic lipid metabolism and intestinal cholesterol absorption was measured with [(14C]cholesterol and [(3H]sitostanol in male C57BL/6 mice fed a high-fat (HF diet with or without 0.6% wt/wt SM for 18 days; and (ii hepatic lipid levels and gene expression were determined in mice given a HF diet with or without egg SM (0.3, 0.6 or 1.2% wt/wt for 4 weeks. Mice supplemented with SM (0.6% wt/wt had significantly increased fecal lipid and cholesterol output and reduced hepatic [(14C]cholesterol levels after 18 days. Relative to HF-fed mice, SM-supplemented HF-fed mice had significantly lower intestinal cholesterol absorption (-30%. Liver weight was significantly lower in the 1.2% wt/wt SM-supplemented mice (-18%. Total liver lipid (mg/organ was significantly reduced in the SM-supplemented mice (-33% and -40% in 0.6% wt/wt and 1.2% wt/wt SM, respectively, as were triglyceride and cholesterol levels. The reduction in liver triglycerides was due to inactivation of the LXR-SREBP-1c pathway. In conclusion, dietary egg SM has pronounced hepatic lipid-lowering properties in mice maintained on an obesogenic diet.

  1. Chemotherapy Agents Alter Plasma Lipids in Breast Cancer Patients and Show Differential Effects on Lipid Metabolism Genes in Liver Cells.

    Science.gov (United States)

    Sharma, Monika; Tuaine, Jo; McLaren, Blair; Waters, Debra L; Black, Katherine; Jones, Lynnette M; McCormick, Sally P A

    2016-01-01

    Cardiovascular complications have emerged as a major concern for cancer patients. Many chemotherapy agents are cardiotoxic and some appear to also alter lipid profiles, although the mechanism for this is unknown. We studied plasma lipid levels in 12 breast cancer patients throughout their chemotherapy. Patients received either four cycles of doxorubicin and cyclophosphamide followed by weekly paclitaxel or three cycles of epirubicin, cyclophosphamide and 5'-fluorouracil followed by three cycles of docetaxel. Patients demonstrated a significant reduction (0.32 mmol/L) in high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1) levels (0.18 g/L) and an elevation in apolipoprotein B (apoB) levels (0.15 g/L) after treatment. Investigation of the individual chemotherapy agents for their effect on genes involved in lipoprotein metabolism in liver cells showed that doxorubicin decreased ATP binding cassette transporter A1 (ABCA1) via a downregulation of the peroxisomal proliferator activated receptor γ (PPARγ) and liver X receptor α (LXRα) transcription factors. In contrast, ABCA1 levels were not affected by cyclophosphamide or paclitaxel. Likewise, apoA1 levels were reduced by doxorubicin and remained unaffected by cyclophosphamide and paclitaxel. Doxorubicin and paclitaxel both increased apoB protein levels and paclitaxel also decreased low density lipoprotein receptor (LDLR) protein levels. These findings correlate with the observed reduction in HDL-C and apoA1 and increase in apoB levels seen in these patients. The unfavourable lipid profiles produced by some chemotherapy agents may be detrimental in the longer term to cancer patients, especially those already at risk of cardiovascular disease (CVD). This knowledge may be useful in tailoring effective follow-up care plans for cancer survivors.

  2. Impact de la structure de la matière grasse sur l'absorption et le devenir métabolique des lipides et des endotoxines chez l'Homme normo-pondéré ou obèse

    OpenAIRE

    Vors, Cécile

    2012-01-01

    The alteration of postprandial lipid metabolism and associated chronic inflammation emerge as major elements in the obesity pathophysiology. The involvement of the intestinal absorption of endotoxin from microbiota during lipid digestion was recently highlighted. However, the modulation of these phenomena by different amounts of differently structured lipids remains poorly characterized, especially in obese people. We developed a cross-over randomized clinical study to explore in normal weigh...

  3. Reduced intestinal lipid absorption and body weight-independent improvements in insulin sensitivity in high-fat diet-fed Park2 knockout mice.

    Science.gov (United States)

    Costa, Diana K; Huckestein, Brydie R; Edmunds, Lia R; Petersen, Max C; Nasiri, Ali; Butrico, Gina M; Abulizi, Abudukadier; Harmon, Daniel B; Lu, Canying; Mantell, Benjamin S; Hartman, Douglas J; Camporez, João-Paulo G; O'Doherty, Robert M; Cline, Gary W; Shulman, Gerald I; Jurczak, Michael J

    2016-07-01

    Mitochondrial dysfunction is associated with many human diseases and results from mismatch of damage and repair over the life of the organelle. PARK2 is a ubiquitin E3 ligase that regulates mitophagy, a repair mechanism that selectively degrades damaged mitochondria. Deletion of PARK2 in multiple in vivo models results in susceptibility to stress-induced mitochondrial and cellular dysfunction. Surprisingly, Park2 knockout (KO) mice are protected from nutritional stress and do not develop obesity, hepatic steatosis or insulin resistance when fed a high-fat diet (HFD). However, these phenomena are casually related and the physiological basis for this phenotype is unknown. We therefore undertook a series of acute HFD studies to more completely understand the physiology of Park2 KO during nutritional stress. We find that intestinal lipid absorption is impaired in Park2 KO mice as evidenced by increased fecal lipids and reduced plasma triglycerides after intragastric fat challenge. Park2 KO mice developed hepatic steatosis in response to intravenous lipid infusion as well as during incubation of primary hepatocytes with fatty acids, suggesting that hepatic protection from nutritional stress was secondary to changes in energy balance due to altered intestinal triglyceride absorption. Park2 KO mice showed reduced adiposity after 1-wk HFD, as well as improved hepatic and peripheral insulin sensitivity. These studies suggest that changes in intestinal lipid absorption may play a primary role in protection from nutritional stress in Park2 KO mice by preventing HFD-induced weight gain and highlight the need for tissue-specific models to address the role of PARK2 during metabolic stress. PMID:27166280

  4. Absorption spectra and light penetration depth of normal and pathologically altered human skin

    Science.gov (United States)

    Barun, V. V.; Ivanov, A. P.; Volotovskaya, A. V.; Ulashchik, V. S.

    2007-05-01

    A three-layered skin model (stratum corneum, epidermis, and dermis) and engineering formulas for radiative transfer theory are used to study absorption spectra and light penetration depths of normal and pathologically altered skin. The formulas include small-angle and asymptotic approximations and a layer-addition method. These characteristics are calculated for wavelengths used for low-intensity laser therapy. We examined several pathologies such as vitiligo, edema, erythematosus lupus, and subcutaneous wound, for which the bulk concentrations of melanin and blood vessels or tissue structure (for subcutaneous wound) change compared with normal skin. The penetration depth spectrum is very similar to the inverted blood absorption spectrum. In other words, the depth is minimal at blood absorption maxima. The calculated absorption spectra enable the power and irradiation wavelength providing the required light effect to be selected. Relationships between the penetration depth and the diffuse reflectance coefficient of skin (unambiguously expressed through the absorption coefficient) are analyzed at different wavelengths. This makes it possible to find relationships between the light fields inside and outside the tissue.

  5. Triphenyltin alters lipid homeostasis in females of the ramshorn snail Marisa cornuarietis.

    Science.gov (United States)

    Lyssimachou, Angeliki; Navarro, Juan Carlos; Bachmann, Jean; Porte, Cinta

    2009-05-01

    Molluscs are sensitive species to the toxic effects of organotin compounds, particularly to masculinisation. Both tributyltin (TBT) and triphenyltin (TPT) have been recently shown to bind to mollusc retinoid X receptor (RXR). If RXR is involved in lipid homeostasis, exposure to TPT would have an immediate effect on endogenous lipids. To test this hypothesis, the ramshorn snail Marisa cornuarietis was exposed to environmentally relevant concentrations of TPT (30, 125, 500 ng/L as Sn) in a semi-static water regime for 7 days. Percentage of lipids and total fatty acid content decreased significantly in TPT-exposed females while the activity of peroxisomal acyl-CoA oxidase, involved in fatty acid catabolism, increased. In addition, fatty acid profiles (carbon chain length and unsaturation degree) were significantly altered in exposed females but not in males. This work highlights the ability of TPT to disrupt lipid metabolism in M. cornuarietis at environmentally realistic concentrations and the higher susceptibility of females in comparison to males.

  6. RESEARCHES ON THE PRODUCTIVE EFFECT OF A LIPID ABSORPTION IMPROVER, USED IN BROILERS FEEDING

    Directory of Open Access Journals (Sweden)

    I.M. POP

    2013-12-01

    Full Text Available According to the researches results, the chickens within the experimental groups performed better values for the live weight gain and for the feed conversion rate, as compared to those in the control group. Economically speaking, the revenue was 2,30-7,35% higher in the E2 group, which yield the best production parameters (highest live weight and lowest FCR, than those obtained by the chickens in the other studied groups.The best performances, considering all the parameters, were observed in E2 group, which received a concentration of 500 g feed additive (LB/tone of mixed fodder, in order to improve the lipids absorption rate in chickens gut.

  7. Complex and Multidimensional Lipid Raft Alterations in a Murine Model of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Wayne Chadwick

    2010-01-01

    Full Text Available Various animal models of Alzheimer's disease (AD have been created to assist our appreciation of AD pathophysiology, as well as aid development of novel therapeutic strategies. Despite the discovery of mutated proteins that predict the development of AD, there are likely to be many other proteins also involved in this disorder. Complex physiological processes are mediated by coherent interactions of clusters of functionally related proteins. Synaptic dysfunction is one of the hallmarks of AD. Synaptic proteins are organized into multiprotein complexes in high-density membrane structures, known as lipid rafts. These microdomains enable coherent clustering of synergistic signaling proteins. We have used mass analytical techniques and multiple bioinformatic approaches to better appreciate the intricate interactions of these multifunctional proteins in the 3xTgAD murine model of AD. Our results show that there are significant alterations in numerous receptor/cell signaling proteins in cortical lipid rafts isolated from 3xTgAD mice.

  8. Altered lipid and salt taste responsivity in ghrelin and GOAT null mice.

    Directory of Open Access Journals (Sweden)

    Huan Cai

    Full Text Available Taste perception plays an important role in regulating food preference, eating behavior and energy homeostasis. Taste perception is modulated by a variety of factors, including gastric hormones such as ghrelin. Ghrelin can regulate growth hormone release, food intake, adiposity, and energy metabolism. Octanoylation of ghrelin by ghrelin O-acyltransferase (GOAT is a specific post-translational modification which is essential for many biological activities of ghrelin. Ghrelin and GOAT are both widely expressed in many organs including the gustatory system. In the current study, overall metabolic profiles were assessed in wild-type (WT, ghrelin knockout (ghrelin(-/-, and GOAT knockout (GOAT(-/- mice. Ghrelin(-/- mice exhibited decreased food intake, increased plasma triglycerides and increased ketone bodies compared to WT mice while demonstrating WT-like body weight, fat composition and glucose control. In contrast GOAT(-/- mice exhibited reduced body weight, adiposity, resting glucose and insulin levels compared to WT mice. Brief access taste behavioral tests were performed to determine taste responsivity in WT, ghrelin(-/- and GOAT(-/- mice. Ghrelin and GOAT null mice possessed reduced lipid taste responsivity. Furthermore, we found that salty taste responsivity was attenuated in ghrelin(-/- mice, yet potentiated in GOAT(-/- mice compared to WT mice. Expression of the potential lipid taste regulators Cd36 and Gpr120 were reduced in the taste buds of ghrelin and GOAT null mice, while the salt-sensitive ENaC subunit was increased in GOAT(-/- mice compared with WT mice. The altered expression of Cd36, Gpr120 and ENaC may be responsible for the altered lipid and salt taste perception in ghrelin(-/- and GOAT(-/- mice. The data presented in the current study potentially implicates ghrelin signaling activity in the modulation of both lipid and salt taste modalities.

  9. Effect of nondigestible oligosaccharides on large-bowel functions, blood lipid concentrations and glucose absorption in young healthy male subjects

    NARCIS (Netherlands)

    Dokkum, W. van; Wezendonk, B.; Srikumar, T.S.; Heuvel, E.G.H.M. van den

    1999-01-01

    Objective: To study the effect of the intake of 15 g nondigestible oligosaccharides per day on various parameters of large-bowel function, as well as on blood lipid concentrations and glucose absorption in man. Design: Latin square, randomized, double-blind, diet-controlled. Setting: Metabolic resea

  10. Glucagon-like peptide 2 stimulates glucagon secretion, enhances lipid absorption, and inhibits gastric acid secretion in humans

    DEFF Research Database (Denmark)

    Meier, Juris J; Nauck, Michael A; Pott, Andrea;

    2006-01-01

    (P = .07). GLP-2 administration caused an approximately 15% reduction in pentagastrin-stimulated gastric acid and chloride secretion (P secretion but does not seem to have an influence on gastric...... emptying. The stimulation of glucagon secretion by GLP-2 may counteract the glucagonostatic effect of GLP-1. Changes in postprandial lipid excursions seem to reflect enhanced intestinal nutrient absorption during GLP-2 administration....

  11. Effect of quercetin against lindane induced alterations in the serum and hepatic tissue lipids in wistar rats

    Institute of Scientific and Technical Information of China (English)

    Viswanadha Vijaya Padma; Gurusamy Lalitha; Nicholson Puthanveedu Shirony; Rathinasamy Baskaran

    2012-01-01

    Objective: To assess the effect of quercetin (flavonoid) against lindane induced alterations in lipid profile of wistar rats. Methods: Rats were administered orally with lindane (100 mg/kg body weight) and quercetin (10 mg/kg body weight) for 30 days. After the end of treatment period lipid profile was estimated in serum and tissue. Results: Elevated levels of serum cholesterol, triglycerides, low density lipoprotein (LDL), very Low Density Lipoprotein (VLDL) and tissue triglycerides, cholesterol with concomitant decrease in serum HDL and tissue phospholipids were decreased in lindane treated rats were found to be significantly decreased in the quercetin and lindane co-treated rats. Conclusions: Our study suggests that quercetin has hypolipidemic effect and offers protection against lindane induced toxicity in liver by restoring the altered levels of lipids. The quercetin cotreatment along with lindane for 30 days reversed these biochemical alterations in lipids induced by lindane.

  12. SERUM LIPID PROFILE AND TRANSAMINASES LEVELS IN HIV PATIENTS ON HAART WITH ADIPOSE TISSUE ALTERATIONS

    Directory of Open Access Journals (Sweden)

    Vijay

    2016-02-01

    Full Text Available BACKGROUND HIV patients receiving highly active Anti-Retroviral Therapy (HAART usually suffer from side effects like hepatitis, neurological problems, abnormal fat distribution etc. Among these, the most physical, mental and cosmetically disturbing side effect is adipose tissue alterations (ATA, also called as lipodystrophy, which is abnormal fat deposition (Lipohypertrophy and/or fat atrophy (Lipoatrophy. AIM Several studies have shown dyslipidemia in patients on HAART, but there are very few studies on the lipid profile changes in patients on ART with ATA. Hence a study was conducted to assess the serum lipid profile and transaminases activity in patients on ART with ATA and also to evaluate whether lipid profile parameters can predict ATA changes in HIV patients on HAART. METHOD Randomly selected HIV positive patients, who were attending ART centre, were included in the study. Twenty five of these patients in whom HAART was yet to be started were considered as Control group, 25 patients on HAART for more than 12 months but without ATA as ART group and 23 patients on HAART with ATA as ATA group. Lipid profile and serum transaminases in all the groups were assayed by standard methods. RESULTS Serum cholesterol and LDL were significantly increased in ART group and ATA group when compared to control group, but there was no significant difference in lipid profile parameters between ART group and ATA group. Serum AST and ALT levels were significantly increased (p<0.02 in ATA group when compared to ART group. Buffalo hump was seen only in females in our study. Lipoatrophy (facial and limbs and central obesity was seen in males. CONCLUSION There was no significant change in lipid profile parameters in ATA group when compared with ART group. Hence lipid profile parameters are not good predictors of ATA changes in HIV patients on HAART. Significant increase in transaminase levels suggests increased hepatotoxity in ATA patients due to HAART drugs. There

  13. Terazosin-induced alterations in catalase expression and lipid peroxidation in the rat seminal vesicles.

    Science.gov (United States)

    Mitropoulos, D; Patris, E; Deliconstantinos, G; Kyroudi-Voulgari, A; Anastasiou, I; Perea, D

    2013-04-01

    Previous studies have shown that alpha1-adrenergic receptor antagonists may alter seminal vesicle contractility and impair fertility in male rats. This study was designed to investigate the effects of terazosin on the catalase expression in the seminal vesicles and the lipid peroxidation of the seminal fluid in normal adult rats. Wistar rats were treated with terazosin (1.2 mg kg(-1) body weight, given orally every second day) for 120 days. Catalase expression was assessed immunohistochemically in tissue sections of the seminal vesicles, and lipid peroxidation was estimated by measuring the malondialdehyde (MDA) levels in the seminal vesicles' fluid. The seminal vesicles in terazosin-treated rats were particularly distended in comparison with those of controls, and their secreting epithelium was suppressed. Cytoplasmic catalase expression in the secreting epithelial cells (% of cells) was increased in terazosin-treated specimens in comparison with controls (76.1 ± 17.1 versus 51.3 ± 25.1, P = 0.005). MDA levels (μm) were also higher in samples from treated subjects in comparison with controls (2.67 ± 1.19 versus 1.39 ± 0.19, P = 0.01). Although the direct effect of terazosin treatment on the seminal vesicles is that of impaired contractility, an indirect effect is that on fertility by increasing lipid peroxidation in the seminal fluid and/or through degrading of hydrogen peroxide that is essential for sperm capacitation.

  14. A STUDY ON ALTER ATION OF SERUM LIPID PROFILE IN GESTATIONAL PROTEINURIC HYPERTENSION

    Directory of Open Access Journals (Sweden)

    Evelyn

    2015-08-01

    Full Text Available BACKGROUND: Changes in lipid metabolism occurs in normal pregnancy during third trimester. This dyslipidemia indicative of insulin resistance is accentuated with Pre - eclampsia and Eclampsia. It contributes to both the pathogenesis of pre - eclampsia and to the risk of later - life cardiovascular disease in these patients. I have attempted to study the alterations in lipid profile in normal pregnancy, pre - eclampsia and eclampsia. MATERIALS AND METHODS: This study was conducted in Govt . Medical College for a period of 6 months. 25 normotensive non - pregnant women, 25 normal pregnant women, 25 pre eclampsia patients and 25 eclampsia patients were selected All the antenatal were in third trimester. Serum lipid profile was determined. Data analysis was done by excel sheet and SPSS software. RESULTS : Serum Triglycerides, VLDL, Total Cholesterol, LDL Cholesterol and HDL Cholesterol were significantly elevated in last trimester of normal pregnancy when compared to normal non - pregnant women. Also a significant increase in serum triglycerides and VLDL were seen in pre - eclampsia when compared to that of normal pregnancy. Also a significant decrease in HDL Cholesterol levels were seen in eclampsia when compared to normal pregnancy. CONCLUSION : Dyslipidemia suggestive of an exaggerated insulin resistance was found in pre eclampsia and eclampsia. Early interventions like prevention of obesity, exercise and balanced diet can reduce the risk of future cardiovascular morbidity and mortality in these patients.

  15. DHEA-mediated inhibition of the pentose phosphate pathway alters oocyte lipid metabolism in mice.

    Science.gov (United States)

    Jimenez, Patricia T; Frolova, Antonina I; Chi, Maggie M; Grindler, Natalia M; Willcockson, Alexandra R; Reynolds, Kasey A; Zhao, Quihong; Moley, Kelle H

    2013-12-01

    Women with polycystic ovary syndrome (PCOS) and hyperandrogenism have altered hormone levels and suffer from ovarian dysfunction leading to subfertility. We have attempted to generate a model of hyperandrogenism by feeding mice chow supplemented with dehydroepiandrosterone (DHEA), an androgen precursor that is often elevated in women with PCOS. Treated mice had polycystic ovaries, low ovulation rates, disrupted estrous cycles, and altered hormone levels. Because DHEA is an inhibitor of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme in the pentose phosphate pathway, we tested the hypothesis that oocytes from DHEA-exposed mice would have metabolic disruptions. Citrate levels, glucose-6-phosphate dehydrogenase activity, and lipid content in denuded oocytes from these mice were significantly lower than controls, suggesting abnormal tricarboxylic acid and pentose phosphate pathway metabolism. The lipid and citrate effects were reversible by supplementation with nicotinic acid, a precursor for reduced nicotinamide adenine dinucleotide phosphate. These findings suggest that elevations in systemic DHEA can have a negative impact on oocyte metabolism and may contribute to poor pregnancy outcomes in women with hyperandrogenism and PCOS.

  16. Recent discoveries on absorption of dietary fat: Presence, synthesis, and metabolism of cytoplasmic lipid droplets within enterocytes.

    Science.gov (United States)

    D'Aquila, Theresa; Hung, Yu-Han; Carreiro, Alicia; Buhman, Kimberly K

    2016-08-01

    Dietary fat provides essential nutrients, contributes to energy balance, and regulates blood lipid concentrations. These functions are important to health, but can also become dysregulated and contribute to diseases such as obesity, diabetes, cardiovascular disease, and cancer. Within enterocytes, the digestive products of dietary fat are re-synthesized into triacylglycerol, which is either secreted on chylomicrons or stored within cytoplasmic lipid droplets (CLDs). CLDs were originally thought to be inert stores of neutral lipids, but are now recognized as dynamic organelles that function in multiple cellular processes in addition to lipid metabolism. This review will highlight recent discoveries related to dietary fat absorption with an emphasis on the presence, synthesis, and metabolism of CLDs within this process. PMID:27108063

  17. Altered dynamics of a lipid raft associated protein in a kidney model of Fabry disease.

    Science.gov (United States)

    Labilloy, Anatália; Youker, Robert T; Bruns, Jennifer R; Kukic, Ira; Kiselyov, Kirill; Halfter, Willi; Finegold, David; do Monte, Semiramis Jamil Hadad; Weisz, Ora A

    2014-02-01

    Accumulation of globotriaosylceramide (Gb3) and other neutral glycosphingolipids with galactosyl residues is the hallmark of Fabry disease, a lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A (α-gal A). These lipids are incorporated into the plasma membrane and intracellular membranes, with a preference for lipid rafts. Disruption of raft mediated cell processes is implicated in the pathogenesis of several human diseases, but little is known about the effects of the accumulation of glycosphingolipids on raft dynamics in the context of Fabry disease. Using siRNA technology, we have generated a polarized renal epithelial cell model of Fabry disease in Madin-Darby canine kidney cells. These cells present increased levels of Gb3 and enlarged lysosomes, and progressively accumulate zebra bodies. The polarized delivery of both raft-associated and raft-independent proteins was unaffected by α-gal A knockdown, suggesting that accumulation of Gb3 does not disrupt biosynthetic trafficking pathways. To assess the effect of α-gal A silencing on lipid raft dynamics, we employed number and brightness (N&B) analysis to measure the oligomeric status and mobility of the model glycosylphosphatidylinositol (GPI)-anchored protein GFP-GPI. We observed a significant increase in the oligomeric size of antibody-induced clusters of GFP-GPI at the plasma membrane of α-gal A silenced cells compared with control cells. Our results suggest that the interaction of GFP-GPI with lipid rafts may be altered in the presence of accumulated Gb3. The implications of our results with respect to the pathogenesis of Fabry disease are discussed.

  18. Lipid alterations in experimental murine colitis: role of ceramide and imipramine for matrix metalloproteinase-1 expression.

    Directory of Open Access Journals (Sweden)

    Jessica Bauer

    Full Text Available BACKGROUND: Dietary lipids or pharmacologic modulation of lipid metabolism are potential therapeutic strategies in inflammatory bowel disease (IBD. Therefore, we analysed alterations of bioactive lipids in experimental models of colitis and examined the functional consequence of the second messenger ceramide in inflammatory pathways leading to tissue destruction. METHODOLOGY/PRINCIPAL FINDINGS: Chronic colitis was induced by dextran-sulphate-sodium (DSS or transfer of CD4(+CD62L(+ cells into RAG1(-/--mice. Lipid content of isolated murine intestinal epithelial cells (IEC was analysed by tandem mass spectrometry. Concentrations of MMP-1 in supernatants of Caco-2-IEC and human intestinal fibroblasts from patients with ulcerative colitis were determined by ELISA. Imipramine was used for pharmacologic inhibition of acid sphingomyelinase (ASM. Ceramide increased by 71% in chronic DSS-induced colitis and by 159% in the transfer model of colitis. Lysophosphatidylcholine (LPC decreased by 22% in both models. No changes were detected for phosphatidylcholine. Generation of ceramide by exogenous SMase increased MMP-1-protein production of Caco-2-IEC up to 7-fold. Inhibition of ASM completely abolished the induction of MMP-1 by TNF or IL-1beta in Caco-2-IEC and human intestinal fibroblasts. CONCLUSIONS/SIGNIFICANCE: Mucosal inflammation leads to accumulation of ceramide and decrease of LPC in the intestinal epithelium. One aspect of ceramide generation is an increase of MMP-1. Induction of MMP-1 by TNF or IL-1beta is completely blocked by inhibition of ASM with imipramine. Therefore, inhibition of ASM may offer a treatment strategy to reduce MMP-1 expression and tissue destruction in inflammatory conditions.

  19. Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions

    Institute of Scientific and Technical Information of China (English)

    Carol L Fischer; Katherine S Walters; David R Drake; Deborah V Dawson; Derek R Blanchette; Kim A Brogden; Philip W Wertz

    2013-01-01

    Oral mucosal and salivary lipids exhibit potent antimicrobial activity for a variety of Gram-positive and Gram-negative bacteria;however, little is known about their spectrum of antimicrobial activity or mechanisms of action against oral bacteria. In this study, we examine the activity of two fatty acids and three sphingoid bases against Porphyromonas gingivalis, an important colonizer of the oral cavity implicated in periodontitis. Minimal inhibitory concentrations, minimal bactericidal concentrations, and kill kinetics revealed variable, but potent, activity of oral mucosal and salivary lipids against P. gingivalis, indicating that lipid structure may be an important determinant in lipid mechanisms of activity against bacteria, although specific components of bacterial membranes are also likely important. Electron micrographs showed ultrastructural damage induced by sapienic acid and phytosphingosine and confirmed disruption of the bacterial plasma membrane. This information, coupled with the association of treatment lipids with P. gingivalis lipids revealed via thin layer chromatography, suggests that the plasma membrane is a likely target of lipid antibacterial activity. Utilizing a combination of two-dimensional in-gel electrophoresis and Western blot followed by mass spectroscopy and N-terminus degradation sequencing we also show that treatment with sapienic acid induces upregulation of a set of proteins comprising a unique P. gingivalis stress response, including proteins important in fatty acid biosynthesis, metabolism and energy production, protein processing, cell adhesion and virulence. Prophylactic or therapeutic lipid treatments may be beneficial for intervention of infection by supplementing the natural immune function of endogenous lipids on mucosal surfaces.

  20. Untargeted Metabolomics Reveals Predominant Alterations in Lipid Metabolism Following Light Exposure in Broccoli Sprouts.

    Science.gov (United States)

    Maldini, Mariateresa; Natella, Fausta; Baima, Simona; Morelli, Giorgio; Scaccini, Cristina; Langridge, James; Astarita, Giuseppe

    2015-01-01

    The consumption of vegetables belonging to the family Brassicaceae (e.g., broccoli and cauliflower) is linked to a reduced incidence of cancer and cardiovascular diseases. The molecular composition of such plants is strongly affected by growing conditions. Here we developed an unbiased metabolomics approach to investigate the effect of light and dark exposure on the metabolome of broccoli sprouts and we applied such an approach to provide a bird's-eye view of the overall metabolic response after light exposure. Broccoli seeds were germinated and grown hydroponically for five days in total darkness or with a light/dark photoperiod (16 h light/8 h dark cycle). We used an ultra-performance liquid-chromatography system coupled to an ion-mobility, time-of-flight mass spectrometer to profile the large array of metabolites present in the sprouts. Differences at the metabolite level between groups were analyzed using multivariate statistical analyses, including principal component analysis and correlation analysis. Altered metabolites were identified by searching publicly available and in-house databases. Metabolite pathway analyses were used to support the identification of subtle but significant changes among groups of related metabolites that may have gone unnoticed with conventional approaches. Besides the chlorophyll pathway, light exposure activated the biosynthesis and metabolism of sterol lipids, prenol lipids, and polyunsaturated lipids, which are essential for the photosynthetic machinery. Our results also revealed that light exposure increased the levels of polyketides, including flavonoids, and oxylipins, which play essential roles in the plant's developmental processes and defense mechanism against herbivores. This study highlights the significant contribution of light exposure to the ultimate metabolic phenotype, which might affect the cellular physiology and nutritional value of broccoli sprouts. Furthermore, this study highlights the potential of an

  1. Untargeted Metabolomics Reveals Predominant Alterations in Lipid Metabolism Following Light Exposure in Broccoli Sprouts

    Directory of Open Access Journals (Sweden)

    Mariateresa Maldini

    2015-06-01

    Full Text Available The consumption of vegetables belonging to the family Brassicaceae (e.g., broccoli and cauliflower is linked to a reduced incidence of cancer and cardiovascular diseases. The molecular composition of such plants is strongly affected by growing conditions. Here we developed an unbiased metabolomics approach to investigate the effect of light and dark exposure on the metabolome of broccoli sprouts and we applied such an approach to provide a bird’s-eye view of the overall metabolic response after light exposure. Broccoli seeds were germinated and grown hydroponically for five days in total darkness or with a light/dark photoperiod (16 h light/8 h dark cycle. We used an ultra-performance liquid-chromatography system coupled to an ion-mobility, time-of-flight mass spectrometer to profile the large array of metabolites present in the sprouts. Differences at the metabolite level between groups were analyzed using multivariate statistical analyses, including principal component analysis and correlation analysis. Altered metabolites were identified by searching publicly available and in-house databases. Metabolite pathway analyses were used to support the identification of subtle but significant changes among groups of related metabolites that may have gone unnoticed with conventional approaches. Besides the chlorophyll pathway, light exposure activated the biosynthesis and metabolism of sterol lipids, prenol lipids, and polyunsaturated lipids, which are essential for the photosynthetic machinery. Our results also revealed that light exposure increased the levels of polyketides, including flavonoids, and oxylipins, which play essential roles in the plant’s developmental processes and defense mechanism against herbivores. This study highlights the significant contribution of light exposure to the ultimate metabolic phenotype, which might affect the cellular physiology and nutritional value of broccoli sprouts. Furthermore, this study highlights the

  2. Exogenous Alpha-Synuclein Alters Pre- and Post-Synaptic Activity by Fragmenting Lipid Rafts.

    Science.gov (United States)

    Emanuele, Marco; Esposito, Alessandro; Camerini, Serena; Antonucci, Flavia; Ferrara, Silvia; Seghezza, Silvia; Catelani, Tiziano; Crescenzi, Marco; Marotta, Roberto; Canale, Claudio; Matteoli, Michela; Menna, Elisabetta; Chieregatti, Evelina

    2016-05-01

    Alpha-synuclein (αSyn) interferes with multiple steps of synaptic activity at pre-and post-synaptic terminals, however the mechanism/s by which αSyn alters neurotransmitter release and synaptic potentiation is unclear. By atomic force microscopy we show that human αSyn, when incubated with reconstituted membrane bilayer, induces lipid rafts' fragmentation. As a consequence, ion channels and receptors are displaced from lipid rafts with consequent changes in their activity. The enhanced calcium entry leads to acute mobilization of synaptic vesicles, and exhaustion of neurotransmission at later stages. At the post-synaptic terminal, an acute increase in glutamatergic transmission, with increased density of PSD-95 puncta, is followed by disruption of the interaction between N-methyl-d-aspartate receptor (NMDAR) and PSD-95 with ensuing decrease of long term potentiation. While cholesterol loading prevents the acute effect of αSyn at the presynapse; inhibition of casein kinase 2, which appears activated by reduction of cholesterol, restores the correct localization and clustering of NMDARs.

  3. Exogenous Alpha-Synuclein Alters Pre- and Post-Synaptic Activity by Fragmenting Lipid Rafts

    Directory of Open Access Journals (Sweden)

    Marco Emanuele

    2016-05-01

    Full Text Available Alpha-synuclein (αSyn interferes with multiple steps of synaptic activity at pre-and post-synaptic terminals, however the mechanism/s by which αSyn alters neurotransmitter release and synaptic potentiation is unclear. By atomic force microscopy we show that human αSyn, when incubated with reconstituted membrane bilayer, induces lipid rafts' fragmentation. As a consequence, ion channels and receptors are displaced from lipid rafts with consequent changes in their activity. The enhanced calcium entry leads to acute mobilization of synaptic vesicles, and exhaustion of neurotransmission at later stages. At the post-synaptic terminal, an acute increase in glutamatergic transmission, with increased density of PSD-95 puncta, is followed by disruption of the interaction between N-methyl-d-aspartate receptor (NMDAR and PSD-95 with ensuing decrease of long term potentiation. While cholesterol loading prevents the acute effect of αSyn at the presynapse; inhibition of casein kinase 2, which appears activated by reduction of cholesterol, restores the correct localization and clustering of NMDARs.

  4. Chronic consumption of fructose rich soft drinks alters tissue lipids of rats

    Directory of Open Access Journals (Sweden)

    Botezelli Jose D

    2010-06-01

    Full Text Available Abstract Background Fructose-based diets are apparently related to the occurrence of several metabolic dysfunctions, but the effects of the consumption of high amounts of fructose on body tissues have not been well described. The aim of this study was to analyze the general characteristics and the lipid content of different tissues of rats after chronic ingestion of a fructose rich soft drink. Methods Forty-five Wistar rats were used. The rats were divided into three groups (n = 15 and allowed to consume water (C, light Coca Cola ® (L or regular Coca Cola® (R as the sole source of liquids for eight weeks. Results The R group presented significantly higher daily liquid intake and significantly lower food intake than the C and L groups. Moreover, relative to the C and L groups, the R group showed higher triglyceride concentrations in the serum and liver. However, the L group animals presented lower values of serum triglycerides and cholesterol than controls. Conclusions Based on the results, it can be concluded that daily ingestion of a large amount of fructose- rich soft drink resulted in unfavorable alterations to the lipid profile of the rats.

  5. Dietary inulin alters the intestinal absorptive and barrier function of piglet intestine after weaning.

    Science.gov (United States)

    Awad, Wageha A; Ghareeb, Khaled; Paßlack, Nadine; Zentek, Jürgen

    2013-08-01

    glucose across the jejunal mucosa of weaned piglets indicating higher glucose absorption. Furthermore, the Gt was higher in the inulin-supplemented weaned piglets than in control piglets, which could be due to the increased paracellular permeability to Na(+). In conclusion, dietary inulin increased the glucose transport and altered the intestinal barrier by increasing the intestinal permeability in the jejunal mucosa of post-weaned piglets. Furthermore, the results indicated that inulin has a positive effect on glucose absorption in the piglet small intestine after weaning and subsequently the dietary inulin offers a promising approach to avoid post-weaning gastrointestinal tract disorders in pigs.

  6. The Development of Digestion and Absorption and the Energy Protein Lipid and Carbohydrate Requirements of the Premature Infants

    OpenAIRE

    Aydın, Ahmet; Çam, Halit; Fıçıcıoğlu, Can; Mıkla, Şerare

    1994-01-01

    Premature infants have high energy and nutrient requirements for their rapid growth The knowledge of the development of salivary gastric biliary and intestinal enzymes and factors involved in digestion and absorption plays important roles in the choice of the feeding constituents In this review we shall discuss the protein lipid and carbohydrate requirements of the premature infants and the importance of breast feeding Key words: Premature Infant Nutriton Gastrointestinal Functions

  7. Plasma lipids, lipoprotein metabolism and HDL lipid transfers are equally altered in metabolic syndrome and in type 2 diabetes.

    Science.gov (United States)

    Silva, Vanessa M; Vinagre, Carmen G C; Dallan, Luis A O; Chacra, Ana P M; Maranhão, Raul C

    2014-07-01

    Metabolic syndrome (MetS) refers to states of insulin resistance that predispose to development of cardiovascular disease and type 2 diabetes (T2DM). The aim was to investigate whether plasma lipids and lipid metabolism differ in MetS patients compared to those with T2DM with poor glycemic control (glycated hemoglobin > 7.0). Eighteen patients with T2DM, 18 with MetS and 14 controls, paired for age (40-70 years) and body mass index (BMI), were studied. Plasma lipids and the kinetics of a triacylglycerol-rich emulsion labeled with [(3)H]-triolein ([(3)H]-TAG) and [(14)C]-cholesteryl esters ([(14)C]-CE) injected intravenously followed by one-hour blood sampling were determined. Lipid transfers from an artificial nanoemulsion donor to high-density lipoprotien (HDL) were assayed in vitro. Low-density lipoprotein (LDL) and HDL cholesterol (mg/dl) were not different in T2DM (128 ± 7; 42 ± 7) and MetS (142 ± 6; 39 ± 3), but triacylglycerols were even higher in MetS (215 ± 13) than in T2DM (161 ±11, p lipid metabolism examined here, and suggest that there are different thresholds for the insulin action on glucose and lipids. These findings highlight the magnitude of the lipid disturbances in MetS, and may have implications in the prevention of cardiovascular diseases.

  8. Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yansong [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Feng, Jianghua, E-mail: jianghua.feng@xmu.edu.cn [Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071 (China); Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, 361005 (China); Kou, Hao; Liang, Gai [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin [Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China)

    2012-07-15

    The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by {sup 1}H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine

  9. Altered Lipid Synthesis by Lack of Yeast Pah1 Phosphatidate Phosphatase Reduces Chronological Life Span.

    Science.gov (United States)

    Park, Yeonhee; Han, Gil-Soo; Mileykovskaya, Eugenia; Garrett, Teresa A; Carman, George M

    2015-10-16

    In Saccharomyces cerevisiae, Pah1 phosphatidate phosphatase, which catalyzes the dephosphorylation of phosphatidate to yield diacylglycerol, plays a crucial role in the synthesis of the storage lipid triacylglycerol. This evolutionarily conserved enzyme also plays a negative regulatory role in controlling de novo membrane phospholipid synthesis through its consumption of phosphatidate. We found that the pah1Δ mutant was defective in the utilization of non-fermentable carbon sources but not in oxidative phosphorylation; the mutant did not exhibit major changes in oxygen consumption rate, mitochondrial membrane potential, F1F0-ATP synthase activity, or gross mitochondrial morphology. The pah1Δ mutant contained an almost normal complement of major mitochondrial phospholipids with some alterations in molecular species. Although oxidative phosphorylation was not compromised in the pah1Δ mutant, the cellular levels of ATP in quiescent cells were reduced by 2-fold, inversely correlating with a 4-fold increase in membrane phospholipids. In addition, the quiescent pah1Δ mutant cells had 3-fold higher levels of mitochondrial superoxide and cellular lipid hydroperoxides, had reduced activities of superoxide dismutase 2 and catalase, and were hypersensitive to hydrogen peroxide. Consequently, the pah1Δ mutant had a shortened chronological life span. In addition, the loss of Tsa1 thioredoxin peroxidase caused a synthetic growth defect with the pah1Δ mutation. The shortened chronological life span of the pah1Δ mutant along with its growth defect on non-fermentable carbon sources and hypersensitivity to hydrogen peroxide was suppressed by the loss of Dgk1 diacylglycerol kinase, indicating that the underpinning of pah1Δ mutant defects was the excess synthesis of membrane phospholipids. PMID:26338708

  10. Obesity alters the gustatory perception of lipids in the mouse: plausible involvement of lingual CD36[S

    Science.gov (United States)

    Chevrot, Michael; Bernard, Arnaud; Ancel, Déborah; Buttet, Marjorie; Martin, Céline; Abdoul-Azize, Souleymane; Merlin, Jean-François; Poirier, Hélène; Niot, Isabelle; Khan, Naim Akhtar; Passilly-Degrace, Patricia; Besnard, Philippe

    2013-01-01

    A relationship between orosensory detection of dietary lipids, regulation of fat intake, and body mass index was recently suggested. However, involved mechanisms are poorly understood. Moreover, whether obesity can directly modulate preference for fatty foods remains unknown. To address this question, exploration of the oral lipid sensing system was undertaken in diet-induced obese (DIO) mice. By using a combination of biochemical, physiological, and behavioral approaches, we found that i) the attraction for lipids is decreased in obese mice, ii) this behavioral change has an orosensory origin, iii) it is reversed in calorie-restricted DIO mice, revealing an inverse correlation between fat preference and adipose tissue size, iv) obesity suppresses the lipid-mediated downregulation of the lipid-sensor CD36 in circumvallate papillae, usually found during the refeeding of lean mice, and v) the CD36-dependent signaling cascade controlling the intracellular calcium levels ([Ca2+]i) in taste bud cells is decreased in obese mice. Therefore, obesity alters the lipid-sensing system responsible for the oral perception of dietary lipids. This phenomenon seems to take place through a CD36-mediated mechanism, leading to changes in eating behavior. PMID:23840049

  11. Lipid droplet analysis in caveolin-deficient adipocytes: alterations in surface phospholipid composition and maturation defects

    OpenAIRE

    Blouin, C. M.; Le Lay, S.; Eberl, A.; Kofeler, H. C.; Guerrera, I. C.; Klein, C.; Le Liepvre, X.; Lasnier, F.; Bourron, O.; Gautier, J. F.; Ferre, P.; Hajduch, E.; Dugail, I.

    2010-01-01

    Caveolins form plasmalemnal invaginated caveolae. They also locate around intracellular lipid droplets but their role in this location remains unclear. By studying primary adipocytes that highly express caveolin-1, we characterized the impact of caveolin-1 deficiency on lipid droplet proteome and lipidome. We identified several missing proteins on the lipid droplet surface of caveolin-deficient adipocytes and showed that the caveolin-1 lipid droplet pool is organized as multi-protein complexe...

  12. Plasma lipids, lipoprotein metabolism and HDL lipid transfers are equally altered in metabolic syndrome and in type 2 diabetes.

    Science.gov (United States)

    Silva, Vanessa M; Vinagre, Carmen G C; Dallan, Luis A O; Chacra, Ana P M; Maranhão, Raul C

    2014-07-01

    Metabolic syndrome (MetS) refers to states of insulin resistance that predispose to development of cardiovascular disease and type 2 diabetes (T2DM). The aim was to investigate whether plasma lipids and lipid metabolism differ in MetS patients compared to those with T2DM with poor glycemic control (glycated hemoglobin > 7.0). Eighteen patients with T2DM, 18 with MetS and 14 controls, paired for age (40-70 years) and body mass index (BMI), were studied. Plasma lipids and the kinetics of a triacylglycerol-rich emulsion labeled with [(3)H]-triolein ([(3)H]-TAG) and [(14)C]-cholesteryl esters ([(14)C]-CE) injected intravenously followed by one-hour blood sampling were determined. Lipid transfers from an artificial nanoemulsion donor to high-density lipoprotien (HDL) were assayed in vitro. Low-density lipoprotein (LDL) and HDL cholesterol (mg/dl) were not different in T2DM (128 ± 7; 42 ± 7) and MetS (142 ± 6; 39 ± 3), but triacylglycerols were even higher in MetS (215 ± 13) than in T2DM (161 ±11, p < 0.05). Fractional clearance rate (FCR, in min(1)) of [(3)H]-TAG and [(14)C]-CE were equal in T2DM (0.008 ± 0.018; 0.005 ± 0.024) and MetS (0.010 ± 0.016; 0.006 ± 0.013), and both were reduced compared to controls. The transfer of non-esterified cholesterol, phospholipids and triacylglycerols to HDL was higher in MetS and T2DM than in controls (p < 0.01). Cholesteryl ester transfer and HDL size were equal in all groups. Results imply that MetS is equal to poorly controlled T2DM concerning the disturbances of plasma lipid metabolism examined here, and suggest that there are different thresholds for the insulin action on glucose and lipids. These findings highlight the magnitude of the lipid disturbances in MetS, and may have implications in the prevention of cardiovascular diseases. PMID:24719245

  13. Enhanced gastrointestinal absorption of N{sub 3}-O-toluyl-fluorouracil by cationic solid lipid nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Liu Donghua; Liu Chunxi; Zou Weiwei; Zhang Na, E-mail: zhangnancy9@sdu.edu.c [Shandong University, The School of Pharmaceutical Science (China)

    2010-03-15

    This study was aimed to prepare N{sub 3}-O-toluyl-fluorouracil (TFu) loaded cationic solid lipid nanoparticles (TFu-SLNs) and evaluate the potential of a novel lipid-based drug delivery system to enhance the oral absorption of TFu. TFu-SLNs were prepared by the film dispersion-ultrasonication method, using hexadecyltrimethylammonium bromide as cationic tenside. The formulation and manufacture parameters were optimized concerning the drug encapsulation efficiency and the particle size. The in vitro release characteristics, in vivo pharmacokinetic properties and bioavailability, and in situ intestinal absorption features were investigated. The morphology of TFu-SLNs was approximately spherical and the mean particle size was 178.8 {+-} 9.99 nm; the zeta potential was +19.54 {+-} 0.32 mV. The mean entrapment efficiency and drug loading were 71.03 {+-} 1.19% and 3.57 {+-} 0.08%, respectively. The release behaviors of TFu from TFu-SLNs in PBS were fitted to the bioexponential model, while in artificial gastric juice, artificial intestinal juice and artificial gastric juice (2 h) followed by artificial intestinal juice (2-48 h) were fitted to the Weibull equation. The results of the pharmacokinetic studies in mice showed that the bioavailability of TFu-SLNs was significantly increased compared with that of the TFu suspensions after oral administration. The absorption of TFu-SLNs in intestine of rat was fitted to first-order kinetics with passive diffusion mechanism and the main segments of TFu-SLNs absorbed in intestine were duodenum and jejunum for the bioadhesion mediated by electrostatic interaction between the positively charged colloidal particles and the negatively charged mucosal surface. These results indicated that cationic SLNs would offer a promising delivery system for the facilitation of the bioavailability of poorly oral absorption drugs by enhancing the bioadhesion between the absorption mucosal surface and the drug carriers.

  14. Supplementation with complex milk lipids during brain development promotes neuroplasticity without altering myelination or vascular density

    Directory of Open Access Journals (Sweden)

    Rosamond B. Guillermo

    2015-03-01

    Full Text Available Background: Supplementation with complex milk lipids (CML during postnatal brain development has been shown to improve spatial reference learning in rats. Objective: The current study examined histo-biological changes in the brain following CML supplementation and their relationship to the observed improvements in memory. Design: The study used the brain tissues from the rats (male Wistar, 80 days of age after supplementing with either CML or vehicle during postnatal day 10–80. Immunohistochemical staining of synaptophysin, glutamate receptor-1, myelin basic protein, isolectin B-4, and glial fibrillary acidic protein was performed. The average area and the density of the staining and the numbers of astrocytes and capillaries were assessed and analysed. Results: Compared with control rats, CML supplementation increased the average area of synaptophysin staining and the number of GFAP astrocytes in the CA3 sub-region of the hippocampus (p<0.01, but not in the CA4 sub-region. The supplementation also led to an increase in dopamine output in the striatum that was related to nigral dopamine expression (p<0.05, but did not alter glutamate receptors, myelination or vascular density. Conclusion: CML supplementation may enhance neuroplasticity in the CA3 sub-regions of the hippocampus. The brain regions-specific increase of astrocyte may indicate a supporting role for GFAP in synaptic plasticity. CML supplementation did not associate with postnatal white matter development or vascular remodelling.

  15. Alteration of membrane lipid biophysical properties and resistance of human lung adenocarcinoma A549 cells to cisplatin

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Alterations of membrane lipid biophysical properties of sensitiveA549 and resistant A549/DDP cells to the Cis-dichlorodiammine platinum (Cisplatin) were performed by measurements of fluorescence and flow cytometry approaches using fluorescence dyes of DPH, N-AS and Merocyanine 540 (MC 540) respectively. Fatty acids of membrane lipid of the two cell lines were analyzed by gas chromatography. The results indicated clearly that fluorescence polarization (P) of the DPH probe is 0.169 for the sensitive A549 cell and 0.194 for the resistant A549/DDP cells. Statistical analysis showed significant difference between the two cell lines. The polarizations of 2-AS and 7-AS which reflect the fluidity of surface and middle of lipid bilayer are 0.134 and 0.144 for the sensitive A549 cells as well as 0.171 and 0.178 for the resistant A549/DDP cells respectively, but there is no significant difference of the polarization of 12-AS between the two cell lines. This shows that altera-tions of the membrane fluidity of both cells were mainly located on the surface and middle of the lipid bilayer. In addition, the packing density of phospholipid molecules in the membrane of the two cell lines detected by MC540 probe indicated that lipid packing of A549 cell membranes was looser than that of the A549/DDP cells. And unsaturation degree of plasma membrane fatty acids of the A549/DDP cells was also lower than that of A549 cells. Taken together, it was proposed that the al-teration of membrane lipid biophysical state may be involved in the resistance of A549/DDP cells to cisplatin.

  16. Phytotoxic Mechanism of Nanoparticles: Destruction of Chloroplasts and Vascular Bundles and Alteration of Nutrient Absorption.

    Science.gov (United States)

    Nhan, Le Van; Ma, Chuanxin; Rui, Yukui; Liu, Shutong; Li, Xuguang; Xing, Baoshan; Liu, Liming

    2015-01-01

    This study focused on determining the phytotoxic mechanism of CeO2 nanoparticles (NPs): destroying chloroplasts and vascular bundles and altering absorption of nutrients on conventional and Bt-transgenic cottons. Experiments were designed with three concentrations of CeO2 NPs including: 0, 100 and 500 mg·L(-1), and each treatment was three replications. Results indicate that absorbed CeO2 nanoparticles significantly reduced the Zn, Mg, Fe, and P levels in xylem sap compared with the control group and decreased indole-3-acetic acid (IAA) and abscisic acid (ABA) concentrations in the roots of conventional cotton. Transmission electron microscopy (TEM) images revealed that CeO2 NPs were absorbed into the roots and subsequently transported to the stems and leaves of both conventional and Bt-transgenic cotton plants via xylem sap. In addition, the majority of aggregated CeO2 NPs were attached to the external surface of chloroplasts, which were swollen and ruptured, especially in Bt-transgenic cotton. The vascular bundles were destroyed by CeO2 nanoparticles, and more damage was observed in transgenic cotton than conventional cotton. PMID:26108166

  17. In vitro approach to the mechanics of lipid membrane area regulation: vesicle absorption and tube formation

    Science.gov (United States)

    Staykova, Margarita; Holmes, Douglas; Read, Clarke; Stone, Howard A.

    2011-03-01

    We have designed an experimental approach that allows us to study the response of supported lipid bilayers to cycles of biaxial expansion and compression. We observed that the bilayer effectively adjusts its area during dilatational or compressive strains in order to reduce its tension. For example, if there is a sufficient lipid reservoir in the form of attached vesicles, then a lipid bilayer may accommodate strains tens of times larger than the critical strain for rupture by expanding its area. Additionally, upon compression the bilayer reduces its area by expelling lipid tubes out of its plane. These observations offer new insights into how cells regulate their surface area in response to various mechanical stimuli, i.e. during physiological volume changes, locomotion, cyclic expansion and compression of the uro- and the alveolar- epithelium, etc.

  18. Alterations in Lipid Levels of Mitochondrial Membranes Induced by Amyloid-β: A Protective Role of Melatonin

    Science.gov (United States)

    Rosales-Corral, Sergio A.; Lopez-Armas, Gabriela; Cruz-Ramos, Jose; Melnikov, Valery G.; Tan, Dun-Xian; Manchester, Lucien C.; Munoz, Ruben; Reiter, Russel J.

    2012-01-01

    Alzheimer pathogenesis involves mitochondrial dysfunction, which is closely related to amyloid-β (Aβ) generation, abnormal tau phosphorylation, oxidative stress, and apoptosis. Alterations in membranal components, including cholesterol and fatty acids, their characteristics, disposition, and distribution along the membranes, have been studied as evidence of cell membrane alterations in AD brain. The majority of these studies have been focused on the cytoplasmic membrane; meanwhile the mitochondrial membranes have been less explored. In this work, we studied lipids and mitochondrial membranes in vivo, following intracerebral injection of fibrillar amyloid-β (Aβ). The purpose was to determine how Aβ may be responsible for beginning of a vicious cycle where oxidative stress and alterations in cholesterol, lipids and fatty acids, feed back on each other to cause mitochondrial dysfunction. We observed changes in mitochondrial membrane lipids, and fatty acids, following intracerebral injection of fibrillar Aβ in aged Wistar rats. Melatonin, a well-known antioxidant and neuroimmunomodulator indoleamine, reversed some of these alterations and protected mitochondrial membranes from obvious damage. Additionally, melatonin increased the levels of linolenic and n-3 eicosapentaenoic acid, in the same site where amyloid β was injected, favoring an endogenous anti-inflammatory pathway. PMID:22666620

  19. Alterations in Lipid Levels of Mitochondrial Membranes Induced by Amyloid-ß: A Protective Role of Melatonin

    Directory of Open Access Journals (Sweden)

    Sergio A. Rosales-Corral

    2012-01-01

    Full Text Available Alzheimer pathogenesis involves mitochondrial dysfunction, which is closely related to amyloid-ß (Aß generation, abnormal tau phosphorylation, oxidative stress, and apoptosis. Alterations in membranal components, including cholesterol and fatty acids, their characteristics, disposition, and distribution along the membranes, have been studied as evidence of cell membrane alterations in AD brain. The majority of these studies have been focused on the cytoplasmic membrane; meanwhile the mitochondrial membranes have been less explored. In this work, we studied lipids and mitochondrial membranes in vivo, following intracerebral injection of fibrillar amyloid-ß (Aß. The purpose was to determine how Aß may be responsible for beginning of a vicious cycle where oxidative stress and alterations in cholesterol, lipids and fatty acids, feed back on each other to cause mitochondrial dysfunction. We observed changes in mitochondrial membrane lipids, and fatty acids, following intracerebral injection of fibrillar Aß in aged Wistar rats. Melatonin, a well-known antioxidant and neuroimmunomodulator indoleamine, reversed some of these alterations and protected mitochondrial membranes from obvious damage. Additionally, melatonin increased the levels of linolenic and n-3 eicosapentaenoic acid, in the same site where amyloid ß was injected, favoring an endogenous anti-inflammatory pathway.

  20. The C-terminal Cytosolic Region of Rim21 Senses Alterations in Plasma Membrane Lipid Composition: INSIGHTS INTO SENSING MECHANISMS FOR PLASMA MEMBRANE LIPID ASYMMETRY.

    Science.gov (United States)

    Nishino, Kanako; Obara, Keisuke; Kihara, Akio

    2015-12-25

    Yeast responds to alterations in plasma membrane lipid asymmetry and external alkalization via the sensor protein Rim21 in the Rim101 pathway. However, the sensing mechanism used by Rim21 remains unclear. Here, we found that the C-terminal cytosolic domain of Rim21 (Rim21C) fused with GFP was associated with the plasma membrane under normal conditions but dissociated upon alterations in lipid asymmetry or external alkalization. This indicates that Rim21C contains a sensor motif. Rim21C contains multiple clusters of charged residues. Among them, three consecutive Glu residues (EEE motif) were essential for Rim21 function and dissociation of Rim21C from the plasma membrane in response to changes in lipid asymmetry. In contrast, positively charged residues adjacent to the EEE motif were required for Rim21C to associate with the membrane. We therefore propose an "antenna hypothesis," in which Rim21C moves to or from the plasma membrane and functions as the sensing mechanism of Rim21.

  1. Aquaporins in ovine amnion: responses to altered amniotic fluid volumes and intramembranous absorption rates.

    Science.gov (United States)

    Cheung, Cecilia Y; Anderson, Debra F; Brace, Robert A

    2016-07-01

    Aquaporins (AQPs) are transmembrane channel proteins that facilitate rapid water movement across cell membranes. In amniotic membrane, the AQP-facilitated transfer of water across amnion cells has been proposed as a mechanism for amniotic fluid volume (AFV) regulation. To investigate whether AQPs modulate AFV by altering intramembranous absorption (IMA) rate, we tested the hypothesis that AQP gene expression in the amnion is positively correlated with IMA rate during experimental conditions when IMA rate and AFV are modified over a wide range. The relative abundances of AQP1, AQP3, AQP8, AQP9, and AQP11 mRNA and protein were determined in the amnion of 16 late-gestation ovine fetuses subjected to 2 days of control conditions, urine drainage, urine replacement, or intraamniotic fluid infusion. AQP mRNA levels were determined by RT-qPCR and proteins by western immunoblot. Under control conditions, mRNA levels among the five AQPs differed more than 20-fold. During experimental treatments, mean IMA rate in the experimental groups ranged from 100 ± 120 mL/day to 1370 ± 270 mL/day. The mRNA levels of the five AQPs did not change from control and were not correlated with IMA rates. The protein levels of AQP1 were positively correlated with IMA rates (r(2) = 38%, P = 0.01) while the remaining four AQPs were not. These findings demonstrate that five AQPs are differentially expressed in ovine amnion. Our study supports the hypothesis that AQP1 may play a positive role in regulating the rate of fluid transfer across the amnion, thereby participating in the dynamic regulation of AFV.

  2. Plasma membrane lipid alterations associated with cold acclimation of winter rye seedlings (Secale cereale L. cv Puma)

    Energy Technology Data Exchange (ETDEWEB)

    Lynch, D.V.; Steponkus, P.L. (Cornell Univ., Ithaca, NY (USA))

    1987-01-01

    Highly enriched plasma membrane fractions were isolated from leaves of nonacclimated (NA) and acclimated (ACC) rye (Secale cereale L. cv Puma) seedlings. Collectively, free sterols, steryl glucosides, and acylated steryl glucosides constituted > 50 mole % of the total lipid in both NA and ACC plasma membrane fractions. Glucocerebrosides containing hydroxy fatty acids constituted the major glycolipid class of the plasma membrane, accounting for 16 mole % of the total lipid. Phospholipids, primarily phosphatidylcholine and phosphatidylethanolamine with lesser amounts of phosphatidylglycerol, phosphatidic acid, phosphatidylserine, and phosphatidylinositol, comprised only 32 mole% of the total lipid in NA samples. Following cold acclimation, free sterols increased from 33 to 44 mole %, while steryl glucosides and acylated steryl glucosides decreased from 15 to 6 mole % and 4 to 1 mole %, respectively. Sterol analyses of these lipid classes demonstrated that free {beta}-sitosterol increased from 21 to 32 mole % (accounting for the increase in free sterols as a class) at the expense of sterol derivatives containing {beta}-sitosterol. Glucocerebrosides decreased from 16 to 7 mole % of the total lipid following cold acclimation. In addition, the relative proportions of associated hydroxy fatty acids, including 22:0 (h), 24:0 (h), 22:1 (h), and 24:1 (h) were altered. The phospholipid content of the plasma membrane fraction increased to 42 mole % of the total lipid following cold acclimation. Although the relative proportions of the individual phospholipids did not change appreciably after cold acclimation, there were substantial differences in the molecular species. Di-unsaturated molecular species of phosphatidylcholine and phosphatidylethanolamine increased following acclimation. These results demonstrate that cold acclimation results in substantial changes in the lipid composition of the plasma membrane.

  3. Perilipin-2 Modulates Lipid Absorption and Microbiome Responses in the Mouse Intestine.

    Directory of Open Access Journals (Sweden)

    Daniel N Frank

    Full Text Available Obesity and its co-morbidities, such as fatty liver disease, are increasingly prevalent worldwide health problems. Intestinal microorganisms have emerged as critical factors linking diet to host physiology and metabolic function, particularly in the context of lipid homeostasis. We previously demonstrated that deletion of the cytoplasmic lipid drop (CLD protein Perilipin-2 (Plin2 in mice largely abrogates long-term deleterious effects of a high fat (HF diet. Here we test the hypotheses that Plin2 function impacts the earliest steps of HF diet-mediated pathogenesis as well as the dynamics of diet-associated changes in gut microbiome diversity and function. WT and perilipin-2 null mice raised on a standard chow diet were randomized to either low fat (LF or HF diets. After four days, animals were assessed for changes in physiological (body weight, energy balance, and fecal triglyceride levels, histochemical (enterocyte CLD content, and fecal microbiome parameters. Plin2-null mice had significantly lower respiratory exchange ratios, diminished frequencies of enterocyte CLDs, and increased fecal triglyceride levels compared with WT mice. Microbiome analyses, employing both 16S rRNA profiling and metagenomic deep sequencing, indicated that dietary fat content and Plin2 genotype were significantly and independently associated with gut microbiome composition, diversity, and functional differences. These data demonstrate that Plin2 modulates rapid effects of diet on fecal lipid levels, enterocyte CLD contents, and fuel utilization properties of mice that correlate with structural and functional differences in their gut microbial communities. Collectively, the data provide evidence of Plin2 regulated intestinal lipid uptake, which contributes to rapid changes in the gut microbial communities implicated in diet-induced obesity.

  4. Lipid profile alterations and fasting blood glucose levels in primary hypothyroidism

    Directory of Open Access Journals (Sweden)

    Maram Sushma

    2014-08-01

    Conclusions: Hypothyroid patients demonstrate significant increase in serum lipids as compared to healthy individuals. More females are diagnosed with hypothyroidism and dyslipidemia is associated with primary hypothyroidism. [Int J Res Med Sci 2014; 2(4.000: 1694-1698

  5. The effect of nutrition pattern alteration on Chlorella pyrenoidosa growth, lipid biosynthesis-related gene transcription.

    Science.gov (United States)

    Fan, Jianhua; Cui, Yanbin; Zhou, Yang; Wan, Minxi; Wang, Weiliang; Xie, Jingli; Li, Yuanguang

    2014-07-01

    Heterotrophy to photoautotrophy transition leads to the accumulation of lipids in Chlorella, which has potential to produce both healthy food and biofuels. Therefore, it is of key interest to study the metabolism shift and gene expression changes that influenced by the transition. Both total and neutral lipids contents were increased rapidly within 48 h after the switch to light environment, from 24.5% and 18.0% to 35.3% and 27.4%, respectively, along with the sharp decline of starch from 42.3% to 10.4% during 24h photoinduction phase. By analyzing the correlation between lipid content and gene expression, results revealed several genes viz. me g3137, me g6562, pepc g6833, dgat g3280 and dgat g7566, which encode corresponding enzymes in the de novo lipid biosynthesis pathway, are highly related to lipid accumulation and might be exploited as target genes for genetic modification. These results represented the feasibility of lipid production through trophic converting cultivation.

  6. Sex-specific alterations in mRNA level of key lipid metabolism enzymes in skeletal muscle of overweight and obese subjects following endurance exercise

    OpenAIRE

    Smith, Ira J.; Huffman, Kim M.; Durheim, Michael T.; Duscha, Brian D.; Kraus, William E.

    2008-01-01

    Endurance exercise (EE) leads to beneficial alterations in skeletal muscle lipid metabolism in overweight and obese individuals; however, the mechanisms of these improvements are poorly understood. The primary goal of the current investigation was to test the hypothesis that long-term EE training (6 mo) leads to alterations in the mRNA abundance of key lipid metabolism enzymes in skeletal muscle of overweight and obese middle-aged women and men. A secondary aim of this study was to investigat...

  7. A Methionine Deficient Diet Enhances Adipose Tissue Lipid Metabolism and Alters Anti-Oxidant Pathways in Young Growing Pigs.

    Directory of Open Access Journals (Sweden)

    Rosa Castellano

    Full Text Available Methionine is a rate-limiting amino-acid for protein synthesis but non-proteinogenic roles on lipid metabolism and oxidative stress have been demonstrated. Contrary to rodents where a dietary methionine deficiency led to a lower adiposity, an increased lipid accretion rate has been reported in growing pigs fed a methionine deficient diet. This study aimed to clarify the effects of a dietary methionine deficiency on different aspects of tissue lipid metabolism and anti-oxidant pathways in young pigs. Post-weaned pigs (9.8 kg initial body weight were restrictively-fed diets providing either an adequate (CTRL or a deficient methionine supply (MD during 10 days (n=6 per group. At the end of the feeding trial, pigs fed the MD diet had higher lipid content in subcutaneous adipose tissue. Expression levels of genes involved in glucose uptake, lipogenesis but also lipolysis, and activities of NADPH enzyme suppliers were generally higher in subcutaneous and perirenal adipose tissues of MD pigs, suggesting an increased lipid turnover in those pigs. Activities of the anti-oxidant enzymes superoxide dismutase, catalase and glutathione reductase were increased in adipose tissues and muscle of MD pigs. Expression level and activity of the glutathione peroxidase were also higher in liver of MD pigs, but hepatic contents in the reduced and oxidized forms of glutathione and glutathione reductase activity were lower compared with control pigs. In plasma, superoxide dismutase activity was higher but total anti-oxidant power was lower in MD pigs. These results show that a dietary methionine deficiency resulted in increased levels of lipogenesis and lipolytic indicators in porcine adipose tissues. Decreased glutathione content in the liver and coordinated increase of enzymatic antioxidant activities in adipose tissues altered the cellular redox status of young pigs fed a methionine-deficient diet. These findings illustrate that a rapidly growing animal differently

  8. A Methionine Deficient Diet Enhances Adipose Tissue Lipid Metabolism and Alters Anti-Oxidant Pathways in Young Growing Pigs.

    Science.gov (United States)

    Castellano, Rosa; Perruchot, Marie-Hélène; Conde-Aguilera, José Alberto; van Milgen, Jaap; Collin, Anne; Tesseraud, Sophie; Mercier, Yves; Gondret, Florence

    2015-01-01

    Methionine is a rate-limiting amino-acid for protein synthesis but non-proteinogenic roles on lipid metabolism and oxidative stress have been demonstrated. Contrary to rodents where a dietary methionine deficiency led to a lower adiposity, an increased lipid accretion rate has been reported in growing pigs fed a methionine deficient diet. This study aimed to clarify the effects of a dietary methionine deficiency on different aspects of tissue lipid metabolism and anti-oxidant pathways in young pigs. Post-weaned pigs (9.8 kg initial body weight) were restrictively-fed diets providing either an adequate (CTRL) or a deficient methionine supply (MD) during 10 days (n=6 per group). At the end of the feeding trial, pigs fed the MD diet had higher lipid content in subcutaneous adipose tissue. Expression levels of genes involved in glucose uptake, lipogenesis but also lipolysis, and activities of NADPH enzyme suppliers were generally higher in subcutaneous and perirenal adipose tissues of MD pigs, suggesting an increased lipid turnover in those pigs. Activities of the anti-oxidant enzymes superoxide dismutase, catalase and glutathione reductase were increased in adipose tissues and muscle of MD pigs. Expression level and activity of the glutathione peroxidase were also higher in liver of MD pigs, but hepatic contents in the reduced and oxidized forms of glutathione and glutathione reductase activity were lower compared with control pigs. In plasma, superoxide dismutase activity was higher but total anti-oxidant power was lower in MD pigs. These results show that a dietary methionine deficiency resulted in increased levels of lipogenesis and lipolytic indicators in porcine adipose tissues. Decreased glutathione content in the liver and coordinated increase of enzymatic antioxidant activities in adipose tissues altered the cellular redox status of young pigs fed a methionine-deficient diet. These findings illustrate that a rapidly growing animal differently adapts tissue

  9. PLASMA-MEMBRANE LIPID ALTERATIONS INDUCED BY NACL IN WINTER-WHEAT ROOTS

    NARCIS (Netherlands)

    MANSOUR, MMF; VANHASSELT, PR; KUIPER, PJC

    1994-01-01

    A highly enriched plasma membrane fraction was isolated by two phase partitioning from wheat roots (Triticum aestivum L. cv. Vivant) grown with and without 100 mM NaCl. The lipids of the plasma membrane fraction were extracted and characterized. Phosphatidylcholine and phosphatidylethanolamine were

  10. Altered lipid parameters in patients infected with Entamoeba histolytica, Entamoeba dispar and Giardia lamblia.

    Science.gov (United States)

    Bansal, D; Bhatti, H S; Sehgal, R

    2005-01-01

    Information on the effect of parasitic infections on lipid parameters is scarce. Certain parasites induce significant changes in lipid parameters, as demonstrated by the fact that substitution of lipid/cholesterol for serum in axenic culture medium (in vitro) and in experimental models (in vivo) supports vigorous growth of Entamoeba histolytica. Thus, significant changes in lipid parameters may be induced in an infected host. Blood samples are obtained from intestinal amoebiasis patients passing E. histolytica (n=8), E. dispar (n=15) or Giardia lamblia (n=9) cysts, or diagnosed with amoebic liver abscess (ALA; n=50) and from apparently normal healthy individuals (control group; n=30). Levels of total serum cholesterol, high-density lipoprotein and low-density lipoprotein are assessed using commercial kits. E. histolytica and E. dispar isolates are differentiated by hexokinase isoenzyme electrophoresis and by enzyme-linked immunosorbent assay (ELISA; Techlab) tests. Results show that E. histolytica, E. dispar and G. lamblia cyst passers had significantly lower levels of total serum cholesterol (73.42 +/- 2.24 mg/dL), compared to levels in ALA cases (101 +/- 2.85 mg/dL) and in controls (166.26 +/- 2.02 mg/dL). Further study of a greater number of cases is needed to explore the relevance of this finding.

  11. Altered lipid metabolism in residual white adipose tissues of Bscl2 deficient mice.

    Directory of Open Access Journals (Sweden)

    Weiqin Chen

    Full Text Available Mutations in BSCL2 underlie human congenital generalized lipodystrophy type 2 disease. We previously reported that Bscl2 (-/- mice develop lipodystrophy of white adipose tissue (WAT due to unbridled lipolysis. The residual epididymal WAT (EWAT displays a browning phenotype with much smaller lipid droplets (LD and higher expression of brown adipose tissue marker proteins. Here we used targeted lipidomics and gene expression profiling to analyze lipid profiles as well as genes involved in lipid metabolism in WAT of wild-type and Bscl2(-/- mice. Analysis of total saponified fatty acids revealed that the residual EWAT of Bscl2(-/- mice contained a much higher proportion of oleic 18:1n9 acid concomitant with a lower proportion of palmitic 16:0 acid, as well as increased n3- polyunsaturated fatty acids (PUFA remodeling. The acyl chains in major species of triacylglyceride (TG and diacylglyceride (DG in the residual EWAT of Bscl2(-/- mice were also enriched with dietary fatty acids. These changes could be reflected by upregulation of several fatty acid elongases and desaturases. Meanwhile, Bscl2(-/- adipocytes from EWAT had increased gene expression in lipid uptake and TG synthesis but not de novo lipogenesis. Both mitochondria and peroxisomal β-oxidation genes were also markedly increased in Bscl2(-/- adipocytes, highlighting that these machineries were accelerated to shunt the lipolysis liberated fatty acids through uncoupling to dissipate energy. The residual subcutaneous white adipose tissue (ScWAT was not browning but displays similar changes in lipid metabolism. Overall, our data emphasize that, other than being essential for adipocyte differentiation, Bscl2 is also important in fatty acid remodeling and energy homeostasis.

  12. DHEA-Mediated Inhibition of the Pentose Phosphate Pathway Alters Oocyte Lipid Metabolism in Mice

    OpenAIRE

    Jimenez, Patricia T; Frolova, Antonina I.; Chi, Maggie M.; Grindler, Natalia M.; Willcockson, Alexandra R.; Reynolds, Kasey A.; Zhao, Quihong; Moley, Kelle H.

    2013-01-01

    Women with polycystic ovary syndrome (PCOS) and hyperandrogenism have altered hormone levels and suffer from ovarian dysfunction leading to subfertility. We have attempted to generate a model of hyperandrogenism by feeding mice chow supplemented with dehydroepiandrosterone (DHEA), an androgen precursor that is often elevated in women with PCOS. Treated mice had polycystic ovaries, low ovulation rates, disrupted estrous cycles, and altered hormone levels. Because DHEA is an inhibitor of glucos...

  13. Ligand binding alters dimerization and sequestering of urokinase receptors in raft-mimicking lipid mixtures.

    Science.gov (United States)

    Ge, Yifan; Siegel, Amanda P; Jordan, Rainer; Naumann, Christoph A

    2014-11-01

    Lipid heterogeneities, such as lipid rafts, are widely considered to be important for the sequestering of membrane proteins in plasma membranes, thereby influencing membrane protein functionality. However, the underlying mechanisms of such sequestration processes remain elusive, in part, due to the small size and often transient nature of these functional membrane heterogeneities in cellular membranes. To overcome these challenges, here we report the sequestration behavior of urokinase receptor (uPAR), a glycosylphosphatidylinositol-anchored protein, in a planar model membrane platform with raft-mimicking lipid mixtures of well-defined compositions using a powerful optical imaging platform consisting of confocal spectroscopy XY-scans, photon counting histogram, and fluorescence correlation spectroscopy analyses. This methodology provides parallel information about receptor sequestration, oligomerization state, and lateral mobility with single molecule sensitivity. Most notably, our experiments demonstrate that moderate changes in uPAR sequestration are not only associated with modifications in uPAR dimerization levels, but may also be linked to ligand-mediated allosteric changes of these membrane receptors. Our data show that these modifications in uPAR sequestration can be induced by exposure to specific ligands (urokinase plasminogen activator, vitronectin), but not via adjustment of the cholesterol level in the planar model membrane system. Good agreement of our key findings with published results on cell membranes confirms the validity of our model membrane approach. We hypothesize that the observed mechanism of receptor translocation in the presence of raft-mimicking lipid mixtures is also applicable to other glycosylphosphatidylinositol-anchored proteins.

  14. Fish oil supplementation alters levels of lipid mediators of inflammation in microenvironment of acute human wounds

    OpenAIRE

    McDaniel, Jodi C.; Massey, Karen; Nicolaou, Anna

    2011-01-01

    Chronic wounds often result from prolonged inflammation involving excessive polymorphonuclear leukocyte activity. Studies show that the ω-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oils generate bioactive lipid mediators that reduce inflammation and polymorphonuclear leukocyte recruitment in numerous inflammatory disease models. This study’s purpose was to test the hypotheses that boosting plasma levels of EPA and DHA with oral suppl...

  15. Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

    Energy Technology Data Exchange (ETDEWEB)

    Gorrochategui, Eva; Pérez-Albaladejo, Elisabet [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Casas, Josefina [Department of Biomedicinal Chemistry, IQAC–CSIC, 08034 Barcelona, Catalonia (Spain); Lacorte, Sílvia, E-mail: slbqam@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Porte, Cinta, E-mail: cinta.porte@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain)

    2014-06-01

    The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

  16. Model steatogenic compounds (amiodarone, valproic acid, and tetracycline alter lipid metabolism by different mechanisms in mouse liver slices.

    Directory of Open Access Journals (Sweden)

    Ewa Szalowska

    Full Text Available Although drug induced steatosis represents a mild type of hepatotoxicity it can progress into more severe non-alcoholic steatohepatitis. Current models used for safety assessment in drug development and chemical risk assessment do not accurately predict steatosis in humans. Therefore, new models need to be developed to screen compounds for steatogenic properties. We have studied the usefulness of mouse precision-cut liver slices (PCLS as an alternative to animal testing to gain more insight into the mechanisms involved in the steatogenesis. To this end, PCLS were incubated 24 h with the model steatogenic compounds: amiodarone (AMI, valproic acid (VA, and tetracycline (TET. Transcriptome analysis using DNA microarrays was used to identify genes and processes affected by these compounds. AMI and VA upregulated lipid metabolism, whereas processes associated with extracellular matrix remodelling and inflammation were downregulated. TET downregulated mitochondrial functions, lipid metabolism, and fibrosis. Furthermore, on the basis of the transcriptomics data it was hypothesized that all three compounds affect peroxisome proliferator activated-receptor (PPAR signaling. Application of PPAR reporter assays classified AMI and VA as PPARγ and triple PPARα/(β/δ/γ agonist, respectively, whereas TET had no effect on any of the PPARs. Some of the differentially expressed genes were considered as potential candidate biomarkers to identify PPAR agonists (i.e. AMI and VA or compounds impairing mitochondrial functions (i.e. TET. Finally, comparison of our findings with publicly available transcriptomics data showed that a number of processes altered in the mouse PCLS was also affected in mouse livers and human primary hepatocytes exposed to known PPAR agonists. Thus mouse PCLS are a valuable model to identify early mechanisms of action of compounds altering lipid metabolism.

  17. Alterations in Lipids and Adipocyte Hormones in Female-to-Male Transsexuals

    Directory of Open Access Journals (Sweden)

    Prakash Chandra

    2010-01-01

    Full Text Available Testosterone therapy in men and women results in decreased high-density lipoprotein cholesterol (HDL and increased low-density lipoprotein cholesterol (LDL. We sought to determine whether testosterone therapy has this same effect on lipid parameters and adipocyte hormones in female-to-male (FTM transsexuals. Twelve FTM transsexuals provided a fasting lipid profile including serum total cholesterol, HDL, LDL, and triglycerides prior to and after 1 year of testosterone therapy (testosterone enanthate or cypionate 50–125 mg IM every two weeks. Subjects experienced a significant decrease in mean serum HDL (52±11 to 40±7 mg/dL (P<.001. The mean LDL (P=.316, triglyceride (P=.910, and total cholesterol (P=.769 levels remained unchanged. In a subset of subjects, we measured serum leptin levels which were reduced by 25% but did not reach statistical significance (P=.181 while resistin levels remained unchanged. We conclude that testosterone therapy in FTM transsexuals can promote an increased atherogenic lipid profile by lowering HDL and possibly reduce serum leptin levels. However, long-term studies are needed to determine whether decreases in HDL result in adverse cardiovascular outcomes.

  18. Exposure to a northern contaminant mixture (NCM alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.

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    Ryan J Mailloux

    Full Text Available Non-alcoholic fatty liver disease (NAFLD, defined by the American Liver Society as the buildup of extra fat in liver cells that is not caused by alcohol, is the most common liver disease in North America. Obesity and type 2 diabetes are viewed as the major causes of NAFLD. Environmental contaminants have also been implicated in the development of NAFLD. Northern populations are exposed to a myriad of persistent organic pollutants including polychlorinated biphenyls, organochlorine pesticides, flame retardants, and toxic metals, while also affected by higher rates of obesity and alcohol abuse compared to the rest of Canada. In this study, we examined the impact of a mixture of 22 contaminants detected in Inuit blood on the development and progression of NAFLD in obese JCR rats with or without co-exposure to 10% ethanol. Hepatosteatosis was found in obese rat liver, which was worsened by exposure to 10% ethanol. NCM treatment increased the number of macrovesicular lipid droplets, total lipid contents, portion of mono- and polyunsaturated fatty acids in the liver. This was complemented by an increase in hepatic total cholesterol and cholesterol ester levels which was associated with changes in the expression of genes and proteins involved in lipid metabolism and transport. In addition, NCM treatment increased cytochrome P450 2E1 protein expression and decreased ubiquinone pool, and mitochondrial ATP synthase subunit ATP5A and Complex IV activity. Despite the changes in mitochondrial physiology, hepatic ATP levels were maintained high in NCM-treated versus control rats. This was due to a decrease in ATP utilization and an increase in creatine kinase activity. Collectively, our results suggest that NCM treatment decreases hepatic cholesterol export, possibly also increases cholesterol uptake from circulation, and promotes lipid accumulation and alters ATP homeostasis which exacerbates the existing hepatic steatosis in genetically obese JCR rats with

  19. Exposure to a northern contaminant mixture (NCM) alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.

    Science.gov (United States)

    Mailloux, Ryan J; Florian, Maria; Chen, Qixuan; Yan, Jin; Petrov, Ivan; Coughlan, Melanie C; Laziyan, Mahemuti; Caldwell, Don; Lalande, Michelle; Patry, Dominique; Gagnon, Claude; Sarafin, Kurtis; Truong, Jocelyn; Chan, Hing Man; Ratnayake, Nimal; Li, Nanqin; Willmore, William G; Jin, Xiaolei

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD), defined by the American Liver Society as the buildup of extra fat in liver cells that is not caused by alcohol, is the most common liver disease in North America. Obesity and type 2 diabetes are viewed as the major causes of NAFLD. Environmental contaminants have also been implicated in the development of NAFLD. Northern populations are exposed to a myriad of persistent organic pollutants including polychlorinated biphenyls, organochlorine pesticides, flame retardants, and toxic metals, while also affected by higher rates of obesity and alcohol abuse compared to the rest of Canada. In this study, we examined the impact of a mixture of 22 contaminants detected in Inuit blood on the development and progression of NAFLD in obese JCR rats with or without co-exposure to 10% ethanol. Hepatosteatosis was found in obese rat liver, which was worsened by exposure to 10% ethanol. NCM treatment increased the number of macrovesicular lipid droplets, total lipid contents, portion of mono- and polyunsaturated fatty acids in the liver. This was complemented by an increase in hepatic total cholesterol and cholesterol ester levels which was associated with changes in the expression of genes and proteins involved in lipid metabolism and transport. In addition, NCM treatment increased cytochrome P450 2E1 protein expression and decreased ubiquinone pool, and mitochondrial ATP synthase subunit ATP5A and Complex IV activity. Despite the changes in mitochondrial physiology, hepatic ATP levels were maintained high in NCM-treated versus control rats. This was due to a decrease in ATP utilization and an increase in creatine kinase activity. Collectively, our results suggest that NCM treatment decreases hepatic cholesterol export, possibly also increases cholesterol uptake from circulation, and promotes lipid accumulation and alters ATP homeostasis which exacerbates the existing hepatic steatosis in genetically obese JCR rats with or without co

  20. Age-Related Alterations of Plasma Lipid Peroxidation and Erythrocyte Superoxide Dismutase Activity in Different Ethnic Groups of Gorgan

    Science.gov (United States)

    Marjani, Abdoljalal; Mansourian, Azad Reza; Veghari, Gholam Reza; Rabiee, Mohammad Reza

    Free radicals have been proposed as important causative agents of ageing. The free radical theory of ageing postulates that ageing is caused by free radical reactions. These highly reactive species can cause oxidative damage in the cell. The purposive of this study was to investigate the alteration in plasma lipid peroxidation and erythrocyte superoxide dismutase activity in 2 different ethnic groups of Fars and Turkmen healthy people. We measured plasma lipid peroxidation levels (lipid peroxidation expressed as malondialdehyde) and erythrocyte superoxide dismutase activity. Study include 350 (175 Fars and 175 Turkmen male) apparently healthy individuals. Erythrocyte superoxide dismutase activities were determined in 2 different ethnic groups of Fars and Turkmen consisting of healthy individuals between 26-60 years of age {26-30 (n = 30), 3-35 (n = 30), 36-40 (n = 30), 41-45 (n = 30), 46-50 (n = 25), 51-55 (n = 15) and 56-60 (n = 15)}, respectively. The data was analyzed by Student` t-test. Erythrocyte superoxide dismutase and plasma lipid peroxidation levels in Fars and Turkmen people with 41-45 ages (group 4) and 36-40 ages (group 3) were significantly lower and higher than in the other age groups (Fars groups 1, 2 and 3, Turkmen groups 1, 2), respectively (p0.05). There were no significant relation between the age groups 3 (Turkmen people) and the age groups 4, 5, 6 and 7 (p>0.05). We found age-related differences in erythrocyte superoxide dismutase activity and plasma lipid peroxidation levels. The results indicate that the balance between antioxidant and prooxidant factors in free radical metabolism shifts towards increased lipid peroxidation with advancing age in 2 ethnic groups. This situation maybe begin in Turkmen people earlier than Fars people. The ethnic origin, diet, heavy working and life style factors of the two populations may explain this differences. Therefore we propose that older Fars and Turkmen people may have elevated requirement for

  1. Major Alterations of Phosphatidylcholine and Lysophosphotidylcholine Lipids in the Substantia Nigra Using an Early Stage Model of Parkinson’s Disease

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    Kyle Farmer

    2015-08-01

    Full Text Available Parkinson’s disease (PD is a progressive neurodegenerative disease affecting the nigrostriatal pathway, where patients do not manifest motor symptoms until >50% of neurons are lost. Thus, it is of great importance to determine early neuronal changes that may contribute to disease progression. Recent attention has focused on lipids and their role in pro- and anti-apoptotic processes. However, information regarding the lipid alterations in animal models of PD is lacking. In this study, we utilized high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS and novel HPLC solvent methodology to profile phosphatidylcholines and sphingolipids within the substantia nigra. The ipsilateral substantia nigra pars compacta was collected from rats 21 days after an infusion of 6-hydroxydopamine (6-OHDA, or vehicle into the anterior dorsal striatum. We identified 115 lipid species from their mass/charge ratio using the LMAPS Lipid MS Predict Database. Of these, 19 lipid species (from phosphatidylcholine and lysophosphotidylcholine lipid classes were significantly altered by 6-OHDA, with most being down-regulated. The two lipid species that were up-regulated were LPC (16:0 and LPC (18:1, which are important for neuroinflammatory signalling. These findings provide a first step in the characterization of lipid changes in early stages of PD-like pathology and could provide novel targets for early interventions in PD.

  2. Low temperature alters plasma membrane lipid composition and ATPase activity of pineapple fruit during blackheart development.

    Science.gov (United States)

    Zhou, Yuchan; Pan, Xiaoping; Qu, Hongxia; Underhill, Steven J R

    2014-02-01

    Plasma membrane (PM) plays central role in triggering primary responses to chilling injury and sustaining cellular homeostasis. Characterising response of membrane lipids to low temperature can provide important information for identifying early causal factors contributing to chilling injury. To this end, PM lipid composition and ATPase activity were assessed in pineapple fruit (Ananas comosus) in relation to the effect of low temperature on the development of blackheart, a form of chilling injury. Chilling temperature at 10 °C induced blackheart development in concurrence with increase in electrolyte leakage. PM ATPase activity was decreased after 1 week at low temperature, followed by a further decrease after 2 weeks. The enzyme activity was not changed during 25 °C storage. Loss of total PM phospholipids was found during postharvest senescence, but more reduction was shown from storage at 10 °C. Phosphatidylcholine and phosphatidylethanolamine were the predominant PM phospholipid species. Low temperature increased the level of phosphatidic acid but decreased the level of phosphatidylinositol. Both phospholipid species were not changed during storage at 25 °C. Postharvest storage at both temperatures decreased the levels of C18:3 and C16:1, and increased level of C18:1. Low temperature decreased the level of C18:2 and increased the level of C14:0. Exogenous application of phosphatidic acid was found to inhibit the PM ATPase activity of pineapple fruit in vitro. Modification of membrane lipid composition and its effect on the functional property of plasma membrane at low temperature were discussed in correlation with their roles in blackheart development of pineapple fruit.

  3. Cerebroside C increases tolerance to chilling injury and alters lipid composition in wheat roots.

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    Hong-Xia Li

    Full Text Available Chilling tolerance was increased in seed germination and root growth of wheat seedlings grown in media containing 20 µg/mL cerebroside C (CC, isolated from the endophytic Phyllosticta sp. TG78. Seeds treated with 20 µg/mL CC at 4 °C expressed the higher germination rate (77.78%, potential (23.46%, index (3.44 and the shorter germination time (6.19 d; root growth was also significantly improved by 13.76% in length, 13.44% in fresh weight and 6.88% in dry mass compared to controls. During the cultivation process at 4 °C for three days and the followed 24 h at 25 °C, lipid peroxidation, expressed by malondialdehyde (MDA content and relative membrane permeability (RMP was significantly reduced in CC-treated roots; activities of lipoxygenase (LOX, phospholipid C (PLC and phospholipid D (PLD were inhibited by 13.62-62.26%, 13.54-63.93% and 13.90-61.17%, respectively; unsaturation degree of fatty acids was enhanced through detecting the contents of CC-induced linoleic acid, linolenic acid, palmitic acid and stearic acid using GC-MS; capacities of superoxide dismutase (SOD, catalase (CAT and glutathione peroxidase (GSH-Px were individually increased by 7.69-46.06%, 3.37-37.96%, and -7.00-178.07%. These results suggest that increased chilling tolerance may be due, in part, to the reduction of lipid peroxidation and alternation of lipid composition of roots in the presence of CC.

  4. Altered lipid metabolism in the aging kidney identified by three layered omic analysis.

    Science.gov (United States)

    Braun, Fabian; Rinschen, Markus M; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Hoeijmakers, Jan H J; Schumacher, Björn; Dollé, Martijn E T; Müller, Roman-Ulrich; Benzing, Thomas; Schermer, Bernhard; Kurschat, Christine E

    2016-03-01

    Aging-associated diseases and their comorbidities affect the life of a constantly growing proportion of the population in developed countries. At the center of these comorbidities are changes of kidney structure and function as age-related chronic kidney disease predisposes to the development of cardiovascular diseases such as stroke, myocardial infarction or heart failure. To detect molecular mechanisms involved in kidney aging, we analyzed gene expression profiles of kidneys from adult and aged wild-type mice by transcriptomic, proteomic and targeted lipidomic methodologies. Interestingly, transcriptome and proteome analyses revealed differential expression of genes primarily involved in lipid metabolism and immune response. Additional lipidomic analyses uncovered significant age-related differences in the total amount of phosphatidylethanolamines, phosphatidylcholines and sphingomyelins as well as in subspecies of phosphatidylserines and ceramides with age. By integration of these datasets we identified Aldh1a1, a key enzyme in vitamin A metabolism specifically expressed in the medullary ascending limb, as one of the most prominent upregulated proteins in old kidneys. Moreover, ceramidase Asah1 was highly expressed in aged kidneys, consistent with a decrease in ceramide C16. In summary, our data suggest that changes in lipid metabolism are involved in the process of kidney aging and in the development of chronic kidney disease. PMID:26886165

  5. Scavenger receptor class B type I (SR-BI) in pig enterocytes: trafficking from the brush border to lipid droplets during fat absorption

    DEFF Research Database (Denmark)

    Hansen, Gert Helge; Niels-Christiansen, Lise-Lotte W; Immerdal, Lissi;

    2003-01-01

    BACKGROUND: Scavenger receptor class B type I (SR-BI) is known to mediate cellular uptake of cholesterol from high density lipoprotein particles and is particularly abundant in liver and steroidogenic tissues. In addition, SR-BI expression in the enterocyte brush border has also been reported but...... fat, SR-BI is endocytosed from the enterocyte brush border and accumulates in cytoplasmic lipid droplets. Internalisation of the receptor occurs mainly by clathrin coated pits rather than by a caveolae/lipid raft based mechanism....... fractionation. RESULTS: In the fasting state, SR-BI was mainly localised in the microvillar membrane and in apical invaginations/pits between adjacent microvilli. In addition, a subapical compartment and small cytoplasmic lipid droplets were distinctly labelled. During lipid absorption, the receptor was found...... in clathrin positive apical coated pits and vesicles. In addition, cytoplasmic lipid droplets that greatly increased in size and number were strongly labelled by the SR-BI antibody whereas apolipoprotein A-1 positive chylomicrons were largely devoid of the receptor. CONCLUSION: During absorption of dietary...

  6. Short-chain fructooligosaccharides do not alter glucose homeostasis but improve the lipid profile in obese rats

    Directory of Open Access Journals (Sweden)

    Fernanda Soares da Silva-Morita

    2015-07-01

    Full Text Available The present study investigated the effects of short-chain fructooligosaccharides (scFOS feeding on body weight, fat accumulation, glucose homeostasis and lipid profile in cafeteria (CAF obese rats. Male Wistar rats were divided randomly into two groups: control group (CTL, n = 10, which received a chow diet and water and CAF (n = 20, which received the cafeteria diet, standard chow and soda. After 30 weeks of diet, 10 animals of CAF group received scFOS in the diet (50 g kg-1 of diet over a period of 50 days, forming the CAF FOS group. Were evaluated the body weight, fat pad as well as, quantity of feces, glucose tolerance, insulin resistance (IR and serum lipids levels. Animals submitted to the CAF diet displayed obesity, hyperglycemia, glucose intolerance, hyperinsulinemia and IR. The scFOS feeding   not altered obesity, glucose intolerance, hyperinsulinemia and IR. CAF rats also presented hypertriglyceridemia and lower levels of HDL-cholesterol. The CAF FOS animals had reduced serum triglycerides (TG and increased HDL-cholesterol. Thus, the use of scFOS in the diet can be considered as a hypolipidemic agent in the obese state.

  7. The surfactant protein C mutation A116D alters cellular processing, stress tolerance, surfactant lipid composition, and immune cell activation

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    Zarbock Ralf

    2012-03-01

    Full Text Available Abstract Background Surfactant protein C (SP-C is important for the function of pulmonary surfactant. Heterozygous mutations in SFTPC, the gene encoding SP-C, cause sporadic and familial interstitial lung disease (ILD in children and adults. Mutations mapping to the BRICHOS domain located within the SP-C proprotein result in perinuclear aggregation of the proprotein. In this study, we investigated the effects of the mutation A116D in the BRICHOS domain of SP-C on cellular homeostasis. We also evaluated the ability of drugs currently used in ILD therapy to counteract these effects. Methods SP-CA116D was expressed in MLE-12 alveolar epithelial cells. We assessed in vitro the consequences for cellular homeostasis, immune response and effects of azathioprine, hydroxychloroquine, methylprednisolone and cyclophosphamide. Results Stable expression of SP-CA116D in MLE-12 alveolar epithelial cells resulted in increased intracellular accumulation of proSP-C processing intermediates. SP-CA116D expression further led to reduced cell viability and increased levels of the chaperones Hsp90, Hsp70, calreticulin and calnexin. Lipid analysis revealed decreased intracellular levels of phosphatidylcholine (PC and increased lyso-PC levels. Treatment with methylprednisolone or hydroxychloroquine partially restored these lipid alterations. Furthermore, SP-CA116D cells secreted soluble factors into the medium that modulated surface expression of CCR2 or CXCR1 receptors on CD4+ lymphocytes and neutrophils, suggesting a direct paracrine effect of SP-CA116D on neighboring cells in the alveolar space. Conclusions We show that the A116D mutation leads to impaired processing of proSP-C in alveolar epithelial cells, alters cell viability and lipid composition, and also activates cells of the immune system. In addition, we show that some of the effects of the mutation on cellular homeostasis can be antagonized by application of pharmaceuticals commonly applied in ILD therapy

  8. Dietary canola oil alters hematological indices and blood lipids in neonatal piglets fed formula.

    Science.gov (United States)

    Innis, S M; Dyer, R A

    1999-07-01

    This study was undertaken to determine the effects of canola oil on platelet characteristics, blood lipids and growth in exclusively formula-fed piglets. Piglets were fed from birth to 10 or 18 d with formula containing 51% energy from fat, with 100% fat as canola or soybean oil; 26% soybean, 59% high oleic acid sunflower and 12% flax oil (canola mimic); or 26% canola (canola blend) or soybean (soybean blend) with high oleic acid sunflower, palm and coconut oil. The canola mimic provided similar carbon chain 16 and 18 fatty acids without the sterol or 20:1 and erucic acid (22:1) of canola oil. The oil blends provided formula resembling infant formulas but with higher 16:0 and lower unsaturated fatty acid levels than in canola or soybean oil. Body weight, weight gain and heart and liver weight were not different after 10 or 18 d feeding canola when compared to soybean oil alone or blended oil formulas. Piglets fed formulas with 100% canola oil had lower platelet counts than piglets fed formula soybean oil or the canola oil mimic. Platelet counts were lower, and platelet distribution width and volume were higher, when formulas with 100% canola or soybean rather than the blended oil formulas were fed. The results show that formula fat composition influences the developing hematological system and that canola oil suppresses the normal developmental increase in platelet count in piglets by a mechanism apparently unrelated to the formula 16:0, 18:1, 18:2(n-6) or 18:3(n-3), or plasma phospholipid 20:4(n-6) or 20:5(n-3).

  9. beta-Sitosterol inhibits HT-29 human colon cancer cell growth and alters membrane lipids.

    Science.gov (United States)

    Awad, A B; Chen, Y C; Fink, C S; Hennessey, T

    1996-01-01

    The purpose of the present study was to examine the effect of beta-sitosterol, the main dietary phytosterol on the growth of HT-29 cells, a human colon cancer cell line. In addition, the incorporation of this phytosterol into cellular membranes and how this might influence the lipid composition of the membranes were investigated. Tumor cells were grown in DMEM containing 10% FBS and supplemented with sterols (cholesterol or beta-sitosterol) at final concentrations up to 16 microM. The sterols were supplied to the media in the form of sterol cyclodextrin complexes. The cyclodextrin used was 2-hydroxypropyl-beta-cyclodextrin. The sterol to cyclodextrin molar ratio was maintained at 1:300. The study indicated that 8 and 16 microM beta-sitosterol were effective at cel growth inhibition as compared to cholesterol or to the control (no sterol supplementation). After supplementation with 16 microM beta-sitosterol for 9 days, cell growth was only one-third that of cells supplemented with equimolar concentration of cholesterol. No effect was observed on total membrane phospholipid concentration. At 16 microM beta-sitosterol supplementation, membrane cholesterol was reduced by 26%. Cholesterol supplementation resulted in a significant increase in the cholesterol/phospholipid ratio compared to either beta-sitosterol supplemented cells or controls. There was a 50% reduction in membrane sphingomyelin (SM) of cells grown in 16 microM beta-sitosterol. Additional changes were observed in the fatty acid composition of minor phospholipids of beta-sitosterol supplemented cells, such as SM, phosphatidylserine (PS), and phosphatidylinositol (PI). Only in the case of PI, was there an effect of these fatty acid changes on the unsaturation index, beta-sitosterol incorporation resulted in an increase in the U.I. It is possible that the observed growth inhibition by beta-sitosterol may be mediated through the influence of signal transduction pathways that involve membrane phospholipids.

  10. Alteration of membrane lipid biophysical properties and resistance of human lung adenocarcinoma A549 cells to cisplatin

    Institute of Scientific and Technical Information of China (English)

    LIANG; Xingjie; (

    2001-01-01

    [1]Simon, S. M., Schindler, M., Cell biological mechanisms of multidrug resistance in tumors, Proc. Natl. Acad. Sci. USA, 1994, 91: 3497.[2]Ambudkar, S. V., Dey, S., Hrycyna, C. A. et al., Biochemical, cellular, and pharmacological aspects of the multidrug trans-porter, Annu. Rev. Pharmacol. Toxicol., 1999, 39: 361.[3]Dudeja, P. K., Anderson, K. M., Harris, J. S. et al., Reversal of multidrug resistance phenotype by surfactants: Relationship to membrane lipid fluidity, Arch. Biochem. Biophys., 1995, 319 (1): 8309.[4]Collins, J. M., Scott, R. B., Grogan, W. M., Plasma membrane fluidity gradients of human peripheral blood leukocytes, J. Cell Physiol., 1990, 144: 42.[5]Collins, J. M., Dominey, R. N., Grogan, W. M., Shape of the fluidity gradient in the plasma membrane of living Hela cells, J. Lipid Res., 1990, 31: 261.[6]Ashman, R. F., Peckham, D., Alhasan, S. et al., Membrane unpacking and the rapid disposal of apoptotic cells, Immunol. Lett., 1995, 48(3): 159.[7]Sentjurc, M., Zorec, M., Cemazar, M. et al., Effect of vinblastine on cell membrane fluidity in vinblastine-sensitive and -resistant HeLa cells, Cancer Lett., 1998, 130(1-2):183.[8]Regev, R., Assaraf, Y. G., Eytan, G. D. et al., Membrane fluidization by ether, other anesthetics, and certain agents abolish-es P-glycoprotein ATPase activity and modulates efflux from multidrug-resistant cells, Eur. J. Biochem., 1999, 259(1-2): 18.[9]Robert, A. S., Mariamme, S., Katherine, L. S., Altered lipid packing identifies apoptotic thymocytes, Immunol. Lett., 1993, 36: 283.[10] Lagerberg, J. W., Kallen, K. J., Haest, C. W. et al., Factors affecting the amount and the mode of merocyanine 540 binding to the membrane of human erythrocytes, Biochim. Biophys. Acta, 1995, 1235(2): 428.[11] Stillwell, W., Wassall, S. R., Dumaual, A. C. et al., Use of merocyanine (MC540) in quantifying lipid domains and pack-ing in phospholipid vesicles and tumor cells, Biochem. Biophys. Acta, 1993

  11. Secretin receptor-knockout mice are resistant to high-fat diet-induced obesity and exhibit impaired intestinal lipid absorption.

    Science.gov (United States)

    Sekar, Revathi; Chow, Billy K C

    2014-08-01

    Secretin, a classical gastrointestinal hormone released from S cells in response to acid and dietary lipid, regulates pleiotropic physiological functions, such as exocrine pancreatic secretion and gastric motility. Subsequent to recently proposed revisit on secretin's metabolic effects, we have confirmed lipolytic actions of secretin during starvation and discovered a hormone-sensitive lipase-mediated mechanistic pathway behind. In this study, a 12 wk high-fat diet (HFD) feeding to secretin receptor-knockout (SCTR(-/-)) mice and their wild-type (SCTR(+/+)) littermates revealed that, despite similar food intake, SCTR(-/-) mice gained significantly less weight (SCTR(+/+): 49.6±0.9 g; SCTR(-/-): 44.7±1.4 g; Pfat content. These SCTR(-/-) mice have corresponding alleviated HFD-associated hyperleptinemia and improved glucose/insulin tolerance. Further analyses indicate that SCTR(-/-) have impaired intestinal fatty acid absorption while having similar energy expenditure and locomotor activity. Reduced fat absorption in the intestine is further supported by lowered postprandial triglyceride concentrations in circulation in SCTR(-/-) mice. In jejunal cells, transcript and protein levels of a key fat absorption regulator, cluster of differentiation 36 (CD36), was reduced in knockout mice, while transcript of Cd36 and fatty-acid uptake in isolated enterocytes was stimulated by secretin. Based on our findings, a novel positive feedback pathway involving secretin and CD36 to enhance intestinal lipid absorption is being proposed. PMID:24769669

  12. Alterations in lipid signaling underlie lipodystrophy secondary to AGPAT2 mutations.

    Science.gov (United States)

    Subauste, Angela R; Das, Arun K; Li, Xiangquan; Elliott, Brandon G; Elliot, Brandon; Evans, Charles; El Azzouny, Mahmoud; Treutelaar, Mary; Oral, Elif; Leff, Todd; Burant, Charles F

    2012-11-01

    Congenital generalized lipodystrophy (CGL), secondary to AGPAT2 mutation is characterized by the absence of adipocytes and development of severe insulin resistance. In the current study, we investigated the adipogenic defect associated with AGPAT2 mutations. Adipogenesis was studied in muscle-derived multipotent cells (MDMCs) isolated from vastus lateralis biopsies obtained from controls and subjects harboring AGPAT2 mutations and in 3T3-L1 preadipocytes after knockdown or overexpression of AGPAT2. We demonstrate an adipogenic defect using MDMCs from control and CGL human subjects with mutated AGPAT2. This defect was rescued in CGL MDMCs with a retrovirus expressing AGPAT2. Both CGL-derived MDMCs and 3T3-L1 cells with knockdown of AGPAT2 demonstrated an increase in cell death after induction of adipogenesis. Lack of AGPAT2 activity reduces Akt activation, and overexpression of constitutively active Akt can partially restore lipogenesis. AGPAT2 modulated the levels of phosphatidic acid, lysophosphatidic acid, phosphatidylinositol species, as well as the peroxisome proliferator-activated receptor γ (PPARγ) inhibitor cyclic phosphatidic acid. The PPARγ agonist pioglitazone partially rescued the adipogenic defect in CGL cells. We conclude that AGPAT2 regulates adipogenesis through the modulation of the lipome, altering normal activation of phosphatidylinositol 3-kinase (PI3K)/Akt and PPARγ pathways in the early stages of adipogenesis. PMID:22872237

  13. Alterations in lipid signaling underlie lipodystrophy secondary to AGPAT2 mutations.

    Science.gov (United States)

    Subauste, Angela R; Das, Arun K; Li, Xiangquan; Elliott, Brandon G; Elliot, Brandon; Evans, Charles; El Azzouny, Mahmoud; Treutelaar, Mary; Oral, Elif; Leff, Todd; Burant, Charles F

    2012-11-01

    Congenital generalized lipodystrophy (CGL), secondary to AGPAT2 mutation is characterized by the absence of adipocytes and development of severe insulin resistance. In the current study, we investigated the adipogenic defect associated with AGPAT2 mutations. Adipogenesis was studied in muscle-derived multipotent cells (MDMCs) isolated from vastus lateralis biopsies obtained from controls and subjects harboring AGPAT2 mutations and in 3T3-L1 preadipocytes after knockdown or overexpression of AGPAT2. We demonstrate an adipogenic defect using MDMCs from control and CGL human subjects with mutated AGPAT2. This defect was rescued in CGL MDMCs with a retrovirus expressing AGPAT2. Both CGL-derived MDMCs and 3T3-L1 cells with knockdown of AGPAT2 demonstrated an increase in cell death after induction of adipogenesis. Lack of AGPAT2 activity reduces Akt activation, and overexpression of constitutively active Akt can partially restore lipogenesis. AGPAT2 modulated the levels of phosphatidic acid, lysophosphatidic acid, phosphatidylinositol species, as well as the peroxisome proliferator-activated receptor γ (PPARγ) inhibitor cyclic phosphatidic acid. The PPARγ agonist pioglitazone partially rescued the adipogenic defect in CGL cells. We conclude that AGPAT2 regulates adipogenesis through the modulation of the lipome, altering normal activation of phosphatidylinositol 3-kinase (PI3K)/Akt and PPARγ pathways in the early stages of adipogenesis.

  14. Whole grain products, fish and bilberries alter glucose and lipid metabolism in a randomized, controlled trial: the Sysdimet study.

    Directory of Open Access Journals (Sweden)

    Maria Lankinen

    Full Text Available BACKGROUND: Due to the growing prevalence of type 2 diabetes, new dietary solutions are needed to help improve glucose and lipid metabolism in persons at high risk of developing the disease. Herein we investigated the effects of low-insulin-response grain products, fatty fish, and berries on glucose metabolism and plasma lipidomic profiles in persons with impaired glucose metabolism. METHODOLOGY/PRINCIPAL FINDINGS: Altogether 106 men and women with impaired glucose metabolism and with at least two other features of the metabolic syndrome were included in a 12-week parallel dietary intervention. The participants were randomized into three diet intervention groups: (1 whole grain and low postprandial insulin response grain products, fatty fish three times a week, and bilberries three portions per day (HealthyDiet group, (2 Whole grain enriched diet (WGED group, which includes principally the same grain products as group (1, but with no change in fish or berry consumption, and (3 refined wheat breads (Control. Oral glucose tolerance, plasma fatty acids and lipidomic profiles were measured before and after the intervention. Self-reported compliance with the diets was good and the body weight remained constant. Within the HealthyDiet group two hour glucose concentration and area-under-the-curve for glucose decreased and plasma proportion of (n-3 long-chain PUFAs increased (False Discovery Rate p-values <0.05. Increases in eicosapentaenoic acid and docosahexaenoic acid associated curvilinearly with the improved insulin secretion and glucose disposal. Among the 364 characterized lipids, 25 changed significantly in the HealthyDiet group, including multiple triglycerides incorporating the long chain (n-3 PUFA. CONCLUSIONS/SIGNIFICANCE: The results suggest that the diet rich in whole grain and low insulin response grain products, bilberries, and fatty fish improve glucose metabolism and alter the lipidomic profile. Therefore, such a diet may have a

  15. Azithromycin treatment alters gene expression in inflammatory, lipid metabolism, and cell cycle pathways in well-differentiated human airway epithelia.

    Directory of Open Access Journals (Sweden)

    Carla Maria P Ribeiro

    Full Text Available Prolonged macrolide antibiotic therapy at low doses improves clinical outcome in patients affected with diffuse panbronchiolitis and cystic fibrosis. Consensus is building that the therapeutic effects are due to anti-inflammatory, rather than anti-microbial activities, but the mode of action is likely complex. To gain insights into how the macrolide azithromycin (AZT modulates inflammatory responses in airways, well-differentiated primary cultures of human airway epithelia were exposed to AZT alone, an inflammatory stimulus consisting of soluble factors from cystic fibrosis airways, or AZT followed by the inflammatory stimulus. RNA microarrays were conducted to identify global and specific gene expression changes. Analysis of gene expression changes revealed that the AZT treatment alone altered the gene profile of the cells, primarily by significantly increasing the expression of lipid/cholesterol genes and decreasing the expression of cell cycle/mitosis genes. The increase in cholesterol biosynthetic genes was confirmed by increased filipin staining, an index of free cholesterol, after AZT treatment. AZT also affected genes with inflammatory annotations, but the effect was variable (both up- and down-regulation and gene specific. AZT pretreatment prevented the up-regulation of some genes, such as MUC5AC and MMP9, triggered by the inflammatory stimulus, but the up-regulation of other inflammatory genes, e.g., cytokines and chemokines, such as interleukin-8, was not affected. On the other hand, HLA genes were increased by AZT. Notably, secreted IL-8 protein levels did not reflect mRNA levels, and were, in fact, higher after AZT pretreatment in cultures exposed to the inflammatory stimulus, suggesting that AZT can affect inflammatory pathways other than by altering gene expression. These findings suggest that the specific effects of AZT on inflamed and non-inflamed airway epithelia are likely relevant to its clinical activity, and their apparent

  16. Sulforaphane ameliorates the insulin responsiveness and the lipid profile but does not alter the antioxidant response in diabetic rats.

    Science.gov (United States)

    de Souza, Carolina Guerini; da Motta, Leonardo Lisbôa; de Assis, Adriano Martimbianco; Rech, Anderson; Bruch, Ricardo; Klamt, Fábio; Souza, Diogo Onofre

    2016-04-20

    Diabetes is one of the most prevalent chronic non-communicable diseases and is characterized by hyperglycemia and increased oxidative stress. These two alterations are also responsible for the main diabetic complications: cardiovascular disease, retinopathy, nephropathy and peripheral neuropathy. Diabetes progression is governed by pancreatic β-cell failure, and recent studies showed that sulforaphane (SFN) might be able to prevent this change, preserving insulin production. Consequently, our goal was to test the effects of SFN on metabolic parameters related to diabetic complications and antioxidant defenses (superoxide dismutase, catalase and sulfhydryl groups) in the pancreas, liver and kidney of non-diabetic and diabetic rats. Male Wistar rats were treated with water or 0.5 mg kg(-1) SFN i.p. for 21 days after diabetes induction. In diabetic animals treated with SFN, the serum levels of total cholesterol, non-HDL cholesterol and triacylglycerols were similar to those of non-diabetic animals, and the insulin responsiveness was higher than that of the diabetic animals that did not receive the compound. No effect of SFN on the superoxide dismutase and catalase activity or sulfhydryl groups was observed in the pancreas, liver or kidney of the treated animals. We conclude that SFN ameliorates some features of clinical diabetic complications particularly the lipid profile and insulin responsiveness, but it does not modulate the antioxidant response induced by superoxide dismutase, catalase and sulfhydryl groups in the evaluated organs. PMID:27025193

  17. Αcute Exercise Alters the Levels of Human Saliva miRNAs Involved in Lipid Metabolism.

    Science.gov (United States)

    Konstantinidou, A; Mougios, V; Sidossis, L S

    2016-06-01

    The response of micro-ribonucleic acid (miRNA) expression to exercise has not been studied in saliva, although saliva combines non-invasive collection with the largest number of miRNA species among biological fluids and tissues. Thus, the purpose of this study was to investigate the effect of acute exercise on the expression of 8 human saliva miRNAs involved in lipid metabolism. 19 healthy, physically active men (VO2max, 40.9±1.6 mL·kg(-1)·min(-1), mean±se) performed a 50-min interval exercise program on stationary bicycle (spinning). Saliva samples were collected before and after exercise for miRNA expression analysis by real-time polymerase chain reaction. Statistically significant (pexercise were found in 2 of the 8 miRNAs, namely, hsa-miR-33a (fold change, 7.66±2.94; p=0.012), which regulates cholesterol homeostasis and fatty acid metabolism in the liver, and hsa-miR-378a (fold change 0.79±0.11, p=0.048), which regulates energy homeostasis and affects lipogenesis and adipogenesis. These alterations may contribute to our understanding of physiological responses to exercise and the therapeutic potential of exercise against cardiovascular disease, obesity, and the metabolic syndrome. Moreover, our findings open the possibility of noninvasively studying miRNAs that regulate the function of specific organs. PMID:27116339

  18. Biophysical alterations in lipid rafts from human cerebral cortex associate with increased BACE1/AβPP interaction in early stages of Alzheimer's disease.

    Science.gov (United States)

    Díaz, Mario; Fabelo, Noemí; Martín, Virginia; Ferrer, Isidre; Gómez, Tomás; Marín, Raquel

    2015-01-01

    In the present study, we have assessed the biophysical properties of lipid rafts from different brain areas in subjects exhibiting early neuropathological stages of Alzheimer's disease (AD). By means of steady-state fluorescence polarization analyses using two environment-sensitive fluorescent probes, we demonstrate that lipid rafts from cerebellum, and frontal and entorhinal cortices, exhibit different biophysical behaviors depending on the stage of the disease. Thus, while membrane anisotropies were similar in the cerebellum along stages, lipid rafts from frontal and entorhinal cortices at AD stages I/II and AD III were significantly more liquid-ordered than in control subjects, both at the aqueous interface and hydrophobic core of the raft membrane. Thermotropic analyses demonstrated the presence of Arrhenius breakpoints between 28.3-32.0 °C, which were not influenced by the disease stage. However, analyses of membrane microviscosity (ηapp) demonstrate that frontal and entorhinal lipid rafts are notably more viscous and liquid-ordered all across the membrane from early stages of the disease. These physicochemical alterations in lipid rafts do not correlate with changes in cholesterol or sphingomyelin levels, but to reduced unsaturation index and increased saturate/polyunsaturated ratios in phospholipid acyl chains. Moreover, we demonstrate that β-secretase/AβPP (amyloid-β protein precursor) interaction and lipid raft microviscosity are strongly, and positively, correlated in AD frontal and entorhinal cortices. These observations strengthens the hypothesis that physical properties of these microdomains modulate the convergence of amyloidogenic machinery toward lipid rafts, and also points to a critical role of polyunsaturated fatty acids in amyloidogenic processing of AβPP.

  19. Osbpl8 Deficiency in Mouse Causes an Elevation of High-Density Lipoproteins and Gender-Specific Alterations of Lipid Metabolism

    Science.gov (United States)

    Béaslas, Olivier; Metso, Jari; Nissilä, Eija; Laurila, Pirkka-Pekka; Kaiharju, Essi; Batchu, Krishna Chaithanya; Kaipiainen, Leena; Mäyränpää, Mikko I.; Yan, Daoguang; Gylling, Helena; Jauhiainen, Matti; Olkkonen, Vesa M.

    2013-01-01

    OSBP-related protein 8 (ORP8) encoded by Osbpl8 is an endoplasmic reticulum sterol sensor implicated in cellular lipid metabolism. We generated an Osbpl8−/− (KO) C57Bl/6 mouse strain. Wild-type and Osbpl8KO animals at the age of 13-weeks were fed for 5 weeks either chow or high-fat diet, and their plasma lipids/lipoproteins and hepatic lipids were analyzed. The chow-fed Osbpl8KO male mice showed a marked elevation of high-density lipoprotein (HDL) cholesterol (+79%) and phospholipids (+35%), while only minor increase of apolipoprotein A-I (apoA-I) was detected. In chow-fed female KO mice a less prominent increase of HDL cholesterol (+27%) was observed, while on western diet the HDL increment was prominent in both genders. The HDL increase was accompanied by an elevated level of HDL-associated apolipoprotein E in male, but not female KO animals. No differences between genotypes were observed in lecithin:cholesterol acyltransferase (LCAT) or hepatic lipase (HL) activity, or in the fractional catabolic rate of fluorescently labeled mouse HDL injected in chow-diet fed animals. The Osbpl8KO mice of both genders displayed reduced phospholipid transfer protein (PLTP) activity, but only on chow diet. These findings are consistent with a model in which Osbpl8 deficiency results in altered biosynthesis of HDL. Consistent with this hypothesis, ORP8 depleted mouse hepatocytes secreted an increased amount of nascent HDL into the culture medium. In addition to the HDL phenotype, distinct gender-specific alterations in lipid metabolism were detected: Female KO animals on chow diet showed reduced lipoprotein lipase (LPL) activity and increased plasma triglycerides, while the male KO mice displayed elevated plasma cholesterol biosynthetic markers cholestenol, desmosterol, and lathosterol. Moreover, modest gender-specific alterations in the hepatic expression of lipid homeostatic genes were observed. In conclusion, we report the first viable OsbplKO mouse model, demonstrating a

  20. Alterations in cholesterol and ganglioside GM1 content of lipid rafts in platelets from patients with Alzheimer disease.

    Science.gov (United States)

    Liu, Li; Zhang, Ke; Tan, Liang; Chen, Yu-Hua; Cao, Yun-Peng

    2015-01-01

    The aim of this study was to investigate the changes in the protein, cholesterol, and ganglioside GM1 content of lipid rafts in platelets from patients with Alzheimer disease (AD), and identify potential blood biomarkers of the disease. A total of 31 Chinese patients with AD and 31 aged-matched control subjects were selected. Lipid rafts were isolated from platelets using Optiprep gradient centrifugation. The protein content of lipid rafts was evaluated using Micro BCA assay, the cholesterol content using molecular probes, ganglioside GM1 content using colorimetry and dot-blotting analysis. The results showed that the cholesterol and ganglioside GM1 content of lipid rafts from platelets was significantly higher in patients with AD than aged-matched control subjects, whereas the protein content of lipid rafts did not show any differences between the 2 groups. These results indicate that the increases in the cholesterol and ganglioside GM1 content of lipid rafts from the platelets of patients with AD might serve as a biochemical adjunct to the clinical diagnosis of AD.

  1. Muscle and liver-specific alterations in lipid and acylcarnitine metabolism after a single bout of exercise in mice.

    Science.gov (United States)

    Hoene, Miriam; Li, Jia; Li, Yanjie; Runge, Heike; Zhao, Xinjie; Häring, Hans-Ulrich; Lehmann, Rainer; Xu, Guowang; Weigert, Cora

    2016-01-01

    Intracellular lipid pools are highly dynamic and tissue-specific. Physical exercise is a strong physiologic modulator of lipid metabolism, but most studies focus on changes induced by long-term training. To assess the acute effects of endurance exercise, mice were subjected to one hour of treadmill running, and (13)C16-palmitate was applied to trace fatty acid incorporation in soleus and gastrocnemius muscle and liver. The amounts of carnitine, FFA, lysophospholipids and diacylglycerol and the post-exercise increase in acetylcarnitine were pronouncedly higher in soleus than in gastrocnemius. In the liver, exercise increased the content of lysophospholipids, plasmalogens and carnitine as well as transcript levels of the carnitine transporter. (13)C16-palmitate was detectable in several lipid and acylcarnitine species, with pronounced levels of tracer-derived palmitoylcarnitine in both muscles and a strikingly high incorporation into triacylglycerol and phosphatidylcholine in the liver. These data illustrate the high lipid storing activity of the liver immediately after exercise whereas in muscle, fatty acids are directed towards oxidation. The observed muscle-specific differences accentuate the need for single-muscle analyses as well as careful consideration of the particular muscle employed when studying lipid metabolism in mice. In addition, our results reveal that lysophospholipids and plasmalogens, potential lipid signalling molecules, are acutely regulated by physical exercise. PMID:26916151

  2. Ameliorating effect of black tea extract on cadmium chloride-induced alteration of serum lipid profile and liver histopathology in rats.

    Science.gov (United States)

    Mantur, Venkappa S; Somannavarib, Manjunath S; Yendigeri, Saeed; Das, Kusal K; Goudar, Shivaprasad S

    2014-01-01

    Cadmium is one among the most environmental pollutants that affects many organs like kidney, liver and testis. The present study was aimed to assess the simultaneous effects of black tea extracts (BTE) on cadmium chloride induced alterations in lipid profile and liver histology. Adult rats were divided into four groups (n=6/group), group I (normal saline), group II (CdCl2, 1.0 mg/kg, b.wt; i.p), group III (black tea extract, 2.5 gm tea leaf/dl of water that is 2.5% of aqueous BTE) and group IV (cadmium chloride + BTE). Cadmium chloride intoxicated rats showed significant increase in serum total cholesterol, triglycerides, and low density lipoprotein-cholesterol and there is a significant decrease in the serum high density lipoprotein-cholesterol. In the liver, cadmium chloride showed changes in normal architecture, swollen hepatocytes, kupffer cells hyperplasia, dilation and congestion of central vein. Oral administration of black tea extracts with cadmium chloride significantly improves lipid profile and liver architecture as compared to the cadmium chloride group. The results indicate that BTE is beneficial in preventing cadmium-induced lipid alterations and hepatocellular damage.

  3. Preparation, in vitro evaluation and statistical optimization of carvedilol-loaded solid lipid nanoparticles for lymphatic absorption via oral administration.

    Science.gov (United States)

    Shah, Mansi K; Madan, Parshotam; Lin, Senshang

    2014-06-01

    Carvedilol-loaded solid lipid nanoparticles (SLNs) were prepared using solubility parameter (δ) to select the lipid, and hot homogenization to fabricate SLNs. The effect of concentration of Compritol 888 ATO (COMP) and Poloxamer 188 (P-188) on the particle size of blank SLNs was studied using the design of experiments. Further narrow concentration range of COMP and P-188 was selected and carvedilol-loaded SLNs were prepared to obtain an optimized formulation which was lyophilized (L-SLNs), transformed into enteric compression-coated tablet and evaluated for drug release, X-ray diffraction and cellular uptake mechanism. COMP was chosen as lipid due to its least value of Δδ with carvedilol. The optimized formulation (7.5% COMP, 5.0% P-188 and 1.11% carvedilol) had 161 nm particle size and 94.8% entrapment efficiency. The enteric-coated carvedilol-loaded SLNs tablet protected carvedilol from acidic environment and similar prolonged release profiles were obtained from L-SLNs, core tablet and enteric-coated tablet. Absence of crystalline carvedilol XRD peak indicated the presence of amorphous carvedilol in SLNs. Higher carvedilol uptake from SLNs compared to drug solution in the Caco-2 cell line exhibited a potential prolonged drug release. Moreover, upon cellular uptake, SLNs could then enter the lymphatic system which will avoid first pass metabolism and hence higher oral bioavailability. PMID:23697916

  4. Iron dextran increases hepatic oxidative stress and alters expression of genes related to lipid metabolism contributing to hyperlipidaemia in murine model.

    Science.gov (United States)

    Silva, Maísa; da Costa Guerra, Joyce Ferreira; Sampaio, Ana Flávia Santos; de Lima, Wanderson Geraldo; Silva, Marcelo Eustáquio; Pedrosa, Maria Lucia

    2015-01-01

    The objective of this study was to investigate the effects of iron dextran on lipid metabolism and to determine the involvement of oxidative stress. Fischer rats were divided into two groups: the standard group (S), which was fed the AIN-93M diet, and the standard plus iron group (SI), which was fed the same diet but also received iron dextran injections. Serum cholesterol and triacylglycerol levels were higher in the SI group than in the S group. Iron dextran was associated with decreased mRNA levels of pparα, and its downstream gene cpt1a, which is involved in lipid oxidation. Iron dextran also increased mRNA levels of apoB-100, MTP, and L-FABP indicating alterations in lipid secretion. Carbonyl protein and TBARS were consistently higher in the liver of the iron-treated rats. Moreover, a significant positive correlation was found between oxidative stress products, lfabp expression, and iron stores. In addition, a negative correlation was found between pparα expression, TBARS, carbonyl protein, and iron stores. In conclusion, our results suggest that the increase observed in the transport of lipids in the bloodstream and the decreased fatty acid oxidation in rats, which was promoted by iron dextran, might be attributed to increased oxidative stress. PMID:25685776

  5. Iron Dextran Increases Hepatic Oxidative Stress and Alters Expression of Genes Related to Lipid Metabolism Contributing to Hyperlipidaemia in Murine Model

    Directory of Open Access Journals (Sweden)

    Maísa Silva

    2015-01-01

    Full Text Available The objective of this study was to investigate the effects of iron dextran on lipid metabolism and to determine the involvement of oxidative stress. Fischer rats were divided into two groups: the standard group (S, which was fed the AIN-93M diet, and the standard plus iron group (SI, which was fed the same diet but also received iron dextran injections. Serum cholesterol and triacylglycerol levels were higher in the SI group than in the S group. Iron dextran was associated with decreased mRNA levels of pparα, and its downstream gene cpt1a, which is involved in lipid oxidation. Iron dextran also increased mRNA levels of apoB-100, MTP, and L-FABP indicating alterations in lipid secretion. Carbonyl protein and TBARS were consistently higher in the liver of the iron-treated rats. Moreover, a significant positive correlation was found between oxidative stress products, lfabp expression, and iron stores. In addition, a negative correlation was found between pparα expression, TBARS, carbonyl protein, and iron stores. In conclusion, our results suggest that the increase observed in the transport of lipids in the bloodstream and the decreased fatty acid oxidation in rats, which was promoted by iron dextran, might be attributed to increased oxidative stress.

  6. Maternal chocolate and sucrose soft drink intake induces hepatic steatosis in rat offspring associated with altered lipid gene expression profile

    DEFF Research Database (Denmark)

    Kjærgaard, Maj; Nilsson, C.; Rosendal, A.;

    2014-01-01

    to decrease. Litter size reduction in offspring from high-fat/high-sucrose-fed dams further increased body weight and adiposity, and up-regulated genes involved in hepatic mitochondrial lipid oxidation and VLDL transport compared with all other groups. Litter size reduction did not have any impact on body...... until weaning, giving four dietary groups. Results: At postnatal day 1, offspring from high-fat/high-sucrose-fed dams were heavier and had increased hepatic triglycerides (TG), hepatic glycogen, blood glucose and plasma insulin compared with offspring from chow-fed dams. Hepatic genes involved in lipid...... weight gain and adiposity in offspring born to chow-fed dams. Conclusion: Our results suggest that supplementation of chocolate and soft drink during gestation and lactation contributes to early onset of hepatic steatosis associated with changes in hepatic gene expression and lipid handling. © 2013...

  7. Altered colonic mucosal Polyunsaturated Fatty Acid (PUFA derived lipid mediators in ulcerative colitis: new insight into relationship with disease activity and pathophysiology.

    Directory of Open Access Journals (Sweden)

    Mojgan Masoodi

    Full Text Available OBJECTIVES: Ulcerative colitis (UC is a relapsing inflammatory disorder of unconfirmed aetiology, variable severity and clinical course, characterised by progressive histological inflammation and with elevation of eicosanoids which have a known pathophysiological role in inflammation. Therapeutic interventions targetting eicosanoids (5-aminosalicylates (ASA are effective first line and adjunctive treatments in mild-moderate UC for achieving and sustaining clinical remission. However, the variable clinical response to 5-ASA and frequent deterioration in response to cyclo-oxygenase (COX inhibitors, has prompted an in depth simultaneous evaluation of multiple lipid mediators (including eicosanoids within the inflammatory milieu in UC. We hypothesised that severity of inflammation is associated with alteration of lipid mediators, in relapsing UC. DESIGN: Study was case-control design. Mucosal lipid mediators were determined by LC-MS/MS lipidomics analysis on mucosal biopsies taken from patients attending outpatients with relapsing UC. Univariate and multivariate statistical analyses were used to investigate the association of mucosal lipid mediators, with the disease state and severity graded histologically. RESULTS: Levels of PGE2, PGD2, TXB2, 5-HETE, 11-HETE, 12-HETE and 15-HETE are significantly elevated in inflamed mucosa and correlate with severity of inflammation, determined using validated histological scoring systems. CONCLUSIONS: Our approach of capturing inflammatory mediator signature at different stages of UC by combining comprehensive lipidomics analysis and computational modelling could be used to classify and predict mild-moderate inflammation; however, predictive index is diminished in severe inflammation. This new technical approach could be developed to tailor drug treatments to patients with active UC, based on the mucosal lipid mediator profile.

  8. Aminoclay–lipid hybrid composite as a novel drug carrier of fenofibrate for the enhancement of drug release and oral absorption

    Science.gov (United States)

    Yang, Liang; Shao, Yating; Han, Hyo-Kyung

    2016-01-01

    This study aimed to prepare the aminoclay–lipid hybrid composite to enhance the drug release and improve the oral bioavailability of poorly water-soluble fenofibrate. Antisolvent precipitation coupled with an immediate freeze-drying method was adopted to incorporate fenofibrate into aminoclay–lipid hybrid composite (ALC). The optimal composition of the ALC formulation was determined as the ratios of aminoclay to krill oil of 3:1 (w/w), krill oil to fenofibrate of 2:1 (w/w), and antisolvent to solvent of 6:4 (v/v). The morphological characteristics of ALC formulation were determined using scanning electron microscopy, differential scanning calorimetry, and X-ray powder diffraction, which indicated microcrystalline state of fenofibrate in ALC formulation. The ALC formulation achieved almost complete dissolution within 30 minutes, whereas the untreated powder and physical mixture exhibited less than 15% drug release. Furthermore, ALC formulation effectively increased the peak plasma concentration (Cmax) and area under the curve (AUC) of fenofibric acid (an active metabolite) in rats by approximately 13- and seven-fold, respectively. Furthermore, ALC formulation exhibited much lower moisture sorption behavior than the lyophilized formulation using sucrose as a cryoprotectant. Taken together, the present findings suggest that ALC formulation is promising for improving the oral absorption of poorly soluble fenofibrate. PMID:27042061

  9. Effects of Statin versus the Combination of Ezetimibe plus Statin on Serum Lipid Absorption Markers in Patients with Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Erisa Watanabe

    2015-01-01

    Full Text Available Background. The use of statins is essential for aggressive lipid-lowering treatment in acute coronary syndrome (ACS patients with dyslipidemia. Recently, elevation of sitosterol, a lipid absorption marker, was reported to be associated with premature atherosclerosis. The purpose of the present study was to examine the impact of ezetimibe, a selective intestinal cholesterol transporter inhibitor, in ACS patients. Methods. A total of 197 ACS patients were randomized to pitavastatin + ezetimibe (n=100 or pitavastatin (n=97. Low-density lipoprotein cholesterol (LDL-C and sitosterol levels were evaluated on admission and after 12 weeks. Results. After 12 weeks, the pitavastatin + ezetimibe group showed a significantly greater decrease of sitosterol (baseline versus after 12 weeks; 2.9 ± 2.5 versus 1.7 ± 1.0 ng/mL, P<0.001 than the pitavastatin group (2.7 ± 1.5 versus 3.0 ± 1.4 ng/mL. The baseline sitosterol level was significantly higher in patients with achieved LDL-C levels ≥ 70 mg/dL than in patients with levels < 70 mg/dL (3.2 ± 2.5 versus 2.4 ± 1.3 ng/mL, P=0.006. Conclusions. Ezetimibe plus statin therapy in ACS patients with dyslipidemia decreased LDL-C and sitosterol levels more than statin therapy solo. Sitosterol Elevation was a predictor of poor response to aggressive lipid-lowering treatment in ACS patients.

  10. Intestinal absorption of the antiepileptic drug substance vigabatrin is altered by infant formula in vitro and in vivo

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd

    2014-01-01

    formula and selected amino acids on the pharmacokinetic profile of vigabatrin was investigated after oral coadministration to male Sprague–Dawley rats using acetaminophen as a marker for gastric emptying. The presence of infant formula significantly reduced the uptake rate and permeability of vigabatrin....... The infant formula decreased the rate of gastric emptying. Here we provide experimental evidence for an in vivo role of PAT1 in the intestinal absorption of vigabatrin. The effect of infant formula on the oral absorption of vigabatrin was found to be due to delayed gastric emptying, however, it seems...

  11. Modification of the mannitol biosynthetic pathway in Aureobasidium pullulans to alter the structure of the polyol lipid liamocin

    Science.gov (United States)

    Aureobasidium pullulans is an important industrial organism that is utilized for the production of numerous bioproducts, such as pullulan, ß-glucan, aureobasidin, and polymalic acid. Our laboratory is also interested in production of the extracellular polyol lipids, called liamocins, produced by cer...

  12. Embryo-specific expression of soybean oleosin altered oil body morphogenesis and increased lipid content in transgenic rice seeds.

    Science.gov (United States)

    Liu, Wen Xian; Liu, Hua Liang; Qu, Le Qing

    2013-09-01

    Oleosin is the most abundant protein in the oil bodies of plant seeds, playing an important role in regulating oil body formation and lipid accumulation. To investigate whether lipid accumulation in transgenic rice seeds depends on the expression level of oleosin, we introduced two soybean oleosin genes encoding 24 kDa proteins into rice under the control of an embryo-specific rice promoter REG-2. Overexpression of soybean oleosin in transgenic rice leads to an increase of seed lipid content up to 36.93 and 46.06 % higher than that of the non-transgenic control, respectively, while the overall fatty acid profiles of triacylglycerols remained unchanged. The overexpression of soybean oleosin in transgenic rice seeds resulted in more numerous and smaller oil bodies compared with wild type, suggesting that an inverse relationship exists between oil body size and the total oleosin level. The increase in lipid content is accompanied by a reduction in the accumulation of total seed protein. Our results suggest that it is possible to increase rice seed oil content for food use and for use as a low-cost feedstock for biodiesel by overexpressing oleosin in rice seeds.

  13. Salt stress induced lipid accumulation in heterotrophic culture cells of Chlorella protothecoides: Mechanisms based on the multi-level analysis of oxidative response, key enzyme activity and biochemical alteration.

    Science.gov (United States)

    Wang, Tao; Ge, Haiyan; Liu, Tingting; Tian, Xiwei; Wang, Zejian; Guo, Meijin; Chu, Ju; Zhuang, Yingping

    2016-06-20

    Salt stress as an effective stress factor that could improve the lipid content and lipid yield of glucose in the heterotrophic culture cells of Chlorella protothecoides was demonstrated in this study. The highest lipid content of 41.2% and lipid yield of 185.8mg/g were obtained when C. protothecoides was stressed under 30g/L NaCl condition at its late logarithmic growth phase. Moreover, the effects of salt and osmotic stress on lipid accumulation were comparatively analyzed, and it was found that the effects of NaCl and KCl stress had no significant differences at the same osmolarity level of 1150mOsm/kg with lipid contents of 41.7 and 40.8% as well as lipid yields of 192.9 and 186.8mg/g, respectively, whereas these results were obviously higher than those obtained under the iso-osmotic glycerol and sorbitol stresses. Furthermore, basing on the multi-level analysis of oxidative response, key enzyme activity and biochemical alteration, the superior performance of salt stress driving lipid over-synthesis was probably ascribed to the more ROS production as a result of additional ion effect besides the osmotic effect, subsequently mediating the alteration from carbohydrate storage to lipid accumulation in signal transduction process of C. protothecoides. PMID:27085889

  14. Polychlorinated biphenyls (PCB 101, PCB 153 and PCB 180) alter leptin signaling and lipid metabolism in differentiated 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Non-dioxin-like polychlorinated biphenyls (NDL-PCBs) are highly lipophilic environmental contaminants that accumulate in lipid-rich tissues, such as adipose tissue. Here, we reported the effects induced by PCBs 101, 153 and 180, three of the six NDL-PCBs defined as indicators, on mature 3T3-L1 adipocytes. We observed an increase in lipid content, in leptin gene expression and a reduction of leptin receptor expression and signaling, when cells were exposed to PCBs, alone or in combination. These modifications were consistent with the occurrence of “leptin-resistance” in adipose tissue, a typical metabolic alteration related to obesity. Therefore, we investigated how PCBs affect the expression of pivotal proteins involved in the signaling of leptin receptor. We evaluated the PCB effect on the intracellular pathway JAK/STAT, determining the phosphorylation of STAT3, a downstream activator of the transcription of leptin gene targets, and the expression of SOCS3 and PTP1B, two important regulators of leptin resistance. In particular, PCBs 153 and 180 or all PCB combinations induced a significant reduction in pSTAT3/STAT3 ratio and an increase in PTP1B and SOCS3, evidencing an additive effect. The impairment of leptin signaling was associated with the reduction of AMPK/ACC pathway activation, leading to the increase in lipid content. These pollutants were also able to increase the transcription of inflammatory cytokines (IL-6 and TNFα). It is worthy to note that the PCB concentrations used are comparable to levels detectable in human adipose tissue. Our data strongly support the hypothesis that NDL-PCBs may interfere with the lipid metabolism contributing to the development of obesity and related diseases. - Highlights: • NDL-PCBs alter lipid content and metabolism in 3T3-L1 adipocytes. • Impairment of leptin signaling was induced by NDL-PCBs. • NDL-PCBs reduce AMPK and ACC activation. • NDL-PCBs induce the synthesis of pro-inflammatory cytokine by

  15. Polychlorinated biphenyls (PCB 101, PCB 153 and PCB 180) alter leptin signaling and lipid metabolism in differentiated 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ferrante, Maria C. [Department of Veterinary Medicine and Animal Productions, Federico II University of Naples, Via Delpino 1, 80137 Naples (Italy); Amero, Paola; Santoro, Anna [Department of Pharmacy, Federico II University of Naples, Via Montesano 49, 80131 Naples (Italy); Monnolo, Anna [Department of Veterinary Medicine and Animal Productions, Federico II University of Naples, Via Delpino 1, 80137 Naples (Italy); Simeoli, Raffaele; Di Guida, Francesca [Department of Pharmacy, Federico II University of Naples, Via Montesano 49, 80131 Naples (Italy); Mattace Raso, Giuseppina, E-mail: mattace@unina.it [Department of Pharmacy, Federico II University of Naples, Via Montesano 49, 80131 Naples (Italy); Meli, Rosaria, E-mail: meli@unina.it [Department of Pharmacy, Federico II University of Naples, Via Montesano 49, 80131 Naples (Italy)

    2014-09-15

    Non-dioxin-like polychlorinated biphenyls (NDL-PCBs) are highly lipophilic environmental contaminants that accumulate in lipid-rich tissues, such as adipose tissue. Here, we reported the effects induced by PCBs 101, 153 and 180, three of the six NDL-PCBs defined as indicators, on mature 3T3-L1 adipocytes. We observed an increase in lipid content, in leptin gene expression and a reduction of leptin receptor expression and signaling, when cells were exposed to PCBs, alone or in combination. These modifications were consistent with the occurrence of “leptin-resistance” in adipose tissue, a typical metabolic alteration related to obesity. Therefore, we investigated how PCBs affect the expression of pivotal proteins involved in the signaling of leptin receptor. We evaluated the PCB effect on the intracellular pathway JAK/STAT, determining the phosphorylation of STAT3, a downstream activator of the transcription of leptin gene targets, and the expression of SOCS3 and PTP1B, two important regulators of leptin resistance. In particular, PCBs 153 and 180 or all PCB combinations induced a significant reduction in pSTAT3/STAT3 ratio and an increase in PTP1B and SOCS3, evidencing an additive effect. The impairment of leptin signaling was associated with the reduction of AMPK/ACC pathway activation, leading to the increase in lipid content. These pollutants were also able to increase the transcription of inflammatory cytokines (IL-6 and TNFα). It is worthy to note that the PCB concentrations used are comparable to levels detectable in human adipose tissue. Our data strongly support the hypothesis that NDL-PCBs may interfere with the lipid metabolism contributing to the development of obesity and related diseases. - Highlights: • NDL-PCBs alter lipid content and metabolism in 3T3-L1 adipocytes. • Impairment of leptin signaling was induced by NDL-PCBs. • NDL-PCBs reduce AMPK and ACC activation. • NDL-PCBs induce the synthesis of pro-inflammatory cytokine by

  16. Neonatal Exposure to Parathion Alters Lipid Metabolism in Adulthood: Interactions with Dietary Fat Intake and Implications for Neurodevelopmental Deficits

    OpenAIRE

    Lassiter, T. Leon; Ryde, Ian T.; Levin, Edward D.; Seidler, Frederic J; Slotkin, Theodore A.

    2010-01-01

    Organophosphates are developmental neurotoxicants but recent evidence also points to metabolic dysfunction. We determined whether neonatal parathion exposure in rats has long-term effects on regulation of adipokines and lipid peroxidation. We also assessed the interaction of these effects with increased fat intake. Rats were given parathion on postnatal days 1–4 using doses (0.1 or 0.2 mg/kg/day) that straddle the threshold for barely detectable cholinesterase inhibition and the first signs o...

  17. Role of C-peptide in Altered Lipid Profile among Apparently Healthy Adults of Vijayapura City, Karnataka

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    Chandrahas M.Kulkarni

    2016-04-01

    Full Text Available Background: C-peptide is produced in equimolar concentration during insulin production as inactive molecule by beta islet cells of Langerhans. C-peptide is most useful biomarker of endogenous insulin production. Aim and Objectives: To predict metabolic syndrome in advance by estimation of C-peptide and lipid profile in healthy adults. Material and Methods: Serum C-peptide, fasting blood glucose and lipid profile of 128 healthy individuals were estimated. Adults in the age group of 18 to 60 years of both sexes were included in study. Results: C-peptide levels were increased in 27%, Serum cholesterol in 30%, LDL Cholesterol in 55% and triglyceride levels in 21% of healthy individuals. Significant correlation was observed between C peptide, age, serum cholesterol, LDL and cholesterol LDL ratio in male subjects only. In our study group most of the subjects (both males and females fell in overweight group. Conclusion: Cpeptide level and lipid profile may be considered as useful biomarkers to predict type 2 diabetes mellitus in advance, possibly due to insulin resistance.

  18. Alteration of viral lipid composition by expression of the phospholipid floppase ABCB4 reduces HIV vector infectivity

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    van Til Niek P

    2008-02-01

    Full Text Available Abstract Background The presence of cholesterol in the Human Immunodeficiency Virus (HIV lipid envelop is important for viral function as cholesterol depleted viral particles show reduced infectivity. However, it is less well established whether other viral membrane lipids are also important for HIV infection. The ABCB4 protein is a phosphatidyl choline (PC floppase that mediates transport of PC from the inner to the outer membrane leaflet. This property enabled us to modulate the lipid composition of HIV vectors and study the effects on membrane composition and infection efficiency. Results Virus generated in the presence of ABCB4 was enriched in PC and cholesterol but contained less sphingomyelin (SM. Viral titers were reduced 5.9 fold. These effects were not observed with an inactive ABCB4 mutant. The presence of the ABC transport inhibitor verapamil abolished the effect of ABCB4 expression on viral titers. The ABCB4 mediated reduction in infectivity was caused by changes in the viral particles and not by components co purified with the virus because virus made in the presence of ABCB4 did not inhibit virus made without ABCB4 in a competition assay. Incorporation of the envelope protein was not affected by the expression of ABCB4. The inhibitory effect of ABCB4 was independent of the viral envelope as the effect was observed with two different envelope proteins. Conclusion Our data indicate that increasing the PC content of HIV particles reduces infectivity.

  19. Dietary omega-3 polyunsaturated fatty acids alter the fatty acid composition of hepatic and plasma bioactive lipids in C57BL/6 mice: a lipidomic approach.

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    Kayode A Balogun

    Full Text Available BACKGROUND: Omega (n-3 polyunsaturated fatty acids (PUFA are converted to bioactive lipid components that are important mediators in metabolic and physiological pathways; however, which bioactive compounds are metabolically active, and their mechanisms of action are still not clear. We investigated using lipidomic techniques, the effects of diets high in n-3 PUFA on the fatty acid composition of various bioactive lipids in plasma and liver. METHODOLOGY AND PRINCIPAL FINDINGS: Female C57BL/6 mice were fed semi-purified diets (20% w/w fat containing varying amounts of n-3 PUFA before mating, during gestation and lactation, and until weaning. Male offspring were continued on their mothers' diets for 16 weeks. Hepatic and plasma lipids were extracted in the presence of non-naturally occurring internal standards, and tandem electrospray ionization mass spectrometry methods were used to measure the fatty acyl compositions. There was no significant difference in total concentrations of phospholipids in both groups. However, there was a significantly higher concentration of eicosapentaenoic acid containing phosphatidylcholine (PC, lysophosphatidylcholine (LPC, and cholesteryl esters (CE (p < 0.01 in the high n-3 PUFA group compared to the low n-3 PUFA group in both liver and plasma. Plasma and liver from the high n-3 PUFA group also had a higher concentration of free n-3 PUFA (p < 0.05. There were no significant differences in plasma concentrations of different fatty acyl species of phosphatidylethanolamine, triglycerides, sphingomyelin and ceramides. CONCLUSIONS/SIGNIFICANCE: Our findings reveal for the first time that a diet high in n-3 PUFA caused enrichment of n-3 PUFA in PC, LPC, CE and free fatty acids in the plasma and liver of C57BL/6 mice. PC, LPC, and unesterified free n-3 PUFA are important bioactive lipids, thus altering their fatty acyl composition will have important metabolic and physiological roles.

  20. Nanostructured lipid carriers-based flurbiprofen gel after topical administration: acute skin irritation, pharmacodynamics, and percutaneous absorption mechanism.

    Science.gov (United States)

    Song, Aihua; Su, Zhen; Li, Sanming; Han, Fei

    2015-01-01

    In order to assess the preliminary safety and effectiveness of nanostructured lipid carriers-based flurbiprofen gel (FP NLC-gel), the acute irritation test, in vivo pharmacodynamics evaluation and pharmacokinetic study were investigated after topical application. No dropsy and erythema were observed after continuous dosing 7 d of FP NLC-gel on the rabbit skin, and the xylene-induced ear drossy could be inhibited by FP NLC-gel at different dosages. The maximum concentration of FP in rats muscle was 2.03 μg/g and 1.55 μg/g after oral and topical administration, respectively. While the peak concentration in untreated muscle after topical administration was only 0.37 μg/mL. And at any time, following topical administration the mean muscle-plasma concentration ratio Cmuscle/CPlasma was obviously higher than that following oral administration. Results indicated that FP could directly penetrate into the subcutaneous muscle tissue from the administration site. Thus, the developed FP NLC-gel could be a safe and effective vehicle for topical delivery of FP.

  1. RAB GTPASES ASSOCIATE WITH ISOLATED LIPID DROPLETS (LDS) AND SHOW ALTERED CONTENT AFTER ETHANOL ADMINISTRATION: POTENTIAL ROLE IN ALCOHOL-IMPAIRED LD METABOLISM

    Science.gov (United States)

    Rasineni, Karuna; McVicker, Benita L.; Tuma, Dean J.; McNiven, Mark A.; Casey, Carol A.

    2013-01-01

    Background Alcoholic liver disease is manifested by the presence of fatty liver, primarily due to accumulation of hepatocellular lipid droplets (LDs). The presence of membrane-trafficking proteins (e.g. Rab GTPases) with LDs indicates that LDs may be involved in trafficking pathways known to be altered in ethanol damaged hepatocytes. Since these Rab GTPases are crucial regulators of protein trafficking, we examined the effect ethanol administration has on hepatic Rab protein content and association with LDs. Methods Male Wistar rats were pair-fed Lieber-DeCarli diets for 5 to 8 weeks. Whole liver and isolated LD fractions were analyzed. Identification of LDs and associated Rab proteins was performed in frozen liver or paraffin-embedded sections followed by immunohistochemical analysis. Results Lipid accumulation was characterized by larger LD vacuoles and increased total triglyceride content in ethanol-fed rats. Rabs 1, 2, 3d, 5, 7 and 18 were analyzed in post-nuclear supernatant (PNS) as well as LDs. All of the Rabs were found in the PNS, and Rabs 1, 2, 5 and 7 did not show alcohol-altered content, while Rab 3d content was reduced by over 80%, and Rab 18 also showed ethanol-induced reduction in content. Rab 3d was not found to associate with LDs, while all other Rabs were found in the LD fractions, and several showed an ethanol-related decrease (Rabs 2, 5, 7, 18). Immunohistochemical analysis revealed the enhanced content of a LD-associated protein, perilipin 2 (PLIN2) that was paralleled with an associated decrease of Rab 18 in ethanol-fed rat sections. Conclusion Chronic ethanol feeding was associated with increased PLIN2 and altered Rab GTPase content in enriched LD fractions. Although mechanisms driving these changes are not established, further studies on intracellular protein trafficking and LD biology after alcohol administration will likely contribute to our understanding of fatty liver disease. PMID:24117505

  2. Trp53 deficient mice predisposed to preterm birth display region-specific lipid alterations at the embryo implantation site

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    Lanekoff, Ingela; Cha, Jeeyeon; Kyle, Jennifer E.; Dey, Sudhansu K.; Laskin, Julia; Burnum-Johnson, Kristin E.

    2016-09-01

    Here we demonstrate that conditional deletion of mouse uterine Trp53 (p53d/d), molecularly linked to mTORC1 activation and causally linked to premature uterine senescence and preterm birth, results in aberrant lipid signatures within the heterogeneous cell types of embryo implantation sites on day 8 of pregnancy. In situ nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI MSI) was used to characterize the molecular speciation of free fatty acids, monoacylglycerol species, unmodified and oxidized phosphatidylcholine (PC/Ox-PC), and diacylglycerol (DG) species within implantation sites of p53d/d mice and floxed littermates. Implantation sites from p53d/d mice exhibited distinct spatially resolved changes demonstrating accumulation of DG species, depletion of Ox-PC species, and increase in species with more unsaturated acyl chains, including arachidonic and docosahexaenoic acid. Understanding abnormal changes in the abundance and localization of individual lipid species early in the progression to premature birth is an important step toward discovering novel targets for treatments and diagnosis.

  3. Response of Arabidopsis thaliana Roots with Altered Lipid Transfer Protein (LTP) Gene Expression to the Clubroot Disease and Salt Stress.

    Science.gov (United States)

    Jülke, Sabine; Ludwig-Müller, Jutta

    2015-01-01

    The clubroot disease of Brassicaceae is caused by the obligate biotrophic protist Plasmodiophora brassicae. The disease is characterized by abnormal tumorous swellings of infected roots that result in reduced drought resistance and insufficient distribution of nutrients, leading to reduced crop yield. It is one of the most damaging diseases among cruciferous crops worldwide. The acquisition of nutrients by the protist is not well understood. Gene expression profiles in Arabidopsis thaliana clubroots indicate that lipid transfer proteins (LTPs) could be involved in disease development or at least in adaptation to the disease symptoms. Therefore, the aim of the study was to examine the role of some, of the still enigmatic LTPs during clubroot development. For a functional approach, we have generated transgenic plants that overexpress LTP genes in a root specific manner or show reduced LTP gene expression. Our results showed that overexpression of some of the LTP genes resulted in reduced disease severity whereas the lipid content in clubs of LTP mutants seems to be unaffected. Additional studies indicate a role for some LTPs during salt stress conditions in roots of A. thaliana. PMID:27135222

  4. Response of Arabidopsis thaliana Roots with Altered Lipid Transfer Protein (LTP Gene Expression to the Clubroot Disease and Salt Stress

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    Sabine Jülke

    2015-12-01

    Full Text Available The clubroot disease of Brassicaceae is caused by the obligate biotrophic protist Plasmodiophora brassicae. The disease is characterized by abnormal tumorous swellings of infected roots that result in reduced drought resistance and insufficient distribution of nutrients, leading to reduced crop yield. It is one of the most damaging diseases among cruciferous crops worldwide. The acquisition of nutrients by the protist is not well understood. Gene expression profiles in Arabidopsis thaliana clubroots indicate that lipid transfer proteins (LTPs could be involved in disease development or at least in adaptation to the disease symptoms. Therefore, the aim of the study was to examine the role of some, of the still enigmatic LTPs during clubroot development. For a functional approach, we have generated transgenic plants that overexpress LTP genes in a root specific manner or show reduced LTP gene expression. Our results showed that overexpression of some of the LTP genes resulted in reduced disease severity whereas the lipid content in clubs of LTP mutants seems to be unaffected. Additional studies indicate a role for some LTPs during salt stress conditions in roots of A. thaliana.

  5. Trp53 deficient mice predisposed to preterm birth display region-specific lipid alterations at the embryo implantation site.

    Science.gov (United States)

    Lanekoff, Ingela; Cha, Jeeyeon; Kyle, Jennifer E; Dey, Sudhansu K; Laskin, Julia; Burnum-Johnson, Kristin E

    2016-01-01

    Here we demonstrate that conditional deletion of mouse uterine Trp53 (p53(d/d)), molecularly linked to mTORC1 activation and causally linked to premature uterine senescence and preterm birth, results in aberrant lipid signatures within the heterogeneous cell types of embryo implantation sites on day 8 of pregnancy. In situ nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI MSI) was used to characterize the molecular speciation of free fatty acids, monoacylglycerol species, unmodified and oxidized phosphatidylcholine (PC/Ox-PC), and diacylglycerol (DG) species within implantation sites of p53(d/d) mice and floxed littermates. Implantation sites from p53(d/d) mice exhibited distinct spatially resolved changes demonstrating accumulation of DG species, depletion of Ox-PC species, and increase in species with more unsaturated acyl chains, including arachidonic and docosahexaenoic acid. Understanding abnormal changes in the abundance and localization of individual lipid species early in the progression to premature birth is an important step toward discovering novel targets for treatments and diagnosis. PMID:27620843

  6. Preparation of andrographolide-loaded solid lipid nanoparticles and their in vitro and in vivo evaluations: characteristics, release, absorption, transports, pharmacokinetics, and antihyperlipidemic activity.

    Science.gov (United States)

    Yang, Tao; Sheng, Huan-Huan; Feng, Nian-Ping; Wei, Hai; Wang, Zheng-Tao; Wang, Chang-Hong

    2013-12-01

    Andrographolide (AND) is one of diterpenoids separated from Andrographis paniculata with a wide spectrum of biological activities of being anti-inflammatory, anticancer, hepatoprotective, and antihyperlipidemic. But its poor water solubility and instability resulted in lower bioavailability and seriously limited its pharmacological function. In this study, AND-loaded solid lipid nanoparticles (AND-SLNs) were prepared by a high-pressure homogenization method and presented as spherically shaped under transmission electron microscopy with an average diameter of 286.1 nm and zeta potential of -20.8 mV. The average drug-entrapment efficiency and drug loading were 91.00% and 3.49%, respectively. The results indicated that the lower bioavailability of AND is not only because of the poor solubility but also owing to its metabolic instability in intestinal segments. Furthermore, the transport mechanism of AND in Caco-2 cell model is complex in which an active transport carrier (P-glycoprotein) is involved in. The bioavailability and antihyperlipidemic activity of AND were improved by AND-SLNs by increasing the solubility and stability of AND in the intestine and by changing its transport mode in Caco-2 cell. The bioavailability of AND was increased to 241% by AND-SLNs as compared with AND suspension. AND-SLNs would be a promising drug-delivery system to enhance the oral absorption and bioavailability of AND. PMID:24166599

  7. Lou/C obesity-resistant rat exhibits hyperactivity, hypermetabolism, alterations in white adipose tissue cellularity, and lipid tissue profiles.

    Science.gov (United States)

    Soulage, Christophe; Zarrouki, Bader; Soares, Anisio Francesco; Lagarde, Michel; Geloen, Alain

    2008-02-01

    Lou/C obesity-resistant rat constitutes an original model to understand the phenomena of overweight and obesity. The aim of the present study was to identify metabolic causes for the outstanding leanness of Lou/C rat. To this end, the metabolic profiles (food intake, energy expenditure, and physical activity) and the cellular characteristics of white adipose tissue (lipogenesis, lipolysis, cellularity, and lipid composition) in 30-wk-old Lou/C rats were compared with age-matched Wistar rats. Lou/C rats exhibited a lower body weight (-45%), reduced adiposity (-80%), increased locomotor activity (+95%), and higher energy expenditure (+11%) than Wistar rats. Epididymal adipose tissue of Lou/C rat was twice lower than that of Wistar rat due to both a reduction in both adipocyte size (-25%) and number (three times). Basal lipolysis and sensitivity to noradrenaline were similar; however, the responsiveness to noradrenaline was lower in adipocytes from Lou/C compared with that from Wistar rats. Lipidomic analysis of plasma, adipose tissue, and liver revealed profound differences in lipid composition between the two strains. Of note, the desaturation indexes (ratio C16:1/C16:0 and C18:1/C18:0) were lower in Lou/C, indicating a blunted activity of delta-9-desaturase such as stearoyl-coenzyme A-desaturase-1. Increased physical activity, increased energy expenditure, and white adipose tissue cellularity are in good agreement with previous observations suggesting that a higher sympathetic tone in Lou/C could contribute to its lifelong leanness. PMID:18006635

  8. Altered lipid peroxidation markers are related to post-traumatic stress disorder (PTSD) and not trauma itself in earthquake survivors.

    Science.gov (United States)

    Atli, Abdullah; Bulut, Mahmut; Bez, Yasin; Kaplan, İbrahim; Özdemir, Pınar Güzel; Uysal, Cem; Selçuk, Hilal; Sir, Aytekin

    2016-06-01

    The traumatic life events, including earthquakes, war, and interpersonal conflicts, cause a cascade of psychological and biological changes known as post-traumatic stress disorder (PTSD). Malondialdehyde (MDA) is a reliable marker of lipid peroxidation, and paraoxonase is a known antioxidant enzyme. The aims of this study were to investigate the relationship between earthquake trauma, PTSD effects on oxidative stress and the levels of serum paraoxonase 1 (PON1) enzyme activity, and levels of serum MDA. The study was carried out on three groups called: the PTSD group, the traumatized with earthquake exercise group, and healthy control group, which contained 32, 31, and 38 individuals, respectively. Serum MDA levels and PON1 enzyme activities from all participants were measured, and the results were compared across all groups. There were no significant differences between the PTSD patients and non-PTSD earthquake survivors in terms of the study variables. The mean PON1 enzyme activity from PTSD patients was significantly lower, while the mean MDA level was significantly higher than that of the healthy control group (p earthquake survivors who did not develop PTSD showed higher MDA levels and lower PON1 activity when compared to healthy controls. However, the differences between these groups did not reach a statistically significant level. Increased MDA level and decreased PON1 activity measured in PTSD patients after earthquake and may suggest increased oxidative stress in these patients. The nonsignificant trends that are observed in lipid peroxidation markers of earthquake survivors may indicate higher impact of PTSD development on these markers than trauma itself. For example, PTSD diagnosis seems to add to the effect of trauma on serum MDA levels and PON1 enzyme activity. Thus, serum MDA levels and PON1 enzyme activity may serve as biochemical markers of PTSD diagnosis. PMID:26324882

  9. Caloric restriction and intermittent fasting alter hepatic lipid droplet proteome and diacylglycerol species and prevent diabetes in NZO mice.

    Science.gov (United States)

    Baumeier, Christian; Kaiser, Daniel; Heeren, Jörg; Scheja, Ludger; John, Clara; Weise, Christoph; Eravci, Murat; Lagerpusch, Merit; Schulze, Gunnar; Joost, Hans-Georg; Schwenk, Robert Wolfgang; Schürmann, Annette

    2015-05-01

    Caloric restriction and intermittent fasting are known to improve glucose homeostasis and insulin resistance in several species including humans. The aim of this study was to unravel potential mechanisms by which these interventions improve insulin sensitivity and protect from type 2 diabetes. Diabetes-susceptible New Zealand Obese mice were either 10% calorie restricted (CR) or fasted every other day (IF), and compared to ad libitum (AL) fed control mice. AL mice showed a diabetes prevalence of 43%, whereas mice under CR and IF were completely protected against hyperglycemia. Proteomic analysis of hepatic lipid droplets revealed significantly higher levels of PSMD9 (co-activator Bridge-1), MIF (macrophage migration inhibitor factor), TCEB2 (transcription elongation factor B (SIII), polypeptide 2), ACY1 (aminoacylase 1) and FABP5 (fatty acid binding protein 5), and a marked reduction of GSTA3 (glutathione S-transferase alpha 3) in samples of CR and IF mice. In addition, accumulation of diacylglycerols (DAGs) was significantly reduced in livers of IF mice (P=0.045) while CR mice showed a similar tendency (P=0.062). In particular, 9 DAG species were significantly reduced in response to IF, of which DAG-40:4 and DAG-40:7 also showed significant effects after CR. This was associated with a decreased PKCε activation and might explain the improved insulin sensitivity. In conclusion, our data indicate that protection against diabetes upon caloric restriction and intermittent fasting associates with a modulation of lipid droplet protein composition and reduction of intracellular DAG species. PMID:25645620

  10. Oro-gustatory perception of dietary lipids and calcium signaling in taste bud cells are altered in nutritionally obesity-prone Psammomys obesus.

    Directory of Open Access Journals (Sweden)

    Souleymane Abdoul-Azize

    Full Text Available Since the increasing prevalence of obesity is one of the major health problems of the modern era, understanding the mechanisms of oro-gustatory detection of dietary fat is critical for the prevention and treatment of obesity. We have conducted the present study on Psammomys obesus, the rodent desert gerbil which is a unique polygenic natural animal model of obesity. Our results show that obese animals exhibit a strong preference for lipid solutions in a two-bottle test. Interestingly, the expression of CD36, a lipido-receptor, in taste buds cells (TBC, isolated from circumvallate papillae, was decreased at mRNA level, but remained unaltered at protein level, in obese animals. We further studied the effects of linoleic acid (LA, a long-chain fatty acid, on the increases in free intracellular calcium (Ca(2+ concentrations, [Ca(2+]i, in the TBC of P. obesus. LA induced increases in [Ca(2+]i, largely via CD36, from intracellular pool, followed by the opening of store-operated Ca(2+ (SOC channels in the TBC of these animals. The action of this fatty acid on the increases in [Ca(2+]i was higher in obese animals than that in controls. However, the release of Ca(2+ from intracellular stores, studied also by employing thapsigargin, was lower in TBC of obese animals than control rodents. In this study, we show, for the first time, that increased lipid intake and altered Ca(2+ signaling in TBC are associated with obesity in Psammomys obesus.

  11. Oro-Gustatory Perception of Dietary Lipids and Calcium Signaling in Taste Bud Cells Are Altered in Nutritionally Obesity-Prone Psammomys obesus

    Science.gov (United States)

    Bitam, Arezki; Sadou, Hassimi; Koceïr, Elhadj Ahmed; Khan, Naim Akhtar

    2013-01-01

    Since the increasing prevalence of obesity is one of the major health problems of the modern era, understanding the mechanisms of oro-gustatory detection of dietary fat is critical for the prevention and treatment of obesity. We have conducted the present study on Psammomys obesus, the rodent desert gerbil which is a unique polygenic natural animal model of obesity. Our results show that obese animals exhibit a strong preference for lipid solutions in a two-bottle test. Interestingly, the expression of CD36, a lipido-receptor, in taste buds cells (TBC), isolated from circumvallate papillae, was decreased at mRNA level, but remained unaltered at protein level, in obese animals. We further studied the effects of linoleic acid (LA), a long-chain fatty acid, on the increases in free intracellular calcium (Ca2+) concentrations, [Ca2+]i, in the TBC of P. obesus. LA induced increases in [Ca2+]i, largely via CD36, from intracellular pool, followed by the opening of store-operated Ca2+ (SOC) channels in the TBC of these animals. The action of this fatty acid on the increases in [Ca2+]i was higher in obese animals than that in controls. However, the release of Ca2+ from intracellular stores, studied also by employing thapsigargin, was lower in TBC of obese animals than control rodents. In this study, we show, for the first time, that increased lipid intake and altered Ca2+ signaling in TBC are associated with obesity in Psammomys obesus. PMID:23936306

  12. Lipids and bariatric procedures part 1 of 2: Scientific statement from the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and Obesity Medicine Association: EXECUTIVE SUMMARY.

    Science.gov (United States)

    Bays, Harold E; Jones, Peter H; Jacobson, Terry A; Cohen, David E; Orringer, Carl E; Kothari, Shanu; Azagury, Dan E; Morton, John; Nguyen, Ninh T; Westman, Eric C; Horn, Deborah B; Scinta, Wendy; Primack, Craig

    2016-01-01

    Bariatric procedures often improve lipid levels in patients with obesity. This 2-part scientific statement examines the potential lipid benefits of bariatric procedures and represents contributions from authors representing the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and the Obesity Medicine Association. The foundation for this scientific statement was based on data published through June 2015. Part 1 of this 2-part scientific statement provides an overview of: (1) adipose tissue, cholesterol metabolism, and lipids; (2) bariatric procedures, cholesterol metabolism, and lipids; (3) endocrine factors relevant to lipid influx, synthesis, metabolism, and efflux; (4) immune factors relevant to lipid influx, synthesis, metabolism, and efflux; (5) bariatric procedures, bile acid metabolism, and lipids; and (6) bariatric procedures, intestinal microbiota, and lipids, with specific emphasis on how the alterations in the microbiome by bariatric procedures influence obesity, bile acids, and inflammation, which in turn, may all affect lipid levels. Included in part 2 of this comprehensive scientific statement will be a review of: (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on cardiovascular disease; and finally (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies that may occur after bariatric procedures. This document represents the executive summary of part 1.

  13. Lipids and bariatric procedures part 1 of 2: Scientific statement from the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and Obesity Medicine Association: FULL REPORT.

    Science.gov (United States)

    Bays, Harold E; Jones, Peter H; Jacobson, Terry A; Cohen, David E; Orringer, Carl E; Kothari, Shanu; Azagury, Dan E; Morton, John; Nguyen, Ninh T; Westman, Eric C; Horn, Deborah B; Scinta, Wendy; Primack, Craig

    2016-01-01

    Bariatric procedures often improve lipid levels in patients with obesity. This 2 part scientific statement examines the potential lipid benefits of bariatric procedures and represents the contributions from authors representing the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and the Obesity Medicine Association. The foundation for this scientific statement was based on published data through June 2015. Part 1 of this 2 part scientific statement provides an overview of: (1) adipose tissue, cholesterol metabolism, and lipids; (2) bariatric procedures, cholesterol metabolism, and lipids; (3) endocrine factors relevant to lipid influx, synthesis, metabolism, and efflux; (4) immune factors relevant to lipid influx, synthesis, metabolism, and efflux; (5) bariatric procedures, bile acid metabolism, and lipids; and (6) bariatric procedures, intestinal microbiota, and lipids, with specific emphasis on how the alterations in the microbiome by bariatric procedures influence obesity, bile acids, and inflammation, which in turn, may all affect lipid levels. Included in part 2 of this comprehensive scientific statement will be a review of (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease (CVD) risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on CVD; and finally, (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies that may occur after bariatric procedures. This document represents the full report of part 1.

  14. Lipids and bariatric procedures part 1 of 2: Scientific statement from the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and Obesity Medicine Association: EXECUTIVE SUMMARY.

    Science.gov (United States)

    Bays, Harold E; Jones, Peter H; Jacobson, Terry A; Cohen, David E; Orringer, Carl E; Kothari, Shanu; Azagury, Dan E; Morton, John; Nguyen, Ninh T; Westman, Eric C; Horn, Deborah B; Scinta, Wendy; Primack, Craig

    2016-01-01

    Bariatric procedures often improve lipid levels in patients with obesity. This 2-part scientific statement examines the potential lipid benefits of bariatric procedures and represents contributions from authors representing the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and the Obesity Medicine Association. The foundation for this scientific statement was based on data published through June 2015. Part 1 of this 2-part scientific statement provides an overview of: (1) adipose tissue, cholesterol metabolism, and lipids; (2) bariatric procedures, cholesterol metabolism, and lipids; (3) endocrine factors relevant to lipid influx, synthesis, metabolism, and efflux; (4) immune factors relevant to lipid influx, synthesis, metabolism, and efflux; (5) bariatric procedures, bile acid metabolism, and lipids; and (6) bariatric procedures, intestinal microbiota, and lipids, with specific emphasis on how the alterations in the microbiome by bariatric procedures influence obesity, bile acids, and inflammation, which in turn, may all affect lipid levels. Included in part 2 of this comprehensive scientific statement will be a review of: (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on cardiovascular disease; and finally (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies that may occur after bariatric procedures. This document represents the executive summary of part 1. PMID:26892119

  15. Lipids and bariatric procedures part 1 of 2: Scientific statement from the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and Obesity Medicine Association: FULL REPORT.

    Science.gov (United States)

    Bays, Harold E; Jones, Peter H; Jacobson, Terry A; Cohen, David E; Orringer, Carl E; Kothari, Shanu; Azagury, Dan E; Morton, John; Nguyen, Ninh T; Westman, Eric C; Horn, Deborah B; Scinta, Wendy; Primack, Craig

    2016-01-01

    Bariatric procedures often improve lipid levels in patients with obesity. This 2 part scientific statement examines the potential lipid benefits of bariatric procedures and represents the contributions from authors representing the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and the Obesity Medicine Association. The foundation for this scientific statement was based on published data through June 2015. Part 1 of this 2 part scientific statement provides an overview of: (1) adipose tissue, cholesterol metabolism, and lipids; (2) bariatric procedures, cholesterol metabolism, and lipids; (3) endocrine factors relevant to lipid influx, synthesis, metabolism, and efflux; (4) immune factors relevant to lipid influx, synthesis, metabolism, and efflux; (5) bariatric procedures, bile acid metabolism, and lipids; and (6) bariatric procedures, intestinal microbiota, and lipids, with specific emphasis on how the alterations in the microbiome by bariatric procedures influence obesity, bile acids, and inflammation, which in turn, may all affect lipid levels. Included in part 2 of this comprehensive scientific statement will be a review of (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease (CVD) risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on CVD; and finally, (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies that may occur after bariatric procedures. This document represents the full report of part 1. PMID:26892120

  16. Altered Methylation Profile of Lymphocytes Is Concordant with Perturbation of Lipids Metabolism and Inflammatory Response in Obesity

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    Mette J. Jacobsen

    2016-01-01

    Full Text Available Obesity is associated with immunological perturbations that contribute to insulin resistance. Epigenetic mechanisms can control immune functions and have been linked to metabolic complications, although their contribution to insulin resistance still remains unclear. In this study, we investigated the link between metabolic dysfunction and immune alterations with the epigenetic signature in leukocytes in a porcine model of obesity. Global DNA methylation of circulating leukocytes, adipose tissue leukocyte trafficking, and macrophage polarisation were established by flow cytometry. Adipose tissue inflammation and metabolic function were further characterised by quantification of metabolites and expression levels of genes associated with obesity and inflammation. Here we show that obese pigs showed bigger visceral fat pads, higher levels of circulating LDL cholesterol, and impaired glucose tolerance. These changes coincided with impaired metabolism, sustained macrophages infiltration, and increased inflammation in the adipose tissue. Those immune alterations were linked to global DNA hypermethylation in both B-cells and T-cells. Our results provide novel insight into the possible contribution of immune cell epigenetics into the immunological disturbances observed in obesity. The dramatic changes in the transcriptomic and epigenetic signature of circulating lymphocytes reinforce the concept that epigenetic processes participate in the increased immune cell activation and impaired metabolic functions in obesity.

  17. Toxicological effects of particulate matter (PM2.5) on rats: Bioaccumulation, antioxidant alterations, lipid damage, and ABC transporter activity.

    Science.gov (United States)

    Ribeiro, Joaquim de Paula; Kalb, Ana Cristina; Campos, Paula Peixoto; Cruz, Alex Rubén Huaman De La; Martinez, Pablo Elias; Gioda, Adriana; Souza, Marta Marques de; Gioda, Carolina Rosa

    2016-11-01

    Previous studies have demonstrated the harmful effects of atmospheric pollutants on cardiac systems because of the presence of particulate matter (PM), a complex mixture of numerous substances including trace metals. In this study, the toxicity of PM2.5 from two regions, rural (PM2.5 level of 8.5 ± 4.0 μg m(-3)) and industrial (PM2.5 level of 14.4 ± 4.1 μg m(-3)) in Brazil, was investigated through in vivo experiments in rats. Metal accumulation and biochemical responses were evaluated after rats were exposed to three different concentrations of PM2.5 in saline extract (10× dilution, 5× dilution, and concentrated). The experimental data showed the bioaccumulation of diverse trace metals in the hearts of groups exposed to PM2.5 from both regions. Furthermore, mobilization of the antioxidant defenses and an increase in lipid peroxidation of the cardiac tissue was observed in response to the industrial and rural area PM2.5. Glutathione-S-transferase activity was increased in groups exposed to the 5× and concentrated rural PM2.5. Additionally, ATP-binding cassette (ABC) transporter activity in the cardiac tissue exposed to PM2.5 was reduced in response to the 5× dilution of the rural and industrial region PM2.5. Histological analysis showed a decrease in the percentage of cardiac cells in the heart at all tested concentrations. The results indicate that exposure to different concentrations of PM2.5 from both sources causes biochemical and histological changes in the heart with consequent damage to biological structures; these factors can favor the development of cardiac diseases. PMID:27567156

  18. Acute exposure to ergot alkaloids from endophyte-infected tall fescue does not alter absorptive or barrier function of the isolated bovine ruminal epithelium.

    Science.gov (United States)

    Foote, A P; Penner, G B; Walpole, M E; Klotz, J L; Brown, K R; Bush, L P; Harmon, D L

    2014-07-01

    Ergot alkaloids in endophyte-infected (Neotyphodium coenophialum) tall fescue (Lolium arundinaceum) have been shown to cause a reduction in blood flow to the rumen epithelium as well as a decrease in volatile fatty acids (VFA) absorption from the washed rumen of steers. Previous data also indicates that incubating an extract of endophyte-infected tall fescue seed causes an increase in the amount of VFA absorbed per unit of blood flow, which could result from an alteration in the absorptive or barrier function of the rumen epithelium. An experiment was conducted to determine the acute effects of an endophyte-infected tall fescue seed extract (EXT) on total, passive or facilitated acetate and butyrate flux across the isolated bovine rumen as well as the barrier function measured by inulin flux and tissue conductance (G t ). Flux of ergovaline across the rumen epithelium was also evaluated. Rumen tissue from the caudal dorsal sac of Holstein steers (n=6), fed a common diet, was collected and isolated shortly after slaughter and mounted between two halves of Ussing chambers. In vitro treatments included vehicle control (80% methanol, 0.5% of total volume), Low EXT (50 ng ergovaline/ml) and High EXT (250 ng ergovaline/ml). Results indicate that there is no effect of acute exposure to ergot alkaloids on total, passive or facilitated flux of acetate or butyrate across the isolate bovine rumen epithelium (P>0.51). Inulin flux (P=0.16) and G t (P>0.17) were not affected by EXT treatment, indicating no alteration in barrier function due to acute ergot alkaloid exposure. Ergovaline was detected in the serosal buffer of the High EXT treatment indicating that the flux rate is ~0.25 to 0.44 ng/cm2 per hour. Data indicate that specific pathways for VFA absorption and barrier function of the rumen epithelium are not affected by acute exposure to ergot alkaloids from tall fescue at the concentrations tested. Ergovaline has the potential to be absorbed from the rumen of cattle that

  19. Distinct patterns of the lipid alterations between genotype 1 and 2 chronic hepatitis C patients after viral clearance.

    Directory of Open Access Journals (Sweden)

    Ming-Ling Chang

    Full Text Available The hepatitis C virus (HCV genotype-specific impacts on the host metabolic alterations remained inconclusive.A prospective study including 229 (118 genotype 1 (G1 and 111 G2 consecutive chronic HCV patients who had completed a course of anti-HCV treatment and underwent pre- and 24 weeks post-treatment surveys of metabolic profiles was conducted. Patients were stratified according to the therapeutic response, viral genotype and baseline insulin resistance (IR: homeostasis model assessments of IR (HOMA-IR ≥ 2.5. Paired t-tests were used to compare the pre- and post-treatment variables.Significant post-therapeutic increases in cholesterol, triglyceride, HDL, LDL, apolipoprotein A1 and apolipoprotein B were observed in patients with sustained virological response (SVR but not in those without. Among those with SVR, post-therapeutic increases in HDL (p<0.001 and apolipoprotein A1 (p = 0.012 were only found in G2, whereas increased triglyceride/HDL (p = 0.01 ratios were only found in G1 patients. When stratified by baseline IR among those with SVR, a significant increase in post-treatment HDL (p = 0.019 and apolipoprotein A1 (p = 0.012 but a decrease in HOMA-IR (p = 0.04, C-peptide (p = 0.019 and hemoglobin A1c (p = 0.047 were found in patients with baseline IR; a significant increase in HOMA-IR (p = 0.002 was found in patients without baseline IR. The latter change was observed only in G1 (p = 0.01 but not G2 patients. Although the pre-treatment metabolic profiles of G1 and G2 patients were indifferent, G1 had higher post-treatment triglyceride/HDL ratios (p = 0.041 and triglyceride (p = 0.044 levels than G2 patients.G2 benefit more than G1 patients from viral clearance in metabolic alterations, particularly in those without baseline IR.

  20. Differential alterations of the concentrations of endocannabinoids and related lipids in the subcutaneous adipose tissue of obese diabetic patients

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    Verde Roberta

    2010-04-01

    Full Text Available Abstract Background The endocannabinoids, anandamide and 2-AG, are produced by adipocytes, where they stimulate lipogenesis via cannabinoid CB1 receptors and are under the negative control of leptin and insulin. Endocannabinoid levels are elevated in the blood of obese individuals and nonobese type 2 diabetes patients. To date, no study has evaluated endocannabinoid levels in subcutaneous adipose tissue (SAT of subjects with both obesity and type 2 diabetes (OBT2D, characterised by similar adiposity and whole body insulin resistance and lower plasma leptin levels as compared to non-diabetic obese subjects (OB. Design and Methods The levels of anandamide and 2-AG, and of the anandamide-related PPARα ligands, oleoylethanolamide (OEA and palmitoylethanolamide (PEA, in the SAT obtained by abdominal needle biopsy in 10 OBT2D, 11 OB, and 8 non-diabetic normal-weight (NW subjects, were measured by liquid chromatography-mass spectrometry. All subjects underwent a hyperinsulinaemic euglycaemic clamp. Results As compared to NW, anandamide, OEA and PEA levels in the SAT were 2-4.4-fold elevated (p Conclusions The observed alterations emphasize, for the first time in humans, the potential different role and regulation of adipose tissue anandamide (and its congeners and 2-AG in obesity and type 2 diabetes.

  1. Fasting Blood Glucose and Lipid Profile Alterations following Twelve-Month Androgen Deprivation Therapy in Men with Prostate Cancer

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    Hasan S. Sağlam

    2012-01-01

    Full Text Available Purpose. In this retrospective study, we aimed to investigate the effects of androgen deprivation therapy (ADT on blood glucose and blood cholesterol levels over a 12-month period. Materials and Methods. Between January 2010 and June 2012, the data of 44 patients with prostate cancer who were receiving ADT were collected from a hospital database. Patients with additional malignancy or diabetes and those who had been prescribed and were currently taking cholesterol-lowering medication were excluded from the study. Data (including fasting blood glucose levels and a cholesterol profile were collected and analysed statistically. A value <0.05 was considered statistically significant. Results. Twelve months after the initiation of ADT, fasting blood glucose (FBG, total cholesterol (TC, low-density lipoprotein (LDL cholesterol, high-density lipoprotein (HDL cholesterol, and triglyceride (TG levels changed. FBG, TC, LDL cholesterol, and TG increased significantly (, 0.000, 0.000, and 0.000, resp., while HDL cholesterol decreased (. Conclusion. ADT may increase FBG, TC, LDL cholesterol, and TG but decrease HDL cholesterol by the end of a year of treatment. Therefore, close followup may be needed as a consequence of one-year ADT regarding metabolic alterations.

  2. Intake of a Western diet containing cod instead of pork alters fatty acid composition in tissue phospholipids and attenuates obesity and hepatic lipid accumulation in mice.

    Science.gov (United States)

    Liisberg, Ulrike; Fauske, Kristin Røen; Kuda, Ondrej; Fjære, Even; Myrmel, Lene Secher; Norberg, Nina; Frøyland, Livar; Graff, Ingvild Eide; Liaset, Bjørn; Kristiansen, Karsten; Kopecky, Jan; Madsen, Lise

    2016-07-01

    The content of the marine n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is far lower in lean than in fatty seafood. Cod filets contain less than 2g fat per kg, whereof approximately 50% is EPA and DHA. However, a large fraction of these n-3 PUFAs is present in the phospholipid (PL) fraction and may have high bioavailability and capacity to change the endocannabinoid profile. Here we investigated whether exchanging meat from a lean terrestrial animal with cod in a background Western diet would alter the endocannabinoid tone in mice and thereby attenuate obesity development and hepatic lipid accumulation. Accordingly, we prepared iso-caloric diets with 15.1 energy (e) % protein, 39.1 e% fat and 45.8 e% carbohydrates using freeze-dried meat from cod filets or pork sirloins, and using a combination of soybean oil, corn oil, margarine, milk fat, and lard as the fat source. Compared with mice receiving diets containing pork, mice fed cod gained less adipose tissue mass and had a lower content of hepatic lipids. This was accompanied by a lower n-6 to n-3 ratio in liver PLs and in red blood cells (RBCs) in the mice. Furthermore, mice receiving the cod-containing diet had lower circulating levels of the two major endocannabinoids, N-arachidonoylethanolamine and 2-arachidonoylglycerol. Together, our data demonstrate that despite the relatively low content of n-3 PUFAs in cod fillets, the cod-containing diet could exert beneficial metabolic effects. PMID:27155918

  3. Clinical Significance of Serum Lipids Alteration in Patients with Acute Leukemia%急性白血病患者血脂变化的临床意义

    Institute of Scientific and Technical Information of China (English)

    孙秀丽; 孙国珍

    2011-01-01

    Objective To investigate the clinical significance of serum lipids alteration ( total cholesterol, low density lipoprotein,high density lipoprotein and triglyceride ) in patients with acute leukemia ( AL ). Methods Serum lipids of 271 AL patients ( including untreated 115, completely remission CR 85 and relapsed 71 ) were measured by automatic biochemistry analyzer using enzymatic methods. Results AL patients had the characteristics of low TC,low LDL,low HDL and high TG level. The level of TC ,LDL and HDL in period of untreated and relapsed were significantly lower than completely remission ( CR ) and constrast group( P < 0.01 ). But TG were significantly higher than CR and constrast group ( P < 0.01 ). The level of TC, LDL and HDL were negatively correlated with peripheral WBC counts and leukemia cells of bone marrow, but TG were positively correlated with them( P < 0.05 ). The level of serum lipids were correlated with AL subtypes, such as TC, LDL and HDL were lower in subtypes of M7, M6 and L1, while TG were higher in subtypes of M3, L1 and L2( P < 0.01 ). The refractory and relapsed AL patients and those with poor prognostic chrosome had more unsteady serum lipids than the others when they diagnosed. Conclusion The level of serum lipids can be considered as important indicators for therapeutic effects and prognosis of AL patients.%目的 探讨急性白血病(AL)患者血脂[胆固醇(TC),甘油三酯(TG),高密度脂蛋白(HDL)和低密度脂蛋白(LDL)]变化的临床意义.方法 采用酶学法检测271例AL患者(初治115例,完全缓解 CR 85例,复发71例)的血脂值.结果 AL患者具有低TC、低HDL、低LDL和高TG血症特点,初治、复发的AL患者TC、HDL和LDL值明显低于CR组和对照组(P<0.01),而TG则明显高于CR组和对照组(P<0.01);TC、HDL和LDL值与外周血WBC数及骨髓中白血病细胞数成负相关,TG则与之成正相关(P<0.05);血脂与AL亚型有关,TC、HDL和LDL在M7、M6和L1中较低,TG在M3、L1

  4. Ethanol extracts of chickpeas alter the total lipid content and expression levels of genes related to fatty acid metabolism in mouse 3T3-L1 adipocytes.

    Science.gov (United States)

    Shinohara, Shigeo; Gu, Yuanjun; Yang, Ying; Furuta, Yasuo; Tanaka, Masahiko; Yue, Xiaohua; Wang, Weiqing; Kitano, Masaru; Kimura, Hiroshi

    2016-08-01

    -type chickpeas, which are used worldwide. The effects were similar, but of much lesser magnitude compared to those of ECP described above. Thus, Desi-type chickpeas may prove to be effective for the treatment of diabetes, as they can alter the lipid content, thus reducing fat storage. PMID:27353085

  5. Ethanol extracts of chickpeas alter the total lipid content and expression levels of genes related to fatty acid metabolism in mouse 3T3-L1 adipocytes

    Science.gov (United States)

    Shinohara, Shigeo; Gu, Yuanjun; Yang, Ying; Furuta, Yasuo; Tanaka, Masahiko; Yue, Xiaohua; Wang, Weiqing; Kitano, Masaru; Kimura, Hiroshi

    2016-01-01

    used worldwide. The effects were similar, but of much lesser magnitude compared to those of ECP described above. Thus, Desi-type chickpeas may prove to be effective for the treatment of diabetes, as they can alter the lipid content, thus reducing fat storage. PMID:27353085

  6. Clerodendron glandulosum Coleb., Verbenaceae, ameliorates high fat diet-induced alteration in lipid and cholesterol metabolism in rats Clerodendron glandulosum Coleb., Verbenaceae, melhora a dieta rica em gordura induzida por alteração no metabolismo de lipídios e colesterol em ratos

    Directory of Open Access Journals (Sweden)

    RN Jadeja

    2010-03-01

    Full Text Available The present study was undertaken to evaluate the efficacy of freeze dried extract of Clerodendron glandulosum Coleb., Verbenaceae, leaves (FECG on alteration in lipid and cholesterol metabolism in high fat diet fed hyperlipidemic rats. Plasma and hepatic lipid profiles, lipid and cholesterol metabolizing enzymes in target tissues and fecal total lipids and bile acid contents were evaluated in FECG treated normolipidemic and hyperlipidemic rats. These results were compared with synthetic hypolipidemic drug Lovastatin (LVS. Results indicate that FECG was able to positively regulate induced experimental hyperlipidemia by significant alteration in plasma and tissue lipid profiles. These results can be attributed to reduced absorption, effective elimination and augmented catabolism of lipids and cholesterol possibly due to high content of saponin and phytosterols in C. glandulosum. Use of C. glandulosum extract as a potential therapeutic agent against hypercholesterolemia and hypertriglyceridemia is indicated.Este estudo foi realizado para avaliar a eficácia do extrato liofilizado das folhas de Clerodendron glandulosum Coleb., Verbenaceae (FECG, em alterar o metabolismo de lipídios e colesterol em ratos hiperlipidêmicos alimentados em uma dieta rica em gordura. Plasma e perfil lipídico hepático, lipídeos e enzimas que metabolizam o colesterol em tecidos-alvo e o conteúdo de lipídeos fecais totais e ácidos biliares foram avaliados em ratos normolipidêmicos e hiperlipidêmicos tratados com FECG. Os resultados foram comparados com a droga sintética hipolipemiante Lovastatina (LVS. Os resultados indicam que FECG foi capaz de regular positivamente a hiperlipidemia induzida experimentalmente por alteração significativa no perfil lipídico do plasma e tecidos. Estes resultados podem ser atribuídos à absorção reduzida, a eliminação efetiva e catabolismo aumentado de lipídeos e colesterol, possivelmente devido ao alto teor de saponina e

  7. Re-esterified palm oils, compared to native palm oil, do not alter fat absorption, postprandial lipemia or growth performance in broiler chicks.

    Science.gov (United States)

    Vilarrasa, E; Tres, A; Bayés-García, L; Parella, T; Esteve-Garcia, E; Barroeta, A C

    2014-08-01

    Re-esterified palm oils are obtained from the chemical esterification of palm acid oils (rich in free fatty acids) with glycerol, both economically interesting by-products from oil refining and biodiesel industries, respectively. Thus, re-esterified palm oils could be an economically interesting alternative to native palm oil in broiler chick diets. However, because they may have different physicochemical properties than have their corresponding native oil, we assessed the effect of fatty acid (FA) positional distribution within acylglycerol molecules and the effect of acylglycerol composition on FA apparent absorption, and their possible consequences on the evolution of postprandial lipemia and growth performance in broiler chicks. Seventy-two 1-day-old female broiler chicks were randomly distributed into 18 cages. The three treatments used were the result of a basal diet supplemented with 6 wt% of native palm oil (N-TAG), re-esterified palm oil (E-TAG), or re-esterified palm oil high in mono- and diacylglycerols (E-MDAG). Chemical esterification raised the fraction of palmitic acid at the sn-2 position from 9.63 mol% in N-TAG oil to 17.9 mol% in E-TAG oil. Furthermore, E-MDAG oil presented a high proportion of mono- (23.1 wt%) and diacylglycerols (51.2 wt%), with FA mainly located at the sn-1,3 positions, which resulted in a lower gross-energy content and an increased solid-fat index at the chicken's body temperature. However, re-esterified palm oils did not alter fat absorption, postprandial lipemia, or growth performance, compared to native palm oil, so they can be used as alternative fat sources in broiler chick diets.

  8. Visualization and quantification of heterogeneous diffusion rates in granodiorite samples by X-ray absorption imaging. Diffusion within gouge materials, altered rim and intact rock matrix

    Energy Technology Data Exchange (ETDEWEB)

    Altman, S.J.; Tidwell, V.C. [Sandia National Laboratories, Albuquerque, NM (United States); Uchida, M. [Japan Nuclear Cycle Development Inst., Ibaraki (Japan)

    2001-08-01

    Matrix diffusion is one of the most important contaminant migration retardation processes in crystalline rocks. Performance assessment calculations in various countries assume that only the area of the fracture surface where advection is active provides access to the rock matrix. However, accessibility to the matrix could be significantly enhanced with diffusion into stagnant zones, fracture fillings, and through an alteration rim in the matrix. Laboratory visualization experiments were conducted on granodiorite samples to investigate and quantify diffusion rates within different zones of a Cretaceous granodiorite. Samples were collected from the Kamaishi experimental site in the northern part of the main island of Japan. Diffusion of iodine out of the sample is visualized and rates are measured using x-ray absorption imaging. X-ray images allow for measurements of relative iodine concentration and relative iodine mass as a function of time and two-dimensional space at a sub-millimeter spatial resolution. In addition, two-dimensional heterogeneous porosity fields (at the same resolution as the relative concentration fields) are measured. This imaging technique allows for a greater understanding of the spatial variability of diffusion rates than can be accomplished with standard bulk measurements. It was found that diffusion rates were fastest in partially gouge-filled fractures. Diffusion rates in the recrystallized calcite-based fracture-filling material were up to an order of magnitude lower than in gouge-filled fractures. Diffusion in altered matrix around the fractures was over an order of magnitude lower than that in the gouge-filled fractures. Healed fractures did not appear to have different diffusion rates than the unaltered matrix.

  9. Pantethine Alters Lipid Composition and Cholesterol Content of Membrane Rafts, With Down-Regulation of CXCL12-Induced T Cell Migration.

    Science.gov (United States)

    van Gijsel-Bonnello, Manuel; Acar, Niyazi; Molino, Yves; Bretillon, Lionel; Khrestchatisky, Michel; de Reggi, Max; Gharib, Bouchra

    2015-10-01

    Pantethine, a natural low-molecular-weight thiol, shows a broad activity in a large range of essential cellular pathways. It has been long known as a hypolipidemic and hypocholesterolemic agent. We have recently shown that it exerts a neuroprotective action in mouse models of cerebral malaria and Parkinson's disease through multiple mechanisms. In the present study, we looked at its effects on membrane lipid rafts that serve as platforms for molecules engaged in cell activity, therefore providing a target against inappropriate cell response leading to a chronic inflammation. We found that pantethine-treated cells showed a significant change in raft fatty acid composition and cholesterol content, with ultimate downregulation of cell adhesion, CXCL12-driven chemotaxis, and transendothelial migration of various T cell types, including human Jurkat cell line and circulating effector T cells. The mechanisms involved include the alteration of the following: (i) CXCL12 binding to its target cells; (ii) membrane dynamics of CXCR4 and CXCR7, the two CXCL12 receptors; and (iii) cell redox status, a crucial determinant in the regulation of the chemokine system. In addition, we considered the linker for activation of T cells molecule to show that pantethine effects were associated with the displacement from the rafts of the acylated signaling molecules which had their palmitoylation level reduced.. In conclusion, the results presented here, together with previously published findings, indicate that due to its pleiotropic action, pantethine can downregulate the multifaceted process leading to pathogenic T cell activation and migration.

  10. Pantethine Alters Lipid Composition and Cholesterol Content of Membrane Rafts, With Down-Regulation of CXCL12-Induced T Cell Migration.

    Science.gov (United States)

    van Gijsel-Bonnello, Manuel; Acar, Niyazi; Molino, Yves; Bretillon, Lionel; Khrestchatisky, Michel; de Reggi, Max; Gharib, Bouchra

    2015-10-01

    Pantethine, a natural low-molecular-weight thiol, shows a broad activity in a large range of essential cellular pathways. It has been long known as a hypolipidemic and hypocholesterolemic agent. We have recently shown that it exerts a neuroprotective action in mouse models of cerebral malaria and Parkinson's disease through multiple mechanisms. In the present study, we looked at its effects on membrane lipid rafts that serve as platforms for molecules engaged in cell activity, therefore providing a target against inappropriate cell response leading to a chronic inflammation. We found that pantethine-treated cells showed a significant change in raft fatty acid composition and cholesterol content, with ultimate downregulation of cell adhesion, CXCL12-driven chemotaxis, and transendothelial migration of various T cell types, including human Jurkat cell line and circulating effector T cells. The mechanisms involved include the alteration of the following: (i) CXCL12 binding to its target cells; (ii) membrane dynamics of CXCR4 and CXCR7, the two CXCL12 receptors; and (iii) cell redox status, a crucial determinant in the regulation of the chemokine system. In addition, we considered the linker for activation of T cells molecule to show that pantethine effects were associated with the displacement from the rafts of the acylated signaling molecules which had their palmitoylation level reduced.. In conclusion, the results presented here, together with previously published findings, indicate that due to its pleiotropic action, pantethine can downregulate the multifaceted process leading to pathogenic T cell activation and migration. PMID:25728249

  11. Penetration of the signal sequence of Escherichia coli PhoE protein into phospholipid model membranes leads to lipid-specific changes in signal peptide structure and alterations of lipid organization

    Energy Technology Data Exchange (ETDEWEB)

    Batenburg, A.M.; Demel, R.A.; Verkleij, A.J.; de Kruijff, B.

    1988-07-26

    In order to obtain more insight in the initial steps of the process of protein translocation across membranes, biophysical investigations were undertaken on the lipid specificity and structural consequences of penetration of the PhoE signal peptide into lipid model membranes and on the conformation of the signal peptide adopted upon interaction with the lipids. When the monolayer technique and differential scanning calorimetry are used, a stronger penetration is observed for negatively charged lipids, significantly influenced by the physical state of the lipid but not by temperature or acyl chain unsaturation as such. Although the interaction is principally electrostatic, as indicated also by the strong penetration of N-terminal fragments into negatively charged lipid monolayers, the effect of ionic strength suggests an additional hydrophobic component. Most interestingly with regard to the mechanism of protein translocation, the molecular area of the peptide in the monolayer also shows lipid specificity: the area in the presence of PC is consistent with a looped helical orientation, whereas in the presence of cardiolipin a time-dependent conformational change is observed, most likely leading from a looped to a stretched orientation with the N-terminus directed toward the water. This is in line also with the determined peptide-lipid stoichiometry. Preliminary /sup 31/P NMR and electron microscopy data on the interaction with lipid bilayer systems indicate loss of bilayer structure.

  12. Penetration of the signal sequence of Escherichia coli PhoE protein into phospholipid model membranes leads to lipid-specific changes in signal peptide structure and alterations of lipid organization

    International Nuclear Information System (INIS)

    In order to obtain more insight in the initial steps of the process of protein translocation across membranes, biophysical investigations were undertaken on the lipid specificity and structural consequences of penetration of the PhoE signal peptide into lipid model membranes and on the conformation of the signal peptide adopted upon interaction with the lipids. When the monolayer technique and differential scanning calorimetry are used, a stronger penetration is observed for negatively charged lipids, significantly influenced by the physical state of the lipid but not by temperature or acyl chain unsaturation as such. Although the interaction is principally electrostatic, as indicated also by the strong penetration of N-terminal fragments into negatively charged lipid monolayers, the effect of ionic strength suggests an additional hydrophobic component. Most interestingly with regard to the mechanism of protein translocation, the molecular area of the peptide in the monolayer also shows lipid specificity: the area in the presence of PC is consistent with a looped helical orientation, whereas in the presence of cardiolipin a time-dependent conformational change is observed, most likely leading from a looped to a stretched orientation with the N-terminus directed toward the water. This is in line also with the determined peptide-lipid stoichiometry. Preliminary 31P NMR and electron microscopy data on the interaction with lipid bilayer systems indicate loss of bilayer structure

  13. Lipid-altering efficacy and safety of ezetimibe/simvastatin versus atorvastatin in patients with hypercholesterolemia and the metabolic syndrome (from the VYMET study)

    DEFF Research Database (Denmark)

    Robinson, Jennifer G; Ballantyne, Christie M; Grundy, Scott M;

    2009-01-01

    -density lipoprotein (LDL) cholesterol. Additional end points included changes in other lipids, lipoprotein ratios, high-sensitivity C-reactive protein, and attainment of prespecified lipid levels. Significantly greater improvements in the levels of LDL cholesterol, non-high-density lipoprotein cholesterol......, apolipoprotein B, and lipid/lipoprotein ratios resulted with ezetimibe/simvastatin compared with atorvastatin at all specified dose comparisons (p LDL cholesterol and non-high-density lipoprotein cholesterol levels was also significantly greater with ezetimibe...

  14. Percutaneous absorption in diseased skin: an overview.

    Science.gov (United States)

    Chiang, Audris; Tudela, Emilie; Maibach, Howard I

    2012-08-01

    The stratum corneum's (SC) functions include protection from external hazardous environments, prevention of water loss and regulation of body temperature. While intact skin absorption studies are abundant, studies on compromised skin permeability are less common, although products are often used to treat affected skin. We reviewed literature on percutaneous absorption through abnormal skin models. Tape stripping is used to disrupt water barrier function. Studies demonstrated that physicochemical properties influence the stripping effect: water-soluble drugs are more affected. Abrasion did not affect absorption as much. Freezing is commonly used to preserve skin. It does not seem to modify water absorption, but still increases the penetration of compounds. Comparatively, heating the skin consistently increased percutaneous absorption. Removing SC lipids may increase percutaneous absorption of drugs. Many organic solvents are employed to delipidize. Delipidization with chloroform-methanol increased hydrophilic compound permeability, but not lipophilic. Acetone pre-treatment enhanced hydrophilic compound penetration. More data is needed to determine influence on highly lipophilic compound penetration. Sodium lauryl sulfate (SLS) induces irritant dermatitis and is frequently used as a model. Studies revealed that SLS increases hydrophilic compound absorption, but not lipophilic. However, skin irritation with other chemicals increases lipophilic penetration as much as hydrophilic. Animal studies show that UV exposure increases percutaneous absorption whereas human studies do not. Human studies show increased penetration in psoriatic and atopic dermatitis skin. The data summarized here begin to characterize flux alteration associated with damaged skin. Understanding the degree of alteration requires interpretation of involved conditions and the enlarging of our database to a more complete physicochemical spectrum. PMID:22912973

  15. High-fat diet intake from senescence inhibits the attenuation of cell functions and the degeneration of villi with aging in the small intestine, and inhibits the attenuation of lipid absorption ability in SAMP8 mice.

    Science.gov (United States)

    Yamamoto, Kazushi; E, Shuang; Hatakeyama, Yu; Sakamoto, Yu; Tsuduki, Tsuyoshi

    2015-11-01

    We examined the effect of a high-fat diet from senescence as a means of preventing malnutrition among the elderly. The senescence-accelerated mouse P8 was used and divided into three groups. The 6C group was given a normal diet until 6 months old. The 12N group was given a normal diet until 12 months old. The 12F group was given a normal diet until 6 months old and then a high-fat diet until 12 months old. In the oral fat tolerance test, there was a decrease in area under the curve for serum triacylglycerol level in the 12N group and a significant increase in the 12F group, suggesting that the attenuation of lipid absorption ability with aging was delayed by a high-fat diet from senescence. To examine this mechanism, histological analysis in the small intestine was performed. As a result, the degeneration of villi with aging was inhibited by the high-fat diet. There was also a significant decrease in length of villus in the small intestine in the 12N group and a significant increase in the 12F group. The high-fat diet from senescence inhibited the degeneration of villi with aging in the small intestine, and inhibited the attenuation of lipid absorption ability.

  16. Dysregulated lipid metabolism in cancer

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells. The changes of expression and activity of lipid metabolizing enzymes are directly regulated by the activity of oncogenic signals. The dependence of tumor cells on the dysregulated lipid metabolism suggests that proteins involved in this process are excellent chemotherapeutic targets for cancer treatment. There are currently several drugs under development or in clinical trials that are based on specifically targeting the altered lipid metabolic pathways in cancer cells. Further understanding of dysregulated lipid metabolism and its associated signaling pathways will help us to better design efficient cancer therapeutic strategy.

  17. Preparation and Characterization of Loperamide-Loaded Dynasan 114 Solid Lipid Nanoparticles for Increased Oral Absorption In the Treatment of Diarrhea

    Science.gov (United States)

    Wei, Lili; Yang, Yunfang; Shi, Kun; Wu, Jun; Zhao, Wei; Mo, Jingxin

    2016-01-01

    The aim of the project was to assemble two optimum solid lipid nanoparticle (SLN) formulations for oral delivery of loperamide (LPM) to treat different types of diarrhea, and to evaluate their release profiles in vitro and pharmacokinetic properties in vivo. In this work, glyceryl trimyristate (Dynasan 114) nanoparticles containing the drug LPM and sodium cholate as a stabilizer were prepared using a modified solvent evaporation technique. Two LPM-loaded SLNs, namely LPM-SLN-1 (LPM-SLN with a high ratio rate of lipid to drug) and LPM-SLN-2 (LPM-SLN with a low ratio rate of lipid to drug), were prepared by the solvent evaporation method. A change in the lipid concentration affects the characteristics of LPM-SLNs. The average sizes of the LPM-SLNs were 303 ± 18 nm and 519 ± 36 nm, separately, as analyzed by dynamic light scattering. The LPM-SLNs were found to be round with a smooth surface, as observed using a transmission electron microscope and a scanning electron microscope. The average encapsulation efficiencies were 87 ± 3.78% w/w and 84 ± 5.17%, accordingly. In the in vitro release experiments, LPM-SLNs showed a continuous release profile of LPM without any burst release. The oral bioavailability of LPM-SLNs was analyzed using Wistar rats. The relative bioavailabilities of LPM-SLNs were 227 and 153%, respectively, as compared that of the LPM tablet. There was no difference in the Tmax between LPM-SLN-2 and the LPM tablet. In conclusion, LPM-SLN-1 significantly improved the oral bioavailability of LPM, while LPM-SLN-2 having the same swift action as the LPM tablet. These results demonstrate the potential of LPM-SLNs in the oral delivery of LPM to treat different types of diarrhea.

  18. 脂质制剂体外动态肠吸收模型的建立及评价%Establishment and evaluation of a dynamic in vitro intestinal absorption model of lipid formulations

    Institute of Scientific and Technical Information of China (English)

    刘颖; 易涛; 宦娣; 肖璐; 何吉奎

    2011-01-01

    A new dynamic in vitro intestinal absorption model for screening and evaluating lipid formulations was established by means of the characteristics of the intestinal digestion and absorption of the lipid formulations. This model was composed of two systems, including intestinal digestion and the intestinal tissue culture, which drew the evaluation method of intestinal absorption into the in vitro lipolysis model. The influence of several important model parameters such as Ca2+, D-glucose, K+ on the two systems of this model has been investigated. The results showed that increasing of Ca2+ concentration could be significantly conductive to intestinal digestion. The increasing of .D-glucose concentration could stepped significantly down the decay of the intestinal activity. K+ was able to maintain intestinal activity, but the influence of different concentration levels on the decay of the intestinal activity was of no significant difference. Thus the model parameters were set up as follows: Ca2+ for 10 mmol-L-1, D-glucose for 15 mmol-L-1 and K+ for 5.5 mmol-L-1. Type I lipid formulation was evaluated with this model, and there was a significant correlation between the absorption curve in vitro and absorption curve in vivo of rats (r = 0.995 6, P < 0.01). These results demonstrated that this model can be an attractive and great potential method for the screening, evaluating and predicting of the lipid formulations.%根据脂质制剂肠消化吸收的特性,本文在体外脂解模型基础上,引入肠吸收评价方法,建立了一种用于筛选评价脂质制剂的新型体外动态肠吸收模型,包括肠消化和肠组织培养两大体系.探究模型重要参数(Ca2+、葡萄糖、K+)的影响,发现Ca2+浓度的增加能显著增强脂质制剂的肠消化;葡萄糖浓度的递增能显著减慢肠组织活性衰减;K+虽能维持肠组织的活性,但其浓度变化对肠组织活性衰减并无显著性影响;最终选择Ca2+l0 mmol·L-1、葡萄糖15 mmol

  19. X-ray absorption spectroscopy of soybean lipoxygenase-1 : Influence of lipid hydroperoxide activation and lyophilization on the structure of the non-heme iron active site

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Heijdt, L.M. van der; Feiters, M.C.; Navaratnam, S.; Nolting, H.-F.; Hermes, C.; Veldink, G.A.

    1992-01-01

    X-ray absorption spectra at the Fe K-edge of the non-heme iron site in Fe(II) as well as Fe(III) soybean lipoxygenase-1, in frozen solution or lyophilized, are presented; the latter spectra were obtained by incubation of the Fe(II) enzyme with its product hydroperoxide. An edge shift of about 23 eV

  20. Biological alterations resulting from chronic lung irradiation. I. The pulmonary lipid composition, physiology, and pathology after inhalation by beagle dogs of 144Ce-labeled fused clay aerosols

    International Nuclear Information System (INIS)

    Three groups of four beagle dogs inhaled a 144Ce-labeled fused clay aerosol; two additional dogs per group, exposed to a stable cerium-labeled fused clay aerosol, were used as controls. At monthly intervals, one diaphragmatic lobe of each of two dogs exposed to 144Ce and one control animal from each group was lavaged with isotonic saline. The recovered lavage solutions were centrifuged to isolate lung cells (mostly macrophages) and surfactant for lipid analyses. The groups were sacrificed at 2, 4, and 6 mo after exposure, when the lungs of the dogs exposed to 144Ce had average cumulative radiation doses of 23, 36, and 59 krad, respectively. Chronic irradiation of the lung resulted in a progressive radiation pneumonitis which was assessed clinically and pathologically at various intervals. At sacrifice, the lungs were analyzed for 144Ce and the right apical and diaphragmatic lobes were minced and lyophilized and the lipids were extracted. Total lipids from all lung samples were determined gravimetrically and individual compounds were identified, isolated, and quantitated. The quantities of lipid in lung tissue, in pulmonary cells, and in surfactant increased as a function of time and radiation dose. Neutral lipids (sterol esters and triglycerides) accounted for most of the increase. (U.S.)

  1. Skin-specific Deletion of Stearoyl-CoA Desaturase-1 Alters Skin Lipid Composition and Protects Mice from High Fat Diet-induced Obesity*

    OpenAIRE

    Sampath, Harini; Flowers, Matthew T; Liu, Xueqing; Chad M Paton; Sullivan, Ruth; Chu, Kiki; Zhao, Minghui; Ntambi, James M.

    2009-01-01

    Stearoyl-CoA desaturase-1 (SCD1) catalyzes the synthesis of monounsaturated fatty acids and is an important regulator of whole body energy homeostasis. Severe cutaneous changes in mice globally deficient in SCD1 also indicate a role for SCD1 in maintaining skin lipids. We have generated mice with a skin-specific deletion of SCD1 (SKO) and report here that SKO mice display marked sebaceous gland hypoplasia and depletion of sebaceous lipids. In addition, SKO mice have significantly increased en...

  2. Lipids in Marine Ecosystems

    OpenAIRE

    Christopher C Parrish

    2013-01-01

    Lipids provide the densest form of energy in marine ecosystems. They are also a solvent and absorption carrier for organic contaminants and thus can be drivers of pollutant bioaccumulation. Among the lipids, certain essential fatty acids and sterols are considered to be important determinants of ecosystem health and stability. Fatty acids and sterols are also susceptible to oxidative damage leading to cytotoxicity and a decrease in membrane fluidity. The physical characteristics of biological...

  3. I. Lipid metabolism stimulated by altered intracellular calcium in cultured fibroblasts. II. Regulation of the activity of rat adipose tissue lipoprotein lipase

    International Nuclear Information System (INIS)

    The cell killing process of 3T3 Swiss mouse fibroblasts stimulated by Ca2+ plus A23187, a Ca2+ ionophore has been studied. The aim of this research is to understand the biochemical mechanism of this process, i.e, to elucidate the step involved and to characterize the enzymes involved with each steps in the lipid metabolism stimulated in cultured fibroblasts undergoing a toxic death response. Parallel 3T3 cultures biosynthetically labeled with lipid precursors were examined under Ca2+-mediated killing conditions. Labeled lipids were extracted and analyzed by thin-layer chromatography and autoradiography. Evidence for activation of a phosphatidylinositol-specific phospholipase C has been obtained in injured 3T3 cells labeled with [3H]glycerol and [3H]inositol. To simplify the system for studying the lipoprotein lipase reaction, our laboratory prepared the chromophore containing a substrate: 1,2-dipalmitoyl-3-β-2-furylacryloyltriacylglycerol (DPFATG). By using this artificial lipid we could readily investigate the lipoprotein lipase reactions, since the absorbance change directly represents the hydrolysis of the chromophoric side chain of the substrate

  4. Altered hepatic lipid metabolism in C57BL/6 mice fed alcohol: a targeted lipidomic and gene expression study[S

    Science.gov (United States)

    Clugston, Robin D.; Jiang, Hongfeng; Lee, Man Xia; Piantedosi, Roseann; Yuen, Jason J.; Ramakrishnan, Rajasekhar; Lewis, Michael J.; Gottesman, Max E.; Huang, Li-Shin; Goldberg, Ira J.; Berk, Paul D.; Blaner, William S.

    2011-01-01

    Chronic alcohol consumption is associated with fatty liver disease in mammals. The object of this study was to gain an understanding of dysregulated lipid metabolism in alcohol-fed C57BL/6 mice using a targeted lipidomic approach. Liquid chromatography tandem mass spectrometry was used to analyze several lipid classes, including free fatty acids, fatty acyl-CoAs, fatty acid ethyl esters, sphingolipids, ceramides, and endocannabinoids, in plasma and liver samples from control and alcohol-fed mice. The interpretation of lipidomic data was augmented by gene expression analyses for important metabolic enzymes in the lipid pathways studied. Alcohol feeding was associated with i) increased hepatic free fatty acid levels and decreased fatty acyl-CoA levels associated with decreased mitochondrial fatty acid oxidation and decreased fatty acyl-CoA synthesis, respectively; ii) increased hepatic ceramide levels associated with higher levels of the precursor molecules sphingosine and sphinganine; and iii) increased hepatic levels of the endocannabinoid anandamide associated with decreased expression of its catabolic enzyme fatty acid amide hydrolase. The unique combination of lipidomic and gene expression analyses allows for a better mechanistic understanding of dysregulated lipid metabolism in the development of alcoholic fatty liver disease. PMID:21856784

  5. Defective jejunal and colonic salt absorption and alteredNa +/H+ exchanger 3 (NHE3) activity in NHE regulatory factor 1 (NHERF1) adaptor protein-deficient mice

    NARCIS (Netherlands)

    N. Broere (Nellie); M. Chen (Min); A. Cinar (Ayhan); A.K. Singh (Arbind); J. Hillesheim (Jutta); B. Riederer (Beat Michel); M. Lunnemann; I. Rottinghaus (Ingrid); A. Krabbenhöft (Anja); R. Engelhardt (Regina); B. Rausch; E.J. Weinman (Edward); M. Donowitz (Mark); A. Hubbard; O. Kocher (Olivier); H.R. de Jonge (Hugo); B.M. Hogema (Boris); U. Seidler (Ursula)

    2009-01-01

    textabstractWe investigated the role of the Na+/H+ exchanger regulatory factor 1 (NHERF1) on intestinal salt and water absorption, brush border membrane (BBM) morphology, and on the NHE3 mRNA expression, protein abundance, and transport activity in the murine intestine. NHERF1-deficient mice display

  6. Toward the Establishment of Standardized In Vitro Tests for Lipid-Based Formulations. 5. Lipolysis of Representative Formulations by Gastric Lipase

    DEFF Research Database (Denmark)

    Bakala-N'Goma, Jean-Claude; Williams, Hywel D.; Sassene, Philip J.;

    2015-01-01

    Purpose Lipid-based formulations (LBF) are substrates for digestive lipases and digestion can significantly alter their properties and potential to support drug absorption. LBFs have been widely examined for their behaviour in the presence of pancreatic enzymes. Here, the impact of gastric lipase...

  7. Effect of Garlic (Allium sativum) on Heavy Metal (Nickel II and ChromiumVI) Induced Alteration of Serum Lipid Profile in Male Albino Rats

    OpenAIRE

    Kusal K. Das; Dhundasi, Salim A; Swastika N. Das; Amrita Das Gupta

    2008-01-01

    We have studied the effect of simultaneous oral treatment of aqueous garlic extract (Allium sativum) on heavy metal (nickel II and chromium VI) induced changes in serum lipid profile. Nickel sulfate and potassium dichromate treated rats showed a significant increase in serum low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C) and triglyceride (TG) level as well as decrease in serum high density lipoprotein-cholesterol (HDL-C) level. Simultaneous garl...

  8. Keap1-knockdown decreases fasting-induced fatty liver via altered lipid metabolism and decreased fatty acid mobilization from adipose tissue.

    Directory of Open Access Journals (Sweden)

    Jialin Xu

    Full Text Available AIMS: The purpose of this study was to determine whether Nrf2 activation, via Keap1-knockdown (Keap1-KD, regulates lipid metabolism and mobilization induced by food deprivation (e.g. fasting. METHODS AND RESULTS: Male C57BL/6 (WT and Keap1-KD mice were either fed ad libitum or food deprived for 24 hours. After fasting, WT mice exhibited a marked increase in hepatic lipid accumulation, but Keap1-KD mice had an attenuated increase of lipid accumulation, along with reduced expression of lipogenic genes (acetyl-coA carboxylase, stearoyl-CoA desaturase-1, and fatty acid synthase and reduced expression of genes related to fatty acid transport, such as fatty acid translocase/CD36 (CD36 and Fatty acid transport protein (FATP 2, which may attribute to the reduced induction of Peroxisome proliferator-activated receptor (Ppar α signaling in the liver. Additionally, enhanced Nrf2 activity by Keap1-KD increased AMP-activated protein kinase (AMPK phosphorylation in liver. In white adipose tissue, enhanced Nrf2 activity did not change the lipolysis rate by fasting, but reduced expression of fatty acid transporters--CD36 and FATP1, via a PPARα-dependent mechanism, which impaired fatty acid transport from white adipose tissue to periphery circulation system, and resulted in increased white adipose tissue fatty acid content. Moreover, enhanced Nrf2 activity increased glucose tolerance and Akt phosphorylation levels upon insulin administration, suggesting Nrf2 signaling pathway plays a key role in regulating insulin signaling and enhanced insulin sensitivity in skeletal muscle. CONCLUSION: Enhanced Nrf2 activity via Keap1-KD decreased fasting-induced steatosis, pointing to an important function of Nrf2 on lipid metabolism under the condition of nutrient deprivation.

  9. Effect of inorganic phosphate concentration on the nature of inner mitochondrial membrane alterations mediated by Ca2+ ions. A proposed model for phosphate-stimulated lipid peroxidation.

    Science.gov (United States)

    Kowaltowski, A J; Castilho, R F; Grijalba, M T; Bechara, E J; Vercesi, A E

    1996-02-01

    Addition of high concentrations (>1 mm) of inorganic phosphate (Pi) or arsenate to Ca2+-loaded mitochondria was followed by increased rates of H2O2 production, membrane lipid peroxidation, and swelling. Mitochondrial swelling was only partially prevented either by butylhydroxytoluene, an inhibitor of lipid peroxidation, or cyclosporin A, an inhibitor of the mitochondrial permeability transition pore. This swelling was totally prevented by the simultaneous presence of these compounds. At lower Pi concentrations (1 mm), mitochondrial swelling is reversible and prevented by cyclosporin A, but not by butylhydroxytoluene. In any case (low or high phosphate concentration) exogenous catalase prevented mitochondrial swelling, suggesting that reactive oxygen species (ROS) participate in these mechanisms. Altogether, the data suggest that, at low Pi concentrations, membrane permeabilization is reversible and mediated by opening of the mitochondrial permeability transition pore, whereas at high Pi concentrations, membrane permeabilization is irreversible because lipid peroxidation also takes place. Under these conditions, lipid peroxidation is strongly inhibited by sorbate, a putative quencher of triplet carbonyl species. This suggests that high Pi or arsenate concentrations stimulate propagation of the peroxidative reactions initiated by mitochondrial-generated ROS because these anions are able to catalyze Cn-aldehyde tautomerization producing enols, which can be oxidized by hemeproteins to yield the lower Cn - 1-aldehyde in the triplet state. This proposition was also supported by experiments using a model system consisting of phosphatidylcholine/dicethylphosphate liposomes and the triplet acetone-generating system isobutanal/horseradish peroxidase, where phosphate and Ca2+ cooperate to increase the yield of thiobarbituric acid-reactive substances. PMID:8621682

  10. The impact of auxins used in assisted phytoextraction of metals from the contaminated environment on the alterations caused by lead(II) ions in the organization of model lipid membranes.

    Science.gov (United States)

    Hąc-Wydro, Katarzyna; Sroka, Aleksandra; Jabłońska, Klaudia

    2016-07-01

    Auxins are successfully used to improve phytoextraction efficiency of metal ions from the contaminated environment, however, the mechanism of their activity in this field is not explained. Auxins are known to exert various biochemical alterations in the plant membranes and cells, but their activity involves also direct interactions with lipids leading to changes in membrane organization. Following the suggestion that the auxins-induced modifications in membrane properties alleviate toxic effect of metal ions in this paper we have undertaken the comparative studies on the effect of metal ions and metal ions/auxins mixtures on model membrane systems. The experiments were done on lipid monolayers differing in their composition spread on water subphase and on Pb(2+), Indole-3-acetic acid (IAA), 1-Naphthaleneacetic acid (NAA) and Pb(2+)/IAA and Pb(2+)/NAA water solutions. The analysis of the collected data suggests that metal ions and auxins can change fluidity of the lipid systems and weaken the interactions between monolayer components. This manifested in the increase of the mean area per molecule and the excess area per molecule values for the films on Pb(2+), auxins as well as Pb(2+)/auxin solutions as compared to the values on pure water subphase. However, the presence of auxin in the mixture with lead(II) ions makes the alterations induced by sole metal ions weaker. This effect was more pronounced for the membranes of a higher packing. Thus it was proposed that auxins may enhance phytoextraction of metal ions by weakening their destabilizing effect on membrane. PMID:26998874

  11. Lipid-based liquid crystalline nanoparticles as oral drug delivery vehicles for poorly water-soluble drugs: cellular interaction and in vivo absorption

    Directory of Open Access Journals (Sweden)

    Zeng N

    2012-07-01

    Full Text Available Ni Zeng,1,3,* Xiaoling Gao,2,* Quanyin Hu,1 Qingxiang Song,2 Huimin Xia,1 Zhongyang Liu,1 Guangzhi Gu,1 Mengyin Jiang,1,4 Zhiqing Pang,1 Hongzhuan Chen,2 Jun Chen,1 Liang Fang3 1Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, 2Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, Shanghai, 3Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 4School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong People's Republic of China, *These authors contributed equally to this workBackground: Lipid-based liquid crystalline nanoparticles (LCNPs have attracted growing interest as novel drug-delivery systems for improving the bioavailability of both hydrophilic and hydrophobic drugs. However, their cellular interaction and in vivo behavior have not been fully developed and characterized.Methods: In this study, self-assembled LCNPs prepared from soy phosphatidylcholine and glycerol dioleate were developed as a platform for oral delivery of paclitaxel. The particle size of empty LCNPs and paclitaxel-loaded LCNPs was around 80 nm. The phase behavior of the liquid crystalline matrix was characterized using crossed polarized light microscopy and small-angle X-ray scattering, and showed both reversed cubic and hexagonal phase in the liquid crystalline matrix. Transmission electron microscopy and cryofield emission scanning electron microscopy analysis revealed an inner winding water channel in LCNPs and a "ball-like"/"hexagonal" morphology.Results: Cellular uptake of LCNPs in Caco-2 cells was found to be concentration-dependent and time-dependent, with involvement of both clathrin and caveolae/lipid raft-mediated endocytosis. Under confocal laser scanning microscopy, soy phosphatidylcholine was observed to segregate from the internalized LCNPs and

  12. The ileal lipid binding protein is required for efficient absorption and transport of bile acids in the distal portion of the murine small intestine.

    Science.gov (United States)

    Praslickova, Dana; Torchia, Enrique C; Sugiyama, Michael G; Magrane, Elijah J; Zwicker, Brittnee L; Kolodzieyski, Lev; Agellon, Luis B

    2012-01-01

    The ileal lipid binding protein (ilbp) is a cytoplasmic protein that binds bile acids with high affinity. However evidence demonstrating the role of this protein in bile acid transport and homeostasis is missing. We created a mouse strain lacking ilbp (Fabp6(-/-) mice) and assessed the impact of ilbp deficiency on bile acid homeostasis and transport in vivo. Elimination of ilbp increased fecal bile acid excretion (54.2%, Pexcreted by 24 h after oral administration was 102% (Psmall and large intestines was increased by 22% (P<0.02) and decreased by 62.7% (P<0.01), respectively, in male Fabp6(-/-) mice relative wild-type mice, whereas no changes were seen in female Fabp6(-/-) mice. Mucosal to serosal bile acid transport using everted distal gut sacs was decreased by 74% (P<0.03) in both sexes of Fabp6(-/-) mice as compared to wild-type mice. The results demonstrate that ilbp is involved in the apical to basolateral transport of bile acids in ileal enterocytes, and is vital for the maintenance of bile acid homeostasis in the enterohepatic circulation (EHC) in mice.

  13. Lipid profiles alter from pro-atherogenic into less atherogenic and proinflammatory in juvenile idiopathic arthritis patients responding to anti TNF-α treatment.

    Directory of Open Access Journals (Sweden)

    Kuo-Wei Yeh

    Full Text Available OBJECTIVE: Dyslipidemia with higher inflammatory states, disease activity, and longer disease duration in juvenile idiopathic arthritis (JIA patients seemed to increase the risks of atherosclerosis. Tumor necrosis factor- α (TNF-α receptor blocking agent etanercept has been proven to be effective in JIA. However, data about the correlation of anti-inflammatory treatment on lipid profiles and atherogenic index in JIA patients remains limited. This study aimed to investigate the longitudinal changes on lipid profiles and atherogenic index in JIA patients after etanercept treatment. METHODS: Twenty-three patients diagnosed with JIA (polyarticular type n = 7; oligoarticular type, n = 2; systemic type, n = 10, Enthesitis-related arthritis = 4 received treatment with etanercept during the period 2004-012 in a medical center. We measured their serum lipid profiles at baseline and 2, 4, 6, 12 months later, and determined whether there were differences in complete blood counts, inflammatory mediators, lipid levels and atherogenic indices between patients who had inactive disease (responders and those who were poor responders (non-responders to etanercept treatment. RESULTS: Analysis of dynamic change in total JIA patients before and after TNF inhibitor therapy showed modest increases in hemoglobin levels (P = 0.02 and decreases in WBC counts, Platelet and CRP levels progressively (p = 0.002, p = 0.006 and p = 0.006, respectively.Twelve of the 23 patients achieved inactive disease status (responders after 12-months of treatment. In responders, compared to non-responders, total cholesterol (TC, low-density lipoprotein cholesterol (LDL-C and high-density lipoprotein cholesterol (HDL-C increased significantly (P = 0.007,P = 0.044,P<0.001, whereas triglyceride and atherogenic index (TC/HDL-C ratio significantly decreased (P = 0.04, P = 0.01, respectively after etanercept treatment. CONCLUSION: Disease severity

  14. Absorption intestinale des vitamines liposolubles

    OpenAIRE

    Reboul Emmanuelle

    2011-01-01

    The molecular mechanisms of fat-soluble vitamin intestinal absorption remain partly unknown, despite the fact that a better understanding of this process would certainly allow to improve their bioavailability. If their digestion-absorption process follows the fate of lipids globally, the recent discovery of membranes proteins involved in their absorption questioned the established dogmas. These new data should be taken into account to avoid dietary or drug interactions that may limit some fat...

  15. The ileal lipid binding protein is required for efficient absorption and transport of bile acids in the distal portion of the murine small intestine.

    Directory of Open Access Journals (Sweden)

    Dana Praslickova

    Full Text Available The ileal lipid binding protein (ilbp is a cytoplasmic protein that binds bile acids with high affinity. However evidence demonstrating the role of this protein in bile acid transport and homeostasis is missing. We created a mouse strain lacking ilbp (Fabp6(-/- mice and assessed the impact of ilbp deficiency on bile acid homeostasis and transport in vivo. Elimination of ilbp increased fecal bile acid excretion (54.2%, P<0.05 in female but not male Fabp6(-/- mice. The activity of cholesterol 7α-hydroxylase (cyp7a1, the rate-controlling enzyme of the classical bile acid biosynthetic pathway, was significantly increased in female (63.5%, P<0.05 but not in male Fabp6(-/- mice. The amount of [(3H]taurocholic acid (TCA excreted by 24 h after oral administration was 102% (P<0.025 higher for female Fabp6(-/- mice whereas it was 57.3% (P<0.01 lower for male Fabp6(-/- mice, compared to wild-type mice. The retained fraction of the [(3H]TCA localized in the small and large intestines was increased by 22% (P<0.02 and decreased by 62.7% (P<0.01, respectively, in male Fabp6(-/- mice relative wild-type mice, whereas no changes were seen in female Fabp6(-/- mice. Mucosal to serosal bile acid transport using everted distal gut sacs was decreased by 74% (P<0.03 in both sexes of Fabp6(-/- mice as compared to wild-type mice. The results demonstrate that ilbp is involved in the apical to basolateral transport of bile acids in ileal enterocytes, and is vital for the maintenance of bile acid homeostasis in the enterohepatic circulation (EHC in mice.

  16. Higher high density lipoprotein cholesterol associated with moderate alcohol consumption is not related to altered plasma lecithin : cholesterol acyltransferase and lipid transfer protein activity levels

    NARCIS (Netherlands)

    Riemens, SC; vanTol, A; Hoogenberg, K; vanGent, T; Scheek, LM; Sluiter, WJ; Dullaart, RPF

    1997-01-01

    Lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are important factors involved in HDL metabolism. Altered plasma activity levels of these factors could play a role in the increase in high density lipoprotein (HDL) choles

  17. Skin-specific deletion of stearoyl-CoA desaturase-1 alters skin lipid composition and protects mice from high fat diet-induced obesity.

    Science.gov (United States)

    Sampath, Harini; Flowers, Matthew T; Liu, Xueqing; Paton, Chad M; Sullivan, Ruth; Chu, Kiki; Zhao, Minghui; Ntambi, James M

    2009-07-24

    Stearoyl-CoA desaturase-1 (SCD1) catalyzes the synthesis of monounsaturated fatty acids and is an important regulator of whole body energy homeostasis. Severe cutaneous changes in mice globally deficient in SCD1 also indicate a role for SCD1 in maintaining skin lipids. We have generated mice with a skin-specific deletion of SCD1 (SKO) and report here that SKO mice display marked sebaceous gland hypoplasia and depletion of sebaceous lipids. In addition, SKO mice have significantly increased energy expenditure and are protected from high fat diet-induced obesity, thereby recapitulating the hypermetabolic phenotype of global SCD1 deficiency. Genes of fat oxidation, lipolysis, and thermogenesis, including uncoupling proteins and peroxisome proliferator-activated receptor-gamma co-activator-1alpha, are up-regulated in peripheral tissues of SKO mice. However, unlike mice globally deficient in SCD1, SKO mice have an intact hepatic lipogenic response to acute high carbohydrate feeding. Despite increased basal thermogenesis, SKO mice display severe cold intolerance because of rapid depletion of fuel substrates, including hepatic glycogen, to maintain core body temperature. These data collectively indicate that SKO mice have increased cold perception because of loss of insulating factors in the skin. This results in up-regulation of thermogenic processes for temperature maintenance at the expense of fuel economy, illustrating cross-talk between the skin and peripheral tissues in maintaining energy homeostasis.

  18. Association between altered lipid profile, body mass index, low plasma adiponectin and varied blood pressure in trinidadian type 2 diabetic and non-diabetic subjects

    Directory of Open Access Journals (Sweden)

    Shivananda B Nayak

    2012-01-01

    Full Text Available Background: The obesity and hypertension have become the causes for the development type 2 diabetes. There is a limited study done on the contribution of body mass index (BMI to blood pressure (BP in the Caribbean population. Aim of our study was to determine the associations between lipid profile, BMI, adiponectin, and BP in Trinidadian type 2 diabetic patients with regards to age and ethnicity. Materials and Methods: This was a cohort study comprised of 266 subjects (85 males and 181 females attending primary and tertiary healthcare settings in central Trinidad. Of which, 126 diabetic subjects were matched with 140 non-diabetic subjects. Along with clinical history and anthropometry, adiponectin and lipid profile were measured in fasting blood samples. Results: The diabetic group had higher triglycerides, very low density lipoprotein (VLDL, and BP values which were statistically significant (P < 0.05 when compared to non-diabetic subjects. The high-density lipoprotein cholesterol (HDL-c and adiponectin were lower in diabetic subjects. HDL-c showed significant changes for ethnicity (P = 0.013 and gender (P = 0.043. The mean adiponectin concentrations were found to be significantly different among the ethnic groups (P = 0.001. Systolic pressure varied significantly with age (P = 0.018. As age increased, BP also increased. Ethnic groups had a significant difference in diastolic pressure (P = 0.027. East Indians had the highest mean diastolic pressure (80.74 ± 10.29 when compared to all other ethnic groups. Conclusion: HDL-cholesterol, low levels of adiponectin, and varied BP are associated in Trinidadian type 2 diabetic subjects with regards to age, gender, and ethnicity.

  19. Alterations in thyroid hormones, lipid peroxidation, glutathione content and protein plasma levels of male rats and their male offspring treated with lead acetate

    International Nuclear Information System (INIS)

    Lead is a pervasive environmental pollutant known to induced a broad range of physiological, biochemical and behavioral dysfunction in both laboratory animals as well as in human. The present work was directed to study the impact of lead (Pb) contamination on blood levels of thyroid hormones. Lipid peroxidation, glutathione content, total protein, albumin and globulin in male albino rats and whether this impact extends to their offspring growing up in same conditions. Animals were classified into three main groups; 1- control. 2- painter's (fathers). 3- first generation of male rats yielded from Pb-contaminated parents (fathers and mothers). groups 2 and 3 were levels; 100 and 200 mg l, drinking water with lead acetates at two dose levels; 100 and 200 mg l. drinking water for two months. The results revealed that lead contamination induced significant elevations (P4) and triiodothyronine (T3) in both fathers and offspring. Yet, lead significantly increase the plasma lipid peroxidation (P<0.001) with concomitant decreased in glutathione blood content in both fathers and male offspring. The plasma levels of total; protein were significantly increased as a response to the plasma albumin elevations and in turn the albumin / globulin ratio in both fathers and male offspring. Collectively, it was evident that lead high dose (200 mg) dose and the male offspring were highly contaminated than their fathers. The present investigation recommended that urban population ad persons whose work is associated with exposure to lead. Would expected to be at increased risk for lead exposure that will extend to their offspring, and they should be submitted with antioxidants and subjected to periodical medical examinations

  20. Fat absorption and deposition in Japanese quail (Coturnix coturnix japonica fed a high fat diet

    Directory of Open Access Journals (Sweden)

    Mhlengi M. Magubane

    2013-02-01

    Full Text Available Dietary fat contributes significantly to the energy requirements of poultry. Not all species are able to increase their absorptive capacity for fats in response to a high fat diet. The effects of a high fat diet (10% canola oil on the lipid absorption and deposition in the liver, breast and thigh muscles of male and female Japanese quail were investigated. Thirty-eight Japanese quail (Coturnix coturnix japonica were randomly divided into a high fat diet (HFD and a standard diet (STD group. The birds were fed the diets for seven weeks after which half of the birds were subjected to oral fat loading tests (OFLT with plant oils containing long-chain and medium-chain triglycerides. The remaining birds were included for the lipid deposition measurements. Thereafter the birds were euthanised, blood samples were collected and liver, breast and thigh muscle lipid deposition was determined. Female quail on both diets had significantly higher plasma triglyceride concentrations (p < 0.05 compared with their male counterparts. No significant differences in plasma triglyceride concentrations were observed after the OFLTs. Female quail had significantly heavier liver masses compared with the males but there was no significant difference in the liver lipid content per gram liver mass. Female quail on the HFD had higher lipid content (p < 0.05 in the breast muscle compared with their male counterparts whilst male quail on the HFD had higher lipid content (p < 0.05 in the thigh muscle in comparison with both males and females on the standard diet. Dietary supplementation with 10% canola oil did not alter gastrointestinal tract lipid absorption, but it caused differences between the sexes in muscle lipid accumulation, the physiological significance of which requires further investigation.

  1. Fat absorption and deposition in Japanese quail (Coturnix coturnix japonica fed a high fat diet

    Directory of Open Access Journals (Sweden)

    Mhlengi M. Magubane

    2013-05-01

    Full Text Available Dietary fat contributes significantly to the energy requirements of poultry. Not all species are able to increase their absorptive capacity for fats in response to a high fat diet. The effects of a high fat diet (10% canola oil on the lipid absorption and deposition in the liver, breast and thigh muscles of male and female Japanese quail were investigated. Thirty-eight Japanese quail (Coturnix coturnix japonica were randomly divided into a high fat diet (HFD and a standard diet (STD group. The birds were fed the diets for seven weeks after which half of the birds were subjected to oral fat loading tests (OFLT with plant oils containing long-chain and medium-chain triglycerides. The remaining birds were included for the lipid deposition measurements. Thereafter the birds were euthanised, blood samples were collected and liver, breast and thigh muscle lipid deposition was determined. Female quail on both diets had significantly higher plasma triglyceride concentrations (p < 0.05 compared with their male counterparts. No significant differences in plasma triglyceride concentrations were observed after the OFLTs. Female quail had significantly heavier liver masses compared with the males but there was no significant difference in the liver lipid content per gram liver mass. Female quail on the HFD had higher lipid content (p < 0.05 in the breast muscle compared with their male counterparts whilst male quail on the HFD had higher lipid content (p < 0.05 in the thigh muscle in comparison with both males and females on the standard diet. Dietary supplementation with 10% canola oil did not alter gastrointestinal tract lipid absorption, but it caused differences between the sexes in muscle lipid accumulation, the physiological significance of which requires further investigation.

  2. Alteration of the phospho- or neutral lipid content and fatty acid composition in Listeria monocytogenes due to acid adaptation mechanisms for hydrochloric, acetic and lactic acids at pH 5.5 or benzoic acid at neutral pH.

    Science.gov (United States)

    Mastronicolis, Sofia K; Berberi, Anita; Diakogiannis, Ioannis; Petrova, Evanthia; Kiaki, Irene; Baltzi, Triantafillia; Xenikakis, Polydoros

    2010-10-01

    This study provides a first approach to observe the effects on Listeria monocytogenes of cellular exposure to acid stress at low or neutral pH, notably how phospho- or neutral lipids are involved in this mechanism, besides the fatty acid profile alteration. A thorough investigation of the composition of polar and neutral lipids from L. monocytogenes grown at pH 5.5 in presence of hydrochloric, acetic and lactic acids, or at neutral pH 7.3 in presence of benzoic acid, is described relative to cells grown in acid-free medium. The results showed that only low pH values enhance the antimicrobial activity of an acid. We suggest that, irrespective of pH, the acid adaptation response will lead to a similar alteration in fatty acid composition [decreasing the ratio of branched chain/saturated straight fatty acids of total lipids], mainly originating from the neutral lipid class of adapted cultures. Acid adaptation in L. monocytogenes was correlated with a decrease in total lipid phosphorus and, with the exception of cells adapted to benzoic acid, this change in the amount of phosphorus reflected a higher content of the neutral lipid class. Upon acetic or benzoic acid stress the lipid phosphorus proportion was analysed in the main phospholipids present: cardiolipin, phosphatidylglycerol, phosphoaminolipid and phosphatidylinositol. Interestingly only benzoic acid had a dramatic effect on the relative quantities of these four phospholipids.

  3. Kefir consumption does not alter plasma lipid levels or cholesterol fractional synthesis rates relative to milk in hyperlipidemic men: a randomized controlled trial [ISRCTN10820810

    Directory of Open Access Journals (Sweden)

    Mafu Akier

    2002-01-01

    Full Text Available Abstract Background Fermented milk products have been shown to affect serum cholesterol concentrations in humans. Kefir, a fermented milk product, has been traditionally consumed for its potential health benefits but has to date not been studied for its hypocholesterolemic properties. Methods Thirteen healthy mildly hypercholesterolemic male subjects consumed a dairy supplement in randomized crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy supplement consumed. Blood samples were collected at baseline and after 4 wk of supplementation for measurement of plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride concentrations, as well as fatty acid profile and cholesterol synthesis rate. Fecal samples were collected at baseline and after 2 and 4 wk of supplementation for determination of fecal short chain fatty acid level and bacterial content. Results Kefir had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglyceride concentrations nor on cholesterol fractional synthesis rates after 4 wk of supplementation. No significant change on plasma fatty acid levels was observed with diet. However, both kefir and milk increased (p Conclusions Since kefir consumption did not result in lowered plasma lipid concentrations, the results of this study do not support consumption of kefir as a cholesterol-lowering agent.

  4. Combined treatment of sodium orthovanadate and Momordica charantia fruit extract prevents alterations in lipid profile and lipogenic enzymes in alloxan diabetic rats.

    Science.gov (United States)

    Yadav, Umesh C S; Moorthy, K; Baquer, Najma Z

    2005-01-01

    Momordica charantia Linn., commonly called bitter gourd, is a medicinal plant used in the Ayurvedic system of medicine for treating various diseases including diabetes mellitus. Sodium orthovanadate (SOV) is also well-known insulin mimetic and an antidiabetic compound. Our laboratory has been using reduced doses of SOV along with administration of herbal extracts to alloxan diabetic rats and has established this combination as a good antihyperglycemic agent. The present study was undertaken to investigate the effects of treatment of Momordica fruit extract (MFE) and sodium orthovanadate, separately and in combination, on serum and tissue lipid profile and on the activities of lipogenic enzymes in alloxan induced diabetic rats. The results show that there was a significant (p effective prevention was however observed in a combined treatment of Momordica with a reduced dose of SOV (0.2%). The results suggest that Momordica fruit extract and SOV exhibit hypolipidemic as well as hypoglycemic effect in diabetic rats and their effect is pronounced when administered in combination. PMID:15724444

  5. Deficiencies of the lipid-signaling enzymes phospholipase D1 and D2 alter cytoskeletal organization, macrophage phagocytosis, and cytokine-stimulated neutrophil recruitment.

    Directory of Open Access Journals (Sweden)

    Wahida H Ali

    Full Text Available Cell migration and phagocytosis ensue from extracellular-initiated signaling cascades that orchestrate dynamic reorganization of the actin cytoskeleton. The reorganization is mediated by effector proteins recruited to the site of activity by locally-generated lipid second messengers. Phosphatidic acid (PA, a membrane phospholipid generated by multiple enzyme families including Phospholipase D (PLD, has been proposed to function in this role. Here, we show that macrophages prepared from mice lacking either of the classical PLD isoforms PLD1 or PLD2, or wild-type macrophages whose PLD activity has been pharmacologically inhibited, display isoform-specific actin cytoskeleton abnormalities that likely underlie decreases observed in phagocytic capacity. Unexpectedly, PA continued to be detected on the phagosome in the absence of either isoform and even when all PLD activity was eliminated. However, a disorganized phagocytic cup was observed as visualized by imaging PA, F-actin, Rac1, an organizer of the F-actin network, and DOCK2, a Rac1 activator, suggesting that PLD-mediated PA production during phagocytosis is specifically critical for the integrity of the process. The abnormal F-actin reorganization additionally impacted neutrophil migration and extravasation from the vasculature into interstitial tissues. Although both PLD1 and PLD2 were important in these processes, we also observed isoform-specific functions. PLD1-driven processes in particular were observed to be critical in transmigration of macrophages exiting the vasculature during immune responses such as those seen in acute pancreatitis or irritant-induced skin vascularization.

  6. Plasma Micronutrient Concentrations Are Altered by Antiretroviral Therapy and Lipid-Based Nutrient Supplements in Lactating HIV-Infected Malawian Women123

    Science.gov (United States)

    Flax, Valerie L; Adair, Linda S; Allen, Lindsay H; Shahab-Ferdows, Setarah; Hampel, Daniela; Chasela, Charles S; Tegha, Gerald; Daza, Eric J; Corbett, Amanda; Davis, Nicole L; Kamwendo, Deborah; Kourtis, Athena P; van der Horst, Charles M; Jamieson, Denise J; Bentley, Margaret E

    2015-01-01

    Background: Little is known about the influence of antiretroviral therapy with or without micronutrient supplementation on the micronutrient concentrations of HIV-infected lactating women in resource-constrained settings. Objective: We examined associations of highly active antiretroviral therapy (HAART) and lipid-based nutrient supplements (LNS) with concentrations of selected micronutrients in HIV-infected Malawian women at 24 wk postpartum. Methods: Plasma micronutrient concentrations were measured in a subsample (n = 690) of Breastfeeding, Antiretrovirals, and Nutrition (BAN) study participants who were randomly assigned at delivery to receive HAART, LNS, HAART+LNS, or no HAART/no LNS (control). HAART consisted of protease inhibitor–based triple therapy. LNS (140 g/d) met energy and micronutrient requirements of lactation. Multivariable linear regression tested the association of HAART and LNS, plus their interaction, with micronutrient concentrations, controlling for season, baseline viral load, and baseline CD4 count. Results: We found significant HAART by LNS interactions for folate (P = 0.051), vitamin B-12 (P < 0.001), and transferrin receptors (TfRs) (P = 0.085). HAART was associated with lower folate (with LNS: −27%, P < 0.001; without LNS: −12%, P = 0.040) and higher TfR concentrations (with LNS: +14%, P = 0.004; without LNS: +28%, P < 0.001), indicating iron deficiency. LNS increased folate (with HAART: +17%, P = 0.037; without HAART: +39%, P < 0.001) and decreased TfR concentrations (with HAART only: −12%, P = 0.023). HAART was associated with lower vitamin B-12 concentrations only when LNS was present (−18%, P = 0.001), whereas LNS increased vitamin B-12 only when no HAART was present (+27%, P < 0.001). HAART, but not LNS, was associated with higher retinol-binding protein (RBP; +10%, P = 0.007). We detected no association of HAART or LNS with selenium, ferritin, or hemoglobin. Conclusion: The association of HAART with lower folate, iron

  7. Long-chain n-3 fatty acids enhance neonatal insulin-regulated protein metabolism in piglets by differentially altering muscle lipid composition.

    Science.gov (United States)

    Bergeron, Karen; Julien, Pierre; Davis, Teresa A; Myre, Alexandre; Thivierge, M Carole

    2007-11-01

    This study investigated the role of long-chain n-3 polyunsaturated fatty acids (LCn-3PUFAs) of muscle phospholipids in the regulation of neonatal metabolism. Twenty-eight piglets were weaned at 2 days of age and raised on one of two milk formulas that consisted of either a control formula supplying 0% or a formula containing 3.5% LCn-3PUFAs until 10 or 28 days of age. There was a developmental decline in the insulin sensitivity of amino acid disposal in control pigs during the first month of life, with a slope of -2.24 micromol.kg(-1).h(-1) (P = 0.01) per unit of insulin increment, as assessed using hyperinsulinemic-euglycemic-euaminoacidemic clamps. LCn-3PUFA feeding blunted this developmental decline, resulting in differing insulin sensitivities (P < 0.001). When protein metabolism was assessed under parenteral feeding-induced hyperinsulinemia, LCn-3PUFAs reduced by 16% whole body oxidative losses of amino acids (from 238 to 231 micromol.kg(-1).h(-1); P = 0.06), allowing 41% more amino acids to accrete into body proteins (from 90 to 127 micromol.kg(-1).h(-1); P = 0.06). The fractional synthetic rate of muscle mixed proteins remained unaltered by the LCn-3PUFA feeding. However, LCn-3PUFAs retarded a developmental increase in the essential-to-nonessential amino acid ratio of the muscle intracellular free pool (P = 0.05). Overall, alterations in metabolism were concomitant with a preferential incorporation of LCn-3PUFAs into muscle total membrane phospholipids (P < 0.001), in contrast to intramuscular triglycerides. These results underscore the potential role of LCn-3PUFAs as regulators of different aspects of protein metabolism in the neonate. PMID:17673528

  8. 丹参酮ⅡA固体脂质纳米粒的制备及体外释药%Preparation of tanshinone Ⅱ A solid lipid nanoparticle and evaluation of its oral absorption

    Institute of Scientific and Technical Information of China (English)

    张继东; 万江陵

    2012-01-01

    目的:制备丹参酮ⅡA(TSA)口服固体脂质纳米粒(TSA-SLN),根据相关理化性质预测其口服吸收效果.方法:采用成膜-高压均质法制备TSA-SLN,测定纳米粒的粒径、多分散指数(PDI)、Zeta电位,并考察其热力学行为,高效液相色谱(HPLC)法测试其载药量和包封率,结合体外释放试验和Caco-2细胞单层膜转运试验初步评价了TSA-SLN的口服吸收效果.结果:TSA-SLN水分散粒径(83.6±15.4) nm,PDI为0.203±0.019,Zeta电位(-32.6±1.7)mV,载药量(0.92±0.05)%,包封率(84±7)%;X射线衍射(XRD)和差式热量扫描(DSC)测试结果表明TSA在SLN中以无定型态存在,与市售丹参酮胶囊粉末相比,TSA-SLN的体外累积释放度提高将近20%,Caco-2细胞单层膜的通透率提高4~5倍.结论:TSA-SLN体外释放度高,Caco-2细胞单层膜通透性强,有望提高TSA的口服吸收.%OBJECTIVE To prepare tanshinone DA loaded solid lipid nanoparticle (TSA-SLN), and to predict its oral absorption based on physic-chemical properties. METHODS Membranization-high pressure homogeny method was adopted during the preparation of TSA-SLN, its size, PDI and Zeta potential were tested, and its thermodynamic behavior was investigated. The drug-loaded rate and entrapment rate of TSA-SLN were also estimated by HPLC, and the oral absorption behavior was e-valuated depending on the in vitro release rate and the Caco-2 cell monolayer membrane transportation behavior of TSA. RESULTS TSA-SLN dispersed in water had average size of (83 ± 15)nm, PDI of (0. 203 + 0. 019)and Zeta potential of( - 32. 6 ± 1. 7)mV. Its drug-loaded rate was (0. 92 ± 0. 05)% with the entrapment rate of (84 + 7)%. The fact that in SLN particles TSA existing as amorphous was proved by the results of XRD and DSC respectively. The in vitro release rate of TSA-SLN was 20% higher than that of capsule powder, and the permeability of TSA through Caco-2 cells monolayer membrane had been improved by 4-5 times. CONCLUSION TSA

  9. Liver lipid content and inflammometabolic indices in peripartal dairy cows are altered in response to prepartal energy intake and postpartal intramammary inflammatory challenge.

    Science.gov (United States)

    Graugnard, D E; Moyes, K M; Trevisi, E; Khan, M J; Keisler, D; Drackley, J K; Bertoni, G; Loor, J J

    2013-02-01

    -LPS at 14 and 30 d postpartum. Several inflammation-related genes (TNF, IRAK1, NFKB1, ANGPTL4) showed markedly decreased expression between 7 and 14 d, after which expression remained unchanged. No differences were observed in several genes of the growth-hormone/insulin-like growth factor-1 axis, except for SOCS2, expression of which decreased markedly between 7 and 14 d in OVE-LPS but not in CON-LPS. These data suggest that overfeeding a moderate-energy diet prepartum alters the response of the cow to an intramammary challenge after calving and may predispose it to sustained liver lipidosis.

  10. Lipid Regulation of Sodium Channels.

    Science.gov (United States)

    D'Avanzo, N

    2016-01-01

    The lipid landscapes of cellular membranes are complex and dynamic, are tissue dependent, and can change with the age and the development of a variety of diseases. Researchers are now gaining new appreciation for the regulation of ion channel proteins by the membrane lipids in which they are embedded. Thus, as membrane lipids change, for example, during the development of disease, it is likely that the ionic currents that conduct through the ion channels embedded in these membranes will also be altered. This chapter provides an overview of the complex regulation of prokaryotic and eukaryotic voltage-dependent sodium (Nav) channels by fatty acids, sterols, glycerophospholipids, sphingolipids, and cannabinoids. The impact of lipid regulation on channel gating kinetics, voltage-dependence, trafficking, toxin binding, and structure are explored for Nav channels that have been examined in heterologous expression systems, native tissue, and reconstituted into artificial membranes. Putative mechanisms for Nav regulation by lipids are also discussed. PMID:27586290

  11. Effect of dl-ethionine on the intestinal absorption and transport of palmitic acid-1-14C and tripalmitin-14C. Role of intramucosal factors in the uptake of luminal lipids

    Science.gov (United States)

    Kessler, Jacques I.; Mishkin, S.; Stein, J.

    1969-01-01

    The effect of DL-ethionine on the uptake and transport of lipid by the rat small intestine was investigated. A cottonseed oil emulsion containing 14C-labeled tripalmitin or palmitic acid was administered intragastrically to rats pretreated with DL-ethionine, DL-ethionine plus methionine, or saline, and the rats were sacrificed 2, 4, and 6 hr later. Lipids from the plasma, the stomach, the colon, the luminal contents of the small intestine, and the wall of the small intestine were extracted, fractionated, and their radioactivity assayed. Ethionine markedly inhibited the uptake of lipids by the small intestine. This inhibition was not related to impairment of intraluminal lipolysis since analagous inhibitions were observed when palmitic acid or predigested triglyceride (TG), obtained through a jejunal fistula from normal animals, was administered instead of tripalmitin. Ethionine also inhibited the transport of lipid from the wall of the small intestine. A significant fraction of the administered lipid remained in the wall of the small intestine, and only a small fraction was transported to the blood stream. Although most of the wall radioactivity was in the form of TG, significant proportions were also found in the free fatty acid (FFA) and partial glyceride fractions, indicating a marked inhibition of mucosal reesterification to TG. The degree of inhibition of mucosal reesterification and the degree of inhibition of transport of wall lipids were directly related to the degree of inhibition of uptake of luminal radioactivity. This relationship suggests that the rate of reesterification, the level of mucosal FFA, and the rate of transport of intramucosal TG may be of importance in determining the extent of uptake of intraluminal lipid by the mucosal cells. Since a significant fraction of the wall radioactivity was in the form of TG, the decreased transport of wall lipids was attributed to an impairment of chylomicron completion due to inhibition of either the

  12. Lipid nanotechnology.

    Science.gov (United States)

    Mashaghi, Samaneh; Jadidi, Tayebeh; Koenderink, Gijsje; Mashaghi, Alireza

    2013-01-01

    Nanotechnology is a multidisciplinary field that covers a vast and diverse array of devices and machines derived from engineering, physics, materials science, chemistry and biology. These devices have found applications in biomedical sciences, such as targeted drug delivery, bio-imaging, sensing and diagnosis of pathologies at early stages. In these applications, nano-devices typically interface with the plasma membrane of cells. On the other hand, naturally occurring nanostructures in biology have been a source of inspiration for new nanotechnological designs and hybrid nanostructures made of biological and non-biological, organic and inorganic building blocks. Lipids, with their amphiphilicity, diversity of head and tail chemistry, and antifouling properties that block nonspecific binding to lipid-coated surfaces, provide a powerful toolbox for nanotechnology. This review discusses the progress in the emerging field of lipid nanotechnology. PMID:23429269

  13. Lipid Nanotechnology

    Directory of Open Access Journals (Sweden)

    Gijsje Koenderink

    2013-02-01

    Full Text Available Nanotechnology is a multidisciplinary field that covers a vast and diverse array of devices and machines derived from engineering, physics, materials science, chemistry and biology. These devices have found applications in biomedical sciences, such as targeted drug delivery, bio-imaging, sensing and diagnosis of pathologies at early stages. In these applications, nano-devices typically interface with the plasma membrane of cells. On the other hand, naturally occurring nanostructures in biology have been a source of inspiration for new nanotechnological designs and hybrid nanostructures made of biological and non-biological, organic and inorganic building blocks. Lipids, with their amphiphilicity, diversity of head and tail chemistry, and antifouling properties that block nonspecific binding to lipid-coated surfaces, provide a powerful toolbox for nanotechnology. This review discusses the progress in the emerging field of lipid nanotechnology.

  14. A Gly482Ser missense mutation in the peroxisome proliferator-activated receptor gamma coactivator-1 is associated with altered lipid oxidation and early insulin secretion in Pima Indians

    DEFF Research Database (Denmark)

    Muller, Yunhua Li; Bogardus, Clifton; Pedersen, Oluf;

    2003-01-01

    Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) is a transcriptional coactivator of peroxisome proliferator-activated receptor gamma and alpha, which play important roles in adipogenesis and lipid metabolism. A single nucleotide polymorphism within the coding region...

  15. The interaction between purple membrane and membrane lipid

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Bacteriorhodopsin in purple membrane was reconstituted into different lipid vesicles. The effect of three different lipids on the structure and function of bacteriorhodopsin in lipid vesicles was studied by the observation on freeze-fracture eletron microscopy, the rotational diffusion of bacteriorhodopsin in lipid vesicles, the measurement of absorption spectrum, and the absorbance change with time. For these prepared samples, the results showed that DMPC was the stable lipid environment of bacteriorhodopsin; egg-pc causeed the loss of retinal chromophore of bacteriorhodopsin and it was not reversible change, cholesterol could stabilize the bacteriorhodopsin in lipid environment,but it caused the aggregation of bacteriorhodopsin.

  16. Deregulated Lipid Sensing by Intestinal CD36 in Diet-Induced Hyperinsulinemic Obese Mouse Model.

    Science.gov (United States)

    Buttet, Marjorie; Poirier, Hélène; Traynard, Véronique; Gaire, Kévin; Tran, Thi Thu Trang; Sundaresan, Sinju; Besnard, Philippe; Abumrad, Nada A; Niot, Isabelle

    2016-01-01

    The metabolic syndrome (MetS) greatly increases risk of cardiovascular disease and diabetes and is generally associated with abnormally elevated postprandial triglyceride levels. We evaluated intestinal synthesis of triglyceride-rich lipoproteins (TRL) in a mouse model of the MetS obtained by feeding a palm oil-rich high fat diet (HFD). By contrast to control mice, MetS mice secreted two populations of TRL. If the smaller size population represented 44% of total particles in the beginning of intestinal lipid absorption in MetS mice, it accounted for only 17% after 4 h due to the secretion of larger size TRL. The MetS mice displayed accentuated postprandial hypertriglyceridemia up to 3 h due to a defective TRL clearance. These alterations reflected a delay in lipid induction of genes for key proteins of TRL formation (MTP, L-FABP) and blood clearance (ApoC2). These abnormalities associated with blunted lipid sensing by CD36, which is normally required to optimize jejunal formation of large TRL. In MetS mice CD36 was not downregulated by lipid in contrast to control mice. Treatment of controls with the proteosomal inhibitor MG132, which prevented CD36 downregulation, resulted in blunted lipid-induction of MTP, L-FABP and ApoC2 gene expression, as in MetS mice. Absence of CD36 sensing was due to the hyperinsulinemia in MetS mice. Acute insulin treatment of controls before lipid administration abolished CD36 downregulation, lipid-induction of TRL genes and reduced postprandial triglycerides (TG), while streptozotocin-treatment of MetS mice restored lipid-induced CD36 degradation and TG secretion. In vitro, insulin treatment abolished CD36-mediated up-regulation of MTP in Caco-2 cells. In conclusion, HFD treatment impairs TRL formation in early stage of lipid absorption via insulin-mediated inhibition of CD36 lipid sensing. This impairment results in production of smaller TRL that are cleared slowly from the circulation, which might contribute to the reported

  17. Deregulated Lipid Sensing by Intestinal CD36 in Diet-Induced Hyperinsulinemic Obese Mouse Model.

    Directory of Open Access Journals (Sweden)

    Marjorie Buttet

    Full Text Available The metabolic syndrome (MetS greatly increases risk of cardiovascular disease and diabetes and is generally associated with abnormally elevated postprandial triglyceride levels. We evaluated intestinal synthesis of triglyceride-rich lipoproteins (TRL in a mouse model of the MetS obtained by feeding a palm oil-rich high fat diet (HFD. By contrast to control mice, MetS mice secreted two populations of TRL. If the smaller size population represented 44% of total particles in the beginning of intestinal lipid absorption in MetS mice, it accounted for only 17% after 4 h due to the secretion of larger size TRL. The MetS mice displayed accentuated postprandial hypertriglyceridemia up to 3 h due to a defective TRL clearance. These alterations reflected a delay in lipid induction of genes for key proteins of TRL formation (MTP, L-FABP and blood clearance (ApoC2. These abnormalities associated with blunted lipid sensing by CD36, which is normally required to optimize jejunal formation of large TRL. In MetS mice CD36 was not downregulated by lipid in contrast to control mice. Treatment of controls with the proteosomal inhibitor MG132, which prevented CD36 downregulation, resulted in blunted lipid-induction of MTP, L-FABP and ApoC2 gene expression, as in MetS mice. Absence of CD36 sensing was due to the hyperinsulinemia in MetS mice. Acute insulin treatment of controls before lipid administration abolished CD36 downregulation, lipid-induction of TRL genes and reduced postprandial triglycerides (TG, while streptozotocin-treatment of MetS mice restored lipid-induced CD36 degradation and TG secretion. In vitro, insulin treatment abolished CD36-mediated up-regulation of MTP in Caco-2 cells. In conclusion, HFD treatment impairs TRL formation in early stage of lipid absorption via insulin-mediated inhibition of CD36 lipid sensing. This impairment results in production of smaller TRL that are cleared slowly from the circulation, which might contribute to the

  18. Deregulated Lipid Sensing by Intestinal CD36 in Diet-Induced Hyperinsulinemic Obese Mouse Model

    Science.gov (United States)

    Buttet, Marjorie; Poirier, Hélène; Traynard, Véronique; Gaire, Kévin; Tran, Thi Thu Trang; Sundaresan, Sinju; Besnard, Philippe; Abumrad, Nada A.; Niot, Isabelle

    2016-01-01

    The metabolic syndrome (MetS) greatly increases risk of cardiovascular disease and diabetes and is generally associated with abnormally elevated postprandial triglyceride levels. We evaluated intestinal synthesis of triglyceride-rich lipoproteins (TRL) in a mouse model of the MetS obtained by feeding a palm oil-rich high fat diet (HFD). By contrast to control mice, MetS mice secreted two populations of TRL. If the smaller size population represented 44% of total particles in the beginning of intestinal lipid absorption in MetS mice, it accounted for only 17% after 4 h due to the secretion of larger size TRL. The MetS mice displayed accentuated postprandial hypertriglyceridemia up to 3 h due to a defective TRL clearance. These alterations reflected a delay in lipid induction of genes for key proteins of TRL formation (MTP, L-FABP) and blood clearance (ApoC2). These abnormalities associated with blunted lipid sensing by CD36, which is normally required to optimize jejunal formation of large TRL. In MetS mice CD36 was not downregulated by lipid in contrast to control mice. Treatment of controls with the proteosomal inhibitor MG132, which prevented CD36 downregulation, resulted in blunted lipid-induction of MTP, L-FABP and ApoC2 gene expression, as in MetS mice. Absence of CD36 sensing was due to the hyperinsulinemia in MetS mice. Acute insulin treatment of controls before lipid administration abolished CD36 downregulation, lipid-induction of TRL genes and reduced postprandial triglycerides (TG), while streptozotocin-treatment of MetS mice restored lipid-induced CD36 degradation and TG secretion. In vitro, insulin treatment abolished CD36-mediated up-regulation of MTP in Caco-2 cells. In conclusion, HFD treatment impairs TRL formation in early stage of lipid absorption via insulin-mediated inhibition of CD36 lipid sensing. This impairment results in production of smaller TRL that are cleared slowly from the circulation, which might contribute to the reported

  19. Cholecystokinin elevates mouse plasma lipids.

    Directory of Open Access Journals (Sweden)

    Lichun Zhou

    Full Text Available Cholecystokinin (CCK is a peptide hormone that induces bile release into the intestinal lumen which in turn aids in fat digestion and absorption in the intestine. While excretion of bile acids and cholesterol into the feces eliminates cholesterol from the body, this report examined the effect of CCK on increasing plasma cholesterol and triglycerides in mice. Our data demonstrated that intravenous injection of [Thr28, Nle31]-CCK at a dose of 50 ng/kg significantly increased plasma triglyceride and cholesterol levels by 22 and 31%, respectively, in fasting low-density lipoprotein receptor knockout (LDLR(-/- mice. The same dose of [Thr28, Nle31]-CCK induced 6 and 13% increases in plasma triglyceride and cholesterol, respectively, in wild-type mice. However, these particular before and after CCK treatment values did not achieve statistical significance. Oral feeding of olive oil further elevated plasma triglycerides, but did not alter plasma cholesterol levels in CCK-treated mice. The increased plasma cholesterol in CCK-treated mice was distributed in very-low, low and high density lipoproteins (VLDL, LDL and HDL with less of an increase in HDL. Correspondingly, the plasma apolipoprotein (apo B48, B100, apoE and apoAI levels were significantly higher in the CCK-treated mice than in untreated control mice. Ligation of the bile duct, blocking CCK receptors with proglumide or inhibition of Niemann-Pick C1 Like 1 transporter with ezetimibe reduced the hypercholesterolemic effect of [Thr28, Nle31]-CCK in LDLR(-/- mice. These findings suggest that CCK-increased plasma cholesterol and triglycerides as a result of the reabsorption of biliary lipids from the intestine.

  20. Secondary structure and lipid interactions of the N-terminal segment of pulmonary surfactant SP-C in Langmuir films: IR reflection-absorption spectroscopy and surface pressure studies

    DEFF Research Database (Denmark)

    Bi, Xiaohong; Flach, Carol R; Pérez-Gil, Jesus;

    2002-01-01

    syndrome, a pathological condition resulting from deficiency in surfactant. To facilitate rational design of therapeutic agents, a molecular level understanding of lipid interaction with surfactant proteins or their analogues in aqueous monolayer films is necessary. The current work uses infrared...... of IRRAS to detect the surface pressure dependence of protein or peptide structure/interactions in a physiologically relevant model for surfactant is clearly demonstrated. Udgivelsesdato: 2002-Jul-2......Pulmonary surfactant, a thin lipid/protein film lining mammalian lungs, functions in vivo to reduce the work of breathing and to prevent alveolar collapse. Analogues of two hydrophobic surfactant proteins, SP-B and SP-C, have been incorporated into therapeutic agents for respiratory distress...

  1. Proposed human stratum corneum water domain in chemical absorption.

    Science.gov (United States)

    Zhu, Hanjiang; Jung, Eui-Chang; Hui, Xiaoying; Maibach, Howard

    2016-08-01

    Compounds with varying physical and chemical properties may have different affinities to the stratum corneum (SC) and/or its intercellular lipids, keratin protein, and possible water domains. To better understand the mechanism of percutaneous absorption, we utilized 21 carbon-14 labeled chemicals, with wide hydrophilicity (log P = -0.05 to 6.17), and quantified their absorption/adsorption properties for a short incubation time (15 min) with regards to intact SC membrane, delipidized SC membrane and SC lipid. A facile method was developed for SC/lipid absorption, providing a more equivalent procedure and comparable data. SC lipid absorption of chemical solutes positively correlated with the octanol/water partition coefficient (log P). Differences between the percent dose of chemical absorption to intact SC and the total percent dose contributed by the protein and lipid domains suggest the possibility and significance of a water domain. Absorption rate experiments showed a longer lag time for intact SC than for delipidized SC or SC lipid, suggesting that the water domain may delay chemical binding to protein and lipid domains, and may be a factor in the resistance of many chemicals to current decontamination methods. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Proposed human stratum corneum water domain in chemical absorption.

    Science.gov (United States)

    Zhu, Hanjiang; Jung, Eui-Chang; Hui, Xiaoying; Maibach, Howard

    2016-08-01

    Compounds with varying physical and chemical properties may have different affinities to the stratum corneum (SC) and/or its intercellular lipids, keratin protein, and possible water domains. To better understand the mechanism of percutaneous absorption, we utilized 21 carbon-14 labeled chemicals, with wide hydrophilicity (log P = -0.05 to 6.17), and quantified their absorption/adsorption properties for a short incubation time (15 min) with regards to intact SC membrane, delipidized SC membrane and SC lipid. A facile method was developed for SC/lipid absorption, providing a more equivalent procedure and comparable data. SC lipid absorption of chemical solutes positively correlated with the octanol/water partition coefficient (log P). Differences between the percent dose of chemical absorption to intact SC and the total percent dose contributed by the protein and lipid domains suggest the possibility and significance of a water domain. Absorption rate experiments showed a longer lag time for intact SC than for delipidized SC or SC lipid, suggesting that the water domain may delay chemical binding to protein and lipid domains, and may be a factor in the resistance of many chemicals to current decontamination methods. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26206725

  3. A Role for Lipid Shells in Targeting Proteins to Caveolae, Rafts, and Other Lipid Domains

    Science.gov (United States)

    Anderson, Richard G. W.; Jacobson, Ken

    2002-06-01

    The surface membrane of cells is studded with morphologically distinct regions, or domains, like microvilli, cell-cell junctions, and coated pits. Each of these domains is specialized for a particular function, such as nutrient absorption, cell-cell communication, and endocytosis. Lipid domains, which include caveolae and rafts, are one of the least understood membrane domains. These domains are high in cholesterol and sphingolipids, have a light buoyant density, and function in both endocytosis and cell signaling. A major mystery, however, is how resident molecules are targeted to lipid domains. Here, we propose that the molecular address for proteins targeted to lipid domains is a lipid shell.

  4. Lipid metabolism in experimental animals

    Directory of Open Access Journals (Sweden)

    Sánchez-Muñiz, Francisco J.

    1998-08-01

    Full Text Available Publications are scarce in the way in chich metabolic processes are affected by the ingestion of heated fats used to prepare food. Similarly studies measuring metabolic effects of the consumption on fried food are poorly known. The purpose of this presentation is to summarize information on frying fats and frying foods upon lipid metabolism in experimental animals. Food consumption is equivalent or even higher when oils or the fat content of frying foods are poorly alterated decreasing their acceptability when their alteration degree increase. After 4hr. experiment the digestibility and absorption coefficients of a single dosis of thermooxidized oils were significantly decreased in rats, however the digestive utilization of frying thermooxidized oils included in diets showed very little change in comparison with unused oils by feeding trials on rats. Feeding rats different frying fats induced a slight hypercholesterolemic effect being the magnitude of this effect related to the linoleic decrease in diet produced by frying. However HDL, the main rat-cholesterol carrier, also increased, thus the serum cholesterol/HDL-cholesterol ratio did not change. Results suggest that rats fed frying fats adapt their lipoprotein metabolism increasing the number of HDL particles. Deep fat frying deeply changed the fatty acid composition of foods, being possible to increase their n-9 or n-6 fatty acid and to decrease the saturated fatty acid contents by frying. When olive oil-and sunflower oil-fried sardines were used as the only protein and fat sources of rats-diets in order to prevent the dietary hypercholesterolemia it was provided that both fried-sardine diets showed a powerful check effect on the cholesterol raising effect induced by dietary cholesterol. The negative effect of feeding rats cholesterol plus bovine bile to induce hypercholesterolemia on some cell-damage markers such as lactate dehydrogenase, transaminases, alkaline phosphatase, was

  5. Biological effects of 2-oxoglutarate with particular emphasis on the regulation of protein, mineral and lipid absorption/metabolism, muscle performance, kidney function, bone formation and cancerogenesis, all viewed from a healthy ageing perspective state of the art

    DEFF Research Database (Denmark)

    Harrison, Adrian Paul; Pierzynowski, S.G.

    2008-01-01

    's performance and quality of life. Indeed, such changes can be contributory to a loss of independence in the elderly. This state- of-the art address highlights the main changes found to occur with ageing whilst simultaneously reporting findings of in vivo and in vitro studies designed to elucidate the potential...... intermediates in the debilitating changes that occur with end-stage renal failure and the regulation of the lipid metabolism. Finally, focus will be given to the role of 2-oxoglutarate as a potent protective factor in connection with the development of malignant cells in the body....

  6. Maldigestion and malabsorption of dietary lipid during severe childhood malnutrition

    OpenAIRE

    Murphy, J.; Badaloo, A; Chambers, B; Forrester, T; Wootton, S.; A. Jackson

    2002-01-01

    Background: Diets rich in lipid are used to provide energy density in treating children with severe malnutrition, but the extent to which their digestion and absorption can cope with the load effectively is uncertain.

  7. Dietary Salba (Salvia hispanica L) seed rich in α-linolenic acid improves adipose tissue dysfunction and the altered skeletal muscle glucose and lipid metabolism in dyslipidemic insulin-resistant rats.

    Science.gov (United States)

    Oliva, M E; Ferreira, M R; Chicco, A; Lombardo, Y B

    2013-10-01

    This work reports the effect of dietary Salba (chia) seed rich in n-3 α-linolenic acid on the morphological and metabolic aspects involved in adipose tissue dysfunction and the mechanisms underlying the impaired glucose and lipid metabolism in the skeletal muscle of rats fed a sucrose-rich diet (SRD). Rats were fed a SRD for 3 months. Thereafter, half the rats continued with SRD while in the other half, corn oil (CO) was replaced by chia seed for 3 months (SRD+chia). In control group, corn starch replaced sucrose. The replacement of CO by chia seed in the SRD reduced adipocyte hypertrophy, cell volume and size distribution, improved lipogenic enzyme activities, lipolysis and the anti-lipolytic action of insulin. In the skeletal muscle lipid storage, glucose phosphorylation and oxidation were normalized. Chia seed reversed the impaired insulin stimulated glycogen synthase activity, glycogen, glucose-6-phosphate and GLUT-4 protein levels as well as insulin resistance and dyslipidemia.

  8. Plasma Lipoproteins as Mediators of the Oxidative Stress Induced by UV Light in Human Skin: A Review of Biochemical and Biophysical Studies on Mechanisms of Apolipoprotein Alteration, Lipid Peroxidation, and Associated Skin Cell Responses

    Directory of Open Access Journals (Sweden)

    Paulo Filipe

    2013-01-01

    Full Text Available There are numerous studies concerning the effect of UVB light on skin cells but fewer on other skin components such as the interstitial fluid. This review highlights high-density lipoprotein (HDL and low-density lipoprotein (LDL as important targets of UVB in interstitial fluid. Tryptophan residues are the sole apolipoprotein residues absorbing solar UVB. The UVB-induced one-electron oxidation of Trp produces •Trp and O2•- radicals which trigger lipid peroxidation. Immunoblots from buffered solutions or suction blister fluid reveal that propagation of photooxidative damage to other residues such as Tyr or disulfide bonds produces intra- and intermolecular bonds in apolipoproteins A-I, A-II, and B100. Partial repair of phenoxyl tyrosyl radicals (TyrO• by α-tocopherol is observed with LDL and HDL on millisecond or second time scales, whereas limited repair of α-tocopherol by carotenoids occurs in only HDL. More effective repair of Tyr and α-tocopherol is observed with the flavonoid, quercetin, bound to serum albumin, but quercetin is less potent than new synthetic polyphenols in inhibiting LDL lipid peroxidation or restoring α-tocopherol. The systemic consequences of HDL and LDL oxidation and the activation and/or inhibition of signalling pathways by oxidized LDL and their ability to enhance transcription factor DNA binding activity are also reviewed.

  9. Perfil lipídico e composição corporal na deficiência do hormônio de crescimento em adultos Lipid profile and alteration of body composition in growth hormone deficient adults

    Directory of Open Access Journals (Sweden)

    Priscila M. Lobo

    2005-10-01

    Full Text Available OBJETIVO: A síndrome da deficiência de hormônio de crescimento (DGH no adulto e o conseqüente aumento no risco cardiovascular têm sido bastante estudados nos últimos anos. De grande relevância clínica são as alterações na composição corporal com aumento do tecido adiposo visceral e perfil lipídico adverso. MÉTODOS: Estudou-se o perfil lipídico e o tecido adiposo visceral de 31 adultos com DGH comparado com um grupo controle de indivíduos saudáveis pareados por idade, sexo e índice de massa corporal (IMC. A avaliação da gordura visceral foi feita por tomografia computadorizada de abdome e por medidas antropométricas, através do IMC (Kg/m² e da medida da cintura (cm. A avaliação do perfil lipídico foi obtida através de dosagens laboratoriais de colesterol (CT, triglicerídeos (TG, HDL, LDL, apolipoproteínas A e B e lipoproteína (a. RESULTADOS: Foi observado aumento do tecido adiposo visceral nos pacientes DGH (156,66 ± 72,72 vs. 113,51 ± 32,97 cm²; p-valor = 0,049, além de aumento nos níveis de TG (158,80 ± 80,29 vs. 97,17 ± 12,37 mg/dl; p-valor = 0,007 e diminuição nos níveis de HDL (45,41 ± 13,30 vs. 55,34 ± 14,31 mg/dl; p-valor = 0,002. Não houve diferença entre os demais parâmetros do perfil lipídico e nas medidas antropométricas. CONCLUSÃO: Adultos deficientes de GH apresentam aumento da adiposidade visceral e aumento das concentrações de TG com diminuição das concentrações de HDL.BACKGROUND: The growth hormone deficiency (GHD syndrome in adults and the increased associated cardiovascular risk have been extensively studied in recent years. Abnormal body composition with excess of visceral adiposity and adverse lipid profile are important features of this syndrome. Abnormal lipid profile has been described with increased levels of total cholesterol (C, LDL-cholesterol (LDL-C, triglycerides, decreased levels of HDL-cholesterol (HDL-C and apolipoproteins abnormalities. METHODS: Lipid profile

  10. Lipid-based formulations for oral administration of poorly water-soluble drugs

    DEFF Research Database (Denmark)

    Mu, Huiling; Holm, René; Müllertz, Anette

    2013-01-01

    Lipid-based drug delivery systems have shown great potentials in oral delivery of poorly water-soluble drugs, primarily for lipophilic drugs, with several successfully marketed products. Pre-dissolving drugs in lipids, surfactants, or mixtures of lipids and surfactants omits the dissolving....../dissolution step, which is a potential rate limiting factor for oral absorption of poorly water-soluble drugs. Lipids not only vary in structures and physiochemical properties, but also in their digestibility and absorption pathway; therefore selection of lipid excipients and dosage form has a pronounced effect...

  11. Lipid nanoparticle interactions and assemblies

    Science.gov (United States)

    Preiss, Matthew Ryan

    oxide nanoparticles encapsulated in the lipid bilayer, the local temperature and membrane fluidity could be observed. DLNAs were encapsulated with different sized nanoparticles and concentrations in order to observe the effect of the bilayer nanoparticles on the lipid bilayer's phase behavior and leakage. Two different sized nanoparticles were used, a 2 nm gold nanoparticle (GNP) much smaller than the thickness of the bilayer and a 4 nm GNP near the thickness of the lipid bilayer. The 2 nm GNPs were shown to affect the lipid bilayer differently than the 4 nm GNP. Specifically, the two nanoparticles altered the phase behavior and leakage differently in a temperature dependent fashion, demonstrating that embedded nanoparticle size can be used induce or inhibit bilayer leakage. A dual solvent exchange method was used to control the lipid surface composition of an iron oxide nanoparticle with a cationic lipid and a polyethylene glycol (PEG) lipid to produce lipid coated magnetic nanoparticles (LMNPs). PEG is well known for its ability to enhance the pharmacokinetics of nanostructures by preventing uptake by the immune system. By controlling the lipid surface composition, the surface charge and PEG conformation can be controlled which allowed the LMNPs to be used as an MRI contrast agent and a delivery system for siRNA that could be triggered with temperature.

  12. Synthesis and characterization of betaine-like diacyl lipids: zwitterionic lipids with the cationic amine at the bilayer interface.

    Science.gov (United States)

    Kohli, Aditya G; Walsh, Colin L; Szoka, Francis C

    2012-02-01

    We synthesized and characterized a series of zwitterionic, acetate-terminated, quaternized amine diacyl lipids (AQ). These lipids have an inverted headgroup orientation as compared to naturally occurring phosphatidylcholine (PC) lipids; the cationic group is anchored at the membrane interface, while the anionic group extends into the aqueous phase. AQ lipids preferentially interact with highly polarizable anions (ClO(4)(-)) over less polarizable ions (Cl(-)), in accord with the Hofmeister series, as measured by the change in zeta potential of AQ liposomes. Conversely, AQ lipids have a weaker association with calcium than do PC lipids. The transition temperatures (Tm) of the AQ lipids are similar to the Tm observed with phosphatidylethanolamine (PE) lipids of the same chain length. AQ lipids form large lipid sheets after heating and sonication; however, in the presence of cholesterol (Chol), these lipids form stable liposomes that encapsulate carboxyfluorescein. The AQ:Chol liposomes retain their contents in the presence of serum at 37°C, and when injected intravenously into mice, their organ biodistribution is similar to that observed with PC:Chol liposomes. AQ lipids demonstrate that modulating the headgroup charge orientation significantly alters the biophysical properties of liposomes. For the drug carrier field, these new materials provide a non-phosphate containing zwitterlipid for the production of lipid vesicles. PMID:22301334

  13. Lipid partitioning during cardiac stress.

    Science.gov (United States)

    Kolwicz, Stephen C

    2016-10-01

    It is well documented that fatty acids serve as the primary fuel substrate for the contracting myocardium. However, extensive research has identified significant changes in the myocardial oxidation of fatty acids during acute or chronic cardiac stress. As a result, the redistribution or partitioning of fatty acids due to metabolic derangements could have biological implications. Fatty acids can be stored as triacylglycerols, serve as critical components for biosynthesis of phospholipid membranes, and form the potent signaling molecules, diacylglycerol and ceramides. Therefore, the contribution of lipid metabolism to health and disease is more intricate than a balance of uptake and oxidation. In this review, the available data regarding alterations that occur in endogenous cardiac lipid pathways during the pathological stressors of ischemia-reperfusion and pathological hypertrophy/heart failure are highlighted. In addition, changes in endogenous lipids observed in exercise training models are presented for comparison. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:27040509

  14. Rac1 participates in thermally induced alterations of the cytoskeleton, cell morphology and lipid rafts, and regulates the expression of heat shock proteins in B16F10 melanoma cells.

    Directory of Open Access Journals (Sweden)

    Burcin Gungor

    Full Text Available Eukaryotic cells exhibit a characteristic response to hyperthermic treatment, involving morphological and cytoskeletal alterations and the induction of heat shock protein synthesis. Small GTPases of the Ras superfamily are known to serve as molecular switches which mediate responses to extracellular stimuli. We addressed here how small GTPase Rac1 integrates signals from heat stress and simultaneously induces various cellular changes in mammalian cells. As evidence that Rac1 is implicated in the heat shock response, we first demonstrated that both mild (41.5°C and severe (43°C heat shock induced membrane translocation of Rac1. Following inhibition of the activation or palmitoylation of Rac1, the size of its plasma membrane-bound pool was significantly decreased while the heat shock-induced alterations in the cytoskeleton and cell morphology were prevented. We earlier documented that the size distribution pattern of cholesterol-rich rafts is temperature dependent and hypothesized that this is coupled to the triggering mechanism of stress sensing and signaling. Interestingly, when plasma membrane localization of Rac1 was inhibited, a different and temperature independent average domain size was detected. In addition, inhibition of the activation or palmitoylation of Rac1 resulted in a strongly decreased expression of the genes of major heat shock proteins hsp25 and hsp70 under both mild and severe heat stress conditions.

  15. Conversion of α-linolenic acid to long-chain omega-3 fatty acid derivatives and alterations of HDL density subfractions and plasma lipids with dietary polyunsaturated fatty acids in Monk parrots (Myiopsitta monachus).

    Science.gov (United States)

    Petzinger, C; Larner, C; Heatley, J J; Bailey, C A; MacFarlane, R D; Bauer, J E

    2014-04-01

    The effect of α-linolenic acid from a flaxseed (FLX)-enriched diet on plasma lipid and fatty acid metabolism and possible atherosclerosis risk factors was studied in Monk parrots (Myiopsitta monachus). Twenty-four Monk parrots were randomly assigned to diets containing either 10% ground SUNs or 10% ground FLXs. Feed intake was calculated daily. Blood samples, body condition scores and body weights were obtained at -5 weeks, day 0, 7, 14, 28, 42 and 70. Plasma samples were analysed for total cholesterol, free cholesterol, triacylglycerols and lipoproteins. Phospholipid subfraction fatty acid profiles were determined. By day 70, the FLX group had significantly higher plasma phospholipid fatty acids including 18:3n-3 (α-linolenic acid), 20:5n-3 (eicosapentaenoic acid) and 22:6n-3 (docosahexaenoic acid). The sunflower group had significantly higher plasma phospholipid levels of 20:4n-6 (arachidonic acid). By day 70, the high-density lipoprotein (HDL) peak shifted resulting in significantly different HDL peak densities between the two experimental groups (1.097 g/ml FLX group and 1.095 g/ml SUN group, p = 0.028). The plasma fatty acid results indicate that Monk parrots can readily convert α-linolenic acid to the long-chain omega-3 derivatives including docosahexaenoic acid and reduce 20:4n-6 accumulation in plasma phospholipids. The reason for a shift in the HDL peak density is unknown at this time.

  16. Edelfosine and miltefosine effects on lipid raft properties: membrane biophysics in cell death by antitumor lipids.

    Science.gov (United States)

    Castro, Bruno M; Fedorov, Aleksander; Hornillos, Valentin; Delgado, Javier; Acuña, A Ulises; Mollinedo, Faustino; Prieto, Manuel

    2013-07-01

    Edelfosine (1-O-octadecyl-2-O-methyl-sn-glycero-phosphocholine) and miltefosine (hexadecylphosphocholine) are synthetic alkylphospholipids (ALPs) that are reported to selectively accumulate in tumor cell membranes, inducing Fas clustering and activation on lipid rafts, triggering apoptosis. However, the exact mechanism by which these lipids elicit these events is still not fully understood. Recent studies propose that their mode of action might be related with alterations of lipid rafts biophysical properties caused by these lipid drugs. To achieve a clear understanding of this mechanism, we studied the effects of pharmacologically relevant amounts of edelfosine and miltefosine in the properties of model and cellular membranes. The influence of these molecules on membrane order, lateral organization, and lipid rafts molar fraction and size were studied by steady-state and time-resolved fluorescence methods, Förster resonance energy transfer (FRET), confocal and fluorescence lifetime imaging microscopy (FLIM). We found that the global membrane and lipid rafts biophysical properties of both model and cellular membranes were not significantly affected by both the ALPs. Nonetheless, in model membranes, a mild increase in membrane fluidity induced by both alkyl lipids was detected, although this effect was more noticeable for edelfosine than miltefosine. This absence of drastic alterations shows for the first time that ALPs mode of action is unlikely to be directly linked to alterations of lipid rafts biophysical properties caused by these drugs. The biological implications of this result are discussed in the context of ALPs effects on lipid metabolism, mitochondria homeostasis modulation, and their relationship with tumor cell death.

  17. Oxidized lipids and lipid-mediators are involved in cardiovascular injury induced by diesel exhaust particles and ozone

    Science.gov (United States)

    The mechanisms by which air pollutants induce cardiac and vascular injuries are unknown. We hypothesized that these injuries involve alterations in'aortic membrane lipids and lipid-mediators. We exposed male Wistar Kyoto rats (12-15 wk old), nose-only to air, ozone (03; 0.5 ppm),...

  18. Assessing the nature of lipid raft membranes

    DEFF Research Database (Denmark)

    Niemelä, Perttu S; Ollila, Samuli; Hyvönen, Marja T;

    2007-01-01

    evidence that the presence of PSM and CHOL in raft-like membranes leads to strongly packed and rigid bilayers. We also find that the simulated raft bilayers are characterized by nanoscale lateral heterogeneity, though the slow lateral diffusion renders the interpretation of the observed lateral...... heterogeneity more difficult. The findings reveal aspects of the role of favored (specific) lipid-lipid interactions within rafts and clarify the prominent role of CHOL in altering the properties of the membrane locally in its neighborhood. Also, we show that the presence of PSM and CHOL in rafts leads...... to intriguing lateral pressure profiles that are distinctly different from corresponding profiles in nonraft-like membranes. The results propose that the functioning of certain classes of membrane proteins is regulated by changes in the lateral pressure profile, which can be altered by a change in lipid content....

  19. Improved characterization of EV preparations based on protein to lipid ratio and lipid properties.

    Directory of Open Access Journals (Sweden)

    Xabier Osteikoetxea

    Full Text Available In recent years the study of extracellular vesicles has gathered much scientific and clinical interest. As the field is expanding, it is becoming clear that better methods for characterization and quantification of extracellular vesicles as well as better standards to compare studies are warranted. The goal of the present work was to find improved parameters to characterize extracellular vesicle preparations. Here we introduce a simple 96 well plate-based total lipid assay for determination of lipid content and protein to lipid ratios of extracellular vesicle preparations from various myeloid and lymphoid cell lines as well as blood plasma. These preparations included apoptotic bodies, microvesicles/microparticles, and exosomes isolated by size-based fractionation. We also investigated lipid bilayer order of extracellular vesicle subpopulations using Di-4-ANEPPDHQ lipid probe, and lipid composition using affinity reagents to clustered cholesterol (monoclonal anti-cholesterol antibody and ganglioside GM1 (cholera toxin subunit B. We have consistently found different protein to lipid ratios characteristic for the investigated extracellular vesicle subpopulations which were substantially altered in the case of vesicular damage or protein contamination. Spectral ratiometric imaging and flow cytometric analysis also revealed marked differences between the various vesicle populations in their lipid order and their clustered membrane cholesterol and GM1 content. Our study introduces for the first time a simple and readily available lipid assay to complement the widely used protein assays in order to better characterize extracellular vesicle preparations. Besides differentiating extracellular vesicle subpopulations, the novel parameters introduced in this work (protein to lipid ratio, lipid bilayer order, and lipid composition, may prove useful for quality control of extracellular vesicle related basic and clinical studies.

  20. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people

    Directory of Open Access Journals (Sweden)

    DiSilvestro Robert A

    2012-09-01

    Full Text Available Abstract Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old with a low dose of curcumin (80 mg/day in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19 or placebo (N = 19 for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.

  1. Data supporting beta-amyloid dimer structural transitions and protein–lipid interactions on asymmetric lipid bilayer surfaces using MD simulations on experimentally derived NMR protein structures

    Directory of Open Access Journals (Sweden)

    Sara Y. Cheng

    2016-06-01

    Full Text Available This data article supports the research article entitled “Maximally Asymmetric Transbilayer Distribution of Anionic Lipids Alters the Structure and interaction with Lipids of an Amyloidogenic Protein Dimer Bound to the Membrane Surface” [1]. We describe supporting data on the binding kinetics, time evolution of secondary structure, and residue-contact maps of a surface-absorbed beta-amyloid dimer protein on different membrane surfaces. We further demonstrate the sorting of annular and non-annular regions of the protein/lipid bilayer simulation systems, and the correlation of lipid-number mismatch and surface area per lipid mismatch of asymmetric lipid membranes.

  2. Data supporting beta-amyloid dimer structural transitions and protein–lipid interactions on asymmetric lipid bilayer surfaces using MD simulations on experimentally derived NMR protein structures

    Science.gov (United States)

    Cheng, Sara Y.; Chou, George; Buie, Creighton; Vaughn, Mark W.; Compton, Campbell; Cheng, Kwan H.

    2016-01-01

    This data article supports the research article entitled “Maximally Asymmetric Transbilayer Distribution of Anionic Lipids Alters the Structure and interaction with Lipids of an Amyloidogenic Protein Dimer Bound to the Membrane Surface” [1]. We describe supporting data on the binding kinetics, time evolution of secondary structure, and residue-contact maps of a surface-absorbed beta-amyloid dimer protein on different membrane surfaces. We further demonstrate the sorting of annular and non-annular regions of the protein/lipid bilayer simulation systems, and the correlation of lipid-number mismatch and surface area per lipid mismatch of asymmetric lipid membranes. PMID:27054174

  3. Lipid peroxidation and water penetration in lipid bilayers

    DEFF Research Database (Denmark)

    Conte, Elena; Megli, Francesco Maria; Khandelia, Himanshu;

    2012-01-01

    Lipid peroxidation plays a key role in the alteration of cell membrane's properties. Here we used as model systems multilamellar vesicles (MLVs) made of the first two products in the oxidative cascade of linoleoyl lecithin, namely 1-palmitoyl-2-(13-hydroperoxy-9,11-octadecanedienoyl)-lecithin (Hp......(zz) parameters revealed that OHPLPC, but mostly HpPLPC, induced a measurable increase in polarity and H-bonding propensity in the central region of the bilayer. Molecular dynamics simulation performed on 16-DSA in the PLPC-HpPLPC bilayer revealed that water molecules are statistically favored with respect to the...... hydroperoxide groups to interact with the nitroxide at the methyl-terminal, confirming that the H-bonds experimentally observed are due to increased water penetration in the bilayer. The EPR and MD data on model membranes demonstrate that cell membrane damage by oxidative stress cause alteration of water...

  4. Irinotecan Lipid Complex Injection

    Science.gov (United States)

    Irinotecan lipid complex is used in combination with other medications to treat pancreatic cancer that has spread to other ... worsened after treatment with other chemotherapy medications. Irinotecan lipid complex is in a class of antineoplastic medications ...

  5. Doxorubicin Lipid Complex Injection

    Science.gov (United States)

    Doxorubicin lipid complex is used to treat ovarian cancer that has not improved or that has worsened after treatment with other medications. Doxorubicin lipid complex is also used to treat Kaposi's sarcoma ( ...

  6. Vincristine Lipid Complex Injection

    Science.gov (United States)

    Vincristine lipid complex is used to treat a certain type of acute lymphoblastic leukemia (ALL; a type of cancer ... least two different treatments with other medications. Vincristine lipid complex is in a class of medications called ...

  7. Combined Insulin Deficiency and Endotoxin Exposure Stimulate Lipid Mobilization and Alter Adipose Tissue Signaling in an Experimental Model of Ketoacidosis in Subjects With Type 1 Diabetes: A Randomized Controlled Crossover Trial.

    Science.gov (United States)

    Svart, Mads; Kampmann, Ulla; Voss, Thomas; Pedersen, Steen B; Johannsen, Mogens; Rittig, Nikolaj; Poulsen, Per L; Nielsen, Thomas S; Jessen, Niels; Møller, Niels

    2016-05-01

    Most often, diabetic ketoacidosis (DKA) in adults results from insufficient insulin administration and acute infection. DKA is assumed to release proinflammatory cytokines and stress hormones that stimulate lipolysis and ketogenesis. We tested whether this perception of DKA can be reproduced in an experimental human model by using combined insulin deficiency and acute inflammation and tested which intracellular mediators of lipolysis are affected in adipose tissue. Nine subjects with type 1 diabetes were studied twice: 1) insulin-controlled euglycemia and 2) insulin deprivation and endotoxin administration (KET). During KET, serum tumor necrosis factor-α, cortisol, glucagon, and growth hormone levels increased, and free fatty acids and 3-hydroxybutyrate concentrations and the rate of lipolysis rose markedly. Serum bicarbonate and pH decreased. Adipose tissue mRNA contents of comparative gene identification-58 (CGI-58) increased and G0/G1 switch 2 gene (G0S2) mRNA decreased robustly. Neither protein levels of adipose triglyceride lipase (ATGL) nor phosphorylations of hormone-sensitive lipase were altered. The clinical picture of incipient DKA in adults can be reproduced by combined insulin deficiency and endotoxin-induced acute inflammation. The precipitating steps involve the release of proinflammatory cytokines and stress hormones, increased lipolysis, and decreased G0S2 and increased CGI-58 mRNA contents in adipose tissue, compatible with latent ATGL stimulation. PMID:26884439

  8. Monstrous Mycobacterial Lipids.

    Science.gov (United States)

    Seeliger, Jessica; Moody, D Branch

    2016-02-18

    When it comes to lipid diversity, no bacterial genus approaches Mycobacterium. In this issue of Cell Chemical Biology, Burbaud et al. (2016) provide a multi-genic working model for the biosynthesis of trehalose polyphleate (TPP), one of the largest known lipids in mycobacteria. They demonstrate that this lipid is made by diverse mycobacterial species, including those of medical importance. PMID:26971870

  9. Smectite alteration

    International Nuclear Information System (INIS)

    This report contains the proceedings of a second workshop in Washington DC December 8-9, 1983 on the alteration of smectites intended for use as buffer materials in the long-term containment of nuclear wastes. It includes extended summaries of all presentations and a transcript of the detailed scientific discussion. The discussions centered on three main questions: What is the prerequisite for and what is the precise mechanism by which smectite clays may be altered to illite. What are likly sources of potassium with respect to the KBS project. Is it likely that the conversion of smectite to illite will be of importance in the 10 5 to the 10 6 year time frame. The workshop was convened to review considerations and conclusions in connection to these questions and also to broaden the discussion to consider the use of smectite clays as buffer materials for similar applications in different geographical and geological settings. SKBF/KBS technical report 83-03 contains the proceedings from the first workshop on these matters that was held at the State University of New York, Buffalo May 26-27, 1982. (Author)

  10. Lipid raft: A floating island of death or survival

    Energy Technology Data Exchange (ETDEWEB)

    George, Kimberly S. [Edison Biotechnology Institute and Department of Chemistry and Biochemistry, Ohio University, Athens, Ohio 45701 (United States); Department of Chemistry, Marietta College, Marietta, OH 45750 (United States); Wu, Shiyong, E-mail: wus1@ohio.edu [Edison Biotechnology Institute and Department of Chemistry and Biochemistry, Ohio University, Athens, Ohio 45701 (United States)

    2012-03-15

    Lipid rafts are microdomains of the plasma membrane enriched in cholesterol and sphingolipids, and play an important role in the initiation of many pharmacological agent-induced signaling pathways and toxicological effects. The structure of lipid rafts is dynamic, resulting in an ever-changing content of both lipids and proteins. Cholesterol, as a major component of lipid rafts, is critical for the formation and configuration of lipid raft microdomains, which provide signaling platforms capable of activating both pro-apoptotic and anti-apoptotic signaling pathways. A change of cholesterol level can result in lipid raft disruption and activate or deactivate raft-associated proteins, such as death receptor proteins, protein kinases, and calcium channels. Several anti-cancer drugs are able to suppress growth and induce apoptosis of tumor cells through alteration of lipid raft contents via disrupting lipid raft integrity. -- Highlights: ► The role of lipid rafts in apoptosis ► The pro- and anti-apoptotic effects of lipid raft disruption ► Cancer treatments targeting lipid rafts.

  11. Effect of polycarbophil on the absorption of nutrients.

    Science.gov (United States)

    Yamada, T; Nagata, O; Tamai, I; Tsuji, A

    1996-05-01

    The effects of polycarbophil on the absorption of various nutrients were evaluated by several in situ methods. Polycarbophil reduced the absorption of 3-O-methyl-D-glucose (3-OMG) and L-phenylalanine in the in situ loop and the in situ perfusion methods, but it did not affect the absorption of these nutrients in an open system, the in situ modified loop method, which is closer to physiological conditions. It also did not affect the absorption of vitamin A or phosphatidylcholine-L-alpha-dipalmitoyl in the latter system. These results indicate that the absorption of nutrients is probably not altered by polycarbophil under physiological conditions.

  12. On the absorption of alendronate in rats.

    Science.gov (United States)

    Lin, J H; Chen, I W; deLuna, F A

    1994-12-01

    Alendronate is an antiosteolytic agent under investigation for the treatment of a number of bone disorders. Since the compound is a zwitterion with five pKa values and is completely ionized in the intestine at the physiological pH, absorption is poor; less than 1% of an oral dose is available systemically in rats. In the present studies, absorption was found to be predominantly in the upper part of the small intestine. Administration of buffered solutions of alendronate (pH 2-11) did not improve absorption. Whereas food markedly impaired the absorption of alendronate, EDTA enhanced absorption in a dose-dependent manner. Pretreatment of rats with ulcerogenic agents, mepirizole, acetylsalicylic acid, or indomethacin, resulted in a 3-7-fold increase in the oral absorption of alendronate. The absorption of phenol red, added as an indicator of intestinal tissue damage, was also increased in rats with experimental peptic ulcers. The enhanced absorption of alendronate observed in rats with experimental peptic ulcers was attributed to the alteration of the integrity of the intestinal membrane. PMID:7891304

  13. Nutrients and neurodevelopment: lipids.

    Science.gov (United States)

    González, Horacio F; Visentin, Silvana

    2016-10-01

    Nutrients, lipids in particular, make up the central nervous system structure and play major functional roles: they stimulate development, migration, and nerve cell differentiation. They are part of gray matter, white matter, nerve nuclei, and synaptogenesis. Breast milk contains lipids which are crucial for infant brain development. The lipid profile of breast milk was used as a guideline for the development of breast milk substitutes. However, to date, no substitute has matched it. Complementary feeding should include docosahexaenoic acid, arachidonic acid, other polyunsaturated fatty acids, saturated fatty acids, and complex lipids found in milk fat. The lipid composition of breast milk depends on maternal intake and nutritional status during pregnancy and breast-feeding. It has a great impact on development. Our goal is to review scientific literature regarding the role of lipids on infant brain development and the importance of breast milk lipid composition, maternal diet, and complementary feeding. PMID:27606648

  14. Lipid exchange by ultracentrifugation

    DEFF Research Database (Denmark)

    Drachmann, Nikolaj Düring; Olesen, Claus

    2014-01-01

    Lipids play an important role in maintaining P-type ATPase structure and function, and often they are crucial for ATPase activity. When the P-type ATPases are in the membrane, they are surrounded by a mix of different lipids species with varying aliphatic chain lengths and saturation......, and the complex interplay between the lipids and the P-type ATPases are still not well understood. We here describe a robust method to exchange the majority of the lipids surrounding the ATPase after solubilisation and/or purification with a target lipid of interest. The method is based on an ultracentrifugation...... step, where the protein sample is spun through a dense buffer containing large excess of the target lipid, which results in an approximately 80-85 % lipid exchange. The method is a very gently technique that maintains protein folding during the process, hence allowing further characterization...

  15. Lipid Vesicles for the Skin Delivery of Diclofenac: Cerosomes vs. Other Lipid Suspensions

    Directory of Open Access Journals (Sweden)

    Anahita Fathi-Azarbayjani

    2015-03-01

    Full Text Available Purpose: Lipid suspensions as drug carriers, including conventional liposomes, ethosomes, transferosomes, proniosomes, niosomes, PEG-PPG-PEG niosomes and stratum corneum liposomes (cerosomes, were formulated and compared. Methods: Lipid vesicles were formulated and assessed with regards to enhancement of skin permeation of diclofenac and stability profiles of the formulations. Formulation-induced changes of the biophysical structure of excised human skin were monitored using the Fourier transform infrared spectroscopy. Results: The stability profiles of these suspensions over 12 weeks did not show any significant drug leakage from the vesicles of interest (p > 0.05. FTIR observations indicated that the vesicles increased stratum corneum (SC lipid fluidization and altered protein conformation. Skin permeability experiments showed that the free unencapsulated drug in the cerosomal formulations caused significant increase in drug permeation across the skin (p < 0.01. Low skin permeability of drug from the other lipid suspensions could be due to the entrapment of diclofenac within these vesicles which decreased the solubility of the hydrophilic drug in the skin lipids and the partition coefficient of the drug from these vesicles into the SC. Conclusion: Optimal drug entrapment in vesicles or alteration of the skin structure may not necessarily enhance the permeation of hydrophilic drugs across the human skin. These lipid vesicles may be further developed into carriers of both hydrophilic and hydrophobic drugs for topical and transdermal delivery, respectively.

  16. Lipid Vesicles for the Skin Delivery of Diclofenac: Cerosomes vs. Other Lipid Suspensions

    Science.gov (United States)

    Fathi-Azarbayjani, Anahita; Ng, Kai Xin; Chan, Yew Weng; Chan, Sui Yung

    2015-01-01

    Purpose: Lipid suspensions as drug carriers, including conventional liposomes, ethosomes, transferosomes, proniosomes, niosomes, PEG-PPG-PEG niosomes and stratum corneum liposomes (cerosomes), were formulated and compared. Methods: Lipid vesicles were formulated and assessed with regards to enhancement of skin permeation of diclofenac and stability profiles of the formulations. Formulation-induced changes of the biophysical structure of excised human skin were monitored using the Fourier transform infrared spectroscopy. Results: The stability profiles of these suspensions over 12 weeks did not show any significant drug leakage from the vesicles of interest (p > 0.05). FTIR observations indicated that the vesicles increased stratum corneum (SC) lipid fluidization and altered protein conformation. Skin permeability experiments showed that the free unencapsulated drug in the cerosomal formulations caused significant increase in drug permeation across the skin (p < 0.01). Low skin permeability of drug from the other lipid suspensions could be due to the entrapment of diclofenac within these vesicles which decreased the solubility of the hydrophilic drug in the skin lipids and the partition coefficient of the drug from these vesicles into the SC. Conclusion: Optimal drug entrapment in vesicles or alteration of the skin structure may not necessarily enhance the permeation of hydrophilic drugs across the human skin. These lipid vesicles may be further developed into carriers of both hydrophilic and hydrophobic drugs for topical and transdermal delivery, respectively. PMID:25789216

  17. D-xylose absorption

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003606.htm D-xylose absorption To use the sharing features on this page, please enable JavaScript. D-xylose absorption is a laboratory test to determine ...

  18. Estimation of alga growth stage and lipid content growth rate

    Science.gov (United States)

    Embaye, Tsegereda N. (Inventor); Trent, Jonathan D. (Inventor)

    2012-01-01

    Method and system for estimating a growth stage of an alga in an ambient fluid. Measured light beam absorption or reflection values through or from the alga and through an ambient fluid, in each of two or more wavelength sub-ranges, are compared with reference light beam absorption values for corresponding wavelength sub-ranges for in each alga growth stage to determine (1) which alga growth stage, if any, is more likely and (2) whether estimated lipid content of the alga is increasing or has peaked. Alga growth is preferably terminated when lipid content has approximately reached a maximum value.

  19. Effects of dietary plant meal and soya-saponin supplementation on intestinal and hepatic lipid droplet accumulation and lipoprotein and sterol metabolism in Atlantic salmon (Salmo salar L.).

    Science.gov (United States)

    Gu, Min; Kortner, Trond M; Penn, Michael; Hansen, Anne Kristine; Krogdahl, Åshild

    2014-02-01

    Altered lipid metabolism has been shown in fish fed plant protein sources. The present study aimed to gain further insights into how intestinal and hepatic lipid absorption and metabolism are modulated by plant meal (PM) and soya-saponin (SA) inclusion in salmon feed. Post-smolt Atlantic salmon were fed for 10 weeks one of four diets based on fishmeal or PM, with or without 10 g/kg SA. PM inclusion resulted in decreased growth performance, excessive lipid droplet accumulation in the pyloric caeca and liver, and reduced plasma cholesterol levels. Intestinal and hepatic gene expression profiling revealed an up-regulation of the expression of genes involved in lipid absorption and lipoprotein (LP) synthesis (apo, fatty acid transporters, microsomal TAG transfer protein, acyl-CoA cholesterol acyltransferase, choline kinase and choline-phosphate cytidylyltransferase A), cholesterol synthesis (3-hydroxy-3-methylglutaryl-CoA reductase) and associated transcription factors (sterol regulatory element-binding protein 2 and PPARγ). SA inclusion resulted in reduced body pools of cholesterol and bile salts. The hepatic gene expression of the rate-limiting enzyme in bile acid biosynthesis (cytochrome P450 7A1 (cyp7a1)) as well as the transcription factor liver X receptor and the bile acid transporter abcb11 (ATP-binding cassette B11) was down-regulated by SA inclusion. A significant interaction was observed between PM inclusion and SA inclusion for plasma cholesterol levels. In conclusion, gene expression profiling suggested that the capacity for LP assembly and cholesterol synthesis was up-regulated by PM exposure, probably as a compensatory mechanism for excessive lipid droplet accumulation and reduced plasma cholesterol levels. SA inclusion had hypocholesterolaemic effects on Atlantic salmon, accompanied by decreased bile salt metabolism.

  20. Calcium absorption and achlorhydria

    International Nuclear Information System (INIS)

    Defective absorption of calcium has been thought to exist in patients with achlorhydria. The author compared absorption of calcium in its carbonate form with that in a pH-adjusted citrate form in a group of 11 fasting patients with achlorhydria and in 9 fasting normal subjects. Fractional calcium absorption was measured by a modified double-isotope procedure with 0.25 g of calcium used as the carrier. Mean calcium absorption (+/- S.D.) in the patients with achlorhydria was 0.452 +/- 0.125 for citrate and 0.042 +/- 0.021 for carbonate (P less than 0.0001). Fractional calcium absorption in the normal subjects was 0.243 +/- 0.049 for citrate and 0.225 +/- 0.108 for carbonate (not significant). Absorption of calcium from carbonate in patients with achlorhydria was significantly lower than in the normal subjects and was lower than absorption from citrate in either group; absorption from citrate in those with achlorhydria was significantly higher than in the normal subjects, as well as higher than absorption from carbonate in either group. Administration of calcium carbonate as part of a normal breakfast resulted in completely normal absorption in the achlorhydric subjects. These results indicate that calcium absorption from carbonate is impaired in achlorhydria under fasting conditions. Since achlorhydria is common in older persons, calcium carbonate may not be the ideal dietary supplement

  1. [Review: plant polyphenols modulate lipid metabolism and related molecular mechanism].

    Science.gov (United States)

    Dai, Yan-li; Zou, Yu-xiao; Liu, Fan; Li, Hong-zhi

    2015-11-01

    Lipid metabolism disorder is an important risk factor to obesity, hyperlipidemia and type 2 diabetes as well as other chronic metabolic disease. It is also a key target in preventing metabolic syndrome, chronic disease prevention. Plant polyphenol plays an important role in maintaining or improving lipid profile in a variety of ways. including regulating cholesterol absorption, inhibiting synthesis and secretion of triglyceride, and lowering plasma low density lipoprotein oxidation, etc. The purpose of this article is to review the lipid regulation effects of plant polyphenols and its related mechanisms. PMID:27071245

  2. [Review: plant polyphenols modulate lipid metabolism and related molecular mechanism].

    Science.gov (United States)

    Dai, Yan-li; Zou, Yu-xiao; Liu, Fan; Li, Hong-zhi

    2015-11-01

    Lipid metabolism disorder is an important risk factor to obesity, hyperlipidemia and type 2 diabetes as well as other chronic metabolic disease. It is also a key target in preventing metabolic syndrome, chronic disease prevention. Plant polyphenol plays an important role in maintaining or improving lipid profile in a variety of ways. including regulating cholesterol absorption, inhibiting synthesis and secretion of triglyceride, and lowering plasma low density lipoprotein oxidation, etc. The purpose of this article is to review the lipid regulation effects of plant polyphenols and its related mechanisms.

  3. Interleukin-15 modulates adipose tissue by altering mitochondrial mass and activity.

    Directory of Open Access Journals (Sweden)

    Nicole G Barra

    Full Text Available Interleukin-15 (IL-15 is an immunomodulatory cytokine that affects body mass regulation independent of lymphocytes; however, the underlying mechanism(s involved remains unknown. In an effort to investigate these mechanisms, we performed metabolic cage studies, assessed intestinal bacterial diversity and macronutrient absorption, and examined adipose mitochondrial activity in cultured adipocytes and in lean IL-15 transgenic (IL-15tg, overweight IL-15 deficient (IL-15-/-, and control C57Bl/6 (B6 mice. Here we show that differences in body weight are not the result of differential activity level, food intake, or respiratory exchange ratio. Although intestinal microbiota differences between obese and lean individuals are known to impact macronutrient absorption, differing gut bacteria profiles in these murine strains does not translate to differences in body weight in colonized germ free animals and macronutrient absorption. Due to its contribution to body weight variation, we examined mitochondrial factors and found that IL-15 treatment in cultured adipocytes resulted in increased mitochondrial membrane potential and decreased lipid deposition. Lastly, IL-15tg mice have significantly elevated mitochondrial activity and mass in adipose tissue compared to B6 and IL-15-/- mice. Altogether, these results suggest that IL-15 is involved in adipose tissue regulation and linked to altered mitochondrial function.

  4. Marine lipids and the bioavailability of omega-3 fatty acids

    DEFF Research Database (Denmark)

    Mu, Huiling; Müllertz, Anette

    2015-01-01

    Marine lipids are enriched with omega-3 fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acids are important membrane lipids and have many recognized health benefits, the bioavailability of these fatty acids can therefore be important for achieving...... of omega-3 fatty acids has been reported to be affected by several factors; among the important factors were the digestion and absorption processes of omega-3 containing lipids in the gastrointestinal tract. Both lipid structures and food structures can affect the bioavailability of omega-3 fatty acids....... Human studies have shown that the relative bioavailability of omega-3 fatty acids from fish oil (triglyceride formulation) was similar to that from fish, whereas lower relative bioavailability was observed from fatty acid ethyl ester (FAEE) formulation in comparison with other lipid formulations...

  5. Variability of calcium absorption

    International Nuclear Information System (INIS)

    Variability in calcium absorption was estimated in three groups of normal subjects in whom Ca absorption was measured by standard isotopic-tracer methods at interstudy intervals ranging from 1 to 4 mo. Fifty absorption tests were performed in 22 subjects. Each was done in the morning after an overnight fast with an identical standard breakfast containing a Ca load of approximately 250 mg. Individual fractional absorption values were normalized to permit pooling of the data. The coefficient of variation (CVs) for absorption for the three groups ranged from 10.57 to 12.79% with the size of the CV increasing with interstudy duration. One other published study presenting replicate absorption values was analyzed in a similar fashion and was found to have a CV of absorption of 9.78%. From these data we estimate that when the standard double-isotope method is used to measure Ca absorption there is approximately 10% variability around any given absorption value within an individual human subject and that roughly two-thirds of this represents real biological variability in absorption

  6. Assessing the nature of lipid raft membranes.

    Directory of Open Access Journals (Sweden)

    Perttu S Niemelä

    2007-02-01

    Full Text Available The paradigm of biological membranes has recently gone through a major update. Instead of being fluid and homogeneous, recent studies suggest that membranes are characterized by transient domains with varying fluidity. In particular, a number of experimental studies have revealed the existence of highly ordered lateral domains rich in sphingomyelin and cholesterol (CHOL. These domains, called functional lipid rafts, have been suggested to take part in a variety of dynamic cellular processes such as membrane trafficking, signal transduction, and regulation of the activity of membrane proteins. However, despite the proposed importance of these domains, their properties, and even the precise nature of the lipid phases, have remained open issues mainly because the associated short time and length scales have posed a major challenge to experiments. In this work, we employ extensive atom-scale simulations to elucidate the properties of ternary raft mixtures with CHOL, palmitoylsphingomyelin (PSM, and palmitoyloleoylphosphatidylcholine. We simulate two bilayers of 1,024 lipids for 100 ns in the liquid-ordered phase and one system of the same size in the liquid-disordered phase. The studies provide evidence that the presence of PSM and CHOL in raft-like membranes leads to strongly packed and rigid bilayers. We also find that the simulated raft bilayers are characterized by nanoscale lateral heterogeneity, though the slow lateral diffusion renders the interpretation of the observed lateral heterogeneity more difficult. The findings reveal aspects of the role of favored (specific lipid-lipid interactions within rafts and clarify the prominent role of CHOL in altering the properties of the membrane locally in its neighborhood. Also, we show that the presence of PSM and CHOL in rafts leads to intriguing lateral pressure profiles that are distinctly different from corresponding profiles in nonraft-like membranes. The results propose that the functioning of

  7. Biochemical mechanisms involved in the Omega fatty acids digestion, absorption and metabolism

    OpenAIRE

    Léa Silvia Sant´Ana

    2004-01-01

    Lipids consist of a broad group of compounds that are very different from one another and fatty acids are the substances present in greater quantity. The inadequate ingestion of these substances has an influence on the incidence of various diseases, such as coronary heart disease, some types of cancer, immune diseases and rheumatoid arthritis. In order to understand the role of lipids in the animal body it is necessary to know the food lipid composition, as well the absorption and digestion m...

  8. Polyene-lipids: a new tool to image lipids

    DEFF Research Database (Denmark)

    Kuerschner, Lars; Ejsing, Christer S.; Ekroos, Kim;

    2005-01-01

    Microscopy of lipids in living cells is currently hampered by a lack of adequate fluorescent tags. The most frequently used tags, NBD and BODIPY, strongly influence the properties of lipids, yielding analogs with quite different characteristics. Here, we introduce polyene-lipids containing five c...... mammalian cells. For the first time, ether lipids, important for the function of the brain, were successfully visualized.......Microscopy of lipids in living cells is currently hampered by a lack of adequate fluorescent tags. The most frequently used tags, NBD and BODIPY, strongly influence the properties of lipids, yielding analogs with quite different characteristics. Here, we introduce polyene-lipids containing five...... conjugated double bonds as a new type of lipid tag. Polyene-lipids exhibit a unique structural similarity to natural lipids, which results in minimal effects on the lipid properties. Analyzing membrane phase partitioning, an important biophysical and biological property of lipids, we demonstrated...

  9. A lipid transfer protein that transfers lipid

    OpenAIRE

    Levine, T. P.

    2007-01-01

    Very few lipid transfer proteins (LTPs) have been caught in the act of transferring lipids in vivo from a donor membrane to an acceptor membrane. Now, two studies (Halter, D., S. Neumann, S. M. van Dijk, J. Wolthoorn, A. M. de Maziere, O.V. Vieira, P. Mattjus, J. Klumperman, G. van Meer, and H. Sprong. 2007. J. Cell Biol. 179: 101 115; D'Angelo, G., E. Polishchuk, G. D. Tullio, M. Santoro, A. D. Campli, A. Godi, G. West, J. Bielawski, C.C. Chuang, A. C. van der Spoel, et al. 2007. Nature. 449...

  10. Complex roles of hybrid lipids in the composition, order, and size of lipid membrane domains.

    Science.gov (United States)

    Hassan-Zadeh, Ebrahim; Baykal-Caglar, Eda; Alwarawrah, Mohammad; Huang, Juyang

    2014-02-11

    Hybrid lipids (HL) are phospholipids with one saturated chain and one unsaturated chain. HL are hypothesized to act as linactants (i.e., 2D surfactants) in cell membranes, reducing line tension and creating nanoscopic lipid domains. Here we compare three hybrid lipids of different chain unsaturation (16:0-18:1PC (POPC), 16:0-18:2PC (PLPC), and 16:0-20:4PC (PAPC)) in their abilities to alter the composition, line tension, order, and compactness of lipid domains. We found that the liquid-ordered (Lo) and liquid-disordered (Ld) lipid domains in PAPC/di18:0PC(DSPC)/cholesterol and PLPC/DSPC/cholesterol mixtures are micrometer-sized, and only the POPC/DSPC/cholesterol system has nanoscopic domains. The results indicate that some HLs with polyunsaturated chains are not linactants, and the monounsaturated POPC displays both properties of weak linactants and "Ld-phase" lipids such as di18:1PC (DOPC). The obtained phase boundaries from giant unilamellar vesicles (GUV) show that both POPC and PLPC partition well in the Lo phases. Our MD simulations reveal that these hybrid lipids decrease the order and compactness of Lo domains. Thus, hybrid lipids distinguish themselves from other lipid groups in this combined "partitioning and loosening" ability, which could explain why the Lo domains of GUVs, which often do not contain HL, are more compact than the raft domains in cell membranes. Our line tension measurement and Monte Carlo simulation both show that even the monounsaturated POPC is a weak linactant with only modest ability to occupy domain boundaries and reduce line tension. A more important property of HLs is that they can reduce physical property differences of Lo and Ld bulk domains, which also reduces line tension at domain boundaries.

  11. Lipid Vesicles for the Skin Delivery of Diclofenac: Cerosomes vs. Other Lipid Suspensions

    Science.gov (United States)

    Fathi-Azarbayjani, Anahita; Ng, Kai Xin; Chan, Yew Weng; Chan, Sui Yung

    2015-01-01

    Purpose: Lipid suspensions as drug carriers, including conventional liposomes, ethosomes, transferosomes, proniosomes, niosomes, PEG-PPG-PEG niosomes and stratum corneum liposomes (cerosomes), were formulated and compared. Methods: Lipid vesicles were formulated and assessed with regards to enhancement of skin permeation of diclofenac and stability profiles of the formulations. Formulation-induced changes of the biophysical structure of excised human skin were monitored using the Fourier transform infrared spectroscopy. Results: The stability profiles of these suspensions over 12 weeks did not show any significant drug leakage from the vesicles of interest (p > 0.05). FTIR observations indicated that the vesicles increased stratum corneum (SC) lipid fluidization and altered protein conformation. Skin permeability experiments showed that the free unencapsulated drug in the cerosomal formulations caused significant increase in drug permeation across the skin (p hydrophilic drug in the skin lipids and the partition coefficient of the drug from these vesicles into the SC. Conclusion: Optimal drug entrapment in vesicles or alteration of the skin structure may not necessarily enhance the permeation of hydrophilic drugs across the human skin. These lipid vesicles may be further developed into carriers of both hydrophilic and hydrophobic drugs for topical and transdermal delivery, respectively. PMID:25789216

  12. DEVELOPMENT OF NOVEL LIPID BASED DRUG DELIVERY SYSTEM FOR RALOXIFENE HYDROCHLORIDE

    OpenAIRE

    Vijaykumar Nekkanti; Sandeep Kalepu

    2012-01-01

    Lipid-based delivery systems are becoming increasingly popular as carriers of drugs due to their ability to overcome barriers to oral absorption. The objective of the present study was to prepare novel lipid-based formulation of a sparingly soluble drug, Raloxifene hydrochloride (RLX) to increase its saturation solubility and dissolution velocity for enhancing bioavailability while reducing systemic variability. Lipid-based formulations were prepared using melt solubilization technique. The l...

  13. [Prevalence of obesity and altered lipid profile in university students].

    Science.gov (United States)

    González Sandoval, Claudia Elena; Díaz Burke, Yolanda; Mendizabal-Ruiz, Adriana Patricia; Medina Díaz, Eunice; Morales, José Alejandro

    2014-02-01

    Introducción: La obesidad constituye un grave problema de salud pública por su asociación con los riesgos a desarrollar enfermedades crónicas. La dislipidemia aterogénica que acompaña con frecuencia a la obesidad también está asociada al síndrome metabólico y a las enfermedades cardiovasculares. La transición entre la adolescencia y el adulto es un periodo con modificaciones importantes en el estilo de vida que contribuyen al desarrollo de la obesidad, sin embargo es poca la atención brindada a esta etapa. La tendencia a adoptar comportamientos poco saludables durante esta transición puede incrementarse en los universitarios que llevan un estilo de vida caracterizado por la falta de tiempo para llevar una dieta saludable, haciéndolos susceptibles a desarrollar obesidad. Objetivo: Determinar la prevalencia de la obesidad y de las anormalidades en los niveles de lípidos y su relación en un grupo de universitarios. Métodos: Estudio transversal que evalúa Índice de Masa Corporal, diámetro de cintura y perfil de lípidos en universitarios con un rango de edad de 18 a 24 años. Resultados: De los 620 jóvenes estudiados, aproximadamente un tercio tienen sobrepeso u obesidad. El 86% presentó al menos una alteración en los parámetros evaluados. Los resultados del perfil lipídico muestran alta prevalencia de alteraciones leves, particularmente en los niveles de colesterol ligado a lipoproteínas de baja densidad. Conclusiones: Los jóvenes Universitarios presentan alta prevalencia de lípidos plasmáticos por encima de la norma y exceso de peso. Es necesario establecer medidas preventivas dirigidas a promover en los universitarios buenos hábitos alimenticios y mayor actividad física.

  14. Structural interactions of a voltage sensor toxin with lipid membranes

    OpenAIRE

    Mihailescu, Mihaela; Krepkiy, Dmitriy; Milescu, Mirela; Gawrisch, Klaus; Swartz, Kenton J.; White, Stephen

    2014-01-01

    Tarantula venom contains protein toxins that interact with diverse families of ion channels and alter their activity. A number of tarantula toxins are known to interact with membranes and are thought to bind to ion channel proteins within the lipid bilayer. In the present study, we find that tarantula toxins influence the structure and dynamics of the lipid bilayer, and that the toxin orients itself within membranes to facilitate formation of the toxin–channel complexes. Our results have impl...

  15. Lipid Structure in Triolein Lipid Droplets

    DEFF Research Database (Denmark)

    Chaban, Vitaly V; Khandelia, Himanshu

    2014-01-01

    of a mass of hydrophobic lipid esters coved by phospholipid monolayer. The small size and unique architecture of LDs makes it complicated to study LD structure by modern experimental methods. We discuss coarse-grained molecular dynamics (MD) simulations of LD formation in systems containing 1-palmitoyl-2...

  16. Thermal stability of ladderane lipids as determined by hydrous pyrolysis

    Science.gov (United States)

    Jaeschke, A.; Lewan, M.D.; Hopmans, E.C.; Schouten, S.; Sinninghe, Damste J.S.

    2008-01-01

    Anaerobic ammonium oxidation (anammox) has been recognized as a major process resulting in loss of fixed inorganic nitrogen in the marine environment. Ladderane lipids, membrane lipids unique to anammox bacteria, have been used as markers for the detection of anammox in marine settings. However, the fate of ladderane lipids after sediment burial and maturation is unknown. In this study, anammox bacterial cell material was artificially matured by hydrous pyrolysis at constant temperatures ranging from 120 to 365 ??C for 72 h to study the stability of ladderane lipids during progressive dia- and catagenesis. HPLC-MS/MS analysis revealed that structural alterations of ladderane lipids already occurred at 120 ??C. At temperatures >140 ??C, ladderane lipids were absent and only more thermally stable products could be detected, i.e., ladderane derivatives in which some of the cyclobutane rings were opened. These diagenetic products of ladderane lipids were still detectable up to temperatures of 260 ??C using GC-MS. Thus, ladderane lipids are unlikely to occur in ancient sediments and sedimentary rocks, but specific diagenetic products of ladderane lipids will likely be present in sediments and sedimentary rocks of relatively low maturity (i.e., C31 hopane 22S/(22S + 22R) ratio 0.5). ?? 2008 Elsevier Ltd.

  17. Physiology of Intestinal Absorption and Secretion.

    Science.gov (United States)

    Kiela, Pawel R; Ghishan, Fayez K

    2016-04-01

    Virtually all nutrients from the diet are absorbed into blood across the highly polarized epithelial cell layer forming the small and large intestinal mucosa. Anatomical, histological, and functional specializations along the gastrointestinal tract are responsible for the effective and regulated nutrient transport via both passive and active mechanisms. In this chapter, we summarize the current state of knowledge regarding the mechanism of intestinal absorption of key nutrients such as sodium, anions (chloride, sulfate, oxalate), carbohydrates, amino acids and peptides, lipids, lipid- and water-soluble vitamins, as well as the major minerals and micronutrients. This outline, including the molecular identity, specificity, and coordinated activities of key transport proteins and genes involved, serves as the background for the following chapters focused on the pathophysiology of acquired and congenital intestinal malabsorption, as well as clinical tools to test and treat malabsorptive symptoms. PMID:27086882

  18. Lipid-based drug carriers for prodrugs to enhance drug delivery.

    Science.gov (United States)

    Zaro, Jennica L

    2015-01-01

    The combination of lipid drug delivery systems with prodrugs offers several advantages including improved pharmacokinetics, increased absorption, and facilitated targeting. Lipidization and use of lipid carriers can increase the pharmacological half-life of the drug, thus improving pharmacokinetics and allowing less frequent dosing. Lipids also offer advantages such as increased absorption through the intestines for oral drug absorption and to the CNS for brain delivery. Furthermore, the use of lipid delivery systems can enhance drug targeting. Endogenous proteins bind lipids in the blood and carry them to the liver to enable targeting of this organ. Drugs with significant side effects in the stomach can be specifically delivered to enterocytes by exploiting lipases for prodrug activation. Finally, lipids can be used to target the lymphatic system, thus bypassing the liver and avoiding first-pass metabolism. Lymphatic targeting is also important for antiviral drugs in the protection of B and T lymphocytes. In this review, both lipid-drug conjugates and lipid-based carriers will be discussed. An overview, including the chemistry and assembly of the systems, as well as examples from the clinic and in development, will be provided. PMID:25269430

  19. Lipid Rafts Disruption Increases Ochratoxin A Cytotoxicity to Hepatocytes.

    Science.gov (United States)

    Zhang, Yu; Qi, Xiaozhe; Zheng, Juanjuan; Luo, Yunbo; Zhao, Changhui; Hao, Junran; Li, Xiaohong; Huang, Kunlun; Xu, Wentao

    2016-02-01

    Lipid rafts are microdomains in plasma membrane and can mediate cytotoxicity. In this study, the role of lipid rafts in ochratoxin A-induced toxicity was investigated using Hepatoblastoma Cell Line HepG-2 cells. Disruption of cholesterol-containing lipid rafts enhanced Ochratoxin A (OTA) toxicity, as shown by increased lactate dehydrogenase leakage, increased reactive oxygen species level and reduction of superoxide dismutase activity in a time-dependent manner. Isobaric tags for relative and absolute quantitation-based proteomics of the cell membranes showed that nearly 85.5% proteins were downregulated by OTA, indicating that OTA inhibited the membrane protein synthesis. Most of altered proteins were involved in Gene Ontology "transport", "cell adhesion" and "vesicle-mediated transport". In conclusion, lipid rafts play a key role in OTA-induced cytotoxicity. This study provides insight into how OTA toxicity is regulated by the plasma membrane, especially the lipid rafts.

  20. Nutrition and magnesium absorption.

    NARCIS (Netherlands)

    Brink, E.J.

    1992-01-01

    The influence of various nutrients present in dairy products and soybean-based products on absorption of magnesium has been investigated. The studies demonstrate that soybean protein versus casein lowers apparent magnesium absorption in rats through its phytate component. However, true magnesium abs

  1. Macromolecule absorption and cortisol secretion in newborn calves derived from in vitro produced embryos

    DEFF Research Database (Denmark)

    Jacobsen, H; Sangild, P T; Schmidt, M;

    2002-01-01

    an altered macromolecule absorption (immunoglobulin G (IgG) and porcine serum albumin (PSA)) compared with AI calves and whether the macromolecule absorption could be related to the degree of acidosis or to the cortisol secretion around birth. Hence, IgG and PSA absorption in control AI calves (n=7...

  2. Lipid rafts in immune signalling: current progress and future perspective.

    Science.gov (United States)

    Varshney, Pallavi; Yadav, Vikas; Saini, Neeru

    2016-09-01

    Lipid rafts are dynamic assemblies of proteins and lipids that harbour many receptors and regulatory molecules and so act as a platform for signal transduction. They float freely within the liquid-disordered bilayer of cellular membranes and can cluster to form larger ordered domains. Alterations in lipid rafts are commonly found to be associated with the pathogenesis of several human diseases and recent reports have shown that the raft domains can also be perturbed by targeting raft proteins through microRNAs. Over the last few years, the importance of lipid rafts in modulating both innate and acquired immune responses has been elucidated. Various receptors present on immune cells like B cells, T cells, basophils and mast cells associate with lipid rafts on ligand binding and initiate signalling cascades leading to inflammation. Furthermore, disrupting lipid raft integrity alters lipopolysaccharide-induced cytokine secretion, IgE signalling, and B-cell and T-cell activation. The objective of this review is to summarize the recent progress in understanding the role of lipid rafts in the modulation of immune signalling and its related therapeutic potential for autoimmune diseases and inflammatory disorders.

  3. Progestin modulates the lipid profile and sensitivity of breast cancer cells to docetaxel

    OpenAIRE

    Schlaepfer, Isabel R.; Hitz, Carolyn A.; Gijón, Miguel A.; Bergman, Bryan C; Eckel, Robert H.; Jacobsen, Britta M.

    2012-01-01

    Progestins induce lipid accumulation in progesterone receptor (PR)-positive breast cancer cells. We speculated that progestin-induced alterations in lipid biology confer resistance to chemotherapy. To examine the biology of lipid loaded breast cancer cells, we used a model of progestin-induced lipid synthesis. T47D (PR-positive) and MDA-MB-231(PR-negative) cell lines were used to study progestin response. Oil red O staining of T47D cells treated with progestin showed lipid droplet formation w...

  4. Regulation of lipid metabolism

    Institute of Scientific and Technical Information of China (English)

    Peng LI

    2011-01-01

    @@ Lipids including cholesterol, phospholipids, fatty acids and triacylglycerols are important cellular constituents involved in membrane structure, energy homeostasis and many biological processes such as signal transduction, organelle development and cell differentiation.Recently, the area of lipid metabolism has drawn a great deal of attention due to its emerging role in the development of metabolic disorders such as obesity, diabetes, atherosclerosis and liver steatosis.We decided to organize a special issue of Frontiers in Biology focusing on our current understanding of lipid metabolism.

  5. Intestinal alkaline phosphatase: selective endocytosis from the enterocyte brush border during fat absorption

    DEFF Research Database (Denmark)

    Hansen, Gert Helge; Niels-Christiansen, Lise-Lotte; Immerdal, Lissi;

    2007-01-01

    clathrin-coated pits. By 60 min, IAP was seen in subapical endosomes and along membranes surrounding fat droplets. IAP is a well-known lipid raft-associated protein, and fat absorption was accompanied by a marked change in the density and morphology of the detergent-resistant membranes harboring IAP....... A lipid analysis revealed that fat absorption caused a marked increase in the microvillar membrane contents of free fatty acids. In conclusion, fat absorption rapidly induces a transient clathrin-dependent endocytosis via coated pits from the enterocyte brush border. The process selectively internalizes...

  6. Terahertz Saturable Absorption in Superconducting Metamaterials

    CERN Document Server

    Keiser, George R; Zhao, Xiaoguang; Zhang, Xin; Averitt, Richard D

    2016-01-01

    We present a superconducting metamaterial saturable absorber at terahertz frequencies. The absorber consists of an array of split ring resonators (SRRs) etched from a 100nm YBaCu3O7 (YBCO) film. A polyimide spacer layer and gold ground plane are deposited above the SRRs, creating a reflecting perfect absorber. Increasing either the temperature or incident electric field (E) decreases the superconducting condensate density and corresponding kinetic inductance of the SRRs. This alters the impedance matching in the metamaterial, reducing the peak absorption. At low electric fields, the absorption was optimized near 80% at T=10K and decreased to 20% at T=70K. For E=40kV/cm and T=10K, the peak absorption was 70% decreasing to 40% at 200kV/cm, corresponding to a modulation of 43%.

  7. Metabolism. Part III: Lipids.

    Science.gov (United States)

    Bodner, George M.

    1986-01-01

    Describes the metabolic processes of complex lipids, including saponification, activation and transport, and the beta-oxidation spiral. Discusses fatty acid degradation in regard to biochemical energy and ketone bodies. (TW)

  8. Lipid Metabolism Disorders

    Science.gov (United States)

    Metabolism is the process your body uses to make energy from the food you eat. Food is ... disorder, something goes wrong with this process. Lipid metabolism disorders, such as Gaucher disease and Tay-Sachs ...

  9. Transmembrane protein topology mapping by the substituted cysteine accessibility method (SCAM™): Application to lipid-specific membrane protein topogenesis

    OpenAIRE

    Bogdanov, Mikhail; Zhang, Wei; Xie, Jun; Dowhan, William

    2005-01-01

    We provide an overview of lipid-dependent polytopic membrane protein topogenesis, with particular emphasis on Escherichia coli strains genetically altered in their lipid composition and strategies for experimentally determining the transmembrane organization of proteins. A variety of reagents and experimental strategies are described including the use of lipid mutants and thiol-specific chemical reagents to study lipid-dependent and host-specific membrane protein topogenesis by substituted cy...

  10. Intestinal absorption of specific structured triacylglycerols

    DEFF Research Database (Denmark)

    Mu, Huiling; Høy, Carl-Erik

    2001-01-01

    To clarify the intestinal absorption pathway of medium-chain fatty acids from MMM-type structured triaclyglycerols containing both medium- and long-chain fatty acids, we studied the lymphatic transport of 1,3-dioctanoyl-2-linoleoyl-sn- glycerol (8:0/18:2/8:0), 1,3-didecanoyl-2-linoleoyl...... and activated into CoA, and reacylated into triacylglycerols in the enterocyte, The hydrolysis of MLM-type STAG is predominantly partial hydrolysis, whereas part of the STAG can also be hydrolyzed to free glycerol and free fatty acids. - Mu, H., and CE. Hoy. Intestinal absorption of specific structured......-sn-glycerol (10:0/18:2/10:0), and 1,3-didodecanoyl-2-linoleoyl-sn-glycerol (12:0/18:2/12:0) in a rat model. Safflower oil was used in the absorption study in order to compare the absorption of medium- chain fatty acids and long-chain fatty acids, The triacylglycerol species of lymph Lipids were separated...

  11. Alterações lipídicas em pacientes com câncer colorretal em fase pós-operatória: ensaio clínico randomizado e duplo-cego com fungos Agaricus sylvaticus Lipidic alterations in patients with colorectal cancer in post-surgery phase: a randomized and double-blind clinical trial with Agaricus sylvaticus fungus

    Directory of Open Access Journals (Sweden)

    Renata Costa Fortes

    2008-09-01

    Full Text Available INTRODUÇÃO: Alterações no metabolismo lipídico são comuns em pacientes com câncer. Fungos medicinais podem exibir atividade hipolipidêmica. OBJETIVO: Avaliar os efeitos da suplementação dietética com fungos Agaricus sylvaticus no perfil lipídico de pacientes com câncer colorretal em fase pós-operatória. MÉTODOS: Ensaio clínico randomizado, duplo-cego, placebo-controlado, realizado no Hospital de Base do Distrito Federal por seis meses. Amostra constituída por 56 pacientes, estádios I, II e III, separados em dois grupos: placebo e suplementado com Agaricus sylvaticus (30mg/kg/dia. Resultados analisados pelos programas Microsoft Excel 2003 e SPSS 14.0 com p = 0.05. RESULTADOS: O grupo Agaricus sylvaticus apresentou níveis séricos iniciais de colesterol total de 207.36±52.67mg/dL, lipoproteína de baixa densidade de 120.79±44.02mg/dL e triglicérides de 181.64±187.52mg/dL. Após seis meses de suplementação, observou-se redução para 191.11±39.72mg/dL (p = 0.01, 103.08±39.20mg/dL (p = 0.0001 e 168.04±146.91mg/dL (p = 0.18, respectivamente. No grupo placebo, observou-se aumento não-significativo de colesterol total (p = 0.08 e aumento significativo de lipoproteína de baixa densidade (p = 0.01 e triglicérides (p = 0.0001. Não foram observadas, em ambos os grupos, alterações significantes nos níveis de lipoproteína de alta densidade e lipoproteína de muito baixa densidade. CONCLUSÃO: Os resultados sugerem que a suplementação dietética com Agaricus sylvaticus pode melhorar significativamente o perfil lipídico de pacientes com câncer colorretal em fase pós-operatória.INTRODUCTION: Alterations in the lipidic metabolism are common in patients with cancer. Medicinal fungus may show hypolipidemic activity. OBJECTIVE: To evaluate the effects of dietary supplementation with Agaricus sylvaticus fungus in lipidic profile of patients with colorectal cancer in post-surgery phase. MEHTODS: Randomized, double

  12. Lipid rafts and detergent-resistant membranes in epithelial keratinocytes.

    Science.gov (United States)

    McGuinn, Kathleen P; Mahoney, Mỹ G

    2014-01-01

    Our understanding of the plasma membrane has markedly increased since Singer and Nicolson proposed the fluid mosaic model in 1972. While their revolutionary theory of the lipid bilayer remains largely valid, it is now known that lipids and proteins are not randomly dispersed throughout the plasma membrane but instead may be organized within membrane microdomains, commonly referred to as lipid rafts. Lipid rafts are highly dynamic, detergent resistant, and enriched with both cholesterol and glycosphingolipids. The two main types are flotillin-rich planar lipid rafts and caveolin-rich caveolae. It is proposed that flotillin and caveolin proteins regulate cell communication by compartmentalizing and interacting with signal transduction proteins within their respective lipid microdomains. Consequently, membrane rafts play an important role in vital cellular functions including migration, invasion, and signaling; thus, alterations in their microenvironment can initiate signaling pathways that affect cellular function and behavior. Therefore, the identification of lipid rafts and their associated proteins is integral to the study of transmembrane signaling. Here, we review the current standard protocols and biochemical approaches used to isolate and define raft proteins from epithelial cells and tissues. Furthermore, in Section 3 of this chapter, detailed protocols are offered for isolating lipid rafts by subjection to detergent and sucrose density centrifugation, as well as an approach for selectively isolating caveolae. Methods to manipulate rafts with treatments such as methyl-β-cyclodextrin and flotillin III are also described.

  13. Nucleic acid-lipid membrane interactions studied by DSC.

    Science.gov (United States)

    Giatrellis, Sarantis; Nounesis, George

    2011-01-01

    The interactions of nucleic acids with lipid membranes are of great importance for biological mechanisms as well as for biotechnological applications in gene delivery and drug carriers. The optimization of liposomal vectors for clinical use is absolutely dependent upon the formation mechanisms, the morphology, and the molecular organization of the lipoplexes, that is, the complexes of lipid membranes with DNA. Differential scanning calorimetry (DSC) has emerged as an efficient and relatively easy-to-operate experimental technique that can straightforwardly provide data related to the thermodynamics and the kinetics of the DNA-lipid complexation and especially to the lipid organization and phase transitions within the membrane. In this review, we summarize DSC studies considering nucleic acid-membrane systems, accentuating DSC capabilities, and data analysis. Published work involving cationic, anionic, and zwitterionic lipids as well as lipid mixtures interacting with RNA and DNA of different sizes and conformations are included. It is shown that despite limitations, issues such as DNA- or RNA-induced phase separation and microdomain lipid segregation, liposomal aggregation and fusion, alterations of the lipid long-range molecular order, as well as membrane-induced structural changes of the nucleic acids can be efficiently treated by systematic high-sensitivity DSC studies.

  14. Altered membrane lipid dynamics and chemoprevention by non-steroidal anti inflammatory drugs during colon carcinogenesis Alteración de la dinámica de los lípidos de membrana y quimioprevención mediante los fármacos antiinflamatorios no esteroideos en la carcinogénesis de colon

    Directory of Open Access Journals (Sweden)

    S. Singh Kanwar

    2011-10-01

    Full Text Available The present work focuses on the anti-neoplastic role of non steroidal anti-inflammatory drugs (NSAIDs in modulating the biophysical parameters of the colonic membranes in 1,2-dimethylhydrazine dihydrochloride (DMH induced carcinogenesis. The steady-state fluorescence polarization technique was applied to assess membrane fluidity, membrane polarity and lipid phase states. The decline in cholesterol content, biosynthesis and cholesterol: phospholipids ratio with DMH treatment indicates more fluidity associated with carcinogenesis. The DMH group had shown lower order parameter indicating more fluidity whereas NSAIDs resulted in increasing the membrane lipid order. The converging effects of these changes were more in membrane phase separations and membrane phase state. In DMH treatment membrane shows lesser phase separation or high polarity, and more liquid crystalline state while for NSAID groups membranes have higher phase separations or low polarity, and more of the gel phase. Further, NSAIDs induced anti-proliferative effects were evidently observed by apoptosis in the colonocytes by using acridine orange-ethidium bromide fluorescent staining and Terminal de-oxynucleotidyl transferase dUTP nick end labeling (TUNEL assay. The results suggest that NSAIDs induced alteration in the membrane biophysical parameters may be an important initiating event for the chemopreventive action.Este trabajo se centra en el papel antineoplásico de los fármacos antiinflamatorios no esteroideos (AINE en la modulación de los parámetros biofísicos de las membranas colónicas en la carcinogénesis inducida por 1,2-dihidrocloruro de dimetilhidracina (DMH. Se aplicó la técnica de polarización de la fluorescencia en estado de equilibrio para evaluar la fluidez de la membrana, su polaridad y los estados de fase lipídica. El declive del contenido de colesterol, la biosíntesis y el cociente colesterol: fosfolípidos con el tratamiento con DMH indica más fluidez

  15. Revisiting Absorptive Capacity

    DEFF Research Database (Denmark)

    de Araújo, Ana Luiza Lara; Ulhøi, John Parm; Lettl, Christopher

    Absorptive capacity has mostly been perceived as a 'passive' outcome of R&D investments. Recently, however, a growing interest into its 'proactive' potentials has emerged. This paper taps into this development and proposes a dynamic model for conceptualizing the determinants of the complementary...... learning processes of absorptive capacity, which comprise combinative and adaptive capabilities. Drawing on survey data (n=169), the study concludes that combinative capabilities primarily enhance transformative and exploratory learning processes, while adaptive capabilities strengthen all three learning...

  16. Functional analysis of lipid metabolism genes in wine yeasts during alcoholic fermentation at low temperature

    OpenAIRE

    María López-Malo; Estéfani García-Ríos; Rosana Chiva; José Manuel Guillamon

    2014-01-01

    Wine produced by low-temperature fermentation is mostly considered to have improved sensory qualities. However few commercial wine strains available on the market are well-adapted to ferment at low temperature (10 – 15°C). The lipid metabolism of Saccharomyces cerevisiae plays a central role in low temperature adaptation. One strategy to modify lipid composition is to alter transcriptional activity by deleting or overexpressing the key genes of lipid metabolism. In a previous study, we identi...

  17. Oxidative Stress and Lipid Peroxidation Products in Cancer Progression and Therapy

    OpenAIRE

    Giuseppina Barrera

    2012-01-01

    The generation of reactive oxygen species (ROS) and an altered redox status are common biochemical aspects in cancer cells. ROS can react with the polyunsaturated fatty acids of lipid membranes and induce lipid peroxidation. The end products of lipid peroxidation, 4-hydroxynonenal (HNE), have been considered to be a second messenger of oxidative stress. Beyond ROS involvement in carcinogenesis, increased ROS level can inhibit tumor cell growth. Indeed, in tumors in advanced stages, a further ...

  18. Metabolomic profiles of lipid metabolism, arterial stiffness and hemodynamics in male coronary artery disease patients

    Directory of Open Access Journals (Sweden)

    Kaido Paapstel

    2016-06-01

    Conclusions: We demonstrated an independent association between the serum medium- and long-chain acylcarnitine profile and aortic stiffness for the CAD patients. In addition to the lipid-related classical CVD risk markers, the intermediates of lipid metabolism may serve as novel indicators for altered vascular function.

  19. Seven-effect absorption refrigeration

    Science.gov (United States)

    DeVault, Robert C.; Biermann, Wendell J.

    1989-01-01

    A seven-effect absorption refrigeration cycle is disclosed utilizing three absorption circuits. In addition, a heat exchanger is used for heating the generator of the low absorption circuit with heat rejected from the condenser and absorber of the medium absorption circuit. A heat exchanger is also provided for heating the generator of the medium absorption circuit with heat rejected from the condenser and absorber of the high absorption circuit. If desired, another heat exchanger can also be provided for heating the evaporator of the high absorption circuit with rejected heat from either the condenser or absorber of the low absorption circuit.

  20. Synthetic redesign of plant lipid metabolism.

    Science.gov (United States)

    Haslam, Richard P; Sayanova, Olga; Kim, Hae Jin; Cahoon, Edgar B; Napier, Johnathan A

    2016-07-01

    Plant seed lipid metabolism is an area of intensive research, including many examples of transgenic events in which oil composition has been modified. In the selected examples described in this review, progress towards the predictive manipulation of metabolism and the reconstitution of desired traits in a non-native host is considered. The advantages of a particular oilseed crop, Camelina sativa, as a flexible and utilitarian chassis for advanced metabolic engineering and applied synthetic biology are considered, as are the issues that still represent gaps in our ability to predictably alter plant lipid biosynthesis. Opportunities to deliver useful bio-based products via transgenic plants are described, some of which represent the most complex genetic engineering in plants to date. Future prospects are considered, with a focus on the desire to transition to more (computationally) directed manipulations of metabolism. PMID:27483205

  1. Targeted metabolomics to study lipid peroxidation in biological systems

    NARCIS (Netherlands)

    Labuschagne, C.F.

    2013-01-01

    During normal cellular metabolism reactive oxygen species (ROS) are inevitably formed as by-products of respiration. ROS are extremely reactive molecules and can react with and damage surrounding DNA, protein and lipid molecules and subsequently alter their normal function in the cell. This oxidativ

  2. LIPID PEROXIDATION IN PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    T.Sharmila Krishna

    2015-03-01

    Full Text Available Hypertension in pregnancy is a leading cause of both maternal and fetal mortality and morbidity. Preeclampsia is characterised by hypertension and proteinuria. Lipid peroxidation is an important factor in the pathophysiology of Preeclampsia. The present study was undertaken to determine Serum Malondialdehyde (MDA levels , a product of lipid peroxidation , in clinically diagnosed Preeclamptic women(n=30 and the values were compared with that of Normotensive pregnant women (n=30 aged between 18-30yrs. All of them were in their third trimester and were primigravida. Serum MDA was estimated by TBARS (thiobarbituric acid reactive substances method. We observed that Serum MDA levels were significantly increased in Preeclamptic women (p <0.000 as compared to that of Normotensive pregnant women . Increased levels of lipid peroxiation product - MDA may contribute to the pathophysiology of Preeclampsia.

  3. Lipid Ion Channels

    CERN Document Server

    Heimburg, Thomas

    2010-01-01

    The interpretation electrical phenomena in biomembranes is usually based on the assumption that the experimentally found discrete ion conduction events are due to a particular class of proteins called ion channels while the lipid membrane is considered being an inert electrical insulator. The particular protein structure is thought to be related to ion specificity, specific recognition of drugs by receptors and to macroscopic phenomena as nerve pulse propagation. However, lipid membranes in their chain melting regime are known to be highly permeable to ions, water and small molecules, and are therefore not always inert. In voltage-clamp experiments one finds quantized conduction events through protein-free membranes in their melting regime similar to or even undistinguishable from those attributed to proteins. This constitutes a conceptual problem for the interpretation of electrophysiological data obtained from biological membrane preparations. Here, we review the experimental evidence for lipid ion channels...

  4. Central cooling: absorptive chillers

    Energy Technology Data Exchange (ETDEWEB)

    Christian, J.E.

    1977-08-01

    This technology evaluation covers commercially available single-effect, lithium-bromide absorption chillers ranging in nominal cooling capacities of 3 to 1,660 tons and double-effect lithium-bromide chillers from 385 to 1,060 tons. The nominal COP measured at operating conditions of 12 psig input steam for the single-effect machine, 85/sup 0/ entering condenser water, and 44/sup 0/F exiting chilled-water, ranges from 0.6 to 0.65. The nominal COP for the double-effect machine varies from 1.0 to 1.15 with 144 psig entering steam. Data are provided to estimate absorption-chiller performance at off-nominal operating conditions. The part-load performance curves along with cost estimating functions help the system design engineer select absorption equipment for a particular application based on life-cycle costs. Several suggestions are offered which may be useful for interfacing an absorption chiller with the remaining Integrated Community Energy System. The ammonia-water absorption chillers are not considered to be readily available technology for ICES application; therefore, performance and cost data on them are not included in this evaluation.

  5. The use of lipid emulsions for sterol supplementation of spat of the Pacific oyster, Crassostrea gigas

    OpenAIRE

    Soudant, P.; Val Sanles, M.; Quere, C.; Le Coz, J.R.; Marty, Y; Moal, J.; Samain, J. F.; Sorgeloos, P.

    2005-01-01

    To determine the ingestion and absorption of lipid emulsions, spat were fed algae deficient in stigmasterol and cholesterol and an emulsion containing these two sterols. The ingestion-absorption of the emulsion was estimated by measuring incorporation of these two sterols in oyster lipids during the 33-day feeding period. They were supplemented with 0%, 3%, 10% and 20% emulsion wet weight of the algae dry weight. The results showed that after only 7 days of emulsion supplementation, significa...

  6. Lipidomic and Spatio-Temporal Imaging of Fat by Mass Spectrometry in Mice Duodenum during Lipid Digestion

    OpenAIRE

    Alexandre Seyer; Michela Cantiello; Justine Bertrand-Michel; Véronique Roques; Michel Nauze; Valérie Bézirard; Xavier Collet; David Touboul; Alain Brunelle; Christine Coméra

    2013-01-01

    Intestinal absorption of dietary fat is a complex process mediated by enterocytes leading to lipid assembly and secretion of circulating lipoproteins as chylomicrons, vLDL and intestinal HDL (iHDL). Understanding lipid digestion is of importance knowing the correlation between excessive fat absorption and atherosclerosis. By using time-of-flight secondary ion mass spectrometry (TOF-SIMS), we illustrated a spatio-temporal localization of fat in mice duodenum, at different times of digestion af...

  7. The Effect of Polar Lipids on Tear Film Dynamics

    KAUST Repository

    Aydemir, E.

    2010-06-17

    In this paper, we present a mathematical model describing the effect of polar lipids, excreted by glands in the eyelid and present on the surface of the tear film, on the evolution of a pre-corneal tear film. We aim to explain the interesting experimentally observed phenomenon that the tear film continues to move upward even after the upper eyelid has become stationary. The polar lipid is an insoluble surface species that locally alters the surface tension of the tear film. In the lubrication limit, the model reduces to two coupled non-linear partial differential equations for the film thickness and the concentration of lipid. We solve the system numerically and observe that increasing the concentration of the lipid increases the flow of liquid up the eye. We further exploit the size of the parameters in the problem to explain the initial evolution of the system. © 2010 Society for Mathematical Biology.

  8. Percutaneous absorption from soil.

    Science.gov (United States)

    Andersen, Rosa Marie; Coman, Garrett; Blickenstaff, Nicholas R; Maibach, Howard I

    2014-01-01

    Abstract Some natural sites, as a result of contaminants emitted into the air and subsequently deposited in soil or accidental industrial release, have high levels of organic and non-organic chemicals in soil. In occupational and recreation settings, these could be potential sources of percutaneous exposure to humans. When investigating percutaneous absorption from soil - in vitro or vivo - soil load, particle size, layering, soil "age" time, along with the methods of performing the experiment and analyzing the results must be taken into consideration. Skin absorption from soil is generally reduced compared with uptake from water/acetone. However, the absorption of some compounds, e.g., pentachlorophenol, chlorodane and PCB 1254, are similar. Lipophilic compounds like dichlorodiphenyltrichloroethane, benzo[A]pyrene, and metals have the tendency to form reservoirs in skin. Thus, one should take caution in interpreting results directly from in vitro studies for risk assessment; in vivo validations are often required for the most relevant risk assessment. PMID:25205703

  9. Duodenal lipid-induced symptom generation in gastroesophageal reflux disease : role of apolipoprotein A-IV and cholecystokinin

    NARCIS (Netherlands)

    Van Boxel, O. S.; Ter Linde, J. J. M.; Oors, J.; Otto, B.; Feinle-Bisset, C.; Smout, A. J. P. M.; Siersema, P. D.

    2012-01-01

    Background Duodenal lipid intensifies the perception of esophageal acid perfusion. Recently, we showed that genes implicated in lipid absorption were upregulated in the duodenum of fasting gastro-esophageal reflux disease (GERD) patients. This suggests that chylomicron production and secretion may b

  10. Mechanistic studies on the lipid-raising coffee diterpenes cafestol and kahweol in monkeys, mice and man

    NARCIS (Netherlands)

    Roos, de B.

    2000-01-01

    Cafestol and kahweol are lipid-raising diterpenes present in unfiltered coffee. The objective of this thesis was to study their lipid-raising action in man. Unravelling this action might lead to new insights into the regulation of serum cholesterol levels.We first studied the absorption and urinary

  11. Aspirin inhibits formation of cholesterol rafts in fluid lipid membranes.

    Science.gov (United States)

    Alsop, Richard J; Toppozini, Laura; Marquardt, Drew; Kučerka, Norbert; Harroun, Thad A; Rheinstädter, Maikel C

    2015-03-01

    Aspirin and other non-steroidal anti-inflammatory drugs have a high affinity for phospholipid membranes, altering their structure and biophysical properties. Aspirin has been shown to partition into the lipid head groups, thereby increasing membrane fluidity. Cholesterol is another well known mediator of membrane fluidity, in turn increasing membrane stiffness. As well, cholesterol is believed to distribute unevenly within lipid membranes leading to the formation of lipid rafts or plaques. In many studies, aspirin has increased positive outcomes for patients with high cholesterol. We are interested if these effects may be, at least partially, the result of a non-specific interaction between aspirin and cholesterol in lipid membranes. We have studied the effect of aspirin on the organization of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) membranes containing cholesterol. Through Langmuir-Blodgett experiments we show that aspirin increases the area per lipid and decreases compressibility at 32.5 mol% cholesterol, leading to a significant increase of fluidity of the membranes. Differential scanning calorimetry provides evidence for the formation of meta-stable structures in the presence of aspirin. The molecular organization of lipids, cholesterol and aspirin was studied using neutron diffraction. While the formation of rafts has been reported in binary DPPC/cholesterol membranes, aspirin was found to locally disrupt membrane organization and lead to the frustration of raft formation. Our results suggest that aspirin is able to directly oppose the formation of cholesterol structures through non-specific interactions with lipid membranes.

  12. Lipid rescue in children: The prompt decision.

    Science.gov (United States)

    Eizaga Rebollar, Ramón; García Palacios, María V; Morales Guerrero, Javier; Torres Morera, Luis M

    2016-08-01

    We report the case of a 17-month-old child who underwent laparotomy under general anesthesia and caudal block. Electrocardiogram ST-T changes were observed after local anesthetic injection. The prompt use of Intralipid 30% was successful in normalizing ECG alterations. Our experience is consistent with previous literature, mainly carried out in adults. Thereby, we conduct a brief review of the subject in pediatrics. As a major conclusion, we strongly recommend the "fast-track" lipid rescue as soon as this severe complication is detected. PMID:27290983

  13. Exogenous lipid pneumonia

    International Nuclear Information System (INIS)

    Exogenous lipid pneumonia (ELP) is caused by the aspiration of animal, vegetal or, more often, mineral oils. Even though it may also be acute, ELP is most frequently a chronic disease, affecting people with predisposing factors, such as neuromuscular disorders, structural abnormalities and so on; very often exogenous lipid pneumonia is found in tracheotomized patients. The pathology of lipid pneumonia is a chronic inflammatory process evolving in foreign-body-like reaction, and eventually in ''end-stage lung'' condition. Clinically, most patients are asymptomatic; few cases only present with cough, dyspnea and chest pain. Eight cases of ELP, studied over the past 3 years, are described in this paper. All the patients were examined by chest radiographs and standard tomograms; 3 patients underwent CT. X-ray features were mono/bilateral consolidation of the lower zones, with air bronchogram and variable reduction in volume. CT density was not specific for fat tissue. In all cases the diagnosis was confirmed at biopsy. In 5 patients, followed for at least one year, clinical-radiological features showed no change. Thus, complications of ELP (especially malignant evolution) could be excluded. The authors conclude that lipid pneumonia must be considered in differential diagnosis of patients with history of usage of oils and compatible X-ray findings. The usefulness of an accurate follow-up is stressed

  14. Lipids in airway secretions

    International Nuclear Information System (INIS)

    Lipids form a significant portion of airway mucus yet they have not received the same attention that epithelial glycoproteins have. We have analysed, by thin layer chromatography, lipids present in airway mucus under 'normal' and hypersecretory (pathological) conditions.The 'normals' included (1) bronchial lavage obtained from healthy human volunteers and from dogs and (2) secretions produced ''in vitro'' by human (bronchial) and canine (tracheal) explants. Hypersecretory mucus samples included (1) lavage from dogs made bronchitic by exposure to SO2, (2) bronchial aspirates from acute and chronic tracheostomy patients, (3) sputum from patients with cystic fibrosis and chronic bronchitis and (4) postmortem secretions from patients who died from sudden infant death syndrome (SIDS) or from status asthmaticus. Cholesterol was found to be the predominant lipid in 'normal' mucus with lesser amounts of phospholipids. No glycolipids were detected. In the hypersecretory mucus, in addition to neutral and phospholipids, glycolipids were present in appreciable amounts, often the predominant species, suggesting that these may be useful as markers of disease. Radioactive precursors 14C acetate and 14C palmitate were incorporated into lipids secreted ''in vitro'' by canine tracheal explants indicating that they are synthesised by the airway. (author)

  15. Lipids in airway secretions

    Energy Technology Data Exchange (ETDEWEB)

    Bhaskar, K.R.; DeFeudis O' Sullivan, D.; Opaskar-Hincman, H.; Reid, L.M.

    1987-01-01

    Lipids form a significant portion of airway mucus yet they have not received the same attention that epithelial glycoproteins have. We have analysed, by thin layer chromatography, lipids present in airway mucus under 'normal' and hypersecretory (pathological) conditions.The 'normals' included (1) bronchial lavage obtained from healthy human volunteers and from dogs and (2) secretions produced ''in vitro'' by human (bronchial) and canine (tracheal) explants. Hypersecretory mucus samples included (1) lavage from dogs made bronchitic by exposure to SO/sub 2/, (2) bronchial aspirates from acute and chronic tracheostomy patients, (3) sputum from patients with cystic fibrosis and chronic bronchitis and (4) postmortem secretions from patients who died from sudden infant death syndrome (SIDS) or from status asthmaticus. Cholesterol was found to be the predominant lipid in 'normal' mucus with lesser amounts of phospholipids. No glycolipids were detected. In the hypersecretory mucus, in addition to neutral and phospholipids, glycolipids were present in appreciable amounts, often the predominant species, suggesting that these may be useful as markers of disease. Radioactive precursors /sup 14/C acetate and /sup 14/C palmitate were incorporated into lipids secreted ''in vitro'' by canine tracheal explants indicating that they are synthesised by the airway.

  16. Lake Superior lipids

    Data.gov (United States)

    U.S. Environmental Protection Agency — Fish chemistry data (d13C, d15N, C:N, lipid content) published in Rapid Commun. Mass Spectrom. 2015, 29, 2069–2077 DOI: 10.1002/rcm.7367 This dataset is associated...

  17. Amphotericin B Lipid Complex Injection

    Science.gov (United States)

    Amphotericin B lipid complex injection is used to treat serious, possibly life-threatening fungal infections in people who did not respond ... to tolerate conventional amphotericin B therapy. Amphotericin B lipid complex injection is in a class of medications ...

  18. Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism

    Science.gov (United States)

    Ke, Zhang-Hong; Pan, Jie-Xue; Jin, Lu-Yang; Xu, Hai-Yan; Yu, Tian-Tian; Ullah, Kamran; Rahman, Tanzil Ur; Ren, Jun; Cheng, Yi; Dong, Xin-Yan; Sheng, Jian-Zhong; Huang, He-Feng

    2016-08-01

    Accumulating evidence suggests a role of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism is still unclear. Using a mouse BPA exposure model, we investigated the effects of long-term BPA exposure on lipid metabolism and the underlying mechanisms. The male mice exposed to BPA (0.5 μg BPA /kg/day, a human relevant dose) for 10 months exhibited significant hepatic accumulation of triglycerides and cholesterol. The liver cells from the BPA-exposed mice showed significantly increased expression levels of the genes related to lipid synthesis. These liver cells showed decreased DNA methylation levels of Srebf1 and Srebf2, and increased expression levels of Srebf1 and Srebf2 that may upregulate the genes related to lipid synthesis. The expression levels of DNA methyltransferases were decreased in BPA-exposed mouse liver. Hepa1-6 cell line treated with BPA showed decreased expression levels of DNA methyltransferases and increased expression levels of genes involved in lipid synthesis. DNA methyltransferase knockdown in Hepa1-6 led to hypo-methylation and increased expression levels of genes involved in lipid synthesis. Our results suggest that long-term BPA exposure could induce hepatic lipid accumulation, which may be due to the epigenetic reprogramming of the genes involved in lipid metabolism, such as the alterations of DNA methylation patterns.

  19. Chemical Absorption Materials

    DEFF Research Database (Denmark)

    Thomsen, Kaj

    2011-01-01

    Chemical absorption materials that potentially can be used for post combustion carbon dioxide capture are discussed. They fall into five groups, alkanolamines, alkali carbonates, ammonia, amino acid salts, and ionic liquids. The chemistry of the materials is discussed and advantages and drawbacks...

  20. Absorption driven focus shift

    Science.gov (United States)

    Harrop, N.; Wolf, S.; Maerten, O.; Dudek, K.; Ballach, S.; Kramer, R.

    2016-03-01

    Modern high brilliance near infrared lasers have seen a tremendous growth in applications throughout the world. Increased productivity has been achieved by higher laser power and increased brilliance of lasers. Positive impacts on the performance and costs of parts are opposed to threats on process stability and quality, namely shift of focus position over time. A high initial process quality will be reduced by contamination of optics, eventually leading to a focus shift or even destruction of the optics. Focus analysis at full power of multi-kilowatt high brilliance lasers is a very demanding task because of high power densities in the spot and the high power load on optical elements. With the newly developed high power projection optics, the High-Power Micro-Spot Monitor High Brilliance (HP-MSM-HB) is able to measure focus diameter as low as 20 μm at power levels up to 10 kW at very low internal focus shift. A main driving factor behind thermally induced focus shift is the absorption level of the optical element. A newly developed measuring system is designed to determine the relative absorption level in reference to a gold standard. Test results presented show a direct correlation between absorption levels and focus shift. The ability to determine the absorption level of optical elements as well as their performance at full processing power before they are put to use, enables a high level of quality assurance for optics manufacturers and processing head manufacturers alike.

  1. ZINC ABSORPTION BY INFANTS

    Science.gov (United States)

    Zinc is a vital mineral in human nutrition, and rare cases of overt zinc deficiency are well described in term and preterm infants. A variety of methods have been developed to assess zinc absorption, retention, and balance in humans, either using mass (metabolic) balance or stable isotope-based METH...

  2. Preliminary study of cell metabolism, by use of NBT test, determination the intensity of lipid peroxidation and antioxidant activity

    Directory of Open Access Journals (Sweden)

    Diana BEI

    2009-05-01

    Full Text Available Otto Warburg, in the early part of the 20th century, originated a hypothesis, that the cause of cancer is primarily a defect in energy metabolism.A decrease in the capacity of mitochondria to reduce NAD(P, together with a decline in the NAD(PH/NAD(P redox couple, uncouples oxidative phosphorylation, lead to depletion of ATP and decrease the cell viability.Nitro-bleu tetrazolium have been used to assay cell proliferation and viability. The method to measure cell proliferation is based on enzymatic cleavage of the tetrazolium salts to a water-soluble formazan dye.Succinate-tetrazolium reductase, is an enzymatic sistem, which belongs to the respiratory chain of the mitochondria and it is active only in viable cells. The reagent diffuses into the cells and it is cleaved to formazan. The absorption change is measured and analysed.Free radicals such as superoxide, can cause a damage in cellular components, but several antioxidants inhibiting the lipid peroxidation and limiting the level of free radicals in cells.In the present study we had in view the proliferation and viability of leukemia cells during antineoplastic treatment along with the alteration of the serum level of malondialdehyde (MDA and ceruloplasmin (CP. With serum level of malondialdehyde we monitored the presence of the lipid peroxidation by the reactive oxygen species, and with the oxidized ceruloplasmin level in blood serum we evidenced the activity of antioxidant system in blood.

  3. The absorption of fat by intestine of golden hamster in vitro.

    Science.gov (United States)

    STRAUSS, E W

    1963-06-01

    Everted sacs of intestine from golden hamsters were incubated at 37 degrees C for at least 1 hour in vitro with emulsified lipid after removal of both pancreatic lipase and bile salts. The fine structure of intestinal epithelium is well preserved under these conditions. Absorption of fat by the intestinal mucosa in vitro closely resembles lipid absorption in vivo, as observed by both light and electron microscopy. The physiological significance of these observations is discussed. Tubular elements of the agranular endoplasmic reticulum are often strikingly abundant in the apical cytoplasm of intestinal absorptive cells. These have a role in the intracellular transport of fat since they frequently contain droplets of lipid derived from the incubation medium. The rate of fat accumulation in the epithelium appears to be proportional to the concentration in the medium.

  4. Interaction of lipid nanoparticles with human epidermis and an organotypic cell culture model

    DEFF Research Database (Denmark)

    Kuntsche, Judith; Bunjes, Heike; Fahr, Alfred;

    2008-01-01

    Various lipid nanoparticle formulations were investigated with respect to (trans)dermal drug delivery with special regard to the mechanism of their effects on human and an organotypic cell culture epidermis. Potential alterations of stratum corneum lipid domains were studied using fluorescence as...... studies and thermal analysis of human and cell culture epidermis indicate that surface lipids, which are not present to the same extent in the cell culture model than in human epidermis, seem to play an important role.......Various lipid nanoparticle formulations were investigated with respect to (trans)dermal drug delivery with special regard to the mechanism of their effects on human and an organotypic cell culture epidermis. Potential alterations of stratum corneum lipid domains were studied using fluorescence...

  5. Effect of testicular capsulotomy on lipid droplets in the seminiferous tubules of rats

    Institute of Scientific and Technical Information of China (English)

    Da-Nian QIN; Mary A. Lung

    2001-01-01

    Aim: In order to reveal the histochemical alteration that might occur during the processes of the spermatogenic dis mption induced by testicular capsulotomy, the location and alteration of lipid droplets in the seminiferous tubules were observed in the present study. Methods: Osmium tetroxide was used to demonstrate the lipid droplets in the semi niferous tubules of capsulotomized and sham-operated control testes. Results: In the seminiferous tubules of the sham-operated rat testes, many small lipid droplets were located close to the basement membrane of the seminiferous tubules. But for the capsulotomized testes, the lipid droplets in the seminiferous tubules had increased in size and num ber, with many lipid droplets migrated towards the lumen of the tubules. Conclusion: The results indicated that a progressive fatty degeneration occurred in the seminiferous tubules after testicular capsulotomy.

  6. Characterization of a Novel Intestinal Glycerol-3-phosphate Acyltransferase Pathway and Its Role in Lipid Homeostasis.

    Science.gov (United States)

    Khatun, Irani; Clark, Ronald W; Vera, Nicholas B; Kou, Kou; Erion, Derek M; Coskran, Timothy; Bobrowski, Walter F; Okerberg, Carlin; Goodwin, Bryan

    2016-02-01

    Dietary triglycerides (TG) are absorbed by the enterocytes of the small intestine after luminal hydrolysis into monacylglycerol and fatty acids. Before secretion on chylomicrons, these lipids are reesterified into TG, primarily through the monoacylglycerol pathway. However, targeted deletion of the primary murine monoacylglycerol acyltransferase does not quantitatively affect lipid absorption, suggesting the existence of alternative pathways. Therefore, we investigated the role of the glycerol 3-phosphate pathway in dietary lipid absorption. The expression of glycerol-3-phosphate acyltransferase (GPAT3) was examined throughout the small intestine. To evaluate the role for GPAT3 in lipid absorption, mice harboring a disrupted GPAT3 gene (Gpat3(-/-)) were subjected to an oral lipid challenge and fed a Western-type diet to characterize the role in lipid and cholesterol homeostasis. Additional mechanistic studies were performed in primary enterocytes. GPAT3 was abundantly expressed in the apical surface of enterocytes in the small intestine. After an oral lipid bolus, Gpat3(-/-) mice exhibited attenuated plasma TG excursion and accumulated lipid in the enterocytes. Electron microscopy studies revealed a lack of lipids in the lamina propria and intercellular space in Gpat3(-/-) mice. Gpat3(-/-) enterocytes displayed a compensatory increase in the synthesis of phospholipid and cholesteryl ester. When fed a Western-type diet, hepatic TG and cholesteryl ester accumulation was significantly higher in Gpat3(-/-) mice compared with the wild-type mice accompanied by elevated levels of alanine aminotransferase, a marker of liver injury. Dysregulation of bile acid metabolism was also evident in Gpat3-null mice. These studies identify GPAT3 as a novel enzyme involved in intestinal lipid metabolism.

  7. Characterization of a Novel Intestinal Glycerol-3-phosphate Acyltransferase Pathway and Its Role in Lipid Homeostasis.

    Science.gov (United States)

    Khatun, Irani; Clark, Ronald W; Vera, Nicholas B; Kou, Kou; Erion, Derek M; Coskran, Timothy; Bobrowski, Walter F; Okerberg, Carlin; Goodwin, Bryan

    2016-02-01

    Dietary triglycerides (TG) are absorbed by the enterocytes of the small intestine after luminal hydrolysis into monacylglycerol and fatty acids. Before secretion on chylomicrons, these lipids are reesterified into TG, primarily through the monoacylglycerol pathway. However, targeted deletion of the primary murine monoacylglycerol acyltransferase does not quantitatively affect lipid absorption, suggesting the existence of alternative pathways. Therefore, we investigated the role of the glycerol 3-phosphate pathway in dietary lipid absorption. The expression of glycerol-3-phosphate acyltransferase (GPAT3) was examined throughout the small intestine. To evaluate the role for GPAT3 in lipid absorption, mice harboring a disrupted GPAT3 gene (Gpat3(-/-)) were subjected to an oral lipid challenge and fed a Western-type diet to characterize the role in lipid and cholesterol homeostasis. Additional mechanistic studies were performed in primary enterocytes. GPAT3 was abundantly expressed in the apical surface of enterocytes in the small intestine. After an oral lipid bolus, Gpat3(-/-) mice exhibited attenuated plasma TG excursion and accumulated lipid in the enterocytes. Electron microscopy studies revealed a lack of lipids in the lamina propria and intercellular space in Gpat3(-/-) mice. Gpat3(-/-) enterocytes displayed a compensatory increase in the synthesis of phospholipid and cholesteryl ester. When fed a Western-type diet, hepatic TG and cholesteryl ester accumulation was significantly higher in Gpat3(-/-) mice compared with the wild-type mice accompanied by elevated levels of alanine aminotransferase, a marker of liver injury. Dysregulation of bile acid metabolism was also evident in Gpat3-null mice. These studies identify GPAT3 as a novel enzyme involved in intestinal lipid metabolism. PMID:26644473

  8. Laser-based assessment of lipid peroxidation in humans

    Science.gov (United States)

    Giubileo, Gianfranco

    1998-07-01

    Infrared absorption spectroscopy can be performed at very high resolution by tunable diode laser (TDL) based optical systems for any gas with well resolved absorption spectra. In a double beam setup atmospheric trace gas concentration can be measured down to ppb levels. The analysis of trace gases may have useful applications in detecting chemicals in the human breath for non invasive medical diagnostic. The capability of TDL based breath analysis was well demonstrated by monitoring ammonia and methane. In the human body the formation of free radicals does induce oxidative degradation of polyunsaturated fatty acids (lipid peroxidation) which is a damage for cells and organs in the organism. Specific volatile hydrocarbons generated as end product by lipid peroxidation (LP) can be found inside circulating blood and expired breath. TDL based analysis of those specific hydrocarbons (ethane and pentane) in the expired breath can allow a non invasive assessment of the LP extent.

  9. Study of serum lipids in leprosy

    Directory of Open Access Journals (Sweden)

    Gupta Anju

    2002-01-01

    Full Text Available Fifty fresh and untreated patients of leprosy constituted the study group. Fifty, age and sex matched healthy individuals formed the controls. Ridly and Jopling system of classification was used in the study. Majority i.e 21 cases were of BT group, 12 of BB, 7 of BL, 9 of LL and one case was of TT leprosy. The serum triglyceride level was lower than normal in TT, showed no alteration in BT or BB and was insignificantly increased in bL and LL patients. The total cholesterol was lowerthan normal in TT, showed no alteration in BT or BB and was insignificantly increased in Bland LL patients. The total cholesterol was lower than normal in TT, whereas in BT, BB, BL and LL groups the levels were statistically decreased. The HDL cholesterol was within normal range in TT, significantly decreased in BT and LL patients, showed no significant alteration in BB and was insignificantly decreased in BL group. The LDL cholesterol in TT was low but was not so low statistically when compared with the controls, whereas in BT, BB, BL and LL groups the levels were statistically decreased. The VLDL cholesterol was within normal range in TT and BT, was raised insignificantly in 3 of 12 cases of BB, was within normal range in BL and in LL leprosy it was raised in one out of 9 cases. In the absence of any derangement of liver function tests, it can be concluded that leprosy per se leads to alterations in lipid metabolism. However, no correlation could be established between the group/type of leprosy, bacterial indices and levels of different lipid fractions in the present study.

  10. Altered autophagy in human adipose tissues in obesity

    Science.gov (United States)

    Context: Autophagy is a housekeeping mechanism, involved in metabolic regulation and stress response, shown recently to regulate lipid droplets biogenesis/breakdown and adipose tissue phenotype. Objective: We hypothesized that in human obesity autophagy may be altered in adipose tissue in a fat d...

  11. Clozapine promotes glycolysis and myelin lipid synthesis in cultured oligodendrocytes

    Directory of Open Access Journals (Sweden)

    Johann eSteiner

    2014-11-01

    Full Text Available Clozapine has stronger systemic metabolic side effects than haloperidol and it was hypothesized that therapeutic antipsychotic and adverse metabolic effects might be related. Considering that cerebral disconnectivity through oligodendrocyte dysfunction has been implicated in schizophrenia, it is important to determine the effect of these drugs on oligodendrocyte energy metabolism and myelin lipid production.Effects of clozapine and haloperidol on glucose and myelin lipid metabolism were evaluated and compared in cultured OLN-93 oligodendrocytes. First, glycolytic activity was assessed by measurement of extra- and intracellular glucose and lactate levels. Next, the expression of glucose (GLUT and monocarboxylate (MCT transporters was determined after 6h and 24h. And finally mitochondrial respiration, acetyl-CoA carboxylase, free fatty acids, and expression of the myelin lipid galactocerebroside were analyzed.Both drugs altered oligodendrocyte glucose metabolism, but in opposite directions. Clozapine improved the glucose uptake, production and release of lactate, without altering GLUT and MCT. In contrast, haloperidol led to higher extracellular levels of glucose and lower levels of lactate, suggesting reduced glycolysis. Antipsychotics did not alter significantly the number of functionally intact mitochondria, but clozapine enhanced the efficacy of oxidative phosphorylation and expression of galactocerebroside.Our findings support the superior impact of clozapine on white matter integrity in schizophrenia as previously observed, suggesting that this drug improves the energy supply and myelin lipid synthesis in oligodendrocytes. Characterizing the underlying signal transduction pathways may pave the way for novel oligodendrocyte-directed schizophrenia therapies.

  12. Lipid metabolism and nutrient partitioning strategies.

    Science.gov (United States)

    Morris, A M; Calsbeek, D J; Eckel, R H

    2004-10-01

    The increasing prevalence of overweight and obesity worldwide is daunting and requires prompt attention by the affected, health care profession, government and the pharmaceutical industry. Because overweight/obesity are defined as an excess of adipose tissue mass, all approaches in prevention and treatment must consider redirecting lipid storage in adipose tissue to oxidative metabolism. Lipid partitioning is a complex process that involves interaction between fat and other macronutrients, particularly carbohydrate. In an isocaloric environment, when fat is stored carbohydrate is oxidized and vice versa. Processes that influence fat partitioning in a manner in which weight is maintained must be modified by changes in organ-specific fat transport and metabolism. When therapy is considered, however, changes in lipid partitioning alone will be ineffective unless a negative energy balance is also achieved, i.e. energy expenditure exceeds energy intake. The intent of this review is to focus on molecules including hormones, enzymes, cytokines, membrane transport proteins, and transcription factors directly involved in fat trafficking and partitioning that could be potential drug targets. Some examples of favorably altering body composition by systemic and/or tissue specific modification of these molecules have already been provided with gene knockout and/or transgenic approaches in mice. The translation of this science to humans remains a challenging task. PMID:15544448

  13. Absorptive Capacity and Diversity

    DEFF Research Database (Denmark)

    Kristinsson, Kári

    that contribute to the neo-Schumpeterian economics literature and hopefully inspires further research into this area. The main findings of the dissertation can be divided into four distinct parts. First, diversity of individuals within firms is associated with firm innovative performance. This is in line......One of the most influential contributions to neo-Schumpeterian economics is Cohen and Levinthal‘s papers on absorptive capacity. Since their publication in the late 1980s and early 1990s the concept absorptive capacity has had substantial impact on research in economics and management, including...... international business, organizational economics, strategic management, technology management and last but not least neo-Schumpeterian economics. The goal of this dissertation is to examine what many consider as neglected arguments from the work by Cohen and Levinthal and thereby illuminate an otherwise...

  14. Acoustic absorption by sunspots

    Science.gov (United States)

    Braun, D. C.; Labonte, B. J.; Duvall, T. L., Jr.

    1987-01-01

    The paper presents the initial results of a series of observations designed to probe the nature of sunspots by detecting their influence on high-degree p-mode oscillations in the surrounding photosphere. The analysis decomposes the observed oscillations into radially propagating waves described by Hankel functions in a cylindrical coordinate system centered on the sunspot. From measurements of the differences in power between waves traveling outward and inward, it is demonstrated that sunspots appear to absorb as much as 50 percent of the incoming acoustic waves. It is found that for all three sunspots observed, the amount of absorption increases linearly with horizontal wavenumber. The effect is present in p-mode oscillations with wavelengths both significantly larger and smaller than the diameter of the sunspot umbrae. Actual absorption of acoustic energy of the magnitude observed may produce measurable decreases in the power and lifetimes of high-degree p-mode oscillations during periods of high solar activity.

  15. Acoustic absorption by sunspots

    Energy Technology Data Exchange (ETDEWEB)

    Braun, D.C.; Labonte, B.J.; Duvall, T.L. Jr.

    1987-08-01

    The paper presents the initial results of a series of observations designed to probe the nature of sunspots by detecting their influence on high-degree p-mode oscillations in the surrounding photosphere. The analysis decomposes the observed oscillations into radially propagating waves described by Hankel functions in a cylindrical coordinate system centered on the sunspot. From measurements of the differences in power between waves traveling outward and inward, it is demonstrated that sunspots appear to absorb as much as 50 percent of the incoming acoustic waves. It is found that for all three sunspots observed, the amount of absorption increases linearly with horizontal wavenumber. The effect is present in p-mode oscillations with wavelengths both significantly larger and smaller than the diameter of the sunspot umbrae. Actual absorption of acoustic energy of the magnitude observed may produce measurable decreases in the power and lifetimes of high-degree p-mode oscillations during periods of high solar activity. 10 references.

  16. Topological regulation of lipid balance in cells.

    Science.gov (United States)

    Drin, Guillaume

    2014-01-01

    Lipids are unevenly distributed within and between cell membranes, thus defining organelle identity. Such distribution relies on local metabolic branches and mechanisms that move lipids. These processes are regulated by feedback mechanisms that decipher topographical information in organelle membranes and then regulate lipid levels or flows. In the endoplasmic reticulum, the major lipid source, transcriptional regulators and enzymes sense changes in membrane features to modulate lipid production. At the Golgi apparatus, lipid-synthesizing, lipid-flippase, and lipid-transport proteins (LTPs) collaborate to control lipid balance and distribution within the membrane to guarantee remodeling processes crucial for vesicular trafficking. Open questions exist regarding LTPs, which are thought to be lipid sensors that regulate lipid synthesis or carriers that transfer lipids between organelles across long distances or in contact sites. A novel model is that LTPs, by exchanging two different lipids, exploit one lipid gradient between two distinct membranes to build a second lipid gradient. PMID:24606148

  17. Functions of Lipids for Enhancement of Oral Bioavailability of Poorly Water-Soluble Drugs

    OpenAIRE

    Basavaraj K. Nanjwade; Patel, Didhija J.; Udhani, Ritesh A.; Manvi, Fakirappa V.

    2011-01-01

    Lipid-based formulations encompass a diverse group of formulations with very different physical appearance, ranging from simple triglyceride vehicles to more sophisticated formulations such as self-emulsifying drug delivery systems (SEDDS). Lipid-based drug delivery systems may contain a broad range of oils, surfactants, and co-solvents. They represent one of the most popular approaches to overcome the absorption barriers and to improve the bioavailability of poorly water-soluble drugs. Diver...

  18. Investigation of the interaction between modified ISCOMs and stratum corneum lipid model systems

    DEFF Research Database (Denmark)

    Madsen, Henriette Baun; Arboe-Andersen, Helle M.; Rozlosnik, Noemi;

    2010-01-01

    The modified ISCOMs, so-called Posintro (TM) nanoparticles, provide an opportunity for altering the surface charge of the particles, which influences their affinity for the negatively charged antigen sites, cell membranes and lipids in the skin. Hypothetically, this increases the passage of the...... ISCOMs (or their components) and their load through the stratum corneum. The subsequent increase in the uptake by the antigen-presenting cells results in enhanced transcutaneous immunization. To understand the nature of penetration of Posintro (TM) nanoparticles into the intercorneocyte space of the...... stratum corneum, the interaction between the nanoparticles and lipid model systems in form of liposomes and/or supported lipid bilayer was studied. As a lipid model we used Stratum Corneum Lipid (SCL), a mixture similar in composition to the lipids of the intercorneocyte space. By Forster Resonance Energy...

  19. Native low density lipoprotein promotes lipid raft formation in macrophages.

    Science.gov (United States)

    Song, Jian; Ping, Ling-Yan; Duong, Duc M; Gao, Xiao-Yan; He, Chun-Yan; Wei, Lei; Wu, Jun-Zhu

    2016-03-01

    Oxidized low‑density lipoprotein (LDL) has an important role in atherogenesis; however, the mechanisms underlying cell‑mediated LDL oxidation remain to be elucidated. The present study investigated whether native‑LDL induced lipid raft formation, in order to gain further insight into LDL oxidation. Confocal microscopic analysis revealed that lipid rafts were aggregated or clustered in the membrane, which were colocalized with myeloperoxidase (MPO) upon native LDL stimulation; however, in the presence of methyl‑β‑cyclodextrin (MβCD), LDL‑stimulated aggregation, translocation, and colocalization of lipid rafts components was abolished.. In addition, lipid raft disruptors MβCD and filipin decreased malondialdehyde expression levels. Density gradient centrifugation coupled to label‑free quantitative proteomic analysis identified 1,449 individual proteins, of which 203 were significantly upregulated following native‑LDL stimulation. Functional classification of the proteins identified in the lipid rafts revealed that the expression levels of translocation proteins were upregulated. In conclusion, the results of the present study indicated that native‑LDL induced lipid raft clustering in macrophages, and the expression levels of several proteins were altered in the stimulated macrophages, which provided novel insights into the mechanism underlying LDL oxidation.

  20. Formulation, stability and degradation kinetics of intravenous cinnarizine lipid emulsion.

    Science.gov (United States)

    Shi, Shuai; Chen, Hao; Cui, Yue; Tang, Xing

    2009-05-21

    Cinnarizine was loaded in the lipid emulsion to develop an intravenous formulation with good physical and chemical stability. High-pressure homogenization was used to prepare the lipid emulsion. The factors influencing the stability of cinnarizine lipid emulsion, such as different drug loading methods, pH, temperature, sterilization methods and sterilization time were monitored by high-performance liquid chromatograph. The degradation of cinnarizine in aqueous solution and lipid emulsion both followed apparent first-order kinetics. A possible degradation mechanism was postulated by the bell-shaped pH-rate profile of cinnarizine. Localization of the drug in the interfacial lecithin layer significantly improved the chemical stability of cinnarizine and its stabilizing mechanism was thoroughly discussed and proved. The activation energy of cinnarizine in lipid emulsion was calculated to be 51.27 kJ/mol which was similar to that in aqueous solution. This indicates that the stabilizing effect of the drug carrier on cinnarizine was not an alteration of the degradation reaction. In addition, shelf-life of cinnarizine in lipid emulsion was estimated to be 1471.6 days at 4 degrees C, which is much longer compared with 19.8 days in aqueous solution. The final products were stable enough to resist a 121 degrees C rotating steam sterilization for 15 min. PMID:19429300

  1. Lipidated Steroid Saponins from Dioscorea villosa (Wild Yam)†

    Science.gov (United States)

    Dong, Shi-Hui; Cai, Geping; Napolitano, José G.; Nikolić, Dejan; Lankin, David C.; McAlpine, James B.; van Breemen, Richard B.; Soejarto, Djaja D.; Pauli, Guido F.; Chen, Shao-Nong

    2014-01-01

    Two groups of lipidated steroid saponins including seven new compounds (2, 3, 5, and 7–10) were isolated from the widely used botanical, wild yam (Dioscorea villosa), employing a fractionation protocol of metabolomic mining. This methodology has very recently led to the isolation of 14 diarylheptanoids from the same plant. Together with these lipidated steroid saponins, they establish additional new markers for Dioscorea villosa. The lipidation of steroids with analogue long-chain fatty acids containing different degrees of unsaturation generates entire series of compounds which are difficult to purify and analyze. The structures of the two series of lipidated steroid saponins (series A and B) were demonstrated by a combination of 1D and 2D NMR as well as GC-MS after chemical modification. Series A was determined to be a mixture of lipidated spirostanol glycosides (1–5), while series B (6–10) proved to be a mixture of five lipidated clionasterol glucosides. The latter group represents the first derivatives of clionasterol to be found in D. villosa. The discovery of this specific structural type of aliphatic esters of steroid saponins expands the characterization of the secondary metabolome of D. villosa. It also may inspire biological studies which take into account the lipophilic character and significantly altered physiochemical characteristics of these otherwise relatively polar phytoconstituents. PMID:23968665

  2. Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells

    Energy Technology Data Exchange (ETDEWEB)

    Perera, Rushika M.; Riley, Catherine; Isaac, Georgis; Hopf- Jannasch, Amber; Moore, Ronald J.; Weitz, Karl K.; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Adamec, Jiri; Kuhn, Richard J.

    2012-03-22

    Dengue virus causes {approx}50-100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.

  3. Perillyl alcohol: Dynamic interactions with the lipid bilayer and implications for long‐term inhalational chemotherapy for gliomas

    DEFF Research Database (Denmark)

    Khandelia, Himanshu

    2016-01-01

    Background: Gliomas display a high degree of intratumor heterogeneity, including changes in physiological parameters and lipid composition of the plasma membrane, which may contribute to the development of drug resistance. Biophysical interactions between therapeutic agents and the lipid components...... at the outer plasma membrane interface are critical for effective drug uptake. Amphipathic molecules such as perillyl alcohol (POH) have a high partition coefficient and generally lead to altered lipid acyl tail dynamics near the lipid-water interface, impacting the lipid bilayer structure and transport...... group, we have successfully established that intranasal delivery of POH to patients with malignant gliomas is a viable and effective therapeutic strategy. Results: POH altered the plasma membrane potential of the lipid bilayer of gliomas and prolonged intranasal administration of POH in a cohort...

  4. Distribution of Fullerene Nanoparticles between Water and Solid Supported Lipid Membranes: Thermodynamics and Effects of Membrane Composition on Distribution.

    Science.gov (United States)

    Ha, Yeonjeong; Katz, Lynn E; Liljestrand, Howard M

    2015-12-15

    The distribution coefficient (Klipw) of fullerene between solid supported lipid membranes (SSLMs) and water was examined using different lipid membrane compositions. Klipw of fullerene was significantly higher with a cationic lipid membrane compared to that with a zwitterionic or anionic lipid membrane, potentially due to the strong interactions between negative fullerene dispersions and positive lipid head groups. The higher Klipw for fullerene distribution to ternary lipid mixture membranes was attributed to an increase in the interfacial surface area of the lipid membrane resulting from phase separation. These results imply that lipid composition can be a critical factor that affects bioconcentration of fullerene. Distribution of fullerene into zwitterionic unsaturated lipid membranes was dominated by the entropy contribution (ΔS) and the process was endothermic (ΔH > 0). This result contrasts the partitioning thermodynamics of highly and moderately hydrophobic chemicals indicating that the lipid-water distribution mechanism of fullerene may be different from that of molecular level chemicals. Potential mechanisms for the distribution of fullerene that may explain these differences include adsorption on the lipid membrane surfaces and partitioning into the center of lipid membranes (i.e., absorption).

  5. Structural properties of lipid reconstructs and lipid composition of normotensive and hypertensive rat vascular smooth muscle cell membranes

    Directory of Open Access Journals (Sweden)

    T.R. Oliveira

    2009-09-01

    Full Text Available Multiple cell membrane alterations have been reported to be the cause of various forms of hypertension. The present study focuses on the lipid portion of the membranes, characterizing the microviscosity of membranes reconstituted with lipids extracted from the aorta and mesenteric arteries of spontaneously hypertensive (SHR and normotensive control rat strains (WKY and NWR. Membrane-incorporated phospholipid spin labels were used to monitor the bilayer structure at different depths. The packing of lipids extracted from both aorta and mesenteric arteries of normotensive and hypertensive rats was similar. Lipid extract analysis showed similar phospholipid composition for all membranes. However, cholesterol content was lower in SHR arteries than in normotensive animal arteries. These findings contrast with the fact that the SHR aorta is hyporeactive while the SHR mesenteric artery is hyperreactive to vasopressor agents when compared to the vessels of normotensive animal strains. Hence, factors other than microviscosity of bulk lipids contribute to the vascular smooth muscle reactivity and hypertension of SHR. The excess cholesterol in the arteries of normotensive animal strains apparently is not dissolved in bulk lipids and is not directly related to vascular reactivity since it is present in both the aorta and mesenteric arteries. The lower cholesterol concentrations in SHR arteries may in fact result from metabolic differences due to the hypertensive state or to genes that co-segregate with those that determine hypertension during the process of strain selection.

  6. Pion absorption processes

    International Nuclear Information System (INIS)

    Proton and deuteron production from low-energy pion absorption in light nuclei leading to discrete and continuum states were measured. The LEP beam line at LAMPF was used with a stack of 8 intrinsic germanium crystals. The proton energy spectra are in general characterized by a broad bump at an energy approximately corresponding to π+d → pp reaction kinematics, suggestive of pion absorption on 2 nucleons. The energy-integrated cross-section for production of deuterons has an angular distribution similar to that for production of protons. The dependence of the total pion absorption cross-section on A is explained using a semi-classical model for pion transport in nuclei. The (π+,p) as well as (π+,d) reactions generally favor transitions involving larger angular momentum transfer to the residual nucleus when states of similar nuclear structure are considered. The low-energy excitation spectra from the (π+,p) reaction are similar to the spectra from (p,d) reaction on 12C and 13C. However, a calculation of the (π+,p) cross-section using the measured (p,d) reaction with the formulation of Wilkin to relate the two reactions is in moderate disagreement with the measured (π+,p) cross-sections. The excitation spectra from the (π+,p) reaction indicte the importance of two-step processes for the reaction. The (π+,d) reaction leading to the ground state of -- residual nucleus has been seen for 7Li, 12C, and 13C targets. The measured cross section for the 12C(π+,d)10C reaction to the 2+ state is much higher than that for the ground state. For the case of 18O, no counts were seen for excitation energy of +,d) reaction

  7. Absorption heat pumps

    Science.gov (United States)

    Huhtinen, M.; Heikkilae, M.; Andersson, R.

    1987-03-01

    The aim of the study was to analyze the technical and economic feasibility of absorption heat pumps in Finland. The work was done as a case study: the technical and economic analyses have been carried out for six different cases, where in each the suitable size and type of the heat pump plant and the auxiliary components and connections were specified. The study also detailed the costs concerning the procurement, installation and test runs of the machinery, as well as the savings in energy costs incurred by the introduction of the plant. Conclusions were drawn of the economic viability of the applications studied. The following cases were analyzed: heat recovery from flue gases and productin of district heat in plants using peat, natural gas, and municipal wastes as a fuel. Heat recovery in the pulp and paper industry for the upgrading of pressure of secondary steam and for the heating of white liquor and combustion and drying the air. Heat recovery in a peat-fulled heat and power plant from flue gases that have been used for the drying of peat. According to the study, the absorption heat pump suits best to the production of district heat, when the heat source is the primary energy is steam produced by the boiler. Included in the flue as condensing is the purification of flue gases. Accordingly, benefit is gained on two levels in thick applications. In heat and power plants the use of absorption heat pumps is less economical, due to the fact that the steam used by the pump reduces the production of electricity, which is rated clearly higher than heat.

  8. Sustained Epigenetic Drug Delivery Depletes Cholesterol-Sphingomyelin Rafts from Resistant Breast Cancer Cells, Influencing Biophysical Characteristics of Membrane Lipids.

    Science.gov (United States)

    Raghavan, Vijay; Vijayaraghavalu, Sivakumar; Peetla, Chiranjeevi; Yamada, Masayoshi; Morisada, Megan; Labhasetwar, Vinod

    2015-10-27

    Cell-membrane lipid composition can greatly influence biophysical properties of cell membranes, affecting various cellular functions. We previously showed that lipid synthesis becomes altered in the membranes of resistant breast cancer cells (MCF-7/ADR); they form a more rigid, hydrophobic lipid monolayer than do sensitive cell membranes (MCF-7). These changes in membrane lipids of resistant cells, attributed to epigenetic aberration, significantly affected drug transport and endocytic function, thus impacting the efficacy of anticancer drugs. The present study's objective was to determine the effects of the epigenetic drug, 5-aza-2'-deoxycytidine (DAC), delivered in sustained-release nanogels (DAC-NGs), on the composition and biophysical properties of membrane lipids of resistant cells. Resistant and sensitive cells were treated with DAC in solution (DAC-sol) or DAC-NGs, and cell-membrane lipids were isolated and analyzed for lipid composition and biophysical properties. In resistant cells, we found increased formation of cholesterol-sphingomyelin (CHOL-SM) rafts with culturing time, whereas DAC treatment reduced their formation. In general, the effect of DAC-NGs was greater in changing the lipid composition than with DAC-sol. DAC treatment also caused a rise in levels of certain phospholipids and neutral lipids known to increase membrane fluidity, while reducing the levels of certain lipids known to increase membrane rigidity. Isotherm data showed increased lipid membrane fluidity following DAC treatment, attributed to decrease levels of CHOL-SM rafts (lamellar beta [Lβ] structures or ordered gel) and a corresponding increase in lipids that form lamellar alpha-structures (Lα, liquid crystalline phase). Sensitive cells showed marginal or insignificant changes in lipid profile following DAC-treatment, suggesting that epigenetic changes affecting lipid biosynthesis are more specific to resistant cells. Since membrane fluidity plays a major role in drug transport

  9. Sustained Epigenetic Drug Delivery Depletes Cholesterol-Sphingomyelin Rafts from Resistant Breast Cancer Cells, Influencing Biophysical Characteristics of Membrane Lipids.

    Science.gov (United States)

    Raghavan, Vijay; Vijayaraghavalu, Sivakumar; Peetla, Chiranjeevi; Yamada, Masayoshi; Morisada, Megan; Labhasetwar, Vinod

    2015-10-27

    Cell-membrane lipid composition can greatly influence biophysical properties of cell membranes, affecting various cellular functions. We previously showed that lipid synthesis becomes altered in the membranes of resistant breast cancer cells (MCF-7/ADR); they form a more rigid, hydrophobic lipid monolayer than do sensitive cell membranes (MCF-7). These changes in membrane lipids of resistant cells, attributed to epigenetic aberration, significantly affected drug transport and endocytic function, thus impacting the efficacy of anticancer drugs. The present study's objective was to determine the effects of the epigenetic drug, 5-aza-2'-deoxycytidine (DAC), delivered in sustained-release nanogels (DAC-NGs), on the composition and biophysical properties of membrane lipids of resistant cells. Resistant and sensitive cells were treated with DAC in solution (DAC-sol) or DAC-NGs, and cell-membrane lipids were isolated and analyzed for lipid composition and biophysical properties. In resistant cells, we found increased formation of cholesterol-sphingomyelin (CHOL-SM) rafts with culturing time, whereas DAC treatment reduced their formation. In general, the effect of DAC-NGs was greater in changing the lipid composition than with DAC-sol. DAC treatment also caused a rise in levels of certain phospholipids and neutral lipids known to increase membrane fluidity, while reducing the levels of certain lipids known to increase membrane rigidity. Isotherm data showed increased lipid membrane fluidity following DAC treatment, attributed to decrease levels of CHOL-SM rafts (lamellar beta [Lβ] structures or ordered gel) and a corresponding increase in lipids that form lamellar alpha-structures (Lα, liquid crystalline phase). Sensitive cells showed marginal or insignificant changes in lipid profile following DAC-treatment, suggesting that epigenetic changes affecting lipid biosynthesis are more specific to resistant cells. Since membrane fluidity plays a major role in drug transport

  10. Scattering with absorptive interaction

    Science.gov (United States)

    Cassing, W.; Stingl, M.; Weiguny, A.

    1982-07-01

    The S matrix for a wide class of complex and nonlocal potentials is studied, with special attention given to the motion of singularities in the complex k plane as a function of the imaginary coupling strength. Modifications of Levinson's theorem are obtained and discussed. Analytic approximations to the S matrix in the vicinity of narrow resonances are exhibited and compared to numerical results of resonating-group calculations. The problem of defining resonances in the case of complex interactions is discussed, making contact with the usual analysis of scattering in terms of Argand diagrams. NUCLEAR REACTIONS Scattering theory, S matrix for absorptive potentials.

  11. Absorption in dielectric models

    CERN Document Server

    Churchill, R J

    2015-01-01

    We develop a classical microscopic model of a dielectric. The model features nonlinear interaction terms between polarizable dipoles and lattice vibrations. The lattice vibrations are found to act as a pseudo-reservoir, giving broadband absorption of electromagnetic radiation without the addition of damping terms in the dynamics. The effective permittivity is calculated using a perturbative iteration method and is found to have the form associated with real dielectrics. Spatial dispersion is naturally included in the model and we also calculate the wavevector dependence of the permittivity.

  12. Geospatial Absorption and Regional Effects

    Directory of Open Access Journals (Sweden)

    IOAN MAC

    2009-01-01

    Full Text Available The geospatial absorptions are characterized by a specific complexity both in content and in their phenomenological and spatial manifestation fields. Such processes are differentiated according to their specificity to pre-absorption, absorption or post-absorption. The mechanisms that contribute to absorption are extremely numerous: aggregation, extension, diffusion, substitution, resistivity (resilience, stratification, borrowings, etc. Between these mechanisms frequent relations are established determining an amplification of the process and of its regional effects. The installation of the geographic osmosis phenomenon in a given territory (a place for example leads to a homogenization of the geospatial state and to the installation of the regional homogeneity.

  13. Lipid raft disarrangement as a result of neuropathological progresses: a novel strategy for early diagnosis?

    Science.gov (United States)

    Marin, R; Rojo, J A; Fabelo, N; Fernandez, C E; Diaz, M

    2013-08-15

    Lipid rafts are the preferential site of numerous membrane signaling proteins which are involved in neuronal functioning and survival. These proteins are organized in multiprotein complexes, or signalosomes, in close contact with lipid classes particularly represented in lipid rafts (i.e. cholesterol, sphingolipids and saturated fatty acids), which may contribute to physiological responses leading to neuroprotection. Increasing evidence indicates that alteration of lipid composition in raft structures as a consequence of neuropathologies, such as Alzheimer's disease (AD) and Parkinson's disease (PD), causes a dramatic increase in lipid raft order. These phenomena may correlate with perturbation of signalosome activities, likely contributing to neurodegenerative progression. Interestingly, significant disruption of stable raft microenvironments has been already observed in the first stages of either AD or PD, suggesting that these alterations may represent early events in the neuropathological development. In this regard, the search for biochemical markers, such as specific metabolic products altered in the brain at the first steps of the disease, presently represents an important challenge for early diagnostic strategies. Alterations of these biomarkers may be reflected in either plasma or cerebrospinal fluid, thus representing a potential strategy to predict an accurate diagnosis. We propose that pathologically-linked lipid raft markers may be interesting candidates to be explored at this level, although it has not been studied so far to what extent alteration of different signalosome components may be reflected in peripheral fluids. In this mini-review, we will discuss on relevant aspects of lipid rafts that contribute to the modulation of neuropathological events related to AD and PD. An interesting hypothesis is that anomalies on raft biomarkers measured at peripheral fluids might mirror the lipid raft pathology observed in early stages of AD and PD.

  14. Mannosylerythritol lipids: a review.

    Science.gov (United States)

    Arutchelvi, Joseph Irudayaraj; Bhaduri, Sumit; Uppara, Parasu Veera; Doble, Mukesh

    2008-12-01

    Mannosylerythritol lipids (MELs) are surface active compounds that belong to the glycolipid class of biosurfactants (BSs). MELs are produced by Pseudozyma sp. as a major component while Ustilago sp. produces them as a minor component. Although MELs have been known for over five decades, they recently regained attention due to their environmental compatibility, mild production conditions, structural diversity, self-assembling properties and versatile biochemical functions. In this review, the MEL producing microorganisms, the production conditions, their applications, their diverse structures and self-assembling properties are discussed. The biosynthetic pathways and the regulatory mechanisms involved in the production of MEL are also explained here. PMID:18716809

  15. Polar Lipid Extraction

    OpenAIRE

    sprotocols

    2014-01-01

    Author: Biotechniques Polar lipids are generally extracted from dry cell material using chloroform:methanol:0.3% NaCl (1:2:0.8 v/v/v). This may be carried out by adding 9.5 ml of this mixture to 100 mg of freeze dried cells, or by adding a suitable amount of chloroform, methanol and 0.3% NaCl to the cell material, or to the aqueous methanolic phase remaining from the lipoquinone extraction. 1. The aqueous methanolic phase (4 ml total volume), together with the cell material from the ...

  16. Lipid-transfer proteins.

    Science.gov (United States)

    Ng, Tzi Bun; Cheung, Randy Chi Fai; Wong, Jack Ho; Ye, Xiujuan

    2012-01-01

    Lipid-transfer proteins (LTPs) are basic proteins found in abundance in higher plants. LTPs play lots of roles in plants such as participation in cutin formation, embryogenesis, defense reactions against phytopathogens, symbiosis, and the adaptation of plants to various environmental conditions. In addition, LTPs from field mustard and Chinese daffodil exhibit antiproliferative activity against human cancer cells. LTPs from chili pepper and coffee manifest inhibitory activity against fungi pathogenic to humans such as Candida species. The intent of this article is to review LTPs in the plant kingdom. PMID:23193591

  17. [Cutaneous absorption of chemicals].

    Science.gov (United States)

    Schröder, J

    1986-09-01

    Chemicals have become indispensible for the maintenance of health in animals and man. The route of administration of each medicament is decided by factors such as site of desired action, chemistry of the active ingredient, age and species of the patient, and frequency of administration (or desired duration of activity). In situations where the oral and hypodermic routes, which are used most frequently, are inadequate or unsatisfactory, dermal application can provide a valuable alternative method to achieve systemic activity. Examples of formulations currently available for dermal application contain diverse chemicals and are intended for a variety of purposes, such as crufomate against cattle grubs, fenthion against cattle lice, levamisole against gastrointestinal nematodes, nitroglycerine for angina pectoris, and scopolamine for motion sickness. The skin acts as a barrier to penetration by chemicals and micro-organisms by virtue of its morphology and chemical composition. Chemicals which do penetrate, do not necessarily pass through the appendages (hair follicles and gland ducts), but mostly penetrate through the interjacent epidermis, either through the cells, or via the intracellular spaces. These spaces have recently been shown by electron microscopy to be filled by an amorphous substance which exudes on the skin surface in convex ridges. This substance has a lipid nature, but is not hydrophobic as is often accepted. For a chemical to be able to penetrate the skin, it must be partially water and lipid soluble, polar, and weakly ionizing. A variety of factors can possibly affect the permeability of skin for a chemical. These include species differences in morphology (skin thickness, tightness of intercellular junctions, density of hair follicles and other appendages), biochemistry, and physiology; seasonal and climatic variations; and differences between breeds and genders. Species differences in skin permeability are largely unpredictable and inconsistent. An

  18. FORMULATION AND OPTIMIZATION OF CEFPODOXIME PROXETIL LOADED SOLID LIPID NANOPARTICLES BY BOX-BEHNKEN DESIGN

    Directory of Open Access Journals (Sweden)

    Umesh A. Nimbalkar

    2011-06-01

    Full Text Available The objective of this study was to develop and evaluate solid lipid nanoparticles of Cefpodoxime Proxetil for enhancement of bioavailability via its lymphatic absorption. The solid lipid nanoparticles (SLNs were prepared by solvent evaporation method using Precirol as a lipid carrier. A Box Behnken design has been applied to study the effect of independent variables i.e. lipid concentration, span 60 concentration and stirring speed on dependent variables i.e. particle size and entrapment efficiency. Response surface plots and counter plots were drawn and optimum formulations were selected based on feasibility search method. Validation of optimized study performed using four confirmatory runs indicated very high degree of prognostic ability of response surface methodology, with mean percentage error as +0.02. Optimized SLN formulations were freeze dried and its effect on particle size was evaluated. Optimized solid lipid nanoparticles were evaluated for EE, Drug content, FTIR, DSC, SEM and in vitro drug release study.

  19. Oral delivery of peptides and proteins using lipid-based drug delivery systems

    DEFF Research Database (Denmark)

    Li, Ping; Nielsen, Hanne Mørck; Müllertz, Anette

    2012-01-01

    INTRODUCTION: In order to successfully develop lipid-based drug delivery systems (DDS) for oral administration of peptides and proteins, it is important to gain an understanding of the colloid structures formed by these DDS, the mode of peptide and protein incorporation as well as the mechanism...... by which intestinal absorption of peptides and proteins is promoted. AREAS COVERED: The present paper reviews the literature on lipid-based DDS, employed for oral delivery of peptides and proteins and highlights the mechanisms by which the different lipid-based carriers are expected to overcome the two...... most important barriers (extensive enzymatic degradation and poor transmucosal permeability). This paper also gives a clear-cut idea about advantages and drawbacks of using different lipidic colloidal carriers ((micro)emulsions, solid lipid core particles and liposomes) for oral delivery of peptides...

  20. Altered membrane lipid dynamics and chemoprevention by non-steroidal anti inflammatory drugs during colon carcinogenesis Alteración de la dinámica de los lípidos de membrana y quimioprevención mediante los fármacos antiinflamatorios no esteroideos en la carcinogénesis de colon

    OpenAIRE

    S. Singh Kanwar; V. Vaish; S. Nath Sanya

    2011-01-01

    The present work focuses on the anti-neoplastic role of non steroidal anti-inflammatory drugs (NSAIDs) in modulating the biophysical parameters of the colonic membranes in 1,2-dimethylhydrazine dihydrochloride (DMH) induced carcinogenesis. The steady-state fluorescence polarization technique was applied to assess membrane fluidity, membrane polarity and lipid phase states. The decline in cholesterol content, biosynthesis and cholesterol: phospholipids ratio with DMH treatment indicates more f...

  1. Exposure to flaxseed during lactation does not alter prostate area or epithelium height but changes lipid profile in rats Exposición a la linaza durante la lactación no cambia el área o altura epitelial de la próstata pero cambia el perfil lipídico en ratones

    OpenAIRE

    L. Ferreira Medeiros de França Cardozo; M. Alves Chagas; L. Leal Soares; A. Andrade Troina; G. Teles Bonaventura

    2010-01-01

    Flaxseed intake has increased owing to beneficial effects to health and prevention of diseases. Provided that it's an important source of lignan, a phytoestrogen, the present study aimed at evaluating the possible effect of the intake of this seed during lactation upon prostate, sexual hormones and lipidic profile of the offspring in adult life. Material and methods: 16 female Wistar rats were used. After delivery, they were divided into two different groups to receive one of the following di...

  2. Absorption Spectra of Astaxanthin Aggregates

    CERN Document Server

    Olsina, Jan; Minofar, Babak; Polivka, Tomas; Mancal, Tomas

    2012-01-01

    Carotenoids in hydrated polar solvents form aggregates characterized by dramatic changes in their absorption spectra with respect to monomers. Here we analyze absorption spectra of aggregates of the carotenoid astaxanthin in hydrated dimethylsulfoxide. Depending on water content, two types of aggregates were produced: H-aggregates with absorption maximum around 390 nm, and J-aggregates with red-shifted absorption band peaking at wavelengths >550 nm. The large shifts with respect to absorption maximum of monomeric astaxanthin (470-495 nm depending on solvent) are caused by excitonic interaction between aggregated molecules. We applied molecular dynamics simulations to elucidate structure of astaxanthin dimer in water, and the resulting structure was used as a basis for calculations of absorption spectra. Absorption spectra of astaxanthin aggregates in hydrated dimethylsulfoxide were calculated using molecular exciton model with the resonance interaction energy between astaxanthin monomers constrained by semi-e...

  3. Electromagnetically-enhanced saturable absorption

    CERN Document Server

    Su, Chun-Hsu; Beausoleil, Raymond G; Hollenberg, Lloyd C L; Munro, William J; Nemoto, Kae; Spiller, Timothy P

    2009-01-01

    Electromagnetically-induced transparency (EIT) exploits quantum coherence to burn subnatural linewidth holes within a spectral line. It is typically discussed in the context of a pump-probe configuration in a three-level L system, where the pump is often significantly stronger than the probe. Here we remove such restrictions on the relative intensities of pump and probe fields, and furthermore show that the absorptive properties associated with EIT can be of benefit in absorptive nonlinear processes, especially saturable absorption. We show that in a three-level medium near the EIT condition, we can generate saturable absorption qualitatively similar to two-state saturable absorption. The difference is that we can explore saturable absorption against the ground-state dephasing, rather than spontaneous emission. This has the advantages of significantly more controllability, and more importantly, different intensity scalings in the absorption. Such effects could prove useful for signal regeneration at very low ...

  4. Lipids and membrane lateral organization

    Directory of Open Access Journals (Sweden)

    Sandro eSonnino

    2010-11-01

    Full Text Available Shortly after the elucidation of the very basic structure and properties of cellular membranes, it became evident that cellular membranes are highly organized structures with multiple and multi-dimensional levels of order. Very early observations suggested that the lipid components of biological membranes might be active players in the creations of these levels of order. In the late 80’s, several different and diverse experimental pieces of evidence coalesced together giving rise to the lipid raft hypothesis. Lipid rafts became enormously (and, in the opinion of these authors, sometimes acritically popular, surprisingly not just within the lipidologist community (who is supposed to be naturally sensitive to the fascination of lipid rafts. Today, a PubMed search using the key word lipid rafts returned a list of 3767 papers, including 690 reviews (as a term of comparison, searching over the same time span for a very hot lipid-related key word, ceramide returned 6187 hits with 799 reviews, and a tremendous number of different cellular functions have been described as lipid raft-dependent. However, a clear consensus definition of lipid raft has been proposed only in recent times, and the basic properties, the ruling forces, and even the existence of lipid rafts in living cells have been recently matter of intense debate. The scenario that is gradually emerging from the controversies elicited by the lipid raft hypothesis emphasize multiple roles for membrane lipids in determining membrane order, that encompasses their tendency to phase separation but are clearly not limited to this. In this review, we would like to re-focus the attention of the readers on the importance of lipids in organizing the fine structure of cellular membranes.

  5. DEVELOPMENT OF NOVEL LIPID BASED DRUG DELIVERY SYSTEM FOR RALOXIFENE HYDROCHLORIDE

    Directory of Open Access Journals (Sweden)

    Vijaykumar Nekkanti

    2012-09-01

    Full Text Available Lipid-based delivery systems are becoming increasingly popular as carriers of drugs due to their ability to overcome barriers to oral absorption. The objective of the present study was to prepare novel lipid-based formulation of a sparingly soluble drug, Raloxifene hydrochloride (RLX to increase its saturation solubility and dissolution velocity for enhancing bioavailability while reducing systemic variability. Lipid-based formulations were prepared using melt solubilization technique. The liquid formulations were converted into a solid intermediate by adsorbing onto an inert carrier and blended with excipients for encapsulation. The solid state properties, surface morphology and in-vitro release characteristics of the lipid formulations were investigated and compared with commercial formulation. The characterization of lipid formulations using Differential scanning calorimetry (DSC, X-ray powder diffraction (XRPD and Scanning electron microscopy (SEM indicated that the drug is completely enveloped in the lipid core. The dissolution characteristics of lipid based formulation filled in hard gelatin capsules showed faster rate of drug dissolution as compared to commercial tablet formulation (Fiona®. The in-vitro release studies in fed state simulated intestinal fluid (FeSSIF and fasted state simulated intestinal fluid (FaSSIF media indicated that, the variability in fed and fasted conditions was significantly reduced with lipid based formulation. The results from this study suggest the potential use of lipid based formulation a means of improving solubility, dissolution and concomitantly the bioavailability of a sparingly soluble drug like RLX.

  6. Lipid nano/submicron emulsions as vehicles for topical flurbiprofen delivery.

    Science.gov (United States)

    Fang, Jia-You; Leu, Yann-Lii; Chang, Chia-Chun; Lin, Chia-Hsuan; Tsai, Yi-Hung

    2004-01-01

    The application of lipid nano/submicron emulsions as topical drug carrier systems for the percutaneous absorption of flurbiprofen was investigated. The lipid emulsions were made up of isopropyl myristate (IPM), soybean oil, or coconut oil as the oil phase, egg lecithin as the predominant emulsifier, and double-distilled water as the external phase. Stearylamine (SA) and deoxycholic acid (DA) also were used to produce positively and negatively charged emulsions. To evaluate the physicochemical properties of the lipid emulsions, particle size by laser light scattering, the image of atomic force microscopy, and relaxation time values by Nuclear Magnetic Resonance (NMR) were determined. The in vitro permeation data showed that incorporation of SA significantly reduced the topical delivery of flurbiprofen. On the other hand, incorporation of DA exhibited no or a negligible effect on drug permeation. Enhancement of drug absorption was observed when adding oleic acid as part of the oil phase. The in vivo topical application of flurbiprofen from selected lipid emulsions showed a similar trend to the in vitro status. Furthermore, the intersubject variability was considerably reduced by lipid emulsions than by aqueous suspensions in both the in vitro and in vivo experiments. The irritant profiles of lipid emulsions showed that IPM elicited higher irritation than soybean oil. The incorporation of oleic acid also produced skin disruption. The results in the present study suggest the feasibility of lipid emulsions for the topical delivery of flurbiprofen.

  7. The HI absorption 'Zoo'

    CERN Document Server

    Gereb, K; Morganti, R; Oosterloo, T A

    2014-01-01

    We present an analysis of the HI absorption in a sample of 101 flux-selected radio AGN (S_1.4 GHz > 50 mJy) observed with the Westerbork Synthesis Radio Telescope (WSRT). HI absorption is detected in 32 galaxies, showing a broad variety of widths, shapes and kinematical properties. We characterize the HI spectra of the individual detections using the busy function (Westmeier et al. 2014). With the goal of identifying different morphological structures of HI, we study the kinematical and radio source properties of the detections as function of their width. Narrow lines (FWHM = 500 km/s). These detections are good candidates for being HI outflows. The detection rate of HI outflows is 5 percent in the total radio AGN sample. This fraction represents a lower limit, however it could suggests that, if outflows are a characteristic phenomenon of all radio sources, they would have a short depletion timescale compared to the lifetime of the AGN. Blueshifted and broad/asymmetric lines are more often present among young...

  8. Lipid-lowering agents.

    Science.gov (United States)

    Ewang-Emukowhate, Mfon; Wierzbicki, Anthony S

    2013-09-01

    The role of lipid lowering in reducing the risk of mortality and morbidity from cardiovascular disease (CVD) is well established. Treatment particularly aimed at decreasing low-density lipoprotein cholesterol (LDL-C) is effective in reducing the risk of death from coronary heart disease and stroke. Statins form the cornerstone of treatment. However, in some individuals with a high risk of CVD who are unable to achieve their target LDL-C due to either intolerance or lack of efficacy, there is the need for alternative therapies. This review provides an overview of the different classes of currently available lipid-lowering medications including statins, fibrates, bile acid sequestrants (resins), and omega-3 fatty acids. Data are presented on their indications, pharmacology, and the relevant end point clinical trial data with these drugs. It also discusses the human trial data on some novel therapeutic agents that are being developed including those for homozygous familial hypercholesterolemia--the antisense oligonucleotide mipomersen and the microsomal transfer protein inhibitor lomitapide. Data are presented on phase II and III trials on agents with potentially wider applications, cholesterol ester transfer protein inhibitors and proprotein convertase subtilisin kexin 9 inhibitors. The data on a licensed gene therapy for lipoprotein lipase deficiency are also presented.

  9. Lipid hydroperoxides in plants.

    Science.gov (United States)

    Griffiths, G; Leverentz, M; Silkowski, H; Gill, N; Sánchez-Serrano, J J

    2000-12-01

    Hydroperoxides are the primary oxygenated products of polyunsaturated fatty acids and were determined spectrophotometrically based on their reaction with an excess of Fe2+ at low pH in the presence of the dye Xylenol Orange. Triphenylphosphine-mediated hydroxide formation was used to authenticate the signal generated by the hydroperoxides. The method readily detected lipid peroxidation in a range of plant tissues including Phaseolus hypocotyls (26 +/- 5 nmol.g of fresh weight(-1); mean +/- S.D.), Alstroemeria floral tissues (sepals, 66+/-13 nmol.g of fresh weight(-1); petals, 49+/-6 nmol.g of fresh weight(-1)), potato leaves (334+/-75 nmol.g of fresh weight(-1)), broccoli florets (568+/-68 nmol.g of fresh weight(-1)) and Chlamydomonas cells (602+/-40 nmol.g of wet weight(-1)). Relative to the total fatty acid content of the tissues, the percentage hydroperoxide content was within the range of 0.6-1.7% for all tissue types (photosynthetic and non-photosynthetic) and represents the basal oxidation level of membrane fatty acids in plant cells. Leaves of transgenic potato with the fatty acid hydroperoxide lyase enzyme expressed in the antisense orientation were elevated by 38%, indicating a role for this enzyme in the maintenance of cellular levels of lipid hydroperoxides. PMID:11171226

  10. Design, Synthesis, and Characterization of Novel Zwitterionic Lipids for Drug and siRNA Delivery Applications

    Science.gov (United States)

    Walsh, Colin L.

    Lipid-based nanoparticles have long been used to deliver biologically active molecules such as drugs, proteins, peptides, DNA, and siRNA in vivo. Liposomes and lipoplexes alter the biodistribution, pharmacokinetics, and cellular uptake of their encapsulated or associated cargo. This can increase drug efficacy while reducing toxicity, resulting in an increased therapeutic index and better clinical outcomes. Unlike small molecule drugs, which passively diffuse through lipid membranes, nucleic acids and proteins require an active, carrier mediated escape mechanism to reach their site of action. As such, the therapeutic application and drug properties dictate the required biophysical characteristics of the lipid nanoparticle. These carrier properties depend on the structure and biophysical characteristics of the lipids and other components used to formulate them. This dissertation presents a series of studies related to the development of novel synthetic lipids for use in drug delivery systems. First, we developed a novel class of zwitterionic lipids with head groups containing a cationic amine and anionic carboxylate and ester-linked oleic acid tails. These lipids exhibit structure-dependent, pH-responsive biophysical properties, and may be useful components for next-generation drug delivery systems. Second, we extended the idea of amine/carboxylate containing zwitterionic head groups and synthesized a series of acetate terminated diacyl lipids containing a quaternary amine. These lipids have an inverted headgroup orientation compared to naturally occurring zwitterionic lipids, and show interesting salt-dependent biophysical properties. Third, we synthesized and characterized a focused library of ionizable lysine-based lipids, which contain a lysine head group linked to a long-chain dialkylamine. A focused library was synthesized to determine the impact of hydrophobic fluidity, lipid net charge, and lipid pKa on the biophysical and siRNA transfection characteristics

  11. Modelling phagosomal lipid networks that regulate actin assembly

    Directory of Open Access Journals (Sweden)

    Schwarz Roland

    2008-12-01

    Full Text Available Abstract Background When purified phagosomes are incubated in the presence of actin under appropriate conditions, microfilaments start growing from the membrane in a process that is affected by ATP and the lipid composition of the membrane. Isolated phagosomes are metabolically active organelles that contain enzymes and metabolites necessary for lipid interconversion. Hence, addition of ATP, lipids, and actin to the system alter the steady-state composition of the phagosomal membrane at the same time that the actin nucleation is initiated. Our aim was to model all these processes in parallel. Results We compiled detailed experimental data on the effects of different lipids and ATP on actin nucleation and we investigated experimentally lipid interconversion and ATP metabolism in phagosomes by using suitable radioactive compounds. In a first step, a complex lipid network interconnected by chemical reactions catalyzed by known enzymes was modelled in COPASI (Complex Pathway Simulator. However, several lines of experimental evidence indicated that only the phosphatidylinositol branch of the network was active, an observation that dramatically reduced the number of parameters in the model. The results also indicated that a lipid network-independent ATP-consuming activity should be included in the model. When this activity was introduced, the set of differential equations satisfactorily reproduced the experimental data. On the other hand, a molecular mechanism connecting membrane lipids, ATP, and the actin nucleation process is still missing. We therefore adopted a phenomenological (black-box approach to represent the empirical observations. We proposed that lipids and ATP influence the dynamic interconversion between active and inactive actin nucleation sites. With this simple model, all the experimental data were satisfactorily fitted with a single positive parameter per lipid and ATP. Conclusion By establishing an active 'dialogue' between an

  12. Fsp27 promotes lipid droplet growth by lipid exchange and transfer at lipid droplet contact sites

    OpenAIRE

    Gong, Jingyi; Sun, Zhiqi; Wu, Lizhen; Xu, Wenyi; Schieber, Nicole; Xu, Dijin; Shui, Guanghou; Yang, Hongyuan; Parton, Robert G.; Li, Peng

    2011-01-01

    Lipid droplets (LDs) are dynamic cellular organelles that control many biological processes. However, molecular components determining LD growth are poorly understood. Genetic analysis has indicated that Fsp27, an LD-associated protein, is important in controlling LD size and lipid storage in adipocytes. In this paper, we demonstrate that Fsp27 is focally enriched at the LD–LD contacting site (LDCS). Photobleaching revealed the occurrence of lipid exchange between contacted LDs in wild-type a...

  13. Solid lipid nanoparticles for parenteral drug delivery

    NARCIS (Netherlands)

    Wissing, S.A.; Kayser, Oliver; Muller, R.H.

    2004-01-01

    This review describes the use of nanoparticles based on solid lipids for the parenteral application of drugs. Firstly, different types of nanoparticles based on solid lipids such as "solid lipid nanoparticles" (SLN), "nanostructured lipid carriers" (NLC) and "lipid drug conjugate" (LDC) nanoparticle

  14. Avocado oils and hepatic lipid metabolism in growing rats.

    Science.gov (United States)

    Werman, M J; Neeman, I; Mokady, S

    1991-02-01

    The effect of various avocado oils on liver metabolism was studied in growing female rats. The rats were fed diets containing 10% (w/w) avocado oil for 4 wk. In comparison with rats fed refined avocado oil obtained from cored fruit by centrifugal separation, rats fed unrefined avocado oil obtained by organic solvent extraction from intact fruit, or its unsaponifiable components, showed a significant increase in total liver lipogenesis as well as in phospholipid and triglceride synthesis. Rats fed avocado-seed oil exhibited enhanced [1-14C]acetate incorporation into total liver lipids but showed the same distribution of label in the three main lipid classes as that of rats fed refined avocado oil. In addition, a significant reduction of triglycerides and protein content of plasma very-low-density lipoprotein and high-density lipoprotein fractions was observed in rats fed avocado-seed oil as compared with rats fed refined oil. Electron micrographs suggested that the alterations in hepatic lipogenesis are related to the marked proliferation of the smooth endoplasmic reticulum, which is known to be associated with induction of enzymes involved with lipid biosynthesis. The differences between the animals fed seed oil and those fed the unrefined oils, in the distribution of label within the main lipid classes, indicate that more than one factor is involved in the alterations caused by these oils.

  15. The ether lipid-deficient mouse: tracking down plasmalogen functions.

    Science.gov (United States)

    Gorgas, Karin; Teigler, Andre; Komljenovic, Dorde; Just, Wilhelm W

    2006-12-01

    Chemical and physico-chemical properties as well as physiological functions of major mammalian ether-linked glycerolipids, including plasmalogens were reviewed. Their chemical structures were described and their effect on membrane fluidity and membrane fusion discussed. The recent generation of mouse models with ether lipid deficiency offered the possibility to study ether lipid and particularly plasmalogen functions in vivo. Ether lipid-deficient mice revealed severe phenotypic alterations, including arrest of spermatogenesis, development of cataract and defects in central nervous system myelination. In several cell culture systems lack of plasmalogens impaired intracellular cholesterol distribution affecting plasma membrane functions and structural changes of ER and Golgi cisternae. Based on these phenotypic anomalies that were accurately described conclusions were drawn on putative functions of plasmalogens. These functions were related to cell-cell or cell-extracellular matrix interactions, formation of lipid raft microdomains and intracellular cholesterol homeostasis. There are several human disorders, such as Zellweger syndrome, rhizomelic chondrodysplasia punctata, Alzheimer's disease, Down syndrome, and Niemann-Pick type C disease that are distinguished by altered tissue plasmalogen concentrations. The role plasmalogens might play in the pathology of these disorders is discussed. PMID:17027098

  16. A Molecular Probe for the Detection of Polar Lipids in Live Cells

    Science.gov (United States)

    Bader, Christie A.; Shandala, Tetyana; Carter, Elizabeth A.; Ivask, Angela; Guinan, Taryn; Hickey, Shane M.; Werrett, Melissa V.; Wright, Phillip J.; Simpson, Peter V.; Stagni, Stefano; Voelcker, Nicolas H.; Lay, Peter A.; Massi, Massimiliano; Brooks, Douglas A.

    2016-01-01

    Lipids have an important role in many aspects of cell biology, including membrane architecture/compartment formation, intracellular traffic, signalling, hormone regulation, inflammation, energy storage and metabolism. Lipid biology is therefore integrally involved in major human diseases, including metabolic disorders, neurodegenerative diseases, obesity, heart disease, immune disorders and cancers, which commonly display altered lipid transport and metabolism. However, the investigation of these important cellular processes has been limited by the availability of specific tools to visualise lipids in live cells. Here we describe the potential for ReZolve-L1™ to localise to intracellular compartments containing polar lipids, such as for example sphingomyelin and phosphatidylethanolamine. In live Drosophila fat body tissue from third instar larvae, ReZolve-L1™ interacted mainly with lipid droplets, including the core region of these organelles. The presence of polar lipids in the core of these lipid droplets was confirmed by Raman mapping and while this was consistent with the distribution of ReZolve-L1™ it did not exclude that the molecular probe might be detecting other lipid species. In response to complete starvation conditions, ReZolve-L1™ was detected mainly in Atg8-GFP autophagic compartments, and showed reduced staining in the lipid droplets of fat body cells. The induction of autophagy by Tor inhibition also increased ReZolve-L1™ detection in autophagic compartments, whereas Atg9 knock down impaired autophagosome formation and altered the distribution of ReZolve-L1™. Finally, during Drosophila metamorphosis fat body tissues showed increased ReZolve-L1™ staining in autophagic compartments at two hours post puparium formation, when compared to earlier developmental time points. We concluded that ReZolve-L1™ is a new live cell imaging tool, which can be used as an imaging reagent for the detection of polar lipids in different intracellular

  17. Lipids differentially degraded during tissue freezing and thawing

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Plants cope with freezing and thawing by altering the lipid composition of their cell membranes. Such cellular responses go through three phases Successful test flight of an airship Researchers with the Balloon Aircraft Research Center (BARC) of the Academy of Opto-electronics, CAS, succeeded in their first test flight of an aeroboat with a flight altitude up to 1,000 meters and an effective payload of 20 kilograms in Shandong on 25 December, 2007.

  18. Diffuse interstellar absorption bands

    Institute of Scientific and Technical Information of China (English)

    XIANG FuYuan; LIANG ShunLin; LI AiGen

    2009-01-01

    The diffuse interstellar bands (DIBs) are a large number of absorption bands that are superposed on the interstellar extinction curve and are of interstellar origin. Since the discovery of the first two DIBs in the 1920s, the exact nature of DIBs still remains unclear. This article reviews the history of the detec-tions of DIBs in the Milky Way and external galaxies, the major observational characteristics of DIBs, the correlations or anti-correlations among DIBs or between DIBs and other interstellar features (e.g. the prominent 2175 Angstrom extinction bump and the far-ultraviolet extinction rise), and the proposed candidate carriers. Whether they are also present in circumstellar environments is also discussed.

  19. Diffuse interstellar absorption bands

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The diffuse interstellar bands(DIBs) are a large number of absorption bands that are superposed on the interstellar extinction curve and are of interstellar origin. Since the discovery of the first two DIBs in the 1920s,the exact nature of DIBs still remains unclear. This article reviews the history of the detections of DIBs in the Milky Way and external galaxies,the major observational characteristics of DIBs,the correlations or anti-correlations among DIBs or between DIBs and other interstellar features(e.g. the prominent 2175 Angstrom extinction bump and the far-ultraviolet extinction rise),and the proposed candidate carriers. Whether they are also present in circumstellar environments is also discussed.

  20. The HI absorption "Zoo"

    Science.gov (United States)

    Geréb, K.; Maccagni, F. M.; Morganti, R.; Oosterloo, T. A.

    2015-03-01

    We present an analysis of the H I 21 cm absorption in a sample of 101 flux-selected radio AGN (S1.4 GHz> 50 mJy) observed with the Westerbork Synthesis Radio Telescope (WSRT). We detect H I absorption in 32 objects (30% of the sample). In a previous paper, we performed a spectral stacking analysis on the radio sources, while here we characterize the absorption spectra of the individual detections using the recently presented busy function. The H I absorption spectra show a broad variety of widths, shapes, and kinematical properties. The full width half maximum (FWHM) of the busy function fits of the detected H I lines lies in the range 32 km s-1 200 km s-1). We study the kinematical and radio source properties of each group, with the goal of identifying different morphological structures of H I. Narrow lines mostly lie at the systemic velocity and are likely produced by regularly rotating H I disks or gas clouds. More H I disks can be present among galaxies with lines of intermediate widths; however, the H I in these sources is more unsettled. We study the asymmetry parameter and blueshift/redshift distribution of the lines as a function of their width. We find a trend for which narrow profiles are also symmetric, while broad lines are the most asymmetric. Among the broadest lines, more lines appear blueshifted than redshifted, similarly to what was found by previous studies. Interestingly, symmetric broad lines are absent from the sample. We argue that if a profile is broad, it is also asymmetric and shifted relative to the systemic velocity because it is tracing unsettled H I gas. In particular, besides three of the broadest (up to FW20 = 825 km s-1) detections, which are associated with gas-rich mergers, we find three new cases of profiles with blueshifted broad wings (with FW20 ≳ 500 km s-1) in high radio power AGN. These detections are good candidates for being HI outflows. Together with the known cases of outflows already included in the sample (3C 293 and

  1. Genotype-induced changes in biophysical properties of frontal cortex lipid raft from APP/PS1 transgenic mice

    Directory of Open Access Journals (Sweden)

    Mario L Diaz

    2012-11-01

    Full Text Available Alterations in the lipid composition of lipid rafts have been demonstrated both in human brain and transgenic mouse models, and it has been postulated that aberrant lipid composition in lipid rafts is partly responsible for neuronal degeneration. In order to assess the impact of lipid changes on lipid raft functional properties, we have aimed at determining relevant physicochemical modifications in lipid rafts purified from frontal cortex of wild type (WT and APP/PS1 double transgenic mice. By means of steady-state fluorescence anisotropy analyses using two lipid soluble fluorescent probes, TMA-DPH (1-[(4-trimethyl-aminophenyl]-6-phenyl-1,3,5-hexatriene and DPH (1,6-diphenyl-1,3,5-hexatriene, we demonstrate that cortical lipid rafts from WT and APP/PS1 animals exhibit different biophysical behaviours, depending on genotype but also on age. Thus, aged APP/PS1 animals exhibited slightly more liquid-ordered lipid rafts than WT counterparts. Membrane microviscosity napp analyses demonstrate that WT lipid rafts are more fluid than APP/PS1 animals of similar age, both at the aqueous interface and hydrophobic core of the membrane. napp in APP/PS1 animals was higher for DPH than for TMA-DPH under similar experimental conditions, indicating that the internal core of the membrane is more viscous than the raft membrane at the aqueous interface. The most dramatic changes in biophysical properties of lipid rafts were observed when membrane cholesterol was depleted with methyl-beta-cyclodextrin. Overall, our results indicate that APP/PS1 genotype strongly affects physicochemical properties of lipid raft. Such alterations appear not to be homogeneous across the raft membrane axis, but rather are more prominent at the membrane plane. These changes correlate with aberrant proportions of sphingomyelin, cholesterol and saturated fatty acids, as well as polyunsaturated fatty acids, measured in lipid rafts from frontal cortex in this familial model of

  2. Perspectives on marine zooplankton lipids

    DEFF Research Database (Denmark)

    Kattner, G.; Hagen, W.; Lee, R.F.;

    2007-01-01

    and quantify food web relationships? With the fourth, hypotheses are presented on effects of global warming, which may result in the reduction or change in abundance of large, lipid-rich copepods in polar oceans, thereby strongly affecting higher trophic levels. The key question is how will lipid dynamics...... respond to changes in ocean climate at high latitudes?....

  3. The Flexibility of Ectopic Lipids

    Science.gov (United States)

    Loher, Hannah; Kreis, Roland; Boesch, Chris; Christ, Emanuel

    2016-01-01

    In addition to the subcutaneous and the visceral fat tissue, lipids can also be stored in non-adipose tissue such as in hepatocytes (intrahepatocellular lipids; IHCL), skeletal (intramyocellular lipids; IMCL) or cardiac muscle cells (intracardiomyocellular lipids; ICCL). Ectopic lipids are flexible fuel stores that can be depleted by physical exercise and repleted by diet. They are related to obesity and insulin resistance. Quantification of IMCL was initially performed invasively, using muscle biopsies with biochemical and/or histological analysis. 1H-magnetic resonance spectroscopy (1H-MRS) is now a validated method that allows for not only quantifying IMCL non-invasively and repeatedly, but also assessing IHCL and ICCL. This review summarizes the current available knowledge on the flexibility of ectopic lipids. The available evidence suggests a complex interplay between quantitative and qualitative diet, fat availability (fat mass), insulin action, and physical exercise, all important factors that influence the flexibility of ectopic lipids. Furthermore, the time frame of the intervention on these parameters (short-term vs. long-term) appears to be critical. Consequently, standardization of physical activity and diet are critical when assessing ectopic lipids in predefined clinical situations. PMID:27649157

  4. The Flexibility of Ectopic Lipids

    Directory of Open Access Journals (Sweden)

    Hannah Loher

    2016-09-01

    Full Text Available In addition to the subcutaneous and the visceral fat tissue, lipids can also be stored in non-adipose tissue such as in hepatocytes (intrahepatocellular lipids; IHCL, skeletal (intramyocellular lipids; IMCL or cardiac muscle cells (intracardiomyocellular lipids; ICCL. Ectopic lipids are flexible fuel stores that can be depleted by physical exercise and repleted by diet. They are related to obesity and insulin resistance. Quantification of IMCL was initially performed invasively, using muscle biopsies with biochemical and/or histological analysis. 1H-magnetic resonance spectroscopy (1H-MRS is now a validated method that allows for not only quantifying IMCL non-invasively and repeatedly, but also assessing IHCL and ICCL. This review summarizes the current available knowledge on the flexibility of ectopic lipids. The available evidence suggests a complex interplay between quantitative and qualitative diet, fat availability (fat mass, insulin action, and physical exercise, all important factors that influence the flexibility of ectopic lipids. Furthermore, the time frame of the intervention on these parameters (short-term vs. long-term appears to be critical. Consequently, standardization of physical activity and diet are critical when assessing ectopic lipids in predefined clinical situations.

  5. Neuroimaging of Lipid Storage Disorders

    Science.gov (United States)

    Rieger, Deborah; Auerbach, Sarah; Robinson, Paul; Gropman, Andrea

    2013-01-01

    Lipid storage diseases, also known as the lipidoses, are a group of inherited metabolic disorders in which there is lipid accumulation in various cell types, including the central nervous system, because of the deficiency of a variety of enzymes. Over time, excessive storage can cause permanent cellular and tissue damage. The brain is particularly…

  6. Texture of lipid bilayer domains

    DEFF Research Database (Denmark)

    Jensen, Uffe Bernchou; Brewer, Jonathan R.; Midtiby, Henrik Skov;

    2009-01-01

    We investigate the texture of gel (g) domains in binary lipid membranes composed of the phospholipids DPPC and DOPC. Lateral organization of lipid bilayer membranes is a topic of fundamental and biological importance. Whereas questions related to size and composition of fluid membrane domain...

  7. Lipids in liver transplant recipients.

    Science.gov (United States)

    Hüsing, Anna; Kabar, Iyad; Schmidt, Hartmut H

    2016-03-28

    Hyperlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. The etiology of lipid disorders in these patients is multifactorial, with different lipid profiles observed depending on the immunosuppressive agents administered and the presence of additional risk factors, such as obesity, diabetes mellitus and nutrition. Due to recent improvements in survival of liver transplant recipients, the prevention of cardiovascular events has become more important, especially as approximately 64% of liver transplant recipients present with an increased risk of cardiovascular events. Management of dyslipidemia and of other modifiable cardiovascular risk factors, such as hypertension, diabetes and smoking, has therefore become essential in these patients. Treatment of hyperlipidemia after liver transplantation consists of life style modification, modifying the dose or type of immunosuppressive agents and use of lipid lowering agents. At the start of administration of lipid lowering medications, it is important to monitor drug-drug interactions, especially between lipid lowering agents and immunosuppressive drugs. Furthermore, as combinations of various lipid lowering drugs can lead to severe side effects, such as myopathies and rhabdomyolysis, these combinations should therefore be avoided. To our knowledge, there are no current guidelines targeting the management of lipid metabolism disorders in liver transplant recipients. This paper therefore recommends an approach of managing lipid abnormalities occurring after liver transplantation. PMID:27022213

  8. Fasting and nonfasting lipid levels

    DEFF Research Database (Denmark)

    Langsted, Anne; Freiberg, Jacob J; Nordestgaard, Børge G

    2008-01-01

    Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events.......Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events....

  9. The Flexibility of Ectopic Lipids.

    Science.gov (United States)

    Loher, Hannah; Kreis, Roland; Boesch, Chris; Christ, Emanuel

    2016-01-01

    In addition to the subcutaneous and the visceral fat tissue, lipids can also be stored in non-adipose tissue such as in hepatocytes (intrahepatocellular lipids; IHCL), skeletal (intramyocellular lipids; IMCL) or cardiac muscle cells (intracardiomyocellular lipids; ICCL). Ectopic lipids are flexible fuel stores that can be depleted by physical exercise and repleted by diet. They are related to obesity and insulin resistance. Quantification of IMCL was initially performed invasively, using muscle biopsies with biochemical and/or histological analysis. ¹H-magnetic resonance spectroscopy (¹H-MRS) is now a validated method that allows for not only quantifying IMCL non-invasively and repeatedly, but also assessing IHCL and ICCL. This review summarizes the current available knowledge on the flexibility of ectopic lipids. The available evidence suggests a complex interplay between quantitative and qualitative diet, fat availability (fat mass), insulin action, and physical exercise, all important factors that influence the flexibility of ectopic lipids. Furthermore, the time frame of the intervention on these parameters (short-term vs. long-term) appears to be critical. Consequently, standardization of physical activity and diet are critical when assessing ectopic lipids in predefined clinical situations. PMID:27649157

  10. Lipid droplets, lipophagy, and beyond.

    Science.gov (United States)

    Wang, Chao-Wen

    2016-08-01

    Lipids are essential components for life. Their various structural and physical properties influence diverse cellular processes and, thereby, human health. Lipids are not genetically encoded but are synthesized and modified by complex metabolic pathways, supplying energy, membranes, signaling molecules, and hormones to affect growth, physiology, and response to environmental insults. Lipid homeostasis is crucial, such that excess fatty acids (FAs) can be harmful to cells. To prevent such lipotoxicity, cells convert excess FAs into neutral lipids for storage in organelles called lipid droplets (LDs). These organelles do not simply manage lipid storage and metabolism but also are involved in protein quality management, pathogenesis, immune responses, and, potentially, neurodegeneration. In recent years, a major trend in LD biology has centered around the physiology of lipid mobilization via lipophagy of fat stored within LDs. This review summarizes key findings in LD biology and lipophagy, offering novel insights into this rapidly growing field. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID:26713677

  11. Roles of Lipids in Photosynthesis.

    Science.gov (United States)

    Kobayashi, Koichi; Endo, Kaichiro; Wada, Hajime

    2016-01-01

    Thylakoid membranes in cyanobacterial cells and chloroplasts of algae and higher plants are the sites of oxygenic photosynthesis. The lipid composition of the thylakoid membrane is unique and highly conserved among oxygenic photosynthetic organisms. Major lipids in thylakoid membranes are glycolipids, monogalactosyldiacylglycerol, digalactosyldiacylglycerol and sulfoquinovosyldiacylglycerol, and the phospholipid, phosphatidylglycerol. The identification of almost all genes involved in the biosynthesis of each lipid class over the past decade has allowed the generation and isolation of mutants of various photosynthetic organisms incapable of synthesizing specific lipids. Numerous studies using such mutants have revealed that these lipids play important roles not only in the formation of the lipid bilayers of thylakoid membranes but also in the folding and assembly of the protein subunits in photosynthetic complexes. In addition to the studies with the mutants, recent X-ray crystallography studies of photosynthetic complexes in thylakoid membranes have also provided critical information on the association of lipids with photosynthetic complexes and their activities. In this chapter, we summarize our current understanding about the structural and functional involvement of thylakoid lipids in oxygenic photosynthesis.

  12. Altered hypothalamic protein expression in a rat model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Wei-na Cong

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP, heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4, glycogen synthase1 (Gys1 and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1. In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD.

  13. Lipids changes in liver cancer

    Institute of Scientific and Technical Information of China (English)

    JIANG Jing-ting; XU Ning; ZHANG Xiao-ying; WU Chang-ping

    2007-01-01

    Liver is one of the most important organs in energy metabolism.Most plasma apolipoproteins and endogenous lipids and lipoproteins are synthesized in the liver.It depends on the integrity of liver cellular function,which ensures homeostasis of lipid and lipoprotein metabolism.When liver cancer occurs,these processes are impaired and the plasma lipid and lipoprotein patterns may be changed.Liver cancer is the fifth common malignant tumor worldwide,and is closely related to the infections of hepatitis B virus (HBV) and hepatitis C virus (HCV).HBV and HCV infections are quite common in China and other Southeast Asian countries.In addition,liver cancer is often followed by a procession of chronic hepatitis or cirrhosis,so that hepatic function is damaged obviously on these bases,which may significantly influence lipid and lipoprotein metabolism in vivo.In this review we summarize the clinical significance of lipid and lipoprotein metabolism under liver cancer.

  14. Cholesterol's location in lipid bilayers.

    Science.gov (United States)

    Marquardt, Drew; Kučerka, Norbert; Wassall, Stephen R; Harroun, Thad A; Katsaras, John

    2016-09-01

    It is well known that cholesterol modifies the physical properties of lipid bilayers. For example, the much studied liquid-ordered Lo phase contains rapidly diffusing lipids with their acyl chains in the all trans configuration, similar to gel phase bilayers. Moreover, the Lo phase is commonly associated with cholesterol-enriched lipid rafts, which are thought to serve as platforms for signaling proteins in the plasma membrane. Cholesterol's location in lipid bilayers has been studied extensively, and it has been shown - at least in some bilayers - to align differently from its canonical upright orientation, where its hydroxyl group is in the vicinity of the lipid-water interface. In this article we review recent works describing cholesterol's location in different model membrane systems with emphasis on results obtained from scattering, spectroscopic and molecular dynamics studies. PMID:27056099

  15. Infant digestion physiology and the relevance of in vitro biochemical models to test infant formula lipid digestion.

    Science.gov (United States)

    Poquet, Laure; Wooster, Tim J

    2016-08-01

    Lipids play an important role in the diet of preterm and term infants providing a key energy source and essential lipid components for development. While a lot is known about adult lipid digestion, our understanding of infant digestion physiology is still incomplete, the greatest gap being on the biochemistry of the small intestine, particularly the activity and relative importance of the various lipases active in the intestine. The literature has been reviewed to identify the characteristics of lipid digestion of preterm and term infants, but also to better understand the physiology of the infant gastrointestinal tract compared to adults that impacts the absorption of lipids. The main differences are a higher gastric pH, submicellar bile salt concentration, a far more important role of gastric lipases as well as differences at the level of the intestinal barrier. Importantly, the consequences of improper in vitro replication of gastric digestions conditions (pH and lipase specificity) are demonstrated using examples from the most recent of studies. It is true that some animal models could be adapted to study infant lipid digestion physiology, however the ethical relevance of such models is questionable, hence the development of accurate in vitro models is a must. In vitro models that combine up to date knowledge of digestion biochemistry with intestinal cells in culture are the best choice to replicate digestion and absorption in infant population, this would allow the adaptation of infant formula for a better digestion and absorption of dietary lipids by preterm and term infants. PMID:27279140

  16. The Relationship Between Chronic Inflammation and Glucidic-Lipidic Profile Disorders in Kidney Transplant Recipients

    OpenAIRE

    Tarța I.D.; Căldăraru Carmen Denise; Gliga Mirela; Huțanu Adina; Bajko Z; Carașca E; Dogaru G.A.

    2016-01-01

    Introduction: Chronic inflammation has a proven role in atherogenesis, lipid profile parameters being related to cytokine production. In kidney transplant recipients, interleukin 6 (IL-6) is significantly associated with graft-related outcomes and also alterations of cholesterol and triglyceride metabolism. The aim of this study was to investigate the relationship between chronic inflammation and glucidic-lipidic metabolism disorders in a group of patients with kidney transplantation as renal...

  17. Sexual dimorphism in the effects of exercise on metabolism of lipids to support resting metabolism

    OpenAIRE

    Henderson, Gregory C.

    2014-01-01

    Exercise training is generally a healthful activity and an effective intervention for reducing the risk of numerous chronic diseases including cardiovascular disease and diabetes. This is likely both a result of prevention of weight gain over time as well as direct effects of exercise on metabolism of lipids and the other macronutrient classes. Importantly, a single bout of exercise can alter lipid metabolism and metabolic rate for hours and even into the day following exercise, so individu...

  18. X-ray Absorption Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Yano, Junko; Yachandra, Vittal K.

    2009-07-09

    This review gives a brief description of the theory and application of X-ray absorption spectroscopy, both X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS), especially, pertaining to photosynthesis. The advantages and limitations of the methods are discussed. Recent advances in extended EXAFS and polarized EXAFS using oriented membranes and single crystals are explained. Developments in theory in understanding the XANES spectra are described. The application of X-ray absorption spectroscopy to the study of the Mn4Ca cluster in Photosystem II is presented.

  19. Lipid traffic: the ABC of transbilayer movement

    NARCIS (Netherlands)

    Raggers, R.J.; Pomorski, T.; Holthuis, J.C.M.; Kälin, N.; van Meer, G.

    2000-01-01

    Membrane lipids do not spontaneously exchange between the two leaflets of lipid bilayers because the polar headgroups cannot cross the hydrophobic membrane interior. Cellular membranes, notably eukaryotic plasma membranes, are equipped with special proteins that actively translocate lipids from one

  20. Meibum lipid composition in Asians with dry eye disease.

    Directory of Open Access Journals (Sweden)

    Sin Man Lam

    Full Text Available BACKGROUND: Previous lipidomic analyses of the human meibum had largely focused on individuals from non-Asian populations, despite the higher prevalence of dysfunctional tear syndrome (DTS observed across Asia. Information pertaining to the alterations in lipid profiles in relation to DTS onset and progression is also lacking and warrants comprehensive experimental analysis. METHODOLOGIES/PRINCIPAL FINDINGS: We examined the meibum lipidome of 27 DTS patients and 10 control subjects for a total of 256 lipid species from 12 major lipid classes, including cholesteryl ester (CE, wax ester (WE, triacylglyceride (TAG, (O-acyl-ω-hydroxy fatty acid (OAHFA, glycerophospholipids (phosphatidylcholine, PC; phosphatidylethanolamine, PE; phosphatidylinositol, PI; phosphatidylglycerol, PG and sphingolipids (sphingomyelin, SM; ceramide, Cer; glucosylceramide, GluCer; dihexosylceramide, DihexCer. Neutral lipids were analysed using high-performance liquid-chromatography coupled with mass spectrometry (HPLC/MS and tandem mass spectrometry (MS/MS was used for the qualitative and quantitative analysis of polar lipid species. DTS patients were classified into three severity groups (i.e. mild, moderate and severe based on the ocular surface disease index (OSDI. A significantly lower level of TAG (p<0.05 was observed in patients under the moderate category compared to the mild category. Notably, a number of OAHFA species displayed consistently decreasing levels that correlate with increasing disease severity. An attempt was also made to investigate the changes in meibum lipid profiles of DTS patients compared to normal individuals classified based on OSDI score. Several unsaturated TAG and PC species were found at significantly higher levels (p<0.05 in patients than controls. CONCLUSION: The current study presents, for the first time, a comprehensive lipidome of meibum from individuals of an Asian ethnicity, which can potentially offer new insights into the higher

  1. Effect of docosahexaenoic acid on interleukin-2 receptor signaling pathway in lipid rafts

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Recent studies have shown that polyunsaturated fatty acids (PUFA) regulated the functions of membrane receptors in T cells and suppressed T cell -mediated immune responses. But the molecular mechanisms of immune regulation are not yet elucidated. Lipid rafts are plasma membrane microdomains, in which many receptors localized. The purpose of this study was to investigate the effect of DHA on IL-2R signaling pathway in lipid rafts. We isolated lipid rafts by discontinuous sucrose density gradient ultracentrifugation, and found that DHA could change the composition of lipid rafts and alter the distribution of key molecules of IL-2R signaling pathway, which transferred from lipid rafts to detergent-soluble membrane fractions. These results revealed that DHA treatment increased the proportion of polyunsaturated fatty acids especially n(3 polyunsaturated fatty acids in lipid rafts and changed the lipid environment of membrane microdomains in T cells. Compared with controls, DHA changed the localization of IL-2R, STAT5a and STAT5b in lipid rafts and suppressed the expression of JAK1, JAK3 and tyrosine phosphotyrosine in soluble membrane fractions. Summarily, this study concluded the effects of DHA on IL-2R signaling pathway in lipid rafts and explained the regulation of PUFAs in T cell-mediated immune responses.

  2. Lipoproteins in Drosophila melanogaster--assembly, function, and influence on tissue lipid composition.

    Directory of Open Access Journals (Sweden)

    Wilhelm Palm

    Full Text Available Interorgan lipid transport occurs via lipoproteins, and altered lipoprotein levels correlate with metabolic disease. However, precisely how lipoproteins affect tissue lipid composition has not been comprehensively analyzed. Here, we identify the major lipoproteins of Drosophila melanogaster and use genetics and mass spectrometry to study their assembly, interorgan trafficking, and influence on tissue lipids. The apoB-family lipoprotein Lipophorin (Lpp is the major hemolymph lipid carrier. It is produced as a phospholipid-rich particle by the fat body, and its secretion requires Microsomal Triglyceride Transfer Protein (MTP. Lpp acquires sterols and most diacylglycerol (DAG at the gut via Lipid Transfer Particle (LTP, another fat body-derived apoB-family lipoprotein. The gut, like the fat body, is a lipogenic organ, incorporating both de novo-synthesized and dietary fatty acids into DAG for export. We identify distinct requirements for LTP and Lpp-dependent lipid mobilization in contributing to the neutral and polar lipid composition of the brain and wing imaginal disc. These studies define major routes of interorgan lipid transport in Drosophila and uncover surprising tissue-specific differences in lipoprotein lipid utilization.

  3. Enhancement of Lipid Extraction from Marine Microalga, Scenedesmus Associated with High-Pressure Homogenization Process

    Directory of Open Access Journals (Sweden)

    Seok-Cheol Cho

    2012-01-01

    Full Text Available Marine microalga, Scenedesmus sp., which is known to be suitable for biodiesel production because of its high lipid content, was subjected to the conventional Folch method of lipid extraction combined with high-pressure homogenization pretreatment process at 1200 psi and 35°C. Algal lipid yield was about 24.9% through this process, whereas only 19.8% lipid can be obtained by following a conventional lipid extraction procedure using the solvent, chloroform : methanol (2 : 1, v/v. Present approach requires 30 min process time and a moderate working temperature of 35°C as compared to the conventional extraction method which usually requires >5 hrs and 65°C temperature. It was found that this combined extraction process followed second-order reaction kinetics, which means most of the cellular lipids were extracted during initial periods of extraction, mostly within 30 min. In contrast, during the conventional extraction process, the cellular lipids were slowly and continuously extracted for >5 hrs by following first-order kinetics. Confocal and scanning electron microscopy revealed altered texture of algal biomass pretreated with high-pressure homogenization. These results clearly demonstrate that the Folch method coupled with high-pressure homogenization pretreatment can easily destruct the rigid cell walls of microalgae and release the intact lipids, with minimized extraction time and temperature, both of which are essential for maintaining good quality of the lipids for biodiesel production.

  4. The influence of non-polar lipids on tear film dynamics

    KAUST Repository

    Bruna, M.

    2014-04-04

    © 2014 Cambridge University Press. In this paper we examine the effect that physiological non-polar lipids, residing on the surface of an aqueous tear film, have on the film evolution. In our model we track the evolution of the thickness of the non-polar lipid layer, the thickness of the aqueous layer and the concentration of polar lipids which reside at the interface between the two. We also utilise a force balance in the non-polar lipid layer in order to determine its velocity. We show how to obtain previous models in the literature from our model by making particular choices of the parameters. We see the formation of boundary layers in some of these submodels, across which the concentration of polar lipid and the non-polar lipid velocity and film thickness vary. We solve our model numerically for physically realistic parameter values, and we find that the evolution of the aqueous layer and the polar lipid layer are similar to that described by previous authors. However, there are interesting dynamics for the non-polar lipid layer. The effects of altering the key parameters are highlighted and discussed. In particular, we see that the Marangoni number plays a key role in determining how far over the eye the non-polar lipid spreads.

  5. Singlet Oxygen-Mediated Oxidation during UVA Radiation Alters the Dynamic of Genomic DNA Replication.

    Directory of Open Access Journals (Sweden)

    Dany Graindorge

    Full Text Available UVA radiation (320-400 nm is a major environmental agent that can exert its deleterious action on living organisms through absorption of the UVA photons by endogenous or exogenous photosensitizers. This leads to the production of reactive oxygen species (ROS, such as singlet oxygen (1O2 and hydrogen peroxide (H2O2, which in turn can modify reversibly or irreversibly biomolecules, such as lipids, proteins and nucleic acids. We have previously reported that UVA-induced ROS strongly inhibit DNA replication in a dose-dependent manner, but independently of the cell cycle checkpoints activation. Here, we report that the production of 1O2 by UVA radiation leads to a transient inhibition of replication fork velocity, a transient decrease in the dNTP pool, a quickly reversible GSH-dependent oxidation of the RRM1 subunit of ribonucleotide reductase and sustained inhibition of origin firing. The time of recovery post irradiation for each of these events can last from few minutes (reduction of oxidized RRM1 to several hours (replication fork velocity and origin firing. The quenching of 1O2 by sodium azide prevents the delay of DNA replication, the decrease in the dNTP pool and the oxidation of RRM1, while inhibition of Chk1 does not prevent the inhibition of origin firing. Although the molecular mechanism remains elusive, our data demonstrate that the dynamic of replication is altered by UVA photosensitization of vitamins via the production of singlet oxygen.

  6. Succinobucol’s New Coat — Conjugation with Steroids to Alter Its Drug Effect and Bioavailability

    Directory of Open Access Journals (Sweden)

    Satu Ikonen

    2011-11-01

    Full Text Available Synthesis, detailed structural characterization (X-ray, NMR, MS, IR, elemental analysis, and studies of toxicity, antioxidant activity and bioavailability of unique potent anti-atherosclerotic succinobucol-steroid conjugates are reported. The conjugates consist of, on one side, the therapeutically important drug succinobucol ([4-{2,6-di-tert-butyl-4-[(1-{[3-tert-butyl-4-hydroxy-5-(propan-2-ylphenyl]sulfanyl}ethylsulfanyl]phenoxy}-4-oxo-butanoic acid] possessing an antioxidant and anti-inflammatory activity, and on the other side, plant stanol/sterols (stigmastanol, β-sitosterol and stigmasterol possessing an ability to lower the blood cholesterol level. A cholesterol-succinobucol prodrug was also prepared in order to enhance the absorption of succinobucol through the intestinal membrane into the organism and to target the drug into the place of lipid metabolism—The enterohepatic circulation system. Their low toxicity towards mice fibroblasts at maximal concentrations, their antioxidant activity, comparable or even higher than that of ascorbic acid as determined by direct quenching of the DPPH radical, and their potential for significantly altering total and LDL cholesterol levels, suggest that these conjugates merit further studies in the treatment of cardiovascular or other related diseases. A brief discussion of succinobucol’s ability to quench the radicals, supported with a computational model of the electrostatic potential mapped on the electron density surface of the drug, is also presented.

  7. Nonvesicular Lipid Transfer from the Endoplasmic Reticulum

    OpenAIRE

    Lev, Sima

    2012-01-01

    The transport of lipids from their synthesis site at the endoplasmic reticulum (ER) to different target membranes could be mediated by both vesicular and nonvesicular transport mechanisms. Nonvesicular lipid transport appears to be the major transport route of certain lipid species, and could be mediated by either spontaneous lipid transport or by lipid-transfer proteins (LTPs). Although nonvesicular lipid transport has been extensively studied for more than four decades, its underlying mecha...

  8. Cinnamon extract regulates intestinal lipid metabolism related gene expression in primary enterocytes of rats

    Science.gov (United States)

    Emerging evidence suggests that the small intestine is not a passive organ, but is actively involved in the regulation of lipid absorption, intracellular transport, and metabolism, and is closely linked to systemic lipoprotein metabolism. We have reported previously that the water-soluble components...

  9. Detection of bilayer lipid with graphene nanoribbon

    Science.gov (United States)

    Akbari, Elnaz; Buntat, Zolkafle; Afroozeh, Abdolkarim; Zeinalinezhad, Alireza; Nilashi, Mehrbakhsh

    2015-09-01

    Single-layer graphene consists of sp 2-bonded carbon atoms arranged in a two-dimensional (2D) hexagonal lattice comprising a thin layer of single carbon atoms. Owing to its special characteristics including electrical, physical, and optical properties, graphene is considered more suitable for sensor applications than other materials. Moreover, it is possible to produce biosensors using electrolyte-gated field-effect transistors based on graphene (GFETs) to identify the alterations in charged lipid membrane properties. This paper illustrates how membrane thickness and electrical charge can result in a monolayer GFET, with emphasis on conductance variation. It is proposed that the thickness and electrical charge of the lipid bilayer are functions of carrier density, and equations relating these suitable control parameters were derived. Adaptive neuro fuzzy inference system (ANFIS) has been incorporated to obtain other model for conductance characteristic. The comparison between the analytical models and ANFIS with the experimental data extracted from previous work show an acceptable agreement. [Figure not available: see fulltext.

  10. Protein Kinase A Subunit Balance Regulates Lipid Metabolism in Caenorhabditis elegans and Mammalian Adipocytes.

    Science.gov (United States)

    Lee, Jung Hyun; Han, Ji Seul; Kong, Jinuk; Ji, Yul; Lv, Xuchao; Lee, Junho; Li, Peng; Kim, Jae Bum

    2016-09-23

    Protein kinase A (PKA) is a cyclic AMP (cAMP)-dependent protein kinase composed of catalytic and regulatory subunits and involved in various physiological phenomena, including lipid metabolism. Here we demonstrated that the stoichiometric balance between catalytic and regulatory subunits is crucial for maintaining basal PKA activity and lipid homeostasis. To uncover the potential roles of each PKA subunit, Caenorhabditis elegans was used to investigate the effects of PKA subunit deficiency. In worms, suppression of PKA via RNAi resulted in severe phenotypes, including shortened life span, decreased egg laying, reduced locomotion, and altered lipid distribution. Similarly, in mammalian adipocytes, suppression of PKA regulatory subunits RIα and RIIβ via siRNAs potently stimulated PKA activity, leading to potentiated lipolysis without increasing cAMP levels. Nevertheless, insulin exerted anti-lipolytic effects and restored lipid droplet integrity by antagonizing PKA action. Together, these data implicate the importance of subunit stoichiometry as another regulatory mechanism of PKA activity and lipid metabolism.

  11. Lipids in the nervous system: from biochemistry and molecular biology to patho-physiology.

    Science.gov (United States)

    Cermenati, Gaia; Mitro, Nico; Audano, Matteo; Melcangi, Roberto C; Crestani, Maurizio; De Fabiani, Emma; Caruso, Donatella

    2015-01-01

    Lipids in the nervous system accomplish a great number of key functions, from synaptogenesis to impulse conduction, and more. Most of the lipids of the nervous system are localized in myelin sheaths. It has long been known that myelin structure and brain homeostasis rely on specific lipid-protein interactions and on specific cell-to-cell signaling. In more recent years, the growing advances in large-scale technologies and genetically modified animal models have provided valuable insights into the role of lipids in the nervous system. Key findings recently emerged in these areas are here summarized. In addition, we briefly discuss how this new knowledge can open novel approaches for the treatment of diseases associated with alteration of lipid metabolism/homeostasis in the nervous system. This article is part of a Special Issue entitled Linking transcription to physiology in lipidomics. PMID:25150974

  12. Exogenous ether lipids predominantly target mitochondria

    DEFF Research Database (Denmark)

    Kuerschner, Lars; Richter, Doris; Hannibal-Bach, Hans Kristian;

    2012-01-01

    Ether lipids are ubiquitous constituents of cellular membranes with no discrete cell biological function assigned yet. Using fluorescent polyene-ether lipids we analyzed their intracellular distribution in living cells by microscopy. Mitochondria and the endoplasmic reticulum accumulated high...... amounts of ether-phosphatidylcholine and ether-phosphatidylethanolamine. Both lipids were specifically labeled using the corresponding lyso-ether lipids, which we established as supreme precursors for lipid tagging. Polyfosine, a fluorescent analogue of the anti-neoplastic ether lipid edelfosine...... in ether lipid metabolism and intracellular ether lipid trafficking....

  13. Concentration of polar MFGM lipids from buttermilk by microfiltration and supercritical fluid extraction.

    Science.gov (United States)

    Astaire, J C; Ward, R; German, J B; Jiménez-Flores, R

    2003-07-01

    Buttermilk contains the milk fat globule membrane (MFGM), a material that possesses many complex lipids that function as nutritionally valuable molecules. Milk-derived sphingolipids and phospholipids affect numerous cell functions, including regulating growth and development, molecular transport systems, stress responses, cross membrane trafficking, and absorption processes. We developed a two-step method to produce buttermilk derivative ingredients containing increased concentrations of the polar MFGM lipids by microfiltration and supercritical fluid extraction (SFE). These processes offer environmentally benign alternatives to conventional lipid fractionation methods that rely on toxic solvents. Firstly, using a ceramic tubular membrane with 0.8-micron pore size, we evaluated the cross flow microfiltration system that maximally concentrated the polar MFGM lipids using a 2n factorial design; the experimental factors were buttermilk source (fresh, or reconstituted from powder) and temperature (50 degrees C, and 4 degrees C). Secondly, a SFE process using supercritical carbon dioxide removed exclusively nonpolar lipid material from the microfiltered buttermilk product. Lipid analysis showed that after SFE, the product contained a significantly reduced concentration of nonpolar lipids, and a significantly increased concentration of polar lipids derived from the MFGM. Particle size analysis revealed an impact of SFE on the product structure. The efficiency of the SFE system using the microfiltration-processed powder was compared much more favorably to using buttermilk powder.

  14. Lipid diffusion and swelling in a phase separated biocompatible thermoplastic elastomer.

    Science.gov (United States)

    Fittipaldi, Mauro; Grace, Landon R

    2016-12-01

    Lipid uptake was analyzed via gravimetric measurements in a biocompatible poly(styrene-block-isobutylene-block-styrene) (SIBS) copolymer. Absorption followed Fickian diffusion behavior very closely, although some deviation was noticed once saturation was reached. Diffusion parameters of three different SIBS formulations were calculated and used to predict the behavior of a fourth type based on molecular weight and relative polystyrene content. SIBS with lower polystyrene content and molecular weight showed lower physical stability and developed surface cracks that propagated with exposure to the lipid medium. Saturation lipid content varied from 45% to 63% by weight and was inversely related to polystyrene content, suggesting most of the plasticization is occurring in the isobutylene phase of SIBS. Moreover, swelling of specimens was monitored throughout the immersion in the lipid medium and ranged from 32% to 58%. Swelling in formulations with lower hard phase (polystyrene) was significantly higher than the swelling in SIBS with higher hard phase content. This is consistent with lipid-induced plasticization occurring in the soft (polyisobutylene) segments, relaxing the polymer network and leading to increased swelling and lipid uptake. The biocompatibility and tailorability of SIBS through control of hard/soft phase ratio offer significant advantages for in vivo applications. However, the lipophilic nature of the material and the associated degradation may render the polymer unusable in certain applications. The predictive model of lipid uptake introduced here will allow more accurate evaluation of lipid susceptibility during the preliminary design phase of SIBS-based in vivo structures. PMID:27479889

  15. Development of the Digestive System-Experimental Challenges and Approaches of Infant Lipid Digestion.

    Science.gov (United States)

    Abrahamse, Evan; Minekus, Mans; van Aken, George A; van de Heijning, Bert; Knol, Jan; Bartke, Nana; Oozeer, Raish; van der Beek, Eline M; Ludwig, Thomas

    2012-12-01

    At least during the first 6 months after birth, the nutrition of infants should ideally consist of human milk which provides 40-60 % of energy from lipids. Beyond energy, human milk also delivers lipids with a specific functionality, such as essential fatty acids (FA), phospholipids, and cholesterol. Healthy development, especially of the nervous and digestive systems, depends fundamentally on these. Epidemiological data suggest that human milk provides unique health benefits during early infancy that extend to long-lasting benefits. Preclinical findings show that qualitative changes in dietary lipids, i.e., lipid structure and FA composition, during early life may contribute to the reported long-term effects. Little is known in this respect about the development of digestive function and the digestion and absorption of lipids by the newborn. This review gives a detailed overview of the distinct functionalities that dietary lipids from human milk and infant formula provide and the profound differences in the physiology and biochemistry of lipid digestion between infants and adults. Fundamental mechanisms of infant lipid digestion can, however, almost exclusively be elucidated in vitro. Experimental approaches and their challenges are reviewed in depth.

  16. Interactions between lipids and voltage sensor paddles detected with tarantula toxins

    OpenAIRE

    Milescu, Mirela; Bosmans, Frank; Lee, Seungkyu; Alabi, AbdulRasheed A.; Kim, Jae Il; Swartz, Kenton J.

    2009-01-01

    Voltage-activated ion channels open and close in response to changes in voltage, a property that is essential for generating nerve impulses. Studies on voltage-activated potassium (Kv) channels show that voltage-sensor activation is sensitive to the composition of lipids in the surrounding membrane. Here we explore the interaction of lipids with S1–S4 voltage-sensing domains, and find that the conversion of the membrane lipid sphingomyelin to ceramide-1-phosphate alters voltage-sensor activat...

  17. Absorption of volatile ruthenium

    International Nuclear Information System (INIS)

    Phase equilibrium and mass transfer measurements for the absorption of ruthenium tetroxide (RuO4) in aqueous and nitric acid solutions have been completed. Low concentration phase equilibrium measurements confirm that the system obeys Henry's law across 4 orders of magnitude in concentration. Mass transfer measurements from turbulent gas flow indicate that the diffusivity of RuO4 in air may increase slightly as its concentration is reduced by 5-6 orders of magnitude. The reaction of RuO4 with nitrous acid and nitrites in solution results in precipitated or colloidal RuO2. Initial, immediate decomposition of ∼ 50% of the RuO4 occurs at RuO4: HNO2 mole ratios between 10:1 and 1:2, and does not vary systematically with mole ratio in this range. A mathematical model of the RuO4 decontamination performance of a packed bed scrubber has been developed, and validated experimentally with a laboratory QVF system. A survey of modelling approaches for predicting the ruthenium decontamination performance of off-gas condensers has been carried out. (author)

  18. Models of lipid droplets growth and fission in adipocyte cells

    International Nuclear Information System (INIS)

    Lipid droplets (LD) are spherical cellular inclusion devoted to lipids storage. It is well known that excessive accumulation of lipids leads to several human worldwide diseases like obesity, type 2 diabetes, hepatic steatosis and atherosclerosis. LDs' size range from fraction to one hundred of micrometers in adipocytes and is related to the lipid content, but their growth is still a puzzling question. It has been suggested that LDs can grow in size due to the fusion process by which a larger LD is obtained by the merging of two smaller LDs, but these events seems to be rare and difficult to be observed. Many other processes are thought to be involved in the number and growth of LDs, like the de novo formation and the growth through additional neutral lipid deposition in pre-existing droplets. Moreover the number and size of LDs are influenced by the catabolism and the absorption or interaction with other organelles. The comprehension of these processes could help in the confinement of the pathologies related to lipid accumulation. In this study the LDs' size distribution, number and the total volume of immature (n=12), mature (n=12, 10-days differentiated) and lipolytic (n=12) 3T3-L1 adipocytes were considered. More than 11,000 LDs were measured in the 36 cells after Oil Red O staining. In a previous work Monte Carlo simulations were used to mimic the fusion process alone between LDs. We found that, considering the fusion as the only process acting on the LDs, the size distribution in mature adipocytes can be obtained with numerical simulation starting from the size distribution in immature cells provided a very high rate of fusion events. In this paper Monte Carlo simulations were developed to mimic the interaction between LDs taking into account many other processes in addition to fusion (de novo formation and the growth through additional neutral lipid deposition in pre-existing droplets) in order to reproduce the LDs growth and we also simulated the

  19. Models of lipid droplets growth and fission in adipocyte cells

    Energy Technology Data Exchange (ETDEWEB)

    Boschi, Federico, E-mail: federico.boschi@univr.it [Department of Computer Science, University of Verona, Strada Le Grazie 15, 37134 Verona (Italy); Rizzatti, Vanni; Zamboni, Mauro [Department of Medicine, Geriatric Section, University of Verona, Piazzale Stefani 1, 37126 Verona (Italy); Sbarbati, Andrea [Department of Neurological and Movement Sciences, University of Verona, Strada Le Grazie 8, 37134 Verona (Italy)

    2015-08-15

    Lipid droplets (LD) are spherical cellular inclusion devoted to lipids storage. It is well known that excessive accumulation of lipids leads to several human worldwide diseases like obesity, type 2 diabetes, hepatic steatosis and atherosclerosis. LDs' size range from fraction to one hundred of micrometers in adipocytes and is related to the lipid content, but their growth is still a puzzling question. It has been suggested that LDs can grow in size due to the fusion process by which a larger LD is obtained by the merging of two smaller LDs, but these events seems to be rare and difficult to be observed. Many other processes are thought to be involved in the number and growth of LDs, like the de novo formation and the growth through additional neutral lipid deposition in pre-existing droplets. Moreover the number and size of LDs are influenced by the catabolism and the absorption or interaction with other organelles. The comprehension of these processes could help in the confinement of the pathologies related to lipid accumulation. In this study the LDs' size distribution, number and the total volume of immature (n=12), mature (n=12, 10-days differentiated) and lipolytic (n=12) 3T3-L1 adipocytes were considered. More than 11,000 LDs were measured in the 36 cells after Oil Red O staining. In a previous work Monte Carlo simulations were used to mimic the fusion process alone between LDs. We found that, considering the fusion as the only process acting on the LDs, the size distribution in mature adipocytes can be obtained with numerical simulation starting from the size distribution in immature cells provided a very high rate of fusion events. In this paper Monte Carlo simulations were developed to mimic the interaction between LDs taking into account many other processes in addition to fusion (de novo formation and the growth through additional neutral lipid deposition in pre-existing droplets) in order to reproduce the LDs growth and we also simulated the

  20. Lipid metabolism and body composition in Gclm(-/-) mice

    Energy Technology Data Exchange (ETDEWEB)

    Kendig, Eric L. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Chen, Ying [Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, CO 80045 (United States); Krishan, Mansi; Johansson, Elisabet; Schneider, Scott N. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Genter, Mary Beth; Nebert, Daniel W. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Shertzer, Howard G., E-mail: shertzhg@ucmail.uc.edu [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States)

    2011-12-15

    In humans and experimental animals, high fat diets (HFD) are associated with risk factors for metabolic diseases, such as excessive weight gain and adiposity, insulin resistance and fatty liver. Mice lacking the glutamate-cysteine ligase modifier subunit gene (Gclm(-/-)) and deficient in glutathione (GSH), are resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated regulation of energy metabolism, oxidative stress, and glucose and lipid homeostasis. C57BL/6J Gclm(-/-) mice and littermate wild-type (WT) controls received a normal diet or an HFD for 11 weeks. HFD-fed Gclm(-/-) mice did not display a decreased respiratory quotient, suggesting that they are unable to process lipid for metabolism. Although dietary energy consumption and intestinal lipid absorption were unchanged in Gclm(-/-) mice, feeding these mice an HFD did not produce excess body weight nor fat storage. Gclm(-/-) mice displayed higher basal metabolic rates resulting from higher activities of liver mitochondrial NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(-/-) mice exhibited strong systemic and hepatic oxidative stress responses, HFD did not promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(-/-) mice did not develop fatty liver, likely resulting from very low expression levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is involved in the regulation of basal metabolic rate and the metabolism of dietary lipid. Although Gclm(-/-) mice display a strong oxidative stress response, they are protected from HFD-induced excessive weight gain and adipose deposition, insulin resistance and steatosis. -- Highlights: Black-Right-Pointing-Pointer A high fat diet does not produce body weight and fat gain in Gclm(-/-) mice. Black-Right-Pointing-Pointer A high fat diet does not induce steatosis or insulin resistance in Gclm(-/-) mice. Black-Right-Pointing-Pointer Gclm(-/-) mice have high basal metabolism and mitochondrial

  1. Lipid composition of human meibum

    Directory of Open Access Journals (Sweden)

    R. Schnetler

    2013-12-01

    Full Text Available The structure and function of meibomian gland lipids in the tear film are highly complex. Evidence shows that the precorneal tear film consists of discrete layers: the inner mucin layer, the middle aqueous layer and the outer lipid layer. In this review we focus on the outer, biphasic lipid layer of the tear film which consists of a ‘thick’ outer, non-polar layer  and a ‘thin’ inner, polar layer. We discuss the main composition of the polar and non-polar lipids within meibum (wax esters, cholesteryl esters, mono-, di- and tri-acylglycerols, ceramides, phospholipids  et cetera. We address the composition of meibomian lipids in subjects suffering from various ocular diseases in comparison with the composition in healthy individuals. Further analysis is needed to determine whether a correlation exists between the etiology of various ocular diseases and the fluctuation on the lipids as well as to establish whether or not tear lipid analysis can be used as a diagnostic tool.

  2. Cadmium absorption inhibitors for soil

    Energy Technology Data Exchange (ETDEWEB)

    Kitamura, S.

    1974-05-25

    Cadmium absorption by soil is one cause of soil pollution. Cadmium adsorption inhibitors were prepared by mixing alginic acid which contained brown algae (Ascophyllum nodosum) and an inorganic material, shell fossils. This mixture was highly effective in preventing cadmium absorption by the soil.

  3. Multifunctional hybrids for electromagnetic absorption

    Energy Technology Data Exchange (ETDEWEB)

    Huynen, I. [Research Center in Micro and Nanoscopic Materials and Electronic Devices, CeRMiN, Universite catholique de Louvain, B-1348 Louvain-la-Neuve (Belgium); Information and Communications Technologies, Electronics and Applied Mathematics (ICTEAM), Microwave Laboratory, Universite catholique de Louvain, B-1348 Louvain-la-Neuve (Belgium); Quievy, N. [Institute of Condensed Matter and Nanosciences (IMCN), Universite catholique de Louvain, B-1348 Louvain-la-Neuve (Belgium); Bailly, C. [Research Center in Micro and Nanoscopic Materials and Electronic Devices, CeRMiN, Universite catholique de Louvain, B-1348 Louvain-la-Neuve (Belgium); Institute of Condensed Matter and Nanosciences (IMCN), Universite catholique de Louvain, B-1348 Louvain-la-Neuve (Belgium); Institute of Mechanics, Materials and Civil Engineering (iMMC), Universite catholique de Louvain, B-1348 Louvain-la-Neuve (Belgium); Bollen, P. [Information and Communications Technologies, Electronics and Applied Mathematics (ICTEAM), Microwave Laboratory, Universite catholique de Louvain, B-1348 Louvain-la-Neuve (Belgium); Institute of Condensed Matter and Nanosciences (IMCN), Universite catholique de Louvain, B-1348 Louvain-la-Neuve (Belgium); Institute of Mechanics, Materials and Civil Engineering (iMMC), Universite catholique de Louvain, B-1348 Louvain-la-Neuve (Belgium); Detrembleur, C. [Center for Education and Research on Macromolecules (CERM), University of Liege, Sart-Tilman B6a, 4000 Liege (Belgium); Eggermont, S.; Molenberg, I. [Information and Communications Technologies, Electronics and Applied Mathematics (ICTEAM), Microwave Laboratory, Universite catholique de Louvain, B-1348 Louvain-la-Neuve (Belgium); Thomassin, J.M.; Urbanczyk, L. [Center for Education and Research on Macromolecules (CERM), University of Liege, Sart-Tilman B6a, 4000 Liege (Belgium)

    2011-05-15

    Highlights: > EM absorption requires low dielectric constant and {approx}1 S/m electrical conductivity. > New hybrids were processed with CNT-filled polymer foam inserted in Al honeycomb. > The EM absorption in the GHz range is superior to any known material. > A closed form model is used to guide the design of the hybrid. > The architectured material is light with potential for thermal management. - Abstract: Electromagnetic (EM) interferences are ubiquitous in modern technologies and impact on the reliability of electronic devices and on living cells. Shielding by EM absorption, which is preferable over reflection in certain instances, requires combining a low dielectric constant with high electrical conductivity, which are antagonist properties in the world of materials. A novel class of hybrid materials for EM absorption in the gigahertz range has been developed based on a hierarchical architecture involving a metallic honeycomb filled with a carbon nanotube-reinforced polymer foam. The waveguide characteristics of the honeycomb combined with the performance of the foam lead to unexpectedly large EM power absorption over a wide frequency range, superior to any known material. The peak absorption frequency can be tuned by varying the shape of the honeycomb unit cell. A closed form model of the EM reflection and absorption provides a tool for the optimization of the hybrid. This designed material sets the stage for a new class of sandwich panels combining high EM absorption with mass efficiency, stiffness and thermal management.

  4. Multifunctional hybrids for electromagnetic absorption

    International Nuclear Information System (INIS)

    Highlights: → EM absorption requires low dielectric constant and ∼1 S/m electrical conductivity. → New hybrids were processed with CNT-filled polymer foam inserted in Al honeycomb. → The EM absorption in the GHz range is superior to any known material. → A closed form model is used to guide the design of the hybrid. → The architectured material is light with potential for thermal management. - Abstract: Electromagnetic (EM) interferences are ubiquitous in modern technologies and impact on the reliability of electronic devices and on living cells. Shielding by EM absorption, which is preferable over reflection in certain instances, requires combining a low dielectric constant with high electrical conductivity, which are antagonist properties in the world of materials. A novel class of hybrid materials for EM absorption in the gigahertz range has been developed based on a hierarchical architecture involving a metallic honeycomb filled with a carbon nanotube-reinforced polymer foam. The waveguide characteristics of the honeycomb combined with the performance of the foam lead to unexpectedly large EM power absorption over a wide frequency range, superior to any known material. The peak absorption frequency can be tuned by varying the shape of the honeycomb unit cell. A closed form model of the EM reflection and absorption provides a tool for the optimization of the hybrid. This designed material sets the stage for a new class of sandwich panels combining high EM absorption with mass efficiency, stiffness and thermal management.

  5. The delayed luminescence spectroscopy as tool to investigate the cytotoxic effect on human cancer cells of drug-loaded nanostructured lipid carrier

    Science.gov (United States)

    Grasso, R.; Gulino, M.; Scordino, A.; Musumeci, F.; Campisi, A.; Bonfanti, R.; Carbone, C.; Puglisi, G.

    2016-05-01

    The first results concerning the possibility to use Delayed Luminescence spectroscopy to evaluate the in vitro induction of cytotoxic effects on human glioblastoma cells of nanostructured lipid carrier and drug-loaded nanostructured lipid carrier are showed in this contribution. We tested the effects of nanostructured lipid carrier, ferulic acid and ferulic acidloaded nanostructured lipid carrier on U-87MG cell line. The study seems to confirm the ability of Delayed Luminescence to be sensible indicator of alterations induced on functionality of the mitochondrial respiratory chain complex I in U-87MG cancer cells when treated with nanostructured lipid carriers.

  6. Mechanistic Study of the sPLA2 Mediated Hydrolysis of a Thio-ester Pro Anticancer Ether Lipid

    DEFF Research Database (Denmark)

    Linderoth, Lars; Fristrup, Peter; Hansen, Martin;

    2009-01-01

    ether lipids, which become cytotoxic upon sPLA2-catalyzed hydrolysis has previously been established. To optimize the hydrolysis rate of the lipids and thereby optimizing the release profile of the drugs from the liposomes, we have synthesized a thio-ester pro anticancer ether lipid. Liposomes...... constituted of this lipid showed an altered rate of hydrolysis by sPLA2. We have tested the cytotoxicity of the thio-ester pro anticancer ether lipids toward cancer cells, and the results showed that the cytotoxicity is indeed maintained upon sPLA2 exposure. To further understand the origin for the observed...

  7. A dynamic model of digestion and absorption in pigs

    DEFF Research Database (Denmark)

    Strathe, Anders Bjerring; Danfær, Allan Christian; Chwalibog, Andrzej

    2008-01-01

    The paper describes and evaluates the construction of a mathematical model to study the kinetics of digestion and absorption in growing pigs. The core of the model is based on a compartmental structure, which divides the gastro-intestinal tract into four anatomical segments: the stomach, two parts...... of the small intestine and the large intestine. Within the large intestine, a microbial sub compartment is also considered. In each of these segments, the major organic nutrients are considered: dietary protein, endogenous protein, amino acids, non-amino acid and non-protein nitrogen, lipids, fatty acids...

  8. Hybrid lipid-based nanostructures

    Science.gov (United States)

    Dayani, Yasaman

    Biological membranes serve several important roles, such as structural support of cells and organelles, regulation of ionic and molecular transport, barriers to non-mediated transport, contact between cells within tissues, and accommodation of membrane proteins. Membrane proteins and other vital biomolecules incorporated into the membrane need a lipid membrane to function. Due to importance of lipid bilayers and their vital function in governing many processes in the cell, the development of various models as artificial lipid membranes that can mimic cell membranes has become a subject of great interest. Using different models of artificial lipid membranes, such as liposomes, planar lipid bilayers and supported or tethered lipid bilayers, we are able to study many biophysical processes in biological membranes. The ability of different molecules to interact with and change the structure of lipid membranes can be also investigated in artificial lipid membranes. An important application of lipid bilayer-containing interfaces is characterization of novel membrane proteins for high throughput drug screening studies to investigate receptor-drug interactions and develop biosensor systems. Membrane proteins need a lipid bilayer environment to preserve their stability and functionality. Fabrication of materials that can interact with biomolecules like proteins necessitates the use of lipid bilayers as a mimic of cell membranes. The objective of this research is to develop novel hybrid lipid-based nanostructures mimicking biological membranes. Toward this aim, two hybrid biocompatible structures are introduced: lipid bilayer-coated multi-walled carbon nanotubes (MWCNTs) and hydrogel-anchored liposomes with double-stranded DNA anchors. These structures have potential applications in biosensing, drug targeting, drug delivery, and biophysical studies of cell membranes. In the first developed nanostructure, lipid molecules are covalently attached to the surfaces of MWCNTs, and

  9. Attention Alters Perceived Attractiveness.

    Science.gov (United States)

    Störmer, Viola S; Alvarez, George A

    2016-04-01

    Can attention alter the impression of a face? Previous studies showed that attention modulates the appearance of lower-level visual features. For instance, attention can make a simple stimulus appear to have higher contrast than it actually does. We tested whether attention can also alter the perception of a higher-order property-namely, facial attractiveness. We asked participants to judge the relative attractiveness of two faces after summoning their attention to one of the faces using a briefly presented visual cue. Across trials, participants judged the attended face to be more attractive than the same face when it was unattended. This effect was not due to decision or response biases, but rather was due to changes in perceptual processing of the faces. These results show that attention alters perceived facial attractiveness, and broadly demonstrate that attention can influence higher-level perception and may affect people's initial impressions of one another. PMID:26966228

  10. Encapsulation effects on carbonaceous aerosol light absorption

    Energy Technology Data Exchange (ETDEWEB)

    Sedlacek, A.J.; Onasch, T.; Davidovits, P.; Cross, E.; Mazzoleni, C.

    2010-03-15

    The contribution of aerosol absorption on direct radiative forcing is still an active area of research, in part, because aerosol extinction is dominated by light scattering and, in part, because the primary absorbing aerosol of interest, soot, exhibits complex aging behavior that alters its optical properties. The consequences of this can be evidenced by the work of Ramanathan and Carmichael (2008) who suggest that incorporating the atmospheric heating due to brown clouds (plumes containing soot byproducts from automobiles, biomass burning, wood-burning kitchen stoves, and coal-fired power plants) will increase black carbon (BC) radiative forcing from the Intergovernmental Panel on Climate Change best estimate of 0.34 Wm-2 (±0.25 Wm-2) (IPCC 2007) to 0.9 Wm-2. This noteworthy degree of uncertainty is due largely to the interdependence of BC optical properties on particle mixing state and aggregate morphology, each of which changes as the particle ages in the atmosphere and becomes encapsulated within a coating of inorganic and/or organic substances. In July 2008, a laboratory-based measurement campaign, led by Boston College and Aerodyne, was initiated to begin addressing this interdependence. To achieve insights into the interdependence of BC optical properties on particle mixing state and aggregate morphology, measurements of both the optical and physical properties of flame-generated soot under nascent, coated, and denuded conditions were conducted. This poster presents data on black carbon (BC) light absorption measured by Photothermal Interferometry (Sedlacek and Lee 2007). In addition to examining nascent BC—to provide a baseline measurement—encapsulation with varying thicknesses of either dioctyl sebacate (DOS) or sulfuric acid was conducted to glean insights into the interplay between particle mixing state and optical properties. Additionally, some experiments were carried out where BC was coated and then denuded. In the case of DOS-coated soot, a

  11. Drug absorption in gastrointestinal disease and surgery. Clinical pharmacokinetic and therapeutic implications.

    Science.gov (United States)

    Gubbins, P O; Bertch, K E

    1991-12-01

    Drug absorption from the gastrointestinal (GI) tract and the impact of GI surgery and disease on drug absorption are discussed. Recommendations are made to manage problems of drug malabsorption. Absorption from the GI tract is a first-order process described by its rate and extent. GI surgery changes the anatomy of the GI tract and alters important variables in the absorption process. In the wake of procedures which diminish small bowel surface area, the extent of absorption of phenytoin, digoxin, cyclosporin, aciclovir, hydrochlorothiazide and certain oral contraceptives is reported to be reduced. The underlying cause of the reduction is unknown. When gastric emptying time or pH are altered by surgery, the rate of drug absorption appears to be reduced. However, it is not clear which variable is more important in determining therapeutic effects. The effects of coeliac and inflammatory bowel diseases on the distribution and clearance of drugs must be considered before attributing abnormal serum concentrations of drugs to malabsorption. GI disease may slow gastric emptying and delay the complete absorption of drugs when their rate of absorption depends on gastric emptying time. Other inflammatory GI diseases such as graft-versus-host disease (GVHD) of the gut, Behçet's syndrome and scleroderma involving the GI tract may directly reduce absorption of drugs such as cyclosporin, amitriptyline, benzodiazepines, anticonvulsants, paracetamol (acetaminophen) and penicillamine. GI diseases which alter gut pH affect the absorption only of drugs with limited water solubility and pH-dependent dissolution such as ketoconazole. Clinicians should be aware of the variable absorption seen after GI disease and surgery and monitor their patients accordingly. PMID:1782738

  12. Inclusion of photosensitive molecules into host lipid membranes

    DEFF Research Database (Denmark)

    Jørgensen, Lars; Zargarani, Dordaneh; Elsen, Annika;

    configuration between its cis and trans by absorption of UV and visible light (365nm / 440 nm). It was imbedded in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho¬choline (POPC) monolayer (ratio 6:1, POPC:AzCh) at the air/water interface of a Langmuir trough (Kibron Microtrough) for simultaneous compression...... mN/m. Measurements were done on the monolayer in the dark and during exposure to light. Preliminary results of the reflectivity curves give evidence of the structural details of the lipid monolayer. They indicate changes in the its organization by inoculation of the photosensitive molecules......Phosphocholine (PC) lipid membranes exhibit polymorphic variances including the biologically relevant disordered fluid phase. The incorporation of cholesterol into such a fluid host membrane may readily induce a local ordered, named fluid-ordered, phase. Here, results are reported on the impact...

  13. Alteration of Energy Substrates and ROS Production in Diabetic Cardiomyopathy

    OpenAIRE

    O. Lorenzo; Ramírez, E.; Picatoste, B.; J. Egido; Tuñón, J.

    2013-01-01

    Diabetic cardiomyopathy is initiated by alterations in energy substrates. Despite excess of plasma glucose and lipids, the diabetic heart almost exclusively depends on fatty acid degradation. Glycolytic enzymes and transporters are impaired by fatty acid metabolism, leading to accumulation of glucose derivatives. However, fatty acid oxidation yields lower ATP production per mole of oxygen than glucose, causing mitochondrial uncoupling and decreased energy efficiency. In addition, the oxidatio...

  14. Inhibitor of intramembranous absorption in ovine amniotic fluid.

    Science.gov (United States)

    Brace, Robert A; Cheung, Cecilia Y; Anderson, Debra F

    2014-02-01

    Intramembranous absorption increases during intra-amniotic infusion of physiological saline solutions. The increase may be due partly to the concomitant elevation in fetal urine production as fetal urine contains a stimulator of intramembranous absorption. In this study, we hypothesized that the increase in intramembranous absorption during intra-amniotic infusion is due, in part, to dilution of a nonrenal inhibitor of intramembranous absorption that is present in amniotic fluid. In late-gestation fetal sheep, amniotic fluid volume and the four primary amniotic inflows and outflows were determined over 2-day intervals under three conditions: 1) control conditions when fetal urine entered the amniotic sac, 2) during intra-amniotic infusion of 2 l/day of lactated Ringer solution when urine entered the amniotic sac, and 3) during the same intra-amniotic infusion when fetal urine was continuously replaced with lactated Ringer solution. Amniotic fluid volume, fetal urine production, swallowed volume, and intramembranous absorption rate increased during the infusions independent of fetal urine entry into the amniotic sac or its replacement. Lung liquid secretion rate was unchanged during infusion. Because fetal membrane stretch has been shown not to be involved and because urine replacement did not alter the response, we conclude that the increase in intramembranous absorption that occurs during intra-amniotic infusions is due primarily to dilution of a nonrenal inhibitor of intramembranous absorption that is normally present in amniotic fluid. This result combined with our previous study suggests that a nonrenal inhibitor(s) together with a renal stimulator(s) interact to regulate intramembranous absorption rate and, hence, amniotic fluid volume.

  15. The interaction of eugenol with cell membrane models at the air-water interface is modulated by the lipid monolayer composition.

    Science.gov (United States)

    Gonçalves, Giulia E G; de Souza, Fernanda S; Lago, João Henrique G; Caseli, Luciano

    2015-12-01

    Eugenol, a natural phenylpropanoid derivative with possible action in biological surfaces as microbicide, anesthetic and antioxidant, was incorporated in lipid monolayers of selected lipids at the air-water interface, representing cell membrane models. Interaction of eugenol with the lipids dipalmitoylphosphatidylcholine (DPPC), dioctadecyldimethylammonium bromide (DODAB), and dipalmitoylphosphatidylserine (DPPS) could be inferred by means of surface pressure-area isotherms and Polarization-Modulation Reflection-Absorption Spectroscopy. The interaction showed different effects on the different lipids. A higher monolayer expansion was observed for DPPS and DODAB, while more significant effects on the polar groups of the lipids were observed for DPPS and DPPC. These results pointed to the fact that the interaction of eugenol with lipid monolayers at the air-water interface is modulated by the lipid composition, which may be important to comprehend at the molecular level the interaction of this drug with biological surfaces.

  16. Fasting and nonfasting lipid levels

    DEFF Research Database (Denmark)

    Langsted, Anne; Freiberg, Jacob J; Nordestgaard, Børge G

    2008-01-01

    Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events....

  17. Analysis of Lipid Experiments (ALEX)

    DEFF Research Database (Denmark)

    Husen, Peter; Tarasov, Kirill; Katafiasz, Maciej;

    2013-01-01

    Global lipidomics analysis across large sample sizes produces high-content datasets that require dedicated software tools supporting lipid identification and quantification, efficient data management and lipidome visualization. Here we present a novel software-based platform for streamlined data ...

  18. Lipid dynamics at dendritic spines.

    Science.gov (United States)

    Dotti, Carlos Gerardo; Esteban, Jose Antonio; Ledesma, María Dolores

    2014-01-01

    Dynamic changes in the structure and composition of the membrane protrusions forming dendritic spines underlie memory and learning processes. In recent years a great effort has been made to characterize in detail the protein machinery that controls spine plasticity. However, we know much less about the involvement of lipids, despite being major membrane components and structure determinants. Moreover, protein complexes that regulate spine plasticity depend on specific interactions with membrane lipids for proper function and accurate intracellular signaling. In this review we gather information available on the lipid composition at dendritic spine membranes and on its dynamics. We pay particular attention to the influence that spine lipid dynamism has on glutamate receptors, which are key regulators of synaptic plasticity.

  19. Lipid profile in cerebrovascular accidents

    OpenAIRE

    Soodeh Razeghi; Patricia Khashaiar; Babak Ahmadi; Mohamad Reza Gheini; Mansoureh Togha

    2011-01-01

    Background: Changes in the lipid profile have been suggested as a risk factor for developing ischemic stroke. Their role in intra-cerebral hemorrhage, however, is not clear. The present study was designed to evaluate the lipid profile levels of patients who had experienced an acute stroke during the first 24-hour and to compare these levels in different patients suffering from the stroke, either hemorrhagic or ischemic, and healthy individuals.Methods: In this cross-sectional study, 258 conse...

  20. Gastrointestinal citrate absorption in nephrolithiasis

    Science.gov (United States)

    Fegan, J.; Khan, R.; Poindexter, J.; Pak, C. Y.

    1992-01-01

    Gastrointestinal absorption of citrate was measured in stone patients with idiopathic hypocitraturia to determine if citrate malabsorption could account for low urinary citrate. Citrate absorption was measured directly from recovery of orally administered potassium citrate (40 mEq.) in the intestinal lavage fluid, using an intestinal washout technique. In 7 stone patients citrate absorption, serum citrate levels, peak citrate concentration in serum and area under the curve were not significantly different from those of 7 normal subjects. Citrate absorption was rapid and efficient in both groups, with 96 to 98% absorbed within 3 hours. The absorption of citrate was less efficient from a tablet preparation of potassium citrate than from a liquid preparation, probably due to a delayed release of citrate from wax matrix. However, citrate absorption from solid potassium citrate was still high at 91%, compared to 98% for a liquid preparation. Thus, hypocitraturia is unlikely to be due to an impaired gastrointestinal absorption of citrate in stone patients without overt bowel disease.

  1. The thermodynamics of lipid ion channel formation in the absence and presence of anesthetics. BLM experiments and simulations

    CERN Document Server

    Wodzinska, Katarzyna; Heimburg, Thomas

    2009-01-01

    It is known that lipid membranes become permeable in their melting regime. In microscopic conductance measurements on black lipid membranes one finds that conduction takes place via quantized events closely resembling those reported for protein ion channels. Here, we present data of ion currents through black lipid membranes in the presence and absence of the anesthetics octanol and ethanol, and compare them to a statistical thermodynamics model using parameters that are obtained from experimental calorimetric data. The conductance steps in pure lipid membrane suggest aqueous pores with the size of approximately one lipid cross-section. We model the permeability by assuming empty sites of the size of one lipid. We find that pore formation in the melting transition regime is facilitated by the increase of the lateral compressibility that expresses itself in the area fluctuations. Thus, pore formation is related to critical opalescence in two dimensions. Anesthetics alter the permeability by affecting the therm...

  2. Total light absorption in graphene

    CERN Document Server

    Thongrattanasiri, Sukosin; de Abajo, F Javier Garcia

    2011-01-01

    We demonstrate that 100% light absorption can take place in a single patterned sheet of doped graphene. General analysis shows that a planar array of small lossy particles exhibits full absorption under critical-coupling conditions provided the cross section of each individual particle is comparable to the area of the lattice unit-cell. Specifically, arrays of doped graphene nanodisks display full absorption when supported on a substrate under total internal reflection, and also when lying on a dielectric layer coating a metal. Our results are relevant for infrared light detectors and sources, which can be made tunable via electrostatic doping of graphene.

  3. Interactions of Lipidic Cubic Phase Nanoparticles with Lipid Membranes.

    Science.gov (United States)

    Jabłonowska, Elżbieta; Nazaruk, Ewa; Matyszewska, Dorota; Speziale, Chiara; Mezzenga, Raffaele; Landau, Ehud M; Bilewicz, Renata

    2016-09-20

    The interactions of liquid-crystalline monoolein (GMO) cubic phase nanoparticles with various model lipid membranes spread at the air-solution interface by the Langmuir technique were investigated. Cubosomes have attracted attention as potential biocompatible drug delivery systems, and thus understanding their mode of interaction with membranes is of special interest. Cubosomes spreading at the air-water interface as well as interactions with a monolayer of 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) compressed to different surface pressures were studied by monitoring surface pressure-time dependencies at constant area. Progressive incorporation of the nanoparticles was shown to lead to mixed monolayer formation. The concentration of cubosomes influenced the mechanism of incorporation, as well as the fluidity and permeability of the resulting lipid membranes. Brewster angle microscopy images reflected the dependence of the monolayer structure on the cubosomes presence in the subphase. A parameter Csat was introduced to indicate the point of saturation of the lipid membrane with the cubosomal material. This parameter was found to depend on the surface pressure showing that the cubosomes disintegrate in prolonged contact with the membrane, filling available voids in the lipid membrane. At highest surface pressures when the layer is most compact, the penetration of cubosomal material is not possible and only some exchange with the membrane lipid becomes the route of including GMO into the layer. Finally, comparative studies of the interactions between lipids with various headgroup charges with cubosomes suggest that at high surface pressure an exchange of lipid component between the monolayer and the cubosome in its intact form may occur.

  4. Influence of liver cancer on lipid and lipoprotein metabolism

    Directory of Open Access Journals (Sweden)

    Nilsson-Ehle Peter

    2006-03-01

    Full Text Available Abstract Liver plays a key role in the metabolism of plasma apolipoproteins, endogenous lipids and lipoproteins. Hepatocellular carcinoma (HCC is one of the most common fatal malignant tumors in China and in other Southeast Asian countries. This has been attributed to the high incidence of hepatitis B infection. Hepatitis B proteins, such as the hepatitis B X protein (HBx that is large hepatitis B surface protein could regulate transcription of many candidate genes for liver carcinogenesis. It has known that patients who suffered from acute hepatitis B could have lipid disorders such as decreased plasma level of high-density lipoproteins (HDL. Furthermore, aberrations of lipid metabolism are often seen in the chronic hepatitis B infection. Plasma lipid profiles could be changed under HCC. In majority of the reports in HCC, plasma levels of triglycerides (TG, cholesterol, free fatty acids (FFA, HDL, low-density lipoproteins (LDL, lipoprotein (a (Lp(a, apolipoprotein AI (apoAI and apoB were slight to significantly decreased, however, in some cases plasma levels of TG and Lp(a might be increased. It has been suggested that analysis of plasma levels of lipids, lipoproteins and apolipoproteins in the patients suffered from HCC reflects on the hepatic cellular impairment status. Studies revealed that alterations seen in the plasma levels of lipids, lipoproteins and apolipoproteins reflecting patients' pathologic conditions. Decreased serum levels of cholesterol and apoAI may indicate a poor prognosis. Human leukaemic cells and certain tumor tissues have a higher receptor-mediated uptake of HDL and LDL than the corresponding normal cells or tissues. LDL and HDL have therefore been proposed as a carrier for the water-insoluble anti-cancer agents.

  5. Correlation between anthropometry and lipid profile in healthy subjects of Eastern India

    Directory of Open Access Journals (Sweden)

    Magna Manjareeka

    2015-01-01

    Full Text Available Background: Cardiovascular diseases constitute one class of common contributors to morbidity and mortality worldwide. Prevalence of overweight and obesity has dramatically increased in developing countries and is related to cardiovascular risk factors. Anthropometric parameters have the advantages in daily clinical practice of being a simple to measure tool with good reproducibility, especially in a developing country like India. Aim of this study is to correlate some anthropometric variables with lipid parameters in healthy subjects and to assess the anthropometric variable which best reflects the altered lipid profile. Materials and Methods: A hospital based cross-sectional study was conducted after the Institutional Ethical Committee Clearance. Included participants (1187 were subjected to anthropometric measurements such as height, weight, waist circumference (WC, and hip circumference using standard procedures on the same morning of the day, as the blood sample was collected after overnight fast and estimated for fasting blood sugar and lipid profile. Results: There is a weak correlation between body mass index (BMI and lipid parameters. Among all the anthropometric variables studied, WC is best correlated to lipid parameters. The mean values of lipid parameters were not significantly different in BMI <25 and BMI ≥25 groups. Conclusions: WC remains one of the simple and reliable variables which best reflects the lipid profile. In a developing country like India, where measurement of cardiovascular risk factors such as body fat saturation and lipid profile remains difficult in the rural population, WC may be used as an effective tool, without being used as a substitute.

  6. Formation of supported lipid bilayers containing phase-segregated domains and their interaction with gold nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Melby, Eric S.; Mensch, Arielle C.; Lohse, Samuel E.; Hu, Dehong; Orr, Galya; Murphy, Catherine; Hamers, Robert J.; Pedersen, Joel A.

    2016-02-01

    The cell membrane represents an important biological interface that nanoparticles may encounter after being released into the environment. Interaction of nanoparticles with cellular membranes may alter membrane structure and function, lead to their uptake into cells, and elicit adverse biological responses. Supported lipid bilayers have proven to be valuable ex vivo models for biological membranes, allowing investigation of their mechanisms of interaction with nanoparticles with a degree of control impossible in living cells. To date, the majority of research on nanoparticle interaction with supported lipid bilayers has employed membranes composed of single or binary mixtures of phospholipids. Cellular membranes contain a wide variety of lipids and exhibit lateral organization. Ordered membrane domains enriched in specific membrane components are referred to as lipid rafts and have not been explored with respect to their interaction with nanoparticles. Here we develop model lipid raft-containing membranes amenable to investigation by a variety of surface-sensitive analytical techniques and demonstrate that lipid rafts influence the extent of nanoparticle attachment to model membranes. We determined conditions that allow reliable formation of bilayers containing rafts enriched in sphingomyelin and cholesterol and confirmed their morphology by structured illumination and atomic force microscopies. We demonstrate that lipid rafts increase attachment of cationic gold nanoparticles to model membranes under near physiological ionic strength conditions (0.1 M NaCl) at pH 7.4. We anticipate that these results will serve as the foundation for and motivate further study of nanoparticle interaction with compositionally varied lipid rafts.

  7. Strategies for Lipid Production Improvement in Microalgae as a Biodiesel Feedstock

    Science.gov (United States)

    Li, Z. H.; Hiltunen, E.

    2016-01-01

    In response to the energy crisis, global warming, and climate changes, microalgae have received a great deal of attention as a biofuel feedstock. Due to a high lipid content in microalgal cells, microalgae present as a promising alternative source for the production of biodiesel. Environmental and culturing condition variations can alter lipid production as well as chemical compositions of microalgae. Therefore, application of the strategies to activate lipid accumulation opens the door for lipid overproduction in microalgae. Until now, many original studies regarding the approaches for enhanced microalgal lipid production have been reported in an effort to push forward the production of microalgal biodiesel. However, the current literature demonstrates fragmented information available regarding the strategies for lipid production improvement. From the systematic point of view, the review highlights the main approaches for microalgal lipid accumulation induction to expedite the application of microalgal biodiesel as an alternative to fossil diesel for sustainable environment. Of the several strategies discussed, the one that is most commonly applied is the design of nutrient (e.g., nitrogen, phosphorus, and sulfur) starvation or limitation. Other viable approaches such as light intensity, temperature, carbon dioxide, salinity stress, and metal influence can also achieve enhanced microalgal lipid production. PMID:27725942

  8. Desorption electrospray ionization mass spectrometry reveals lipid metabolism of individual oocytes and embryos.

    Directory of Open Access Journals (Sweden)

    Andrés Felipe González-Serrano

    Full Text Available Alteration of maternal lipid metabolism early in development has been shown to trigger obesity, insulin resistance, type 2 diabetes and cardiovascular diseases later in life in humans and animal models. Here, we set out to determine (i lipid composition dynamics in single oocytes and preimplantation embryos by high mass resolution desorption electrospray ionization mass spectrometry (DESI-MS, using the bovine species as biological model, (ii the metabolically most relevant lipid compounds by multivariate data analysis and (iii lipid upstream metabolism by quantitative real-time PCR (qRT-PCR analysis of several target genes (ACAT1, CPT 1b, FASN, SREBP1 and SCAP. Bovine oocytes and blastocysts were individually analyzed by DESI-MS in both positive and negative ion modes, without lipid extraction and under ambient conditions, and were profiled for free fatty acids (FFA, phospholipids (PL, cholesterol-related molecules, and triacylglycerols (TAG. Principal component analysis (PCA and linear discriminant analysis (LDA, performed for the first time on DESI-MS fused data, allowed unequivocal discrimination between oocytes and blastocysts based on specific lipid profiles. This analytical approach resulted in broad and detailed lipid annotation of single oocytes and blastocysts. Results of DESI-MS and transcript regulation analysis demonstrate that blastocysts produced in vitro and their in vivo counterparts differed significantly in the homeostasis of cholesterol and FFA metabolism. These results should assist in the production of viable and healthy embryos by elucidating in vivo embryonic lipid metabolism.

  9. Aqueous alteration on main-belt asteroids

    Science.gov (United States)

    Fornasier, S.; Lantz, C.; Barucci, M.; Lazzarin, M.

    2014-07-01

    The study of aqueous alteration is particularly important for unraveling the processes occurring during the earliest times in Solar System history, as it can give information both on the thermal processes and on the localization of water sources in the asteroid belt, and for the associated astrobiological implications. The aqueous alteration process produces the low temperature (< 320 K) chemical alteration of materials by liquid water which acts as a solvent and produces materials like phyllosilicates, sulphates, oxides, carbonates, and hydroxides. This means that liquid water was present in the primordial asteroids, produced by the melting of water ice by heating sources, very probably by ^{26}Al decay. Hydrated minerals have been found mainly on Mars surface, on primitive main-belt asteroids (C, G, B, F, and P-type, following the classification scheme by Tholen, 1984) and possibly also on few transneptunian objects. Reflectance spectroscopy of aqueous altered asteroids shows absorption features in the 0.6-0.9 and 2.5-3.5-micron regions, which are diagnostic of, or associated with, hydrated minerals. In this work, we investigate the aqueous alteration process on a large sample of 600 visible spectra of C-complex asteroids available in the literature. We analyzed all these spectra in a similar way to characterize the absorption-band parameters (band center, depth, and width) and spectral slope, and to look for possible correlations between the aqueous alteration process and the asteroids taxonomic classes, orbital elements, heliocentric distances, albedo, and sizes. We find that 4.6 % of P, 7.7 % of F, 9.8 % of B, 50.5 % of C, and 100 % of the G-type asteroids have absorption bands in the visible region due to hydrated silicates. Our analysis shows that the aqueous alteration sequence starts from the P-type objects, practically unaltered, and increases through the P → F → B → C → G asteroids, these last being widely aqueously altered, strengthening thus

  10. Phase structure of liposome in lipid mixtures.

    Science.gov (United States)

    Zhang, Tianxi; Li, Yuzhuo; Mueller, Anja

    2011-11-01

    Gas microbubbles present in ultrasound imaging contrast agents are stabilized by lipid aggregates that typically contain a mixture of lipids. In this study, the phase structure of the lipid mixtures that contained two or three lipids was investigated using three different methods: dynamic light scattering, (1)H NMR, and microfluidity measurements with fluorescence probes. Three lipids that are commonly present in imaging agents (DPPC, DPPE-PEG, and DPPA) were used. Two types of systems, two-lipid model systems and simulated imaging systems were investigated. The results show that liposomes were the dominant aggregates in all the samples studied. The polar PEG side chains from the PEGylated lipid lead to the formation of micelles and micellar aggregates in small sizes. In the ternary lipid systems, almost all the lipids were present in bilayers with micelles absent and free lipids at very low concentration. These results suggest that liposomes, not micelles, contribute to the stabilization of microbubbles in an ultrasound imaging contrast agent.

  11. Differential effects of Mycobacterium bovis - derived polar and apolar lipid fractions on bovine innate immune cells

    Directory of Open Access Journals (Sweden)

    Pirson Chris

    2012-06-01

    Full Text Available Abstract Mycobacterial lipids have long been known to modulate the function of a variety of cells of the innate immune system. Here, we report the extraction and characterisation of polar and apolar free lipids from Mycobacterium bovis AF 2122/97 and identify the major lipids present in these fractions. Lipids found included trehalose dimycolate (TDM and trehalose monomycolate (TMM, the apolar phthiocerol dimycocersates (PDIMs, triacyl glycerol (TAG, pentacyl trehalose (PAT, phenolic glycolipid (PGL, and mono-mycolyl glycerol (MMG. Polar lipids identified included glucose monomycolate (GMM, diphosphatidyl glycerol (DPG, phenylethanolamine (PE and a range of mono- and di-acylated phosphatidyl inositol mannosides (PIMs. These lipid fractions are capable of altering the cytokine profile produced by fresh and cultured bovine monocytes as well as monocyte derived dendritic cells. Significant increases in the production of IL-10, IL-12, MIP-1β, TNFα and IL-6 were seen after exposure of antigen presenting cells to the polar lipid fraction. Phenotypic characterisation of the cells was performed by flow cytometry and significant decreases in the expression of MHCII, CD86 and CD1b were found after exposure to the polar lipid fraction. Polar lipids also significantly increased the levels of CD40 expressed by monocytes and cultured monocytes but no effect was seen on the constitutively high expression of CD40 on MDDC or on the levels of CD80 expressed by any of the cells. Finally, the capacity of polar fraction treated cells to stimulate alloreactive lymphocytes was assessed. Significant reduction in proliferative activity was seen after stimulation of PBMC by polar fraction treated cultured monocytes whilst no effect was seen after lipid treatment of MDDC. These data demonstrate that pathogenic mycobacterial polar lipids may significantly hamper the ability of the host APCs to induce an appropriate immune response to an invading pathogen.

  12. Ectopic lipid deposition and the metabolic profile of skeletal muscle in ovariectomized mice

    OpenAIRE

    Jackson, Kathryn C.; Wohlers, Lindsay M.; Richard M. Lovering; Schuh, Rosemary A.; Maher, Amy C.; Bonen, Arend; Koves, Timothy R.; Ilkayeva, Olga; Thomson, David M.; Muoio, Deborah M.; Spangenburg, Espen E.

    2012-01-01

    Disruptions of ovarian function in women are associated with increased risk of metabolic disease due to dysregulation of peripheral glucose homeostasis in skeletal muscle. Our previous evidence suggests that alterations in skeletal muscle lipid metabolism coupled with altered mitochondrial function may also develop. The objective of this study was to use an integrative metabolic approach to identify potential areas of dysfunction that develop in skeletal muscle from ovariectomized (OVX) femal...

  13. Model Answers to Lipid Membrane Questions

    DEFF Research Database (Denmark)

    Mouritsen, O. G.

    2011-01-01

    Ever since it was discovered that biological membranes have a core of a bimolecular sheet of lipid molecules, lipid bilayers have been a model laboratory for investigating physicochemical and functional properties of biological membranes. Experimental and theoretical models help the experimental...... to pursue. Here we review some membrane models for lipid self-assembly, monolayers, bilayers, liposomes, and lipid-protein interactions and illustrate how such models can help answering questions in modern lipid cell biology....

  14. Reproducibility of The Random Incidence Absorption Coefficient Converted From the Sabine Absorption Coefficient

    DEFF Research Database (Denmark)

    Jeong, Cheol-Ho; Chang, Ji-ho

    2015-01-01

    Absorption coefficients measured in reverberation chambers, Sabine absorption coefficients, suffer from two major problems. Firstly, they sometimes exceed unity. Secondly, the reproducibility of the Sabine absorption coefficients is quite poor, meaning that the Sabine absorption coefficients vary...

  15. OZONE ABSORPTION IN RAW WATERS

    Directory of Open Access Journals (Sweden)

    LJILJANA TAKIĆ

    2008-03-01

    Full Text Available The ozone absorption in raw water entering the main ozonization step at the Belgrade drinking water supply plant was investigated in a continuous stirred tank reactor (CSTR. A slow chemical reaction rate of dissolved ozone and pollutants present in raw water have been experimentally determined. The modified Hatta number was defined and calculated as a criterion which determines whether and to which extent the reactions of ozone and pollutants influence the rate of the pure physical ozone absorption.

  16. Incomplete intestinal absorption of fructose.

    OpenAIRE

    Kneepkens, C M; Vonk, R J; Fernandes, J.

    1984-01-01

    Intestinal D-fructose absorption in 31 children was investigated using measurements of breath hydrogen. Twenty five children had no abdominal symptoms and six had functional bowel disorders. After ingestion of fructose (2 g/kg bodyweight), 22 children (71%) showed a breath hydrogen increase of more than 10 ppm over basal values, indicating incomplete absorption: the increase averaged 53 ppm, range 12 to 250 ppm. Four of these children experienced abdominal symptoms. Three of the six children ...

  17. Berberine Regulated Lipid Metabolism in the Presence of C75, Compound C, and TOFA in Breast Cancer Cell Line MCF-7

    OpenAIRE

    Wen Tan; Zhangfeng Zhong; Shengpeng Wang; Zhanwei Suo; Xian Yang; Xiaodong Hu; Yitao Wang

    2015-01-01

    Berberine interfering with cancer reprogramming metabolism was confirmed in our previous study. Lipid metabolism and mitochondrial function were also the core parts in reprogramming metabolism. In the presence of some energy-related inhibitors, including C75, compound C, and TOFA, the discrete roles of berberine in lipid metabolism and mitochondrial function were elucidated. An altered lipid metabolism induced by berberine was observed under the inhibition of FASN, AMPK, and ACC in breast can...

  18. The Role of Microscopy in Understanding Atherosclerotic Lysosomal Lipid Metabolism

    Science.gov (United States)

    Gray Jerome, W.; Yancey, Patricia G.

    2003-02-01

    Microscopy has played a critical role in first identifying and then defining the role of lysosomes in formation of atherosclerotic foam cells. We review the evidence implicating lysosomal lipid accumulation as a factor in the pathogenesis of atherosclerosis with reference to the role of microscopy. In addition, we explore mechanisms by which lysosomal lipid engorgement occurs. Low density lipoproteins which have become modified are the major source of lipid for foam cell formation. These altered lipoproteins are taken into the cell via receptor-mediated endocytosis and delivered to lysosomes. Under normal conditions, lipids from these lipoproteins are metabolized and do not accumulate in lysosomes. In the atherosclerotic foam cell, this normal metabolism is inhibited so that cholesterol and cholesteryl esters accumulate in lysosomes. Studies of cultured cells incubated with modified lipoproteins suggests this abnormal metabolism occurs in two steps. Initially, hydrolysis of lipoprotein cholesteryl esters occurs normally, but the resultant free cholesterol cannot exit the lysosome. Further lysosomal cholesterol accumulation inhibits hydrolysis, producing a mixture of cholesterol and cholesteryl esters within swollen lysosomes. Various lipoprotein modifications can produce this lysosomal engorgement in vitro and it remains to be seen which modifications are most important in vivo.

  19. Tear film lipid layer: A molecular level view.

    Science.gov (United States)

    Cwiklik, Lukasz

    2016-10-01

    Human cornea is covered by an aqueous tear film, and the outermost layer of the tear film is coated by lipids. This so-called tear film lipid layer (TFLL) reduces surface tension of the tear film and helps with the film re-spreading after blinks. Alterations of tear lipids composition and properties are related to dry eye syndrome. Therefore, unveiling structural and functional properties of TFLL is necessary for understanding tear film function under both normal and pathological conditions. Key properties of TFLL, such as resistance against high lateral pressures and ability to spread at the tear film surface, are directly related to the chemical identity of TFLL lipids. Hence, a molecular-level description is required to get better insight into TFLL properties. Molecular dynamics simulations are particularly well suited for this task and they were recently used for investigating TFLL. The present review discusses molecular level organization and properties of TFLL as seen by these simulation studies. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.

  20. Subgap Absorption in Conjugated Polymers

    Science.gov (United States)

    Sinclair, M.; Seager, C. H.; McBranch, D.; Heeger, A. J; Baker, G. L.

    1991-01-01

    Along with X{sup (3)}, the magnitude of the optical absorption in the transparent window below the principal absorption edge is an important parameter which will ultimately determine the utility of conjugated polymers in active integrated optical devices. With an absorptance sensitivity of conjugated polymers poly(1,4-phenylene-vinylene) (and derivitives) and polydiacetylene-4BCMU in the spectral region from 0.55 eV to 3 eV. Our spectra show that the shape of the absorption edge varies considerably from polymer to polymer, with polydiacetylene-4BCMU having the steepest absorption edge. The minimum absorption coefficients measured varied somewhat with sample age and quality, but were typically in the range 1 cm{sup {minus}1} to 10 cm{sup {minus}1}. In the region below 1 eV, overtones of C-H stretching modes were observed, indicating that further improvements in transparency in this spectral region might be achieved via deuteration of fluorination.

  1. Plasma membrane lipid-protein interactions affect signaling processes in sterol-biosynthesis mutants of Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Henrik eZauber

    2014-03-01

    Full Text Available The plasma membrane is an important organelle providing structure, signaling and transport as major biological functions. Being composed of lipids and proteins with different physicochemical properties, the biological functions of membranes depend on specific protein-protein and protein-lipid interactions. Interactions of proteins with their specific sterol and lipid environment were shown to be important factors for protein recruitment into sub-compartmental structures of the plasma membrane. System-wide implications of altered endogenous sterol levels for membrane functions in living cells were not studied in higher plant cells. In particular, little is known how alterations in membrane sterol composition affect protein and lipid organization and interaction within membranes. Here, we conducted a comparative analysis of the plasma membrane protein and lipid composition in Arabidopsis sterol-biosynthesis mutants smt1 and ugt80A2;B1. smt1 shows general alterations in sterol composition while ugt80A2;B1 is significantly impaired in sterol glycosylation. By systematically analyzing different cellular fractions and combining proteomic with lipidomic data we were able to reveal contrasting alterations in lipid-protein interactions in both mutants, with resulting differential changes in plasma membrane signaling status.

  2. Small intestine bacterial overgrowth and fat digestion and absorption in cystic fibrosis patients

    Directory of Open Access Journals (Sweden)

    Aleksandra Lisowska

    2010-12-01

    Full Text Available Background. Available data suggests that small intestine bacterial overgrowth (SIBO may frequently occur in cystic fibrosis (CF subjects. SIBO may result in synthesis of enterotoxic and unabsorbable metabolites which may cause mucosal damage and – additionally – interfere with digestion and absorption. Such a relationship was documented in CF mouse model. Therefore, in the present study we aimed to assess the influence of bacterial overgrowth in small intestine in CF patients on lipid digestion and absorption. Material and methods. The study comprised 60 pancreatic insufficient CF patients, 30 children and 30 adults. All enrolled CF subjects were tested for the presence of SIBO using hydrogen/methane breath test with glucose loading. According to the obtained results CF patients were divided into SIBO positive and negative subgroups. Subsequently, 13C-labelled mixed triglyceride breath test was performed to assess lipid digestion and absorption. Cumulative percentage dose recovery (cPDR was considered to reflect digestion and absorption of lipids. Results. SIBO was detected in 12 (40.0% children and 11 (36.7% adults with CF. The cPDR did not differ between SIBO positive and negative subgroups, neither when assessed separately for children (mean ±SEM: 5.5 ±0.8 vs. 7.4 ±1.0% and adults (4.9 ±0.8 vs. 7.1 ±0.7% nor for the entire studied population. Conclusions. Small intestine bacterial overgrowth does not seem to play a key role in lipid digestion and absorption in cystic fibrosis patients.

  3. pH-Responsive Micelle Sequestrant Polymers Inhibit Fat Absorption.

    Science.gov (United States)

    Qian, Jian; Sullivan, Bradley P; Berkland, Cory

    2015-08-10

    Current antiobesity therapeutics are associated with side effects and/or poor long-term patient compliance, necessitating development of more efficacious and safer alternatives. Herein, we designed and engineered a new class of orally acting pharmaceutical agents, or micelle sequestrant polymers (MSPs), that could respond to the pH change in the gastrointestinal (GI) tract and potentially sequester lipid micelles; inhibiting lipid absorption through a pH-triggered flocculation process. These MSPs, derived from poly(2-(diisopropylamino)ethyl methacrylate) and poly(2-(dibutylamino)ethyl methacrylate), were soluble in acidic media, but they transitioned to become insoluble around pH 7.2 and 6.1, respectively. MSPs showed substantial bile acid and triglyceride sequestration capacity with fast pH response tested in vitro. In vivo study showed that orally dosed MSPs significantly enhanced fecal elimination of triglycerides and bile acids. Several MSPs increased fecal elimination of triglycerides by 9-10 times compared with that of the control. In contrast, fecal concentration of bile acids, but not triglycerides, was increased by cholestyramine or Welchol. Importantly, fecal elimination of bile acids and triglycerides was unaltered by addition of control dietary fibers. MSPs may serve as a novel approach to weight loss that inhibits excess caloric intake by preventing absorption of excess dietary triglycerides.

  4. Atherogenic ω-6 Lipids Modulate PPAR- EGR-1 Crosstalk in Vascular Cells

    Directory of Open Access Journals (Sweden)

    Jia Fei

    2011-01-01

    Full Text Available Atherogenic ω-6 lipids are physiological ligands of peroxisome proliferator-activated receptors (PPARs and elicit pro- and antiatherogenic responses in vascular cells. The objective of this study was to investigate if ω-6 lipids modulated the early growth response-1 (Egr-1/PPAR crosstalk thereby altering vascular function. Rat aortic smooth muscle cells (RASMCs were exposed to ω-6 lipids, linoleic acid (LA, or its oxidized form, 13-HPODE (OxLA in the presence or absence of a PPARα antagonist (MK886 or PPARγ antagonist (GW9662 or PPAR-specific siRNA. Our results demonstrate that ω-6 lipids, induced Egr-1 and monocyte chemotactic protein-1 (MCP-1 mRNA and protein levels at the acute phase (1–4 hrs when PPARα was downregulated and at subacute phase (4–12 hrs by modulating PPARγ, thus resulting in altered monocyte adhesion to RASMCs. We provide novel insights into the mechanism of action of ω-6 lipids on Egr-1/PPAR interactions in vascular cells and their potential in altering vascular function.

  5. Hybrid Lipid as Biological Surfactants

    Science.gov (United States)

    Brewster, Robert; Pincus, Phil; Safran, Sam

    2009-03-01

    Systems capable of forming finite-sized, equilibrium domains are of biological interest in the context of membrane rafts where it has been observed that certain cellular functions are mediated by small (nanometric to tens of nanometers) domains with specific lipid composition that differs from the average composition of the membrane. These small domains are composed mainly of lipids with completely saturated hydrocarbon tails that show good orientational order in the membrane. The surrounding phase consists mostly of lipids with at least one unsaturated bond in the hydrocarbon tails which forces a ``kink'' in the chain and inhibits ordering. In vitro, this phase separation can be replicated; however, the finite domains coarsen into macroscopic domains with time. We have extended a model for the interactions of lipids in the membrane, akin to that developed in the group of Schick (Elliott et al., PRL 2006 and Garbes Putzel and Schick, Biophys. J. 2008), which depends entirely on the local ordering of hydrocarbon tails. We generalize this model to an additional species and identify a biologically relevant component, a lipid with one fully saturated hydrocarbon chain and one chain with at least one unsaturated bond, that may serve as a line-active component, capable of reducing the line tension between domains to zero, thus stabilizing finite sized domains in equilibrium.

  6. Direct observation of lipid domains in free standing bilayers: from simple to complex lipid mixtures

    DEFF Research Database (Denmark)

    Bagatolli, Luis A

    2003-01-01

    The direct observation of temperature-dependent lipid phase equilibria, using two-photon excitation fluorescence microscopy on giant unilamellar vesicles (GUVs) composed of different lipid mixtures, provides novel information about the physical characteristics of lipid domain coexistence. Physica...

  7. Lipid and protein maps defining arterial layers in atherosclerotic aorta

    Directory of Open Access Journals (Sweden)

    Marta Martin-Lorenzo

    2015-09-01

    Full Text Available Subclinical atherosclerosis cannot be predicted and novel therapeutic targets are needed. The molecular anatomy of healthy and atherosclerotic tissue is pursued to identify ongoing molecular changes in atherosclerosis development. Mass Spectrometry Imaging (MSI accounts with the unique advantage of analyzing proteins and metabolites (lipids while preserving their original localization; thus two dimensional maps can be obtained. Main molecular alterations were investigated in a rabbit model in response to early development of atherosclerosis. Aortic arterial layers (intima and media and calcified regions were investigated in detail by MALDI-MSI and proteins and lipids specifically defining those areas of interest were identified. These data further complement main findings previously published in J Proteomics (M. Martin-Lorenzo et al., J. Proteomics. (In press; M. Martin-Lorenzo et al., J. Proteomics 108 (2014 465–468. [1,2].

  8. EVALUATION OF ANTIOXIDANTS AND LIPID PEROXIDATION STATUS AMONG STUDENTS

    Directory of Open Access Journals (Sweden)

    Anandh T

    2012-12-01

    Full Text Available The study aims to estimate the changes in the plasma levels of lipid peroxidation product malondialdehyde (MDA, non-enzymatic antioxidants: vitamin C and E and enzymatic antioxidant: superoxide dismutase (SOD. The population used were healthy students (100 male, 100 female; mean age 22.4 years, range 18- 25 years. The level of lipid peroxidation was found to be significantly increased among the students which were inversely related to the level of antioxidants (p<0.05. Increased antioxidant levels show a multiple link between fruit and vegetable intake among the study group. Diminished antioxidant status disturbed oxidant-antioxidant balance alleviating oxidative stress state in less fruit and vegetable intake group. Therefore, the alterations in the level of antioxidants in blood plasma could be used as biomarkers for nutritional tribulations.

  9. Lipid and protein maps defining arterial layers in atherosclerotic aorta.

    Science.gov (United States)

    Martin-Lorenzo, Marta; Balluff, Benjamin; Maroto, Aroa S; Carreira, Ricardo J; van Zeijl, Rene J M; Gonzalez-Calero, Laura; de la Cuesta, Fernando; Barderas, Maria G; Lopez-Almodovar, Luis F; Padial, Luis R; McDonnell, Liam A; Vivanco, Fernando; Alvarez-Llamas, Gloria

    2015-09-01

    Subclinical atherosclerosis cannot be predicted and novel therapeutic targets are needed. The molecular anatomy of healthy and atherosclerotic tissue is pursued to identify ongoing molecular changes in atherosclerosis development. Mass Spectrometry Imaging (MSI) accounts with the unique advantage of analyzing proteins and metabolites (lipids) while preserving their original localization; thus two dimensional maps can be obtained. Main molecular alterations were investigated in a rabbit model in response to early development of atherosclerosis. Aortic arterial layers (intima and media) and calcified regions were investigated in detail by MALDI-MSI and proteins and lipids specifically defining those areas of interest were identified. These data further complement main findings previously published in J Proteomics (M. Martin-Lorenzo et al., J. Proteomics. (In press); M. Martin-Lorenzo et al., J. Proteomics 108 (2014) 465-468.) [1,2]. PMID:26217810

  10. Non-enzymatically derived minor lipids found in Escherichia coli lipid extracts

    OpenAIRE

    Garrett, Teresa A.; Raetz, Christian R. H.; Son, Jennifer D.; Richardson, Travis D.; Bartling, Craig; Guan, Ziqiang

    2011-01-01

    Electrospray ionization mass spectrometry is a powerful technique to analyze lipid extracts especially for the identification of new lipid metabolites. A hurdle to lipid identification is the presence of solvent contaminants that hinder the identification of low abundance species or covalently modify abundant lipid species. We have identified several non-enzymatically derived minor lipid species in lipid extracts of Escherichia coli, phosphatidylmethanol, ethyl and methyl carbamates of PE and...

  11. Nonvesicular lipid transfer from the endoplasmic reticulum.

    Science.gov (United States)

    Lev, Sima

    2012-01-01

    The transport of lipids from their synthesis site at the endoplasmic reticulum (ER) to different target membranes could be mediated by both vesicular and nonvesicular transport mechanisms. Nonvesicular lipid transport appears to be the major transport route of certain lipid species, and could be mediated by either spontaneous lipid transport or by lipid-transfer proteins (LTPs). Although nonvesicular lipid transport has been extensively studied for more than four decades, its underlying mechanism, advantage and regulation, have not been fully explored. In particular, the function of LTPs and their involvement in intracellular lipid movement remain largely controversial. In this article, we describe the pathways by which lipids are synthesized at the ER and delivered to different cellular membranes, and discuss the role of LTPs in lipid transport both in vitro and in intact cells. PMID:23028121

  12. Targeted multifunctional lipid-based nanocarriers for image-guided drug delivery

    NARCIS (Netherlands)

    G.A. Koning (Gerben); G.C. Krijger (Gerard )

    2007-01-01

    textabstractLipid-based nanocarriers have proven successful in the delivery of mainly chemotherapeutic agents, and currently they are being applied clinically in the treatment of various types of cancer. These drug delivery systems achieve increased therapeutic efficacy by altering the pharmacokinet

  13. Gramicidin-based fluorescence assay; for determining small molecules potential for modifying lipid bilayer properties

    NARCIS (Netherlands)

    Ingólfsson, Helgi I; Sanford, R Lea; Kapoor, Ruchi; Andersen, Olaf S

    2010-01-01

    Many drugs and other small molecules used to modulate biological function are amphiphiles that adsorb at the bilayer/solution interface and thereby alter lipid bilayer properties. This is important because membrane proteins are energetically coupled to their host bilayer by hydrophobic interactions.

  14. Dietary ɛ-Polylysine Decreased Serum and Liver Lipid Contents by Enhancing Fecal Lipid Excretion Irrespective of Increased Hepatic Fatty Acid Biosynthesis-Related Enzymes Activities in Rats

    OpenAIRE

    HOSOMI, Ryota; Yamamoto, Daiki; Otsuka, Ren; Nishiyama, Toshimasa; Yoshida, Munehiro; Fukunaga, Kenji

    2015-01-01

    ɛ-Polylysine (EPL) is used as a natural preservative in food. However, few studies have been conducted to assess the beneficial functions of dietary EPL. The purpose of this study was to elucidate the mechanism underlying the inhibition of neutral and acidic sterol absorption and hepatic enzyme activity-related fatty acid biosynthesis following EPL intake. EPL digest prepared using an in vitro digestion model had lower lipase activity and micellar lipid solubility and higher bile acid binding...

  15. Fuel from microalgae lipid products

    Energy Technology Data Exchange (ETDEWEB)

    Hill, A.M.; Feinberg, D.A.

    1984-04-01

    The large-scale production of microalgae is a promising method of producing a renewable feedstock for a wide variety of fuel products currently refined from crude petroleum. These microalgae-derived products include lipid extraction products (triglycerides, fatty acids, and hydrocarbons) and catalytic conversion products (paraffins and olefins). Microalgal biomass productivity and lipid composition of current experimental systems are estimated at 66.0 metric tons per hectare year and 30% lipid content. Similar yields in a large-scale facility indicate that production costs are approximately six times higher than the average domestic price for crude, well-head petroleum. Based on achievable targets for productivity and production costs, the potential for microalgae as a fuel feedstock is presented in context with selected process refining routes and is compared with conventional and alternative feedstocks (e.g., oilseeds) with which microalgae must compete. 24 references, 9 figures, 4 tables.

  16. Enhancement of intestinal absorption of few cox-2 inhibitors through interaction with β-cyclodextrin

    OpenAIRE

    Rawat Swati; Jain S

    2007-01-01

    Complexing a drug may alter the rate and extent of drug absorption. The complex formation is very well applied in the administration of poorly water-soluble drugs. The drugs selected for the study are cyclooxygenase-2 inhibitors, are potent anti-inflammatory drugs with very low water solubility. The water solubility of these drugs was enhanced by complexing with β -cyclodextrin. In vitro absorption studies using isolated inverted bovine gut technique showed greater rate of transport of...

  17. Lipid Regulation of Acrosome Exocytosis.

    Science.gov (United States)

    Cohen, Roy; Mukai, Chinatsu; Travis, Alexander J

    2016-01-01

    Lipids are critical regulators of mammalian sperm function, first helping prevent premature acrosome exocytosis, then enabling sperm to become competent to fertilize at the right place/time through the process of capacitation, and ultimately triggering acrosome exocytosis. Yet because they do not fit neatly into the "DNA--RNA-protein" synthetic pathway, they are understudied and poorly understood. Here, we focus on three lipids or lipid classes-cholesterol, phospholipids, and the ganglioside G(M1)--in context of the modern paradigm of acrosome exocytosis. We describe how these various- species are precisely segregated into membrane macrodomains and microdomains, simultaneously preventing premature exocytosis while acting as foci for organizing regulatory and effector molecules that will enable exocytosis. Although the mechanisms responsible for these domains are poorly defined, there is substantial evidence for their composition and functions. We present diverse ways that lipids and lipid modifications regulate capacitation and acrosome exocytosis, describing in more detail how removal of cholesterol plays a master regulatory role in enabling exocytosis through at least two complementary pathways. First, cholesterol efflux leads to proteolytic activation of phospholipase B, which cleaves both phospholipid tails. The resultant changes in membrane curvature provide a mechanism for the point fusions now known to occur far before a sperm physically interacts with the zona pellucida. Cholesterol efflux also enables G(M1) to regulate the voltage-dependent cation channel, Ca(V)2.3, triggering focal calcium transients required for acrosome exocytosis in response to subsequent whole-cell calcium rises. We close with a model integrating functions for lipids in regulating acrosome exocytosis. PMID:27194352

  18. Cholesterol lipids and cholesterol-containing lipid rafts in bacteria.

    Science.gov (United States)

    Huang, Zhen; London, Erwin

    2016-09-01

    Sterols are important components of eukaryotic membranes, but rare in bacteria. Some bacteria obtain sterols from their host or environment. In some cases, these sterols form membrane domains analogous the lipid rafts proposed to exist in eukaryotic membranes. This review describes the properties and roles of sterols in Borrelia and Helicobacter.

  19. Cholesterol lipids and cholesterol-containing lipid rafts in bacteria.

    Science.gov (United States)

    Huang, Zhen; London, Erwin

    2016-09-01

    Sterols are important components of eukaryotic membranes, but rare in bacteria. Some bacteria obtain sterols from their host or environment. In some cases, these sterols form membrane domains analogous the lipid rafts proposed to exist in eukaryotic membranes. This review describes the properties and roles of sterols in Borrelia and Helicobacter. PMID:26964703

  20. Uncovering biologically significant lipid isomers with liquid chromatography, ion mobility spectrometry and mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Kyle, Jennifer E.; Zhang, Xing; Weitz, Karl K.; Monroe, Matthew E.; Ibrahim, Yehia M.; Moore, Ronald J.; Cha, Jeeyeon; Sun, Xiaofei; Lovelace, Erica S.; Wagoner, Jessica; Polyak, Stephen J.; Metz, Thomas O.; Dey, Sudhansu K.; Smith, Richard D.; Burnum-Johnson, Kristin E.; Baker, Erin S.

    2016-01-01

    Understanding how biological molecules are generated, metabolized and eliminated in living systems is important for interpreting processes such as immune response and disease pathology. While genomic and proteomic studies have provided vast amounts of information over the last several decades, interest in lipidomics has also grown due to improved analytical technologies revealing altered lipid metabolism in type 2 diabetes, cancer, and lipid storage disease. Liquid chromatography and mass spectrometry (LC-MS) measurements are currently the dominant approach for characterizing the lipidome by providing detailed information on the spatial and temporal composition of lipids. However, interpreting lipids’ biological roles is challenging due to the existence of numerous structural and stereoisomers (i.e. distinct acyl chain and double-bond positions), which are unresolvable using present LC-MS approaches. Here we show that combining structurally-based ion mobility spectrometry (IMS) with LC-MS measurements distinguishes lipid isomers and allows insight into biological and disease processes.

  1. Understanding the control of acyl flux through the lipid metabolic network of plant oil biosynthesis.

    Science.gov (United States)

    Bates, Philip D

    2016-09-01

    Plant oil biosynthesis involves a complex metabolic network with multiple subcellular compartments, parallel pathways, cycles, and pathways that have a dual function to produce essential membrane lipids and triacylglycerol. Modern molecular biology techniques provide tools to alter plant oil compositions through bioengineering, however with few exceptions the final composition of triacylglycerol cannot be predicted. One reason for limited success in oilseed bioengineering is the inadequate understanding of how to control the flux of fatty acids through various fatty acid modification, and triacylglycerol assembly pathways of the lipid metabolic network. This review focuses on the mechanisms of acyl flux through the lipid metabolic network, and highlights where uncertainty resides in our understanding of seed oil biosynthesis. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. PMID:27003249

  2. Blood lipid levels associate with childhood asthma, airway obstruction, bronchial hyperresponsiveness, and aeroallergen sensitization

    DEFF Research Database (Denmark)

    Vinding, Rebecca K; Stokholm, Jakob; Chawes, Bo Lund Krogsgaard;

    2016-01-01

    with assessments of lung function, bronchial responsiveness, fraction of exhaled nitric oxide (Feno), and allergic sensitization. Associations between lipid levels and clinical outcomes were adjusted for sex, passive smoking, and body mass index. RESULTS: High levels of low-density lipoprotein cholesterol were......BACKGROUND: Studies of children's blood lipid profiles in relation to asthma are few, and the results are ambiguous. OBJECTIVE: We sought to examine whether the lipid profile is associated with concurrent asthma, altered lung function, and allergic sensitization in children. METHODS: High...... of increased Feno levels (aβ coefficient, 0.14 log-ppb; 95% CI, -0.02 to 0.30 log-ppb; P = .08). CONCLUSION: The blood lipid profile is associated with asthma, airway obstruction, bronchial responsiveness, and aeroallergen sensitization in 7-year-old children. These findings suggest that asthma and allergy...

  3. Structural interactions between lipids, water and S1-S4 voltage-sensing domains.

    Science.gov (United States)

    Krepkiy, Dmitriy; Gawrisch, Klaus; Swartz, Kenton J

    2012-11-01

    Membrane proteins serve crucial signaling and transport functions, yet relatively little is known about their structures in membrane environments or how lipids interact with these proteins. For voltage-activated ion channels, X-ray structures suggest that the mobile voltage-sensing S4 helix would be exposed to the membrane, and functional studies reveal that lipid modification can profoundly alter channel activity. Here, we use solid-state NMR to investigate structural interactions of lipids and water with S1-S4 voltage-sensing domains and to explore whether lipids influence the structure of the protein. Our results demonstrate that S1-S4 domains exhibit extensive interactions with lipids and that these domains are heavily hydrated when embedded in a membrane. We also find evidence for preferential interactions of anionic lipids with S1-S4 domains and that these interactions have lifetimes on the timescale of ≤ 10(-3)s. Arg residues within S1-S4 domains are well hydrated and are positioned in close proximity to lipids, exhibiting local interactions with both lipid headgroups and acyl chains. Comparative studies with a positively charged lipid lacking a phosphodiester group reveal that this lipid modification has only modest effects on the structure and hydration of S1-S4 domains. Taken together, our results demonstrate that Arg residues in S1-S4 voltage-sensing domains reside in close proximity to the hydrophobic interior of the membrane yet are well hydrated, a requirement for carrying charge and driving protein motions in response to changes in membrane voltage.

  4. Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

    Energy Technology Data Exchange (ETDEWEB)

    Anantachaisilp, Suranan; Smith, Siwaporn Meejoo [Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400 (Thailand); Treetong, Alongkot; Ruktanonchai, Uracha Rungsardthong [National Nanotechnology Center, National Science and Technology Development Agency, 111 Thailand Science Park, Paholyothin Road, Klong 1, Klong Luang, Pathumthani 12120 (Thailand); Pratontep, Sirapat [College of KMITL Nanotechnology, King Mongkut' s Institute of Technology Ladkrabang, Bangkok (Thailand); Puttipipatkhachorn, Satit, E-mail: uracha@nanotec.or.th [Department of Manufacturing Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400 (Thailand)

    2010-03-26

    Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of {gamma}-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812 as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the {gamma}-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance ({sup 1}H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the {sup 1}H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of {gamma}-oryzanol inside the lipid nanoparticles, the {sup 1}H-NMR revealed that the chemical shifts of the liquid lipid in {gamma}-oryzanol loaded systems were found at rather higher field than those in {gamma}-oryzanol free systems, suggesting incorporation of {gamma}-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of {gamma}-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models

  5. Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

    Science.gov (United States)

    Anantachaisilp, Suranan; Meejoo Smith, Siwaporn; Treetong, Alongkot; Pratontep, Sirapat; Puttipipatkhachorn, Satit; Rungsardthong Ruktanonchai, Uracha

    2010-03-01

    Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of γ-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812® as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the γ-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance (1H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the 1H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of γ-oryzanol inside the lipid nanoparticles, the 1H-NMR revealed that the chemical shifts of the liquid lipid in γ-oryzanol loaded systems were found at rather higher field than those in γ-oryzanol free systems, suggesting incorporation of γ-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of γ-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models representing the distribution of γ-oryzanol and

  6. Nanoparticle-lipid bilayer interactions studied with lipid bilayer arrays

    Science.gov (United States)

    Lu, Bin; Smith, Tyler; Schmidt, Jacob J.

    2015-04-01

    The widespread environmental presence and commercial use of nanoparticles have raised significant health concerns as a result of many in vitro and in vivo assays indicating toxicity of a wide range of nanoparticle species. Many of these assays have identified the ability of nanoparticles to damage cell membranes. These interactions can be studied in detail using artificial lipid bilayers, which can provide insight into the nature of the particle-membrane interaction through variation of membrane and solution properties not possible with cell-based assays. However, the scope of these studies can be limited because of the low throughput characteristic of lipid bilayer platforms. We have recently described an easy to use, parallel lipid bilayer platform which we have used to electrically investigate the activity of 60 nm diameter amine and carboxyl modified polystyrene nanoparticles (NH2-NP and COOH-NP) with over 1000 lipid bilayers while varying lipid composition, bilayer charge, ionic strength, pH, voltage, serum, particle concentration, and particle charge. Our results confirm recent studies finding activity of NH2-NP but not COOH-NP. Detailed analysis shows that NH2-NP formed pores 0.3-2.3 nm in radius, dependent on bilayer and solution composition. These interactions appear to be electrostatic, as they are regulated by NH2-NP surface charge, solution ionic strength, and bilayer charge. The ability to rapidly measure a large number of nanoparticle and membrane parameters indicates strong potential of this bilayer array platform for additional nanoparticle bilayer studies.The widespread environmental presence and commercial use of nanoparticles have raised significant health concerns as a result of many in vitro and in vivo assays indicating toxicity of a wide range of nanoparticle species. Many of these assays have identified the ability of nanoparticles to damage cell membranes. These interactions can be studied in detail using artificial lipid bilayers, which

  7. Triglyceride Blisters in Lipid Bilayers: Implications for Lipid Droplet Biogenesis and the Mobile Lipid Signal in Cancer Cell Membranes

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Duelund, Lars; Pakkanen, Kirsi Inkeri;

    2010-01-01

    Triglycerides have a limited solubility, around 3%, in phosphatidylcholine lipid bilayers. Using millisecond-scale course grained molecular dynamics simulations, we show that the model lipid bilayer can accommodate a higher concentration of triolein (TO) than earlier anticipated, by sequestering...

  8. Surface activity, lipid profiles and their implications in cervical cancer.

    Directory of Open Access Journals (Sweden)

    Preetha A

    2005-01-01

    Full Text Available Background: The profiles of lipids in normal and cancerous tissues may differ revealing information about cancer development and progression. Lipids being surface active, changes in lipid profiles can manifest as altered surface activity profiles. Langmuir monolayers offer a convenient model for evaluating surface activity of biological membranes. Aims: The aims of this study were to quantify phospholipids and their effects on surface activity of normal and cancerous human cervical tissues as well as to evaluate the role of phosphatidylcholine (PC and sphingomyelin (SM in cervical cancer using Langmuir monolayers. Methods and Materials: Lipid quantification was done using thin layer chromatography and phosphorus assay. Surface activity was evaluated using Langmuir monolayers. Monolayers were formed on the surface of deionized water by spreading tissue organic phase corresponding to 1 mg of tissue and studying their surface pressure-area isotherms at body temperature. The PC and SM contents of cancerous human cervical tissues were higher than those of the normal human cervical tissues. Role of PC and SM were evaluated by adding varying amounts of these lipids to normal cervical pooled organic phase. Statistical analysis: Student′s t-test (p < 0.05 and one-way analysis of variance (ANOVA was used. Results: Our results reveals that the phosphatidylglycerol level in cancerous cervical tissue was nearly five folds higher than that in normal cervical tissue. Also PC and sphingomyelin SM were found to be the major phospholipid components in cancerous and normal cervical tissues respectively. The addition of either 1.5 µg DPPC or 0.5 µg SM /mg of tissue to the normal organic phase changed its surface activity profile to that of the cancerous tissues. Statistically significant surface activity parameters showed that PC and SM have remarkable roles in shifting the normal cervical lipophilic surface activity towards that of cancerous lipophilic

  9. Absorption characteristics of bacteriorhodopsin molecules

    Indian Academy of Sciences (India)

    H K T Kumar; K Appaji Gowda

    2000-03-01

    The bacteriorhodopsin molecule absorbs light and undergoes a series of structural transformation following a well-defined photocycle. The complex photocycle is transformed to an equivalent level diagram by considering the lifetime of the intermediate states. Assuming that only and states are appreciably populated at any instant of time, the level diagram is further simplified to two-level system. Based on the rate equations for two-level system, an analytic expression for the absorption coefficient of bacteriorhodopsin molecule is derived. It is applied to study the behaviour of absorption coefficient of bacteriorhodopsin film in the visible wavelength region of 514 nm. The dependence of absorption coefficient of bacteriorhodopsin film on the thickness of the film, total number density of active molecules and initial number density of molecules in -state is presented in the graphical form.

  10. Effect of chemical permeation enhancers on stratum corneum barrier lipid organizational structure and interferon alpha permeability.

    Science.gov (United States)

    Moghadam, Shadi H; Saliaj, Evi; Wettig, Shawn D; Dong, Chilbert; Ivanova, Marina V; Huzil, J Torin; Foldvari, Marianna

    2013-06-01

    indicated that, in most cases, absorption of IFNα was low and that an increase in SC lipid disorder does not correspond to an increase in IFNα absorption.

  11. Automated Lipid Bilayer Membrane Formation Using a Polydimethylsiloxane Thin Film.

    Science.gov (United States)

    Choi, Sangbaek; Yoon, Sunhee; Ryu, Hyunil; Kim, Sun Min; Jeon, Tae-Joon

    2016-01-01

    An artificial lipid bilayer, or black lipid membrane (BLM), is a powerful tool for studying ion channels and protein interactions, as well as for biosensor applications. However, conventional BLM formation techniques have several drawbacks and they often require specific expertise and laborious processes. In particular, conventional BLMs suffer from low formation success rates and inconsistent membrane formation time. Here, we demonstrate a storable and transportable BLM formation system with controlled thinning-out time and enhanced BLM formation rate by replacing conventionally used films (polytetrafluoroethylene, polyoxymethylene, polystyrene) to polydimethylsiloxane (PDMS). In this experiment, a porous-structured polymer such as PDMS thin film is used. In addition, as opposed to conventionally used solvents with low viscosity, the use of squalene permitted a controlled thinning-out time via slow solvent absorption by PDMS, prolonging membrane lifetime. In addition, by using a mixture of squalene and hexadecane, the freezing point of the lipid solution was increased (~16 °C), in addition, membrane precursors were produced that can be indefinitely stored and readily transported. These membrane precursors have reduced BLM formation time of gramicidin A demonstrated the feasibility of the membrane system. PMID:27501114

  12. Gemfibrozil disrupts the metabolism of circulating lipids in bobwhite quails.

    Science.gov (United States)

    Bussière-Côté, Sophie; Omlin, Teye; de Càssia Pinheiro, Eliana; Weber, Jean-Michel

    2016-01-01

    The circulating lipids of birds play essential roles for egg production and as an energy source for flight and thermogenesis. How lipid-lowering pharmaceuticals geared to prevent heart disease in humans and that are routinely released in the environment affect their metabolism is unknown. This study assesses the impact of the popular drug gemfibrozil (GEM) on the plasma phospholipids (PL), neutral lipids (NL), and nonesterified fatty acids (NEFA) of bobwhite quails (Colinus virginianus). Results show that bird lipoproteins are rapidly altered by GEM, even at environmentally-relevant doses. After 4 days of exposure, pharmacological amounts cause an 83% increase in circulating PL levels, a major decrease in average lipoprotein size measured as a 56% drop in the NL/PL ratio, and important changes in the fatty acid composition of PL and NEFA (increases in fatty acid unsaturation). The levels of PL carrying all individual fatty acids except arachidonate are strongly stimulated. The large decrease in bird lipoprotein size may reflect the effects seen in humans: lowering of LDL that can cause atherosclerosis and stimulation of HDL that promote cholesterol disposal. Lower (environmental) doses of GEM cause a reduction of %palmitate in all the plasma lipid fractions of quails, but particularly in the core triacylglycerol of lipoproteins (NL). No changes in mRNA levels of bird peroxisome proliferator-activated receptor (PPAR) could be demonstrated. The disrupting effects of GEM on circulating lipids reported here suggest that the pervasive presence of this drug in the environment could jeopardize reproduction and migratory behaviours in wild birds. PMID:26432161

  13. Chlordecone, a mixed pregnane X receptor (PXR) and estrogen receptor alpha (ERα) agonist, alters cholesterol homeostasis and lipoprotein metabolism in C57BL/6 mice

    OpenAIRE

    Lee, Junga; Scheri, Richard C.; Zhang, Yuan; Curtis, Lawrence R.

    2008-01-01

    Chlordecone (CD) is one of many banned organochlorine (OC) insecticides that are widespread persistent organic pollutants. OC insecticides alter lipid homeostasis in rodents at doses that are not neurotoxic or carcinogenic. Pretreatment of mice or rats with CD altered tissue distribution of a subsequent dose of [14C]CD or [14C]cholesterol (CH). Nuclear receptors regulate expression of genes important in the homeostasis of CH and other lipids. In this study, we report that CD suppresses in vit...

  14. Vascular endothelial cell membranes differentiate between stretch and shear stress through transitions in their lipid phases.

    Science.gov (United States)

    Yamamoto, Kimiko; Ando, Joji

    2015-10-01

    Vascular endothelial cells (ECs) respond to the hemodynamic forces stretch and shear stress by altering their morphology, functions, and gene expression. However, how they sense and differentiate between these two forces has remained unknown. Here we report that the plasma membrane itself differentiates between stretch and shear stress by undergoing transitions in its lipid phases. Uniaxial stretching and hypotonic swelling increased the lipid order of human pulmonary artery EC plasma membranes, thereby causing a transition from the liquid-disordered phase to the liquid-ordered phase in some areas, along with a decrease in membrane fluidity. In contrast, shear stress decreased the membrane lipid order and increased membrane fluidity. A similar increase in lipid order occurred when the artificial lipid bilayer membranes of giant unilamellar vesicles were stretched by hypotonic swelling, indicating that this is a physical phenomenon. The cholesterol content of EC plasma membranes significantly increased in response to stretch but clearly decreased in response to shear stress. Blocking these changes in the membrane lipid order by depleting membrane cholesterol with methyl-β-cyclodextrin or by adding cholesterol resulted in a marked inhibition of the EC response specific to stretch and shear stress, i.e., phosphorylation of PDGF receptors and phosphorylation of VEGF receptors, respectively. These findings indicate that EC plasma membranes differently respond to stretch and shear stress by changing their lipid order, fluidity, and cholesterol content in opposite directions and that these changes in membrane physical properties are involved in the mechanotransduction that activates membrane receptors specific to each force.

  15. Heavy metals and epigenetic alterations in brain tumors.

    Science.gov (United States)

    Caffo, Maria; Caruso, Gerardo; Fata, Giuseppe La; Barresi, Valeria; Visalli, Maria; Venza, Mario; Venza, Isabella

    2014-12-01

    Heavy metals and their derivatives can cause various diseases. Numerous studies have evaluated the possible link between exposure to heavy metals and various cancers. Recent data show a correlation between heavy metals and aberration of genetic and epigenetic patterns. From a literature search we noticed few experimental and epidemiological studies that evaluate a possible correlation between heavy metals and brain tumors. Gliomas arise due to genetic and epigenetic alterations of glial cells. Changes in gene expression result in the alteration of the cellular division process. Epigenetic alterations in brain tumors include the hypermethylation of CpG group, hypomethylation of specific genes, aberrant activation of genes, and changes in the position of various histones. Heavy metals are capable of generating reactive oxygen assumes that key functions in various pathological mechanisms. Alteration of homeostasis of metals could cause the overproduction of reactive oxygen species and induce DNA damage, lipid peroxidation, and alteration of proteins. In this study we summarize the possible correlation between heavy metals, epigenetic alterations and brain tumors. We report, moreover, the review of relevant literature. PMID:25646073

  16. Absorption of focused light by spherical plasmas

    International Nuclear Information System (INIS)

    For light focused on spherical plasmas, we obtain new results giving the power absorbed by inverse bremsstrahlung and resonance absorption as a function of the focusing scheme. For a given beam profile and lens, there is an optimum focus to maximize total absorption. Linearly polarized beams lead to asymmetric absorption. Good agreement with experimental absorption and scattered light data is obtained

  17. Gut microbiota may have influence on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian Hallundbæk; Nielsen, Morten Frost; Tvede, Michael;

    2013-01-01

    New gene sequencing-based techniques and the large worldwide sequencing capacity have introduced a new era within the field of gut microbiota. Animal and human studies have shown that obesity and type 2 diabetes are associated with changes in the composition of the gut microbiota...... and that prebiotics, antibiotics or faecal transplantation can alter glucose and lipid metabolism. This paper summarizes the latest research regarding the association between gut microbiota, diabetes and obesity and some of the mechanisms by which gut bacteria may influence host metabolism....

  18. Diabetic lipohypertrophy delays insulin absorption.

    Science.gov (United States)

    Young, R J; Hannan, W J; Frier, B M; Steel, J M; Duncan, L J

    1984-01-01

    The effect of lipohypertrophy at injection sites on insulin absorption has been studied in 12 insulin-dependent diabetic patients. The clearance of 125I-insulin from sites with lipohypertrophy was significantly slower than from complementary nonhypertrophied sites (% clearance in 3 h, 43.8 +/- 3.5 +/- SEM) control; 35.3 +/- 3.9 lipohypertrophy, P less than 0.05). The degree of the effect was variable but sufficient in several patients to be of clinical importance. Injection-site lipohypertrophy is another factor that modifies the absorption of subcutaneously injected insulin.

  19. Solar powered absorption air conditioning

    Science.gov (United States)

    Vardon, J. M.

    1980-04-01

    Artificial means of providing or removing heat from the building are discussed along with the problem of the appropriate building design and construction for a suitable heat climate inside the building. The use of a lithium bromide-water absorption chiller, powered by a hot water store heated by an array of stationary flat collectors, is analyzed. An iterative method of predicting the cooling output from a LiBr-water absorption refrigeration plant having variable heat input is described and a model allowing investigation of the performance of a solar collector and thermal storage system is developed.

  20. Quasistellar Objects Intervening Absorption Lines

    CERN Document Server

    Charlton, J C; Charlton, Jane C.; Churchill, Christopher W.

    2000-01-01

    We briefly review, at a level appropriate for graduate students and non-specialists, the field of quasar absorption lines (QALs). Emphasis is on the intervening absorbers. We present the anatomy of a quasar spectrum due to various classes of intervening absorption systems, and a brief historical review of each absorber class (Lyman-alpha forest and Lyman limit systems, and metal-line and damped Lyman-alpha absorbers). We also provide several heuristic examples on how the physical properties of both the intergalactic medium and the gaseous environments associated with earlier epoch galaxies can be inferred from QALs. The evolution of these environments from z=4 are discussed.