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Sample records for modulates postprandial lipid

  1. Modulation of the lipidomic profile due to a lipid challenge and fitness level: a postprandial study.

    PubMed

    Morris, Ciara; O'Grada, Colm M; Ryan, Miriam F; Gibney, Michael J; Roche, Helen M; Gibney, Eileen R; Brennan, Lorraine

    2015-07-01

    The lipid composition of plasma is known to vary due to both phenotypic factors such as age, gender and BMI as well as with various diseases including cancer and neurological disorders. However, there is little investigation into the variation in the lipidome due to exercise and/ or metabolic challenges. The objectives of this present study were (i) To identify the glycerophospholipid, sphingolipids and ceramide changes in response to an oral lipid tolerance test (OLTT) in healthy adults and (ii) To identify the effect of aerobic fitness level on lipidomic profiles. 214 healthy adults aged 18-60 years were recruited as part of a metabolic challenge study. A sub-group of 40 volunteers were selected for lipidomic analysis based on their aerobic fitness level. Ceramides, glycerophospholipids and sphingomyelins were quantified in baseline fasting plasma samples as well as at 60, 120, 180, 240 and 300 min following a lipid challenge using high-throughput flow injection ESI-MS/MS. Mixed model repeated measures analysis identified lipids which were significantly changing over the time course of the lipid challenge. Included in these lipids were lysophosphoethanolamines (LPE), phosphoethanolamines (PE), phosphoglycerides (PG) and ceramides (Cer). Five lipids (LPE a C18:2, LPE a C18:1, PE aa C36:2, PE aa C36:3 and N-C16:1-Cer) had a fold change > 1.5 at 120 min following the challenge and these lipids remained elevated. Furthermore, three of these lipids (LPE a C18:2, PE aa C36:2 and PE aa C36:3) were predictive of fasting and peak plasma TAG concentrations following the OLTT. Further analysis revealed that fitness level has a significant impact on the response to the OLTT: in particular significant differences between fitness groups were observed for phosphatidylcholines (PC), sphingomyelins (SM) and ceramides. This study identified specific lipids which were modulated by an acute lipid challenge. Furthermore, it identified a series of lipids which were modulated by

  2. Adipocyte LDL receptor–related protein–1 expression modulates postprandial lipid transport and glucose homeostasis in mice

    PubMed Central

    Hofmann, Susanna M.; Zhou, Li; Perez-Tilve, Diego; Greer, Todd; Grant, Erin; Wancata, Lauren; Thomas, Andrew; Pfluger, Paul T.; Basford, Joshua E.; Gilham, Dean; Herz, Joachim; Tschöp, Matthias H.; Hui, David Y.

    2007-01-01

    Diet-induced obesity and its serious consequences such as diabetes, cardiovascular disease, and cancer are rapidly becoming a major global health threat. Therefore, understanding the cellular and molecular mechanisms by which dietary fat causes obesity and diabetes is of paramount importance in order to identify preventive and therapeutic strategies. Increased dietary fat intake results in high plasma levels of triglyceride-rich lipoproteins (TGRL). Tissue uptake of TGRL has been shown to promote glucose intolerance. We generated mice with an adipocyte-specific inactivation of the multifunctional receptor LDL receptor–related protein–1 (LRP1) to determine its role in mediating the effects of TGRL on diet-induced obesity and diabetes. Knockout mice displayed delayed postprandial lipid clearance, reduced body weight, smaller fat stores, lipid-depleted brown adipocytes, improved glucose tolerance, and elevated energy expenditure due to enhanced muscle thermogenesis. We further demonstrated that inactivation of adipocyte LRP1 resulted in resistance to dietary fat–induced obesity and glucose intolerance. These findings identify LRP1 as a critical regulator of adipocyte energy homeostasis, where functional disruption leads to reduced lipid transport, increased insulin sensitivity, and muscular energy expenditure. PMID:17948131

  3. Salivary composition in obese vs normal-weight subjects: towards a role in postprandial lipid metabolism?

    PubMed

    Vors, C; Drai, J; Gabert, L; Pineau, G; Laville, M; Vidal, H; Guichard, E; Michalski, M-C; Feron, G

    2015-09-01

    In the pathophysiological context of obesity, oral exposure to dietary fat can modulate lipid digestion and absorption, but underlying in-mouth mechanisms have not been clearly identified. Therefore, we tested the hypothesis that salivary components related to dietary fat sensitivity would differ according to body mass index (BMI) and postprandial lipid metabolism in young men. Saliva was collected from nine normal-weight (BMI=22.3±0.5 kg m(-2)) and nine non-morbid obese (BMI=31.7±0.3 kg m(-2)) men before an 8-h postprandial metabolic exploration test involving the consumption of a 40-g fat meal, in which obese subjects revealed a delayed postprandial lipid metabolism. Nine salivary characteristics (flow, protein content, lipolysis, amylase, proteolysis, total antioxidant status, lysozyme, lipocalin 1 and carbonic anhydrase-VI) were investigated. We show that, under fasting conditions, salivary lipolysis was lower in obese vs normal-weight subjects, whereas proteolysis and carbonic anhydrase VI were higher. We reveal through multivariate and Mann-Whitney analysis that differences in fasting salivary lipolysis and proteolysis between both groups are related to differences in postprandial lipid metabolism including exogenous fatty-acid absorption and β-oxidation. These results suggest a potential role of salivary composition on postprandial lipid metabolism and bring novel causal hypotheses on the links between salivary composition, sensitivity to dietary fat oral income and postprandial lipid metabolism according to BMI.

  4. Coffee polyphenols modulate whole-body substrate oxidation and suppress postprandial hyperglycaemia, hyperinsulinaemia and hyperlipidaemia.

    PubMed

    Murase, Takatoshi; Yokoi, Yuka; Misawa, Koichi; Ominami, Hideo; Suzuki, Yasuto; Shibuya, Yusuke; Hase, Tadashi

    2012-06-01

    Postprandial energy metabolism, including postprandial hyperglycaemia, hyperinsulinaemia and hyperlipidaemia, is related to the risk for developing obesity and CVD. In the present study, we examined the effects of polyphenols purified from coffee (coffee polyphenols (CPP)) on postprandial carbohydrate and lipid metabolism, and whole-body substrate oxidation in C57BL/6J mice. In mice that co-ingested CPP with a lipid-carbohydrate (sucrose or starch)-mixed emulsion, the respiratory quotient determined by indirect calorimetry was significantly lower than that in control mice, whereas there was no difference in VO2 (energy expenditure), indicating that CPP modulates postprandial energy partitioning. CPP also suppressed postprandial increases in plasma glucose, insulin, glucose-dependent insulinotropic polypeptide and TAG levels. Inhibition experiments on digestive enzymes revealed that CPP inhibits maltase and sucrase, and, to a lesser extent, pancreatic lipase in a concentration-dependent manner. Among the nine kinds of polyphenols (caffeoyl quinic acids (CQA), di-CQA, feruloyl quinic acids (FQA)) contained in CPP, di-CQA showed more potent inhibitory activity than CQA or FQA on these digestive enzymes, suggesting a predominant role of di-CQA in the regulation of postprandial energy metabolism. These results suggest that CPP modulates whole-body substrate oxidation by suppressing postprandial hyperglycaemia and hyperinsulinaemia, and these effects are mediated by inhibiting digestive enzymes.

  5. Postprandial lipids accelerate and redirect nitric oxide consumption in plasma.

    PubMed

    Vrancken, Kurt; Schroeder, Hobe J; Longo, Lawrence D; Power, Gordon G; Blood, Arlin B

    2016-05-01

    Nitric oxide (NO) and O2 are both three-to four-fold more soluble in biological lipids than in aqueous solutions. Their higher concentration within plasma lipids accelerates NO autoxidation to an extent that may be of importance to overall NO bioactivity. This study was undertaken to test the hypothesis that increased plasma lipids after a high-fat meal appreciably accelerate NO metabolism and alter the byproducts formed. We found that plasma collected from subjects after consumption of a single high-fat meal had a higher capacity for NO consumption and consumed NO more rapidly compared to fasting plasma. This increased NO consumption showed a direct correlation with plasma triglyceride concentrations (p = 0.006). The accelerated NO consumption in postprandial plasma was reversed by removal of the lipids from the plasma, was mimicked by the addition of hydrophobic micelles to aqueous buffer, and could not be explained by the presence of either free hemoglobin or ceruloplasmin. The products of NO consumption were shifted in postprandial plasma, with 55% more nitrite (n = 12, p = 0.002) but 50% less SNO (n = 12, p = 0.03) production compared to matched fasted plasma. Modeling calculations indicated that NO autoxidation was accelerated by about 48-fold in the presence of plasma lipids. We conclude that postprandial triglyceride-rich lipoproteins exert a significant influence on NO metabolism in plasma.

  6. Digestible and indigestible carbohydrates: interactions with postprandial lipid metabolism.

    PubMed

    Lairon, Denis; Play, Barbara; Jourdheuil-Rahmani, Dominique

    2007-04-01

    The balance between fats and carbohydrates in the human diet is still a matter of very active debate. Indeed, the processing of ordinary mixed meals involves complex processes within the lumen of the upper digestive tract for digestion, in the small intestine mucosa for absorption and resecretion, and in peripheral tissues and in the circulation for final handling. The purpose of this review is to focus on available knowledge on the interactions of digestible or indigestible carbohydrates with lipid and lipoprotein metabolism in the postprandial state. The observations made in humans after test meals are reported and interpreted in the light of recent findings on the cellular and molecular levels regarding possible interplays between carbohydrates and lipid moieties in some metabolic pathways. Digestible carbohydrates, especially readily digestible starches or fructose, have been shown to exacerbate and/or delay postprandial lipemia, whereas some fiber sources can lower it. While interactions between dietary fibers and the process of lipid digestion and absorption have been studied mainly in the last decades, recent studies have shown that dietary carbohydrate moieties (e.g., glucose) can stimulate the intestinal uptake of cholesterol and lipid resecretion. In addition to the well-known glucose/fructose transporters, a number of transport proteins have recently been involved in intestinal lipid processing, whose implications in such interactions are discussed. The potential importance of postprandial insulinemia in these processes is also evaluated in the light of recent findings. The interactions of carbohydrates and lipid moieties in the postprandial state may result from both acute and chronic effects, both at transcriptional and posttranscriptional levels.

  7. Milk Polar Lipids Affect In Vitro Digestive Lipolysis and Postprandial Lipid Metabolism in Mice.

    PubMed

    Lecomte, Manon; Bourlieu, Claire; Meugnier, Emmanuelle; Penhoat, Armelle; Cheillan, David; Pineau, Gaëlle; Loizon, Emmanuelle; Trauchessec, Michèle; Claude, Mathilde; Ménard, Olivia; Géloën, Alain; Laugerette, Fabienne; Michalski, Marie-Caroline

    2015-08-01

    Polar lipid (PL) emulsifiers such as milk PLs (MPLs) may affect digestion and subsequent lipid metabolism, but focused studies on postprandial lipemia are lacking. We evaluated the impact of MPLs on postprandial lipemia in mice and on lipid digestion in vitro. Female Swiss mice were gavaged with 150 μL of an oil-in-water emulsion stabilized with 5.7 mg of either MPLs or soybean PLs (SPLs) and killed after 1, 2, or 4 h. Plasma lipids were quantified and in the small intestine, gene expression was analyzed by reverse transcriptase-quantitative polymerase chain reaction. Emulsions were lipolyzed in vitro using a static human digestion model; triglyceride (TG) disappearance was followed by thin-layer chromatography. In mice, after 1 h, plasma TGs tended to be higher in the MPL group than in the SPL group (141 μg/mL vs. 90 μg/mL; P = 0.07) and nonesterified fatty acids (NEFAs) were significantly higher (64 μg/mL vs. 44 μg/mL; P < 0.05). The opposite was observed after 4 h with lower TGs (21 μg/mL vs. 35 μg/mL; P < 0.01) and NEFAs (20 μg/mL vs. 32 μg/mL; P < 0.01) in the MPL group compared with the SPL group. This was associated at 4 h with a lower gene expression of apolipoprotein B (Apob) and Secretion Associated, Ras related GTPase 1 gene homolog B (Sar1b), in the duodenum of MPL mice compared with SPL mice (P < 0.05). In vitro, during the intestinal phase, TGs were hydrolyzed more in the MPL emulsion than in the SPL emulsion (decremental AUCs were 1750%/min vs. 180%/min; P < 0.01). MPLs enhance lipid intestinal hydrolysis and promote more rapid intestinal lipid absorption and sharper kinetics of lipemia. Postprandial lipemia in mice can be modulated by emulsifying with MPLs compared with SPLs, partly through differences in chylomicron assembly, and TG hydrolysis rate as observed in vitro. MPLs may thereby contribute to the long-term regulation of lipid metabolism. © 2015 American Society for Nutrition.

  8. The autonomic nervous system regulates postprandial hepatic lipid metabolism.

    PubMed

    Bruinstroop, Eveline; la Fleur, Susanne E; Ackermans, Mariette T; Foppen, Ewout; Wortel, Joke; Kooijman, Sander; Berbée, Jimmy F P; Rensen, Patrick C N; Fliers, Eric; Kalsbeek, Andries

    2013-05-15

    The liver is a key organ in controlling glucose and lipid metabolism during feeding and fasting. In addition to hormones and nutrients, inputs from the autonomic nervous system are also involved in fine-tuning hepatic metabolic regulation. Previously, we have shown in rats that during fasting an intact sympathetic innervation of the liver is essential to maintain the secretion of triglycerides by the liver. In the current study, we hypothesized that in the postprandial condition the parasympathetic input to the liver inhibits hepatic VLDL-TG secretion. To test our hypothesis, we determined the effect of selective surgical hepatic denervations on triglyceride metabolism after a meal in male Wistar rats. We report that postprandial plasma triglyceride concentrations were significantly elevated in parasympathetically denervated rats compared with control rats (P = 0.008), and VLDL-TG production tended to be increased (P = 0.066). Sympathetically denervated rats also showed a small rise in postprandial triglyceride concentrations (P = 0.045). On the other hand, in rats fed on a six-meals-a-day schedule for several weeks, a parasympathetic denervation resulted in >70% higher plasma triglycerides during the day (P = 0.001), whereas a sympathetic denervation had no effect. Our results show that abolishing the parasympathetic input to the liver results in increased plasma triglyceride levels during postprandial conditions.

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

    PubMed

    Xie, Ping; Guo, Feng; Ma, Yinyan; Zhu, Hongling; Wang, Freddy; Xue, Bingzhong; Shi, Hang; Yang, Jian; Yu, Liqing

    2014-01-01

    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.

  10. Postprandial lipid responses to standard carbohydrate challenges used to determine glycemic index values

    USDA-ARS?s Scientific Manuscript database

    Prior studies assessing metabolic effects of different types of carbohydrate have focused on their glycemic response. Not considered has been the response of postprandial cardiometabolic risk indicators. This study assessed the postprandial lipid responses to two forms of carbohydrates used as ref...

  11. Meal triacylglycerol profile modulates postprandial absorption of carotenoids in humans.

    PubMed

    Goltz, Shellen R; Campbell, Wayne W; Chitchumroonchokchai, Chureeporn; Failla, Mark L; Ferruzzi, Mario G

    2012-06-01

    Dietary lipids are considered to be primary potentiators of carotenoid absorption, yet the amount and source required to optimize bioavailability has not been systematically evaluated. The objective of this study was to examine the impact of both amount and source of triacylglycerols on postprandial absorption of carotenoids from vegetable salads. Healthy subjects (n = 29) were randomized using a Latin square design (3 × 3) and consumed three identical salads with 3, 8, or 20 g of canola oil, soybean oil, or butter. Blood was collected from 0-10 h and triacylglycerol-rich fractions (TRLs) were isolated by ultracentrifugation. Carotenoid contents of TRL fractions were analyzed by HPLC-DAD. Considering all lipid sources, 20 g of lipid promoted higher absorption compared to 3 and 8 g for all carotenoid species (p < 0.05), except for α-carotene (p = 0.07). The source of lipid had less impact on the absorption of carotenoids than amount of lipid. Pooling results from all lipid amounts, monounsaturated fatty acid rich canola oil trended toward enhancing absorption of lutein and α-carotene compared to saturated fatty acid rich butter (p = 0.06 and p = 0.08, respectively). While both amount and source of co-consumed lipid affect carotenoid bioavailability from vegetables, amount appears to exert a stronger effect. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Effect of Dietary Lipids on Endotoxemia Influences Postprandial Inflammatory Response.

    PubMed

    López-Moreno, Javier; García-Carpintero, Sonia; Jimenez-Lucena, Rosa; Haro, Carmen; Rangel-Zúñiga, Oriol A; Blanco-Rojo, Ruth; Yubero-Serrano, Elena M; Tinahones, Francisco J; Delgado-Lista, Javier; Pérez-Martínez, Pablo; Roche, Helen M; López-Miranda, José; Camargo, Antonio

    2017-09-06

    Metabolic syndrome (MetS) results in postprandial metabolic alterations that predisposes one to a state of chronic low-grade inflammation and increased oxidative stress. We aimed to assess the effect of the consumption of the quantity and quality of dietary fat on fasting and postprandial plasma lipopolysaccharides (LPS). A subgroup of 75 subjects with metabolic syndrome was randomized to receive 1 of 4 diets: HSFA, rich in saturated fat; HMUFA, rich in monounsaturated fat; LFHCC n-3, low-fat, rich in complex carbohydrate diet supplemented with n-3 polyunsaturated fatty acids; LFHCC low-fat, rich in complex carbohydrate diet supplemented with placebo, for 12 weeks each. We administered a fat challenge reflecting the fatty acid composition of the diets at postintervention. We determined the plasma lipoproteins and glucose and gene expression in peripheral blood mononuclear cells (PBMC) and adipose tissue. LPS and LPS binding protein (LBP) plasma levels were determined by ELISA, at fasting and postprandial (4 h after a fat challenge) states. We observed a postprandial increase in LPS levels after the intake of the HSFA meal, whereas we did not find any postprandial changes after the intake of the other three diets. Moreover, we found a positive relationship between the LPS plasma levels and the gene expression of IkBa and MIF1 in PBMC. No statistically significant differences in the LBP plasma levels at fasting or postprandial states were observed. Our results suggest that the consumption of HSFA diet increases the intestinal absorption of LPS which, in turn, increases postprandial endotoxemia levels and the postprandial inflammatory response.

  13. ABCA1 gene variants regulate postprandial lipid metabolism in healthy men

    PubMed Central

    Delgado-Lista, Javier; Perez-Martinez, Pablo; Perez-Jimenez, Francisco; Garcia-Rios, Antonio; Fuentes, Francisco; Marin, Carmen; Gómez-Luna, Purificación; Camargo, Antonio; Parnell, Laurence D; Ordovas, Jose Maria; Lopez-Miranda, Jose

    2010-01-01

    Objective Genetic variants of ABCA1, an ATP-binding cassette (ABC) transporter, have been linked to altered atherosclerosis progression and fasting lipid concentration, mainly high density lipoproteins (HDL) and Apolipoprotein A1 (APOA1), but results from different studies have been inconsistent. Methods and results In order to further characterize the effects of ABCA1 variants in human postprandial lipid metabolism, we studied the influence of three single nucleotide polymorphisms (SNPs) [i27943 (rs2575875); i48168 (rs4149272); R219K (rs2230806)] in the postprandial lipemia of 88 normolipidemic young men, who were given a fatty meal. For i27943 and i48168 SNPs, fasting and postprandial values of APOA1 were higher, and postprandial lipemia was much lower in homozygotes for the major alleles, for total triglycerides in plasma, and large-triglyceride rich lipoproteins (TRL) triglycerides. These persons also showed higher APOA1/APOB ratio. Major allele homozygotes for i48168 and i27943 showed additionally higher HDL and lower postprandial Apolipoprotein B (ApoB). Conclusions Our work shows that major allele homozygotes for ABCA1 SNPs i27943 and i48168 have a lower postprandial response as compared to minor allele carriers. This finding may further characterize the role of ABCA1 in lipid metabolism. PMID:20185793

  14. Postprandial apoE Isoform and Conformational Changes Associated with VLDL Lipolysis Products Modulate Monocyte Inflammation

    PubMed Central

    den Hartigh, Laura J.; Altman, Robin; Hutchinson, Romobia; Petrlova, Jitka; Budamagunta, Madhu S.; Tetali, Sarada D.; Lagerstedt, Jens O.; Voss, John C.; Rutledge, John C.

    2012-01-01

    Objective Postprandial hyperlipemia, characterized by increased circulating very low-density lipoproteins (VLDL) and circulating lipopolysaccharide (LPS), has been proposed as a mechanism of vascular injury. Our goal was to examine the interactions between postprandial lipoproteins, LPS, and apoE3 and apoE4 on monocyte activation. Methods and Results We showed that apoE3 complexed to phospholipid vesicles attenuates LPS-induced THP-1 monocyte cytokine expression, while apoE4 increases expression. ELISA revealed that apoE3 binds to LPS with higher affinity than apoE4. Electron paramagnetic resonance (EPR) spectroscopy of site-directed spin labels placed on specific amino acids of apoE3 showed that LPS interferes with conformational changes normally associated with lipid binding. Specifically, compared to apoE4, apoE bearing the E3-like R112→Ser mutation displays increased self association when exposed to LPS, consistent with a stronger apoE3-LPS interaction. Additionally, lipolysis of fasting VLDL from normal human donors attenuated LPS-induced TNFα secretion from monocytes to a greater extent than postprandial VLDL, an effect partially reversed by blocking apoE. This effect was reproduced using fasting VLDL lipolysis products from e3/e3 donors, but not from e4/e4 subjects, suggesting that apoE3 on fasting VLDL prevents LPS-induced inflammation more readily than apoE4. Conclusion Postprandial apoE isoform and conformational changes associated with VLDL dramatically modulate vascular inflammation. PMID:23209766

  15. Sleeve Gastrectomy in Rats Improves Post-Prandial Lipid Clearance by Reducing Intestinal Triglyceride Secretion

    PubMed Central

    Stefater, MA; Sandoval, DA; Chambers, AP; Wilson-Pérez, HE; Hofmann, SM; Jandacek, R; Tso, P; Woods, SC; Seeley, RJ

    2011-01-01

    Background & Aims Post-prandial hyperlipidemia is a risk factor for atherosclerotic heart disease and is associated with the consumption of high-fat diets and obesity. Bariatric surgeries result in superior and more durable weight loss than dieting. These surgeries are also associated with multiple metabolic improvements, including reduced plasma lipid levels. We investigated whether the beneficial effects of vertical sleeve gastrectomy (VSG) on plasma lipid levels are weight-independent. Methods VSG was performed on Long-Evans rats with diet-induced obesity and pair-fed and ad libitum-fed rats that received sham operations (controls). We measured fasting and post-prandial levels of plasma lipid. To determine hepatic and intestinal triglyceride secretion, we injected the lipase inhibitor poloxamer 407 alone, or before oral lipid gavage. 13C-Triolein was used to estimate post-prandial uptake of lipid in the intestine. Results Rats that received VSG and high-fat diets (HFDs) had markedly lower fasting levels of plasma triglyceride, cholesterol, and phospholipid than obese and lean (pair-fed) controls that were fed HFD. Rats that received VSG had a marked, weight-independent reduction in secretion of intestinal triglycerides. VSG did not alter total intestinal triglyceride levels or size of the cholesterol storage pool, nor did it affect the expression of genes in the intestine that control triglyceride metabolism and synthesis . VSG did not affect fasting secretion of triglyceride, liver weight, hepatic lipid storage, or transcription of genes that regulate hepatic lipid processing. Conclusions VSG reduced post-prandial levels of plasma lipid, independently of body weight. This resulted from reduced intestinal secretion of triglycerides following ingestion of a lipid meal and indicates that VSG has important effects on metabolism. PMID:21699773

  16. Hormonal response to lipid and carbohydrate meals during the acute postprandial period

    PubMed Central

    2011-01-01

    Background Optimizing the hormonal environment during the postprandial period in favor of increased anabolism is of interest to many active individuals. Data are conflicting regarding the acute hormonal response to high fat and high carbohydrate feedings. Moreover, to our knowledge, no studies have compared the acute hormonal response to ingestion of lipid and carbohydrate meals of different size. Methods We compared the hormonal response to lipid and carbohydrate meals of different caloric content during the acute postprandial period. Nine healthy men (22 ± 2 years) consumed in a random order, cross-over design one of four meals/beverages during the morning hours in a rested and fasted state: dextrose at 75 g (300 kcals), dextrose at 150 g (600 kcals), lipid at 33 g (300 kcals), lipid at 66 g (600 kcals). Blood samples were collected Pre meal, and at 0.5 hr, 1 hr, 2 hr, and 3 hr post meal. Samples were assayed for testosterone, cortisol, and insulin using ELISA techniques. Area under the curve (AUC) was calculated for each variable, and a 4 × 5 ANOVA was used to further analyze data. Results A meal × time effect (p = 0.0003) was noted for insulin, with values highest for the dextrose meals at the 0.5 hr and 1 hr times, and relatively unaffected by the lipid meals. No interaction (p = 0.98) or meal (p = 0.39) effect was noted for testosterone, nor was an interaction (p = 0.99) or meal (p = 0.65) effect noted for cortisol. However, a time effect was noted for both testosterone (p = 0.04) and cortisol (p < 0.0001), with values decreasing during the postprandial period. An AUC effect was noted for insulin (p = 0.001), with values higher for the dextrose meals compared to the lipid meals (p < 0.05). No AUC effect was noted for testosterone (p = 0.85) or cortisol (p = 0.84). Conclusions These data indicate that 1) little difference is noted in serum testosterone or cortisol during the acute postprandial period when healthy men consume lipid and dextrose meals of

  17. The impact of beef steak thermal processing on lipid oxidation and postprandial inflammation related responses.

    PubMed

    Nuora, Anu; Chiang, Vic Shao-Chih; Milan, Amber M; Tarvainen, Marko; Pundir, Shikha; Quek, Siew-Young; Smith, Greg C; Markworth, James F; Ahotupa, Markku; Cameron-Smith, David; Linderborg, Kaisa M

    2015-10-01

    Oxidised lipid species, their bioavailability and impact on inflammatory responses from cooked beef steak are poorly characterised. Oxidised lipid species from pan-fried (PF) and sous-vide (SV) thermally processed beef were determined with UHPLC-ESI/MS. Twenty-three lipid oxidation products increased with thermal processing and differences between the PF and SV steaks were measured. Fifteen oxidised lipids were measured in post-meal plasma after a cross-over randomised clinical study. Postprandial plasma inflammatory markers tended to remain lower following the SV meal than the PF meal. High levels of conjugated dienes were measured in the HDL fraction, suggesting that the protective effect of HDL may extend to the reverse-transport of oxidised lipid species. Oxidised lipids in a single meal may influence postprandial oxidative stress and inflammation. Further studies are required to examine the lipid oxidative responses to increased dietary oxidative lipid load, including the reverse transport activity of HDL. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Modulating absorption and postprandial handling of dietary fatty acids by structuring fat in the meal: a randomized crossover clinical trial.

    PubMed

    Vors, Cécile; Pineau, Gaëlle; Gabert, Laure; Drai, Jocelyne; Louche-Pélissier, Corinne; Defoort, Catherine; Lairon, Denis; Désage, Michel; Danthine, Sabine; Lambert-Porcheron, Stéphanie; Vidal, Hubert; Laville, Martine; Michalski, Marie-Caroline

    2013-01-01

    Prolonged postprandial hypertriglyceridemia is a potential risk factor for cardiovascular diseases. In the context of obesity, this is associated with a chronic imbalance of lipid partitioning oriented toward storage and not toward β-oxidation. We tested the hypothesis that the physical structure of fat in a meal can modify the absorption, chylomicron transport, and further metabolic handling of dietary fatty acids. Nine normal-weight and 9 obese subjects were fed 40 g milk fat (+[(13)C]triacylglycerols), either emulsified or nonemulsified, in breakfasts of identical composition. We measured the postprandial triacylglycerol content and size of the chylomicron-rich fraction, plasma kinetics of [(13)C]fatty acids, exogenous lipid oxidation with breath-test/indirect calorimetry, and fecal excretion. The emulsified fat resulted in earlier (>1 h) and sharper chylomicron and [(13)C]fatty acid peaks in plasma than in spread fat in both groups (P < 0.0001). After 2 h, the emulsified fat resulted in greater apolipoprotein B-48 concentrations (9.7 ± 0.7 compared with 7.1 ± 0.9 mg/L; P < 0.05) in the normal-weight subjects than did the spread fat. In the obese subjects, emulsified fat resulted in a 3-fold greater chylomicron size (218 ± 24 nm) compared with the spread fat (P < 0.05). The emulsified fat induced higher dietary fatty acid spillover in plasma and a sharper (13)CO(2) appearance, which provoked increased exogenous lipid oxidation in each group: from 45% to 52% in normal-weight subjects (P < 0.05) and from 40% to 57% in obese subjects (P < 0.01). This study supports a new concept of "slow vs fast fat," whereby intestinal absorption can be modulated by structuring dietary fat to modulate postprandial lipemia and lipid β-oxidation in humans with different BMIs. This trial was registered at clinicaltrials.gov as NCT01249378.

  19. Hass avocado modulates postprandial vascular reactivity and postprandial inflammatory responses to a hamburger meal in healthy volunteers.

    PubMed

    Li, Zhaoping; Wong, Angela; Henning, Susanne M; Zhang, Yanjun; Jones, Alexis; Zerlin, Alona; Thames, Gail; Bowerman, Susan; Tseng, Chi-Hong; Heber, David

    2013-02-26

    Hass avocados are rich in monounsaturated fatty acids (oleic acid) and antioxidants (carotenoids, tocopherols, polyphenols) and are often eaten as a slice in a sandwich containing hamburger or other meats. Hamburger meat forms lipid peroxides during cooking. After ingestion, the stomach functions as a bioreactor generating additional lipid peroxides and this process can be inhibited when antioxidants are ingested together with the meat. The present pilot study was conducted to investigate the postprandial effect of the addition of 68 g of avocado to a hamburger on vasodilation and inflammation. Eleven healthy subjects on two separate occasions consumed either a 250 g hamburger patty alone (ca. 436 cal and 25 g fat) or together with 68 grams of avocado flesh (an additional 114 cal and 11 g of fat for a total of 550 cal and 36 g fat), a common culinary combination, to assess effects on vascular health. Using the standard peripheral arterial tonometry (PAT) method to calculate the PAT index, we observed significant vasoconstriction 2 hours following hamburger ingestion (2.19 ± 0.36 vs. 1.56 ± 0.21, p = 0.0007), which did not occur when the avocado flesh was ingested together with the burger (2.17 ± 0.57 vs. 2.08 ± 0.51, NS p = 0.68). Peripheral blood mononuclear cells were isolated from postprandial blood samples and the Ikappa-B alpha (IκBα) protein concentration was determined to assess effects on inflammation. At 3 hours, there was a significant preservation of IκBα (131% vs. 58%, p = 0.03) when avocado was consumed with the meat compared to meat alone, consistent with reduced activation of the NF-kappa B (NFκB) inflammatory pathway. IL-6 increased significantly at 4 hours in postprandial serum after consumption of the hamburger, but no change was observed when avocado was added. Postprandial serum triglyceride concentration increased, but did not further increase when avocado was ingested with the burger compared to burger alone despite the added fat and

  20. Postprandial lipid responses to standard carbohydrates used to determine glycaemic index values.

    PubMed

    Vega-López, Sonia; Ausman, Lynne M; Matthan, Nirupa R; Lichtenstein, Alice H

    2013-11-01

    Prior studies assessing the metabolic effects of different types of carbohydrates have focused on their glycaemic response. However, the response of postprandial cardiometabolic risk indicators has not been considered in these studies. The present study assessed postprandial lipid responses to two forms of carbohydrates used as reference foods for glycaemic index determinations, white bread (50 g available carbohydrate) and glucose (50 g), under controlled conditions and with intra-individual replicate determinations. A total of twenty adults (20–70 years) underwent two cycles of challenges with each pair of reference foods (four challenges/person), administered in a random order on separate days under standard conditions. Serum lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and NEFA), glucose and insulin were monitored for 5 h post-ingestion. Oral glucose resulted in greater glycaemic and insulinaemic responses than white bread for the first 90 min and a greater subsequent decline after 120 min (P =0·0001). The initial decline in serum NEFA concentrations was greater after the oral glucose than after the white bread challenge, as was the rebound after 150 min (P = 0·001). Nevertheless, the type of carbohydrate had no significant effect on postprandial total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations. Following an initial modest rise in TAG concentrations in response to both challenges, the values dropped below the fasting values for oral glucose but not for the white bread challenge. These data suggest that the type of carbohydrate used to determine the glycaemic index, bread or glucose, has little or modest effects on postprandial plasma cholesterol concentrations. Differences in TAG and NEFA concentrations over the 5 h time period were modest, and their clinical relevance is unclear.

  1. Postprandial lipid responses to standard carbohydrates used to determine glycaemic index values

    PubMed Central

    Vega-López, Sonia; Ausman, Lynne M.; Matthan, Nirupa R.; Lichtenstein, Alice H.

    2015-01-01

    Prior studies assessing the metabolic effects of different types of carbohydrates have focused on their glycaemic response. However, the response of postprandial cardiometabolic risk indicators has not been considered in these studies. The present study assessed postprandial lipid responses to two forms of carbohydrates used as reference foods for glycaemic index determinations, white bread (50 g available carbohydrate) and glucose (50 g), under controlled conditions and with intra-individual replicate determinations. A total of twenty adults (20–70 years) underwent two cycles of challenges with each pair of reference foods (four challenges/person), administered in a random order on separate days under standard conditions. Serum lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and NEFA), glucose and insulin were monitored for 5 h post-ingestion. Oral glucose resulted in greater glycaemic and insulinaemic responses than white bread for the first 90 min and a greater subsequent decline after 120 min (P = 0.0001). The initial decline in serum NEFA concentrations was greater after the oral glucose than after the white bread challenge, as was the rebound after 150 min (P = 0.001). Nevertheless, the type of carbohydrate had no significant effect on postprandial total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations. Following an initial modest rise in TAG concentrations in response to both challenges, the values dropped below the fasting values for oral glucose but not for the white bread challenge. These data suggest that the type of carbohydrate used to determine the glycaemic index, bread or glucose, has little or modest effects on postprandial plasma cholesterol concentrations. Differences in TAG and NEFA concentrations over the 5 h time period were modest, and their clinical relevance is unclear. PMID:23656707

  2. Enzymatically Modified Starch Ameliorates Postprandial Serum Triglycerides and Lipid Metabolome in Growing Pigs

    PubMed Central

    Metzler-Zebeli, Barbara U.; Eberspächer, Eva; Grüll, Dietmar; Kowalczyk, Lidia; Molnar, Timea; Zebeli, Qendrim

    2015-01-01

    Developing host digestion-resistant starches to promote human health is of great research interest. Chemically modified starches (CMS) are widely used in processed foods and although the modification of the starch molecule allows specific reduction in digestibility, the metabolic effects of CMS have been less well described. This short-term study evaluated the impact of enzymatically modified starch (EMS) on fasting and postprandial profiles of blood glucose, insulin and lipids, and serum metabolome in growing pigs. Eight jugular-vein catheterized pigs (initial body weight, 37.4 kg; 4 months of age) were fed 2 diets containing 72% purified starch (EMS or waxy corn starch (control)) in a cross-over design for 7 days. On day 8, an 8-hour meal tolerance test (MTT) was performed with serial blood samplings. Besides biochemical analysis, serum was analysed for 201 metabolites through targeted mass spectrometry-based metabolomic approaches. Pigs fed the EMS diet showed increased (P<0.05) immediate serum insulin and plasma glucose response compared to pigs fed the control diet; however, area-under-the-curves for insulin and glucose were not different among diets. Results from MTT indicated reduced postprandial serum triglycerides with EMS versus control diet (P<0.05). Likewise, serum metabolome profiling identified characteristic changes in glycerophospholipid, lysophospholipids, sphingomyelins and amino acid metabolome profiles with EMS diet compared to control diet. Results showed rapid adaptations of blood metabolites to dietary starch shifts within 7 days. In conclusion, EMS ingestion showed potential to attenuate postprandial raise in serum lipids and suggested constant alteration in the synthesis or breakdown of sphingolipids and phospholipids which might be a health benefit of EMS consumption. Because serum insulin was not lowered, more research is warranted to reveal possible underlying mechanisms behind the observed changes in the profile of serum lipid

  3. Suppressive effects of dietary fiber in yogurt on the postprandial serum lipid levels in healthy adult male volunteers.

    PubMed

    Kondo, Shizuki; Xiao, Jin-Zhong; Takahashi, Noritoshi; Miyaji, Kazuhiro; Iwatsuki, Keiji; Kokubo, Sadayuki

    2004-05-01

    This study assessed the effect of partially hydrolyzed guar gum (PHGG) in yogurt on the elevation of postprandial serum lipid levels. Eleven healthy adult male subjects were given yogurt with or without 6 g of PHGG in a fat tolerance test as a crossover study. Supplementation with 6 g of PHGG significantly suppressed the incremental peaks and areas under the incremental curve (AUIC) of postprandial serum remnant-like lipoprotein particle cholesterol (RLP-C) and triglyceride (TG). The results suggest the potential of PHGG to reduce the risk of hyperlipemia.

  4. Black soybean extract improves lipid profiles in fenofibrate-treated type 2 diabetics with postprandial hyperlipidemia.

    PubMed

    Kusunoki, Masataka; Sato, Daisuke; Tsutsumi, Kazuhiko; Tsutsui, Hideyo; Nakamura, Takao; Oshida, Yoshiharu

    2015-06-01

    Black soybeans (Glycine max (L.) Merr.) are known to be rich in polyphenols, including anthocyanins, and they have been consumed since ancient times for their beneficial effects on health. In addition, it has been reported that black soybean (BS) seed coat may ameliorate obesity and insulin resistance. In the present study, we administered BS extract to type 2 diabetics for 2 months to investigate the effects of BS on glycemic control and lipid metabolism parameters. In addition, we administered BS and antihyperlipidemic agent, fenofibrate, to patients with type 2 diabetes complicated by postprandial hyperlipidemia for 2 months and assessed the combined effects of fenofibrate and BS on serum lipid profile. The results showed that administration of the BS alone had no effect on the blood glucose or lipid levels, but that administration of fenofibrate alone and fenofibrate in combination with the BS significantly lowered their serum triglyceride (TG) level at fasting state, and the percent decrease in the serum TG level after combined administration was significantly higher than in the subjects who received fenofibrate alone. Furthermore, the serum LDL cholesterol concentration, which did not decrease when fenofibrate was administered alone, decreased significantly when the BS and fenofibrate were administered in combination. These results suggest that combined administration of the BS with fenofibrate enhanced the antihyperlipidemic action of fenofibrate, and the results of this study demonstrated the usefulness of the BS in clinical practice.

  5. Postprandial Total Ghrelin Suppression Is Modulated by Melanocortin Signaling in Humans

    PubMed Central

    van der Klaauw, Agatha A.; Keogh, Julia M.; Henning, Elana; Blackwood, Anthea; Haqq, Andrea M.; Purnell, Jonathan Q.

    2013-01-01

    Contents: Ghrelin is implicated in meal initiation because circulating levels increase before and fall after meal consumption. In rodents, ghrelin stimulates food intake via hypothalamic circuits expressing the melanocortin 4 receptor (MC4R). Objective: The aim of the study was to investigate the impact of central melanocortinergic tone on ghrelin secretion in humans. Design/Setting/Patients/Main Outcome Measure: We measured plasma total ghrelin before and after 3 standardized meals in patients with MC4R mutations and obese and lean controls. Fasting total ghrelin, area under the curve, and early (30-min) and intermeal postprandial total ghrelin suppression (the percentage difference between the premeal and the 30-min postprandial or intermeal nadir total ghrelin concentration) were calculated. Results: Fasting total ghrelin concentrations and area under the curve for total ghrelin concentrations were significantly decreased in both obese groups compared to lean controls (fasting total ghrelin: lean controls, 1083 ± 203 pg/ml; and obese controls, 696 ± 81 pg/ml; MC4R: 609 ± 99 pg/ml, P < .05). Early and intermeal postprandial total ghrelin suppression was attenuated in MC4R-deficient patients compared to lean controls (P < .05); a similar pattern was observed for early postprandial suppression in comparison with obese controls, but this difference did not reach statistical significance (P = .09). Conclusions: These findings are consistent with a role for central melanocortinergic signaling in modulating meal-related total ghrelin suppression. PMID:23316086

  6. Interactions between Starch, Lipids, and Proteins in Foods: Microstructure Control for Glycemic Response Modulation.

    PubMed

    Parada, Javier; Santos, Jose L

    2016-10-25

    In real food, starch is usually forming part of a matrix with lipids and proteins. However, research on this ternary system and interactions between such food components has been scarce so far. The control of food microstructure is crucial to determine the product properties, including sensorial and nutritionals ones. This paper reviews the microstructural principles of interactions between starch, lipids, and proteins in foods as well as their effect on postprandial glycemic response, considering human intrinsic differences on postprandial glycemic responses. Several lines of research support the hypothesis that foods without rapidly digestible starch will not mandatorily generate the lowest postprandial glycemic response, highlighting that the full understanding of food microstructure, which modulates starch digestion, plays a key role on food design from a nutritional viewpoint.

  7. Slow and fast dietary proteins differently modulate postprandial protein accretion

    PubMed Central

    Boirie, Yves; Dangin, Martial; Gachon, Pierre; Vasson, Marie-Paule; Maubois, Jean-Louis; Beaufrère, Bernard

    1997-01-01

    The speed of absorption of dietary amino acids by the gut varies according to the type of ingested dietary protein. This could affect postprandial protein synthesis, breakdown, and deposition. To test this hypothesis, two intrinsically 13C-leucine-labeled milk proteins, casein (CAS) and whey protein (WP), of different physicochemical properties were ingested as one single meal by healthy adults. Postprandial whole body leucine kinetics were assessed by using a dual tracer methodology. WP induced a dramatic but short increase of plasma amino acids. CAS induced a prolonged plateau of moderate hyperaminoacidemia, probably because of a slow gastric emptying. Whole body protein breakdown was inhibited by 34% after CAS ingestion but not after WP ingestion. Postprandial protein synthesis was stimulated by 68% with the WP meal and to a lesser extent (+31%) with the CAS meal. Postprandial whole body leucine oxidation over 7 h was lower with CAS (272 ± 91 μmol⋅kg−1) than with WP (373 ± 56 μmol⋅kg−1). Leucine intake was identical in both meals (380 μmol⋅kg−1). Therefore, net leucine balance over the 7 h after the meal was more positive with CAS than with WP (P < 0.05, WP vs. CAS). In conclusion, the speed of protein digestion and amino acid absorption from the gut has a major effect on whole body protein anabolism after one single meal. By analogy with carbohydrate metabolism, slow and fast proteins modulate the postprandial metabolic response, a concept to be applied to wasting situations. PMID:9405716

  8. The Effect of Tofogliflozin Treatment on Postprandial Glucose and Lipid Metabolism in Japanese Men With Type 2 Diabetes: A Pilot Study

    PubMed Central

    Kakuda, Hirokazu; Kobayashi, Junji; Sakurai, Masaru; Kakuda, Masahiro; Takekoshi, Noboru

    2017-01-01

    Background Postprandial hyperglycemia and hyperlipidemia are highly related to the development of atherosclerosis. Sodium/glucose cotransporter-2 (SGLT2) inhibitors have attracted attention as a new class of anti-diabetic agents for the treatment of type 2 diabetes. We investigated the effect of tofogliflozin on postprandial glucose and lipid metabolism in Japanese male patients with type 2 diabetes. Methods Ten Japanese men with type 2 diabetes (average age 66.3 years) were orally administered tofogliflozin (20 mg per day) for 8 weeks followed by a subsequent 8 weeks of washout of the agent. At 0, 8 and 16 weeks, postprandial metabolic parameters were measured at 0, 60 and 120 min after cookie ingestion. Results There were significant reductions in body weight and body mass index at 8 weeks. There was a reduction in HbA1c at 8 weeks, which returned to pretreatment levels at 16 weeks. Serum insulin levels did not change during the entire study period under either fasting or postprandial state. The area under the curve of plasma glucagon significantly increased at 8 weeks. There were no changes in lipid and lipoprotein levels either in fasting or postprandial state except for tendency toward reduction in postprandial triglycerides at 8 weeks and increase in HDL-C at 16 weeks. Conclusions Tofogliflozin treatment causes an improvement of postprandial glucose metabolism but not considerable postprandial lipid metabolism. PMID:28392860

  9. Acute effects of plant stanol esters on postprandial metabolism and its relation with changes in serum lipids after chronic intake.

    PubMed

    De Smet, E; Mensink, R P; Lütjohann, D; Plat, J

    2015-01-01

    Plant stanol esters lower serum low-density lipoprotein (LDL)-cholesterol (LDL-C), but responses between individuals vary widely. As the ability of subjects to respond to acute dietary challenges may reflect the flexibility to adapt to changes on the longer term, we related subjects' acute postprandial metabolic changes to changes in serum lipoproteins after chronic intake of plant stanol esters. In a double-blind crossover design, 20 healthy subjects received in random order a high-fat shake enriched with or without plant stanol esters (4 g). Blood samples were taken during 4 h to examine lipid, glucose and lipoprotein profiles. Two subjects dropped out. For the 3 weeks after this postprandial test, the subjects who received the shake with plant stanol esters continued the consumption of plant stanol-enriched (3g/day) margarine and subjects receiving the control shake in the postprandial test consumed for the next 3 weeks a control margarine. After the washout period, subjects received the other shake and margarines. The margarine enriched with plant stanol esters lowered concentrations of total cholesterol by 7.3% (P<0.01), LDL-C by 9.5% (P<0.01) and apoB100 by 8.6% (P<0.01). Furthermore, particle concentrations of total very low-density lipoprotein (VLDL), small VLDL and large LDL were reduced by 26.6% (P=0.02), 27.6% (P=0.02) and 12.3% (P=0.04), respectively. Plant stanol esters did not affect parameters related to lipid and glucose metabolism during the postprandial phase. However, the incremental area under the curve (iAUC) of the postprandial glucose concentration after consuming the control shake correlated positively with changes in fasting concentrations of total cholesterol, LDL-C, apoB100, total VLDL, small VLDL and intermediate-density lipoprotein after 3 weeks. A single dose of plant stanol esters does not change postprandial lipid and lipoprotein profiles. However, postprandial glucose responses may predict the effects of chronic plant stanol ester

  10. Effects of variations in the APOA1/C3/A4/A5 gene cluster on different parameters of postprandial lipid metabolism in healthy young men

    USDA-ARS?s Scientific Manuscript database

    Background: The APOA1/C3/A4/A5 gene cluster encodes important regulators of fasting lipids, but the majority of lipid metabolism takes place in the postprandial state, and knowledge about gene regulation in this state is scarce. With the aim of characterizing possible regulators of lipid metabolism...

  11. Acute hyperinsulinism modulates plasma apolipoprotein B-48 triglyceride-rich lipoproteins in healthy subjects during the postprandial period.

    PubMed

    Harbis, A; Defoort, C; Narbonne, H; Juhel, C; Senft, M; Latgé, C; Delenne, B; Portugal, H; Atlan-Gepner, C; Vialettes, B; Lairon, D

    2001-02-01

    The role of postprandial insulin in the regulation of postprandial lipid metabolism is still poorly understood. The roles of hyperinsulinemia and insulin resistance in the alteration of postprandial lipid metabolism are not clear either. To improve knowledge in this area, we submitted healthy men to acute hyperinsulinemia in two different ways. In the first study, we compared in 10 men the effects of four isolipidic test meals that induce different degrees of hyperinsulinemia on postprandial lipid metabolism. Three different carbohydrate sources were compared according to their glycemic indexes (GIs; 35, 75, and 100 for white kidney bean, spaghetti, and white bread test meals, respectively); the fourth test meal did not contain any carbohydrates. Postprandial plasma insulin levels were proportional to the GIs (maximal plasma insulin concentrations: 113 +/- 16 to 266 +/- 36 pmol/l). We found a strong positive correlation during the 6-h postprandial period between apolipoprotein (apo) B-48 plasma concentration and insulin plasma concentration (r2 = 0.70; P = 0.0001). In a second study, 5 of the 10 subjects again ingested the carbohydrate-free meal, but during a 3-h hyperinsulinemic- (550 +/- 145 pmol/l plasma insulin) euglycemic (5.5 +/- 0.8 mmol/l plasma glucose) clamp. A biphasic response was observed with markedly reduced levels of plasma apoB-48 during insulin infusion, followed by a late accumulation of plasma apoB-48 and triglycerides. Overall, the data obtained showed that portal and peripheral hyperinsulinism delays and exacerbates postprandial accumulation of intestinally derived chylomicrons in plasma and thus is involved in the regulation of apoB-48-triglyceride-rich lipoprotein metabolism, in the absence of insulin-resistance syndrome.

  12. In vivo postprandial bioavailability of interesterified-lipids in sodium-caseinate or chitosan based O/W emulsions.

    PubMed

    Farfán, M; Villalón, M J; Ortíz, M E; Nieto, S; Bouchon, P

    2015-03-15

    Recent studies have shown that it should be possible to control lipid bioavailability through food structural approaches. Nevertheless, the gastrointestinal-tract physiological conditions must also be considered. To get a better understanding of this phenomenon, we evaluated the effect of emulsification, as well as the use of sodium caseinate or chitosan, on the postprandial bioavailability of interesterified-lipids in O/W emulsions after oral gastric feeding Sprague-Dawley rats. We verified that emulsification may increase lipid absorption, as determined after feeding sodium-caseinate emulsions. However, this result could not be generalised. Interesterified-lipids that were emulsified with chitosan were equally absorbed as those contained in non-emulsified interesterified-lipids/distilled-water blends. Copyright © 2014. Published by Elsevier Ltd.

  13. Effects of a liquid high-fat meal on postprandial lipid metabolism in type 2 diabetic patients with abdominal obesity.

    PubMed

    Wang, Feng; Lu, Huixia; Liu, Fukang; Cai, Huizhen; Song, Zhixiu; Guo, Fei; Xie, Yulan; Shu, Guofang; Sun, Guiju

    2017-01-01

    Postprandial lipemia and lipoprotein lipase (LPL) activity play crucial roles in the pathogenesis of accelerated atherosclerosis. This study aimed to evaluate the postprandial lipid metabolism after the ingestion of a liquid high-fat meal in type 2 diabetic patients with abdominal obesity, and determine if the PvuII polymorphisms of LPL influence their postprandial lipid responses. Serum glucose, insulin, triglycerides (TG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were measured in fasting and postprandial state at 0.5, 1, 2, 4, 6 and 8 h after a liquid high-fat meal in 51 type 2 diabetic patients with abdominal obesity, 31 type 2 diabetic patients without abdominal obesity and 39 controls. Their PvuII polymorphisms of LPL were tested in fasting. Type 2 diabetic patients with abdominal obesity had significantly higher postprandial areas under the curve (AUC) of glucose [least square mean difference (LSMD) = 30.763, 95% confidence interval (CI) = 23.071-38.455, F = 37.346, P < 0.05] and TC (LSMD = 3.995, 95% CI = 1.043-6.947, F = 3.681, P < 0.05) than controls. Postprandial AUCs for insulin, homeostasis model assessment-insulin resistance (HOMA-IR) and TG were higher (LSMD = 86.987, 95% CI = 37.421-136.553, F = 16.739, P < 0.05; LSMD = 37.456, 95% CI = 16.312-58.600, F = 27.012, P < 0.05; LSMD = 4.684, 95% CI = 2.662-6.705, F = 26.158, P < 0.05), whereas HDL-C AUC was lower (LSMD = -1.652, 95% CI = -2.685 - -0.620, F = 8.190, P < 0.05) in type 2 diabetic subjects with abdominal obesity than those without abdominal obesity. In type 2 diabetic patients with abdominal obesity, postprandial TG AUC was lower in P-/- than in P+/- (LSMD = -4.393, 95% CI = -9.278 - -0.491, F = 4.476, P < 0.05) and P+/+ (LSMD = -7.180, 95% CI = -12.319 - -2.014, F = 4.476, P < 0.05) phenotypes. Postprandial AUCs for glucose, insulin, HOMA-IR, TC and HDL-C were not different according to Pvu

  14. Effects of long-term feeding of chitosan on postprandial lipid responses and lipid metabolism in a high-sucrose-diet-impaired glucose-tolerant rat model.

    PubMed

    Liu, Shing-Hwa; He, Sih-Pin; Chiang, Meng-Tsan

    2012-05-02

    This study was designed to investigate the effects of long-term feeding of chitosan on postprandial lipid response and lipid metabolism in a high-sucrose (HS)-diet-impaired glucose-tolerant rat model. As the results, HS-diet-fed rats supplemented with 5 and 7% chitosan in diets for 9 weeks had lower postprandial plasma total cholesterol (TC) levels, but 7% chitosan in the diet had higher postprandial plasma triglyceride (TG) and TG-rich lipoprotein TG levels. Supplementation of chitosan significantly decreased the postprandial ratio of apolipoprotein B (apoB)48/apoB100 in TG-rich lipoprotein fractions of HS-diet-fed rats. Long-term supplementation of 5 and 7% chitosan in diets for 16 weeks had lower plasma TC, low-density lipoprotein cholesterol (LDL-C) + very low density lipoprotein cholesterol (VLDL-C), TC/high-density lipoprotein (HDL-C) ratio, leptin, and tumor necrosis factor-α (TNF-α) levels in HS-diet-fed rats. Moreover, it was noticed that the VLDL receptor (VLDLR) protein expression in skeletal muscles of HS-diet-fed rats was significantly decreased, which could be significantly reversed by supplementation of 5 and 7% chitosan. Rats supplemented with 7% chitosan in the diet significantly elevated the lipolysis rate and decreased the accumulation of TG in epididymal fat pads of HS-diet-fed rats. The plasma angiopoietin-like 4 (ANGPTL4) protein expression was not affected in HS-diet-fed rats, but it was significantly increased in 7% chitosan-supplemented HS-diet-fed rats. Taken together, these results indicate that supplementation of chitosan in the diet can improve the impairment of lipid metabolism in a HS-diet-fed rat model, but long-term high-dose chitosan feeding may enhance postprandial plasma TG and TG-rich lipoprotein TG levels in HS-diet-fed rats through an ANGPTL4-regulated pathway.

  15. The relationship between the postprandial lipemic response and lipid composition in persons with spinal cord injury

    PubMed Central

    Emmons, Racine R.; Cirnigliaro, Christopher M.; Kirshblum, Steven C.; Bauman, William A.

    2014-01-01

    Objective To determine the influence of lipid concentration, lipid particle size, and total abdominal fat (TAF) on postprandial lipemic response (PPLr) in persons with spinal cord injury (SCI). Methods Thirty-five persons with SCI (17 paraplegia, 18 tetraplegia) and 18 able-bodied (AB) individuals participated. Following a 10-hour fast, blood was drawn for lipids, apolipoprotein (apo) A1 and B concentrations, and low-density (LSP) and high-density (HSP) lipoprotein particle sizes. A high-fat milkshake was consumed (∼1.3 g fat/kg). Blood was drawn at 2, 4, and 6 hours to determine PPLr, (triglyceride (TG) area under the curve). TAF and visceral (VF) fat were measured by ultrasonography; total body fat (TBF) by dual-energy X-ray absorptiometry. Differences between the groups were determined by independent sample t-tests. Pearson correlation coefficients determined the relationship among PPLr and lipids, and TAF. Results There were no significant differences in fasting TG, low-density lipoprotein (LDL), apoB, TAF, or PPLr values between the groups. In SCI, PPLr significantly correlated with: apoB (r = 0.63, P < 0.01, LSP (r = 0.57, P < 0.01), and TAF (r = 0.36, P < 0.01). After controlling for age and duration of injury, PPLr significantly correlated with apoB (r = 0.66, P = 0.001), TBF (r = 0.45, P = 0.03), VF (r = 0.66, P = 0.02), and TAF (r = 0.56, P = 0.007). Conclusions Although concentrations of LDL cholesterol and apoB were not different between SCI and AB groups, LSP, apoB, and TAF correlated with PPLr in persons with SCI. ApoB was associated with a greater PPLr in those with motor complete SCI, after controlling for age and duration of injury. PMID:24961488

  16. Effects of milk and milk constituents on postprandial lipid and glucose metabolism in overweight and obese men.

    PubMed

    van Meijl, Leonie E C; Mensink, Ronald P

    2013-08-28

    Studies have suggested that two major milk constituents, casein and Ca, favourably affect postprandial responses. However, effects of milk on postprandial metabolism are unknown. We therefore investigated effects of using milk with a fat-containing meal on lipid and glucose responses in overweight men. To identify the constituent responsible for possible effects, we also studied responses to Ca and protein. A total of sixteen men (BMI .27 kg/m2) participated in four postprandial tests. They consumed a breakfast (44 g of fat) plus a drink: a control drink, low-fat milk or a protein and Ca drink (500 ml). Blood samples were taken before the meals and at regular time points during 6 h thereafter. Compared with control, the incremental AUC (iAUC) for serum TAG was increased by 44% after the protein meal (P¼0·015). Although the iAUC were not different (P¼0·051), peak glucose concentrations were reduced by 24% after protein intake, as compared with control (P¼0·021). The decrease of 18% after milk intake did not reach statistical significance. Compared with the milk meal, the iAUC for insulin was 52% lower after the control meal (P¼0·035) and 51% after the protein meal (P¼0·005). The present results indicate that the intake of milk with a fat-containing meal enhances postprandial TAG and insulin responses and may blunt glucose increases. The protein fraction of milk seems to be the main determinant for the effects on TAG and glucose. Ca did not change any of the postprandial responses.

  17. Carbohydrate coingestion delays dietary protein digestion and absorption but does not modulate postprandial muscle protein accretion.

    PubMed

    Gorissen, Stefan H M; Burd, Nicholas A; Hamer, Henrike M; Gijsen, Annemie P; Groen, Bart B; van Loon, Luc J C

    2014-06-01

    Dietary protein digestion and absorption is an important factor modulating muscle protein accretion. However, there are few data available on the effects of coingesting other macronutrients with protein on digestion and absorption kinetics and the subsequent muscle protein synthetic response. The objective of the study was to determine the impact of carbohydrate coingestion with protein on dietary protein digestion and absorption and muscle protein accretion in healthy young and older men. Twenty-four healthy young (aged 21± 1 y, body mass index 21.8 ±0.5 kg/m(2)) and 25 older (aged 75 ± 1 y, body mass index 25.4 ± 0.6 kg/m(2)) men received a primed continuous L-[ring-(2)H5]-phenylalanine and L-[ring-3,5-(2)H2]-tyrosine infusion and ingested 20 g intrinsically L-[1-(13)C]-phenylalanine-labeled protein with (Pro+CHO) or without (Pro) 60 g carbohydrate. Plasma samples and muscle biopsies were collected in a postabsorptive and postprandial state. Carbohydrate coingestion delayed the appearance of exogenous phenylalanine in the circulation (P = .001). Dietary protein-derived phenylalanine availability over the 5-hour postprandial period was lower in the older (62 ± 2%) when compared with the young subjects (74 ± 2%; P = .007), with no differences between conditions (P = .20). Carbohydrate coingestion did not modulate postprandial muscle protein synthesis rates (0.035 ± 0.003 vs 0.043 ± 0.004 and 0.033 ± 0.002 vs 0.035 ± 0.003%/h after Pro vs Pro+CHO in the young and older group, respectively). In accordance, no differences in muscle protein-bound L-[1-(13)C]-phenylalanine enrichments were observed between conditions (0.020 ± 0.002 vs 0.020 ± 0.002 and 0.019 ± 0.003 vs 0.022 ± 0.004 mole percent excess after Pro vs Pro+CHO in the young and older subjects, respectively). Carbohydrate coingestion with protein delays dietary protein digestion and absorption but does not modulate postprandial muscle protein accretion in healthy young or older men.

  18. Postprandial triglyceride-rich lipoproteins regulate perilipin-2 and perilipin-3 lipid-droplet-associated proteins in macrophages.

    PubMed

    Varela, Lourdes M; López, Sergio; Ortega-Gómez, Almudena; Bermúdez, Beatriz; Buers, Insa; Robenek, Horst; Muriana, Francisco J G; Abia, Rocío

    2015-04-01

    Lipid accumulation in macrophages contributes to atherosclerosis. Within macrophages, lipids are stored in lipid droplets (LDs); perilipin-2 and perilipin-3 are the main LD-associated proteins. Postprandial triglyceride (TG)-rich lipoproteins induce LD accumulation in macrophages. The role of postprandial lipoproteins in perilipin-2 and perilipin-3 regulation was studied. TG-rich lipoproteins (TRLs) induced the levels of intracellular TGs, LDs and perilipin-2 protein expression in THP-1 macrophages and in Apoe(-/-) mice bone-marrow-derived macrophages with low and high basal levels of TGs. Perilipin-3 was only synthesized in mice macrophages with low basal levels of TGs. The regulation was dependent on the fatty acid composition of the lipoproteins; monounsaturated and polyunsaturated fatty acids (PUFAs) more strongly attenuated these effects compared with saturated fatty acids. In THP-1 macrophages, immunofluorescence microscopy and freeze-fracture immunogold labeling indicated that the lipoproteins translocated perilipin-3 from the cytoplasm to the LD surface; only the lipoproteins that were rich in PUFAs suppressed this effect. Chemical inhibition showed that lipoproteins induced perilipin-2 protein expression through the peroxisome proliferator-activated nuclear receptor (PPAR) PPARα and PPARγ pathways. Overall, our data indicate that postprandial TRLs may be involved in atherosclerotic plaque formation through the regulation of perilipin-2 and perilipin-3 proteins in macrophages. Because the fatty acid composition of the lipoproteins is dependent on the type of fat consumed, the ingestion of olive oil, which is rich in monounsaturated fatty acids, and fish oil, which is rich in omega-3 fatty acids, can be considered a good nutritional strategy to reduce the risk of atherosclerosis by LD-associated proteins decrease. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Postprandial serum endotoxin in healthy humans is modulated by dietary fat in a randomized, controlled, cross-over study.

    PubMed

    Lyte, Joshua M; Gabler, Nicholas K; Hollis, James H

    2016-11-05

    acid composition modulates postprandial serum endotoxin concentration in healthy adults. However, postprandial endotoxin was not associated with systemic inflammation in vivo. This study was retrospectively registered at clinicaltrials.gov as NCT02521779 on July 28, 2015.

  20. Dairy proteins, dairy lipids, and postprandial lipemia in persons with abdominal obesity (DairyHealth): a 12-wk, randomized, parallel-controlled, double-blinded, diet intervention study.

    PubMed

    Bohl, Mette; Bjørnshave, Ann; Rasmussen, Kia V; Schioldan, Anne Grethe; Amer, Bashar; Larsen, Mette K; Dalsgaard, Trine K; Holst, Jens J; Herrmann, Annkatrin; O'Neill, Sadhbh; O'Driscoll, Lorraine; Afman, Lydia; Jensen, Erik; Christensen, Merete M; Gregersen, Søren; Hermansen, Kjeld

    2015-04-01

    Abdominal obesity and exaggerated postprandial lipemia are independent risk factors for cardiovascular disease (CVD) and mortality, and both are affected by dietary behavior. We investigated whether dietary supplementation with whey protein and medium-chain saturated fatty acids (MC-SFAs) improved postprandial lipid metabolism in humans with abdominal obesity. We conducted a 12-wk, randomized, double-blinded, diet intervention study. Sixty-three adults were randomly allocated to one of 4 diets in a 2 × 2 factorial design. Participants consumed 60 g milk protein (whey or casein) and 63 g milk fat (with high or low MC-SFA content) daily. Before and after the intervention, a high-fat meal test was performed. We measured changes from baseline in fasting and postprandial triacylglycerol, apolipoprotein B-48 (apoB-48; reflecting chylomicrons of intestinal origin), free fatty acids (FFAs), insulin, glucose, glucagon, glucagon-like peptide 1 (GLP-1), and gastric inhibitory polypeptide (GIP). Furthermore, changes in the expression of adipose tissue genes involved in lipid metabolism were investigated. Two-factor ANOVA was used to examine the difference between protein types and fatty acid compositions, as well as any interaction between the two. Fifty-two participants completed the study. We found that the postprandial apoB-48 response decreased significantly after whey compared with casein (P = 0.025) independently of fatty acid composition. Furthermore, supplementation with casein resulted in a significant increase in the postprandial GLP-1 response compared with whey (P = 0.003). We found no difference in postprandial triacylglycerol, FFA, insulin, glucose, glucagon, or GIP related to protein type or MC-SFA content. We observed no interaction between milk protein and milk fat on postprandial lipemia. We found that a whey protein supplement decreased the postprandial chylomicron response compared with casein in persons with abdominal obesity, thereby indicating a

  1. Genomics of Post-Prandial Lipidomic Phenotypes in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study

    PubMed Central

    Irvin, Marguerite R.; Zhi, Degui; Aslibekyan, Stella; Claas, Steven A.; Absher, Devin M.; Ordovas, Jose M.; Tiwari, Hemant K.; Watkins, Steve; Arnett, Donna K.

    2014-01-01

    Background Increased postprandial lipid (PPL) response to dietary fat intake is a heritable risk factor for cardiovascular disease (CVD). Variability in postprandial lipids results from the complex interplay of dietary and genetic factors. We hypothesized that detailed lipid profiles (eg, sterols and fatty acids) may help elucidate specific genetic and dietary pathways contributing to the PPL response. Methods and Results We used gas chromatography mass spectrometry to quantify the change in plasma concentration of 35 fatty acids and 11 sterols between fasting and 3.5 hours after the consumption of a high-fat meal (PPL challenge) among 40 participants from the GOLDN study. Correlations between sterols, fatty acids and clinical measures were calculated. Mixed linear regression was used to evaluate associations between lipidomic profiles and genomic markers including single nucleotide polymorphisms (SNPs) and methylation markers derived from the Affymetrix 6.0 array and the Illumina Methyl450 array, respectively. After the PPL challenge, fatty acids increased as well as sterols associated with cholesterol absorption, while sterols associated with cholesterol synthesis decreased. PPL saturated fatty acids strongly correlated with triglycerides, very low-density lipoprotein, and chylomicrons. Two SNPs (rs12247017 and rs12240292) in the sorbin and SH3 domain containing 1 (SORBS1) gene were associated with b-Sitosterol after correction for multiple testing (P≤4.5*10−10). SORBS1 has been linked to obesity and insulin signaling. No other markers reached the genome-wide significance threshold, yet several other biologically relevant loci are highlighted (eg, PRIC285, a co-activator of PPARa). Conclusions Integration of lipidomic and genomic data has the potential to identify new biomarkers of CVD risk. PMID:24905834

  2. Sex-associated effect of CETP and LPL polymorphisms on postprandial lipids in familial hypercholesterolaemia

    PubMed Central

    Anagnostopoulou, Katherine K; Kolovou, Genovefa D; Kostakou, Peggy M; Mihas, Constantinos; Hatzigeorgiou, Georgios; Marvaki, Christina; Degiannis, Dimitrios; Mikhailidis, Dimitri P; Cokkinos, Dennis V

    2009-01-01

    Background This study assessed the gender-specific influence of the cholesteryl ester transfer protein (TaqIB, I405V) and lipoprotein lipase (S447X) polymorphisms on the response to an oral fat tolerance test in heterozygotes for familial hypercholesterolaemia. Methods We selected and genotyped 80 men and postmenopausal women heterozygous for familial hypercholesterolaemia (main group) as well as 11 healthy control subjects. Patients were subgrouped based on their response to oral fat tolerance test. The oral fat tolerance test was defined as pathological when postprandial triglyceride concentration was higher than the highest triglyceride concentration observed in healthy subjects (220 mg/dl) at any time (2, 4, 6 or 8 h). Results In the pathological subgroup, men had significantly higher incremental area under the curve after oral fat tolerance test than postmenopausal women. Furthermore, multivariate analysis revealed a gender association of TaqIB and I405V influence on postprandial lipaemia in this subgroup. Conclusion In conclusion, it seems that gender and TaqIB polymorphism of the cholesteryl ester transfer protein gene were both associated with the distribution of triglyceride values after oral fat tolerance test, only in subjects with a pathological response to oral fat tolerance test. Specifically, men carrying the B2 allele of the TaqIB polymorphism showed a higher postprandial triglyceride peak and a delayed return to basal values compared with women carrying B2. However, further investigations in larger populations are required to replicate and confirm these findings. PMID:19558660

  3. Color of hot soup modulates postprandial satiety, thermal sensation, and body temperature in young women.

    PubMed

    Suzuki, Maki; Kimura, Rie; Kido, Yasue; Inoue, Tomoko; Moritani, Toshio; Nagai, Narumi

    2017-04-01

    The color of food is known to modulate not only consumers' motivation to eat, but also thermal perception. Here we investigated whether the colors of hot soup can influence thermal sensations and body temperature, in addition to the food acceptability and appetite. Twelve young female participants consumed commercial white potage soup, modified to yellow or blue by adding food dyes, at 9 a.m. on 3 separated days. During the test, visual impression (willingness to eat, palatability, comfort, warmth, and anxiety) and thermal sensations were self-reported using visual analog scales. Core (intra-aural) and peripheral (toe) temperatures were continuously recorded 10 min before and 60 min after ingestion. Blue soup significantly decreased willingness to eat, palatability, comfort, and warmth ratings, and significantly increased anxiety feelings compared to the white and yellow soups. After ingestion, the blue soup showed significantly smaller satiety ratings and the tendency of lower thermal sensation scores of the whole body compared to the white and yellow soups. Moreover, a significantly greater increase in toe temperature was found with the yellow soup than the white or blue soup. In conclusion, this study provides new evidence that the colors of hot food may modulate postprandial satiety, thermal sensations and peripheral temperature. Such effects of color may be useful for dietary strategies for individuals who need to control their appetite.

  4. Postprandial lipid responses of butter blend containing fish oil in a single-meal study in humans.

    PubMed

    Overgaard, Julie; Porsgaard, Trine; Guo, Zheng; Lauritzen, Lotte; Mu, Huiling

    2008-10-01

    The postprandial effects of a butter product containing fish oil were investigated in a single-meal, randomized crossover study with a commercial butter product as the control. Twelve healthy males consumed two test meals with (13)C-labelled cholesterol (45 mg) and either an interesterified butter blend with fish oil (352 mg n-3 long-chain PUFA (LCPUFA)) or the commercial butter blend. Blood samples were collected after the meals and in the fasting condition on the test day and the following morning, and were analysed for cholesterol absorption, plasma lipid profile and fatty acid composition. No significant difference in the postprandial plasma fatty acid composition was observed between the groups, neither difference in cholesterol absorption, plasma cholesterol or the cholesterol contents of plasma lipoproteins. The incorporation of fish oil in the butter resulted in a significant lower concentration of triacylglycerols in the plasma 2 h after the meal in comparison with the commercial butter blend (p = 0.02); there was, however, no significant difference 24 h after the meal. In conclusion, fish oil-enriched butter blend provides a source to increase the intake of n-3 LCPUFA in the population, but has no acute effect on cholesterol absorption and plasma cholesterol concentration in human.

  5. Apolipoprotein E polymorphisms and postprandial triglyceridemia before and after fenofibrate treatment in the Genetics of Lipid Lowering and Diet Network (GOLDN) Study

    USDA-ARS?s Scientific Manuscript database

    Background: While much is known about the effect of Apolipoprotein E (APOE) alleles on fasting lipid concentrations, less is known about the effect of APOE alleles on postprandial triglyceridemia or the triglyceride response to fenofibrate. Methods and Results: We evaluated the effects of the APOE l...

  6. The effect of palm oil, lard, and puff-pastry margarine on postprandial lipid and hormone responses in normal-weight and obese young women.

    PubMed

    Jensen, J; Bysted, A; Dawids, S; Hermansen, K; Hølmer, G

    1999-12-01

    Only a few studies have been published on the postprandial effects of different fatty acids in obese subjects. Therefore, the present study investigated the effects of three test meals containing palm oil (PO), lard (LD), or puff-pastry margarine (PPM), all normal dietary ingredients, on postprandial lipid and hormone responses in normal-weight and obese young women. The study was performed as a randomized, crossover design. The fats differed in the content of palmitic acid, stearic acid, and trans monounsaturated fatty acids allowing a dietary comparison of different 'solid' fatty acids. The obese women had significantly higher fasting concentrations and postprandial responses of plasma total triacylglycerol (TAG), chylomicron-TAG, and insulin compared with the normal-weight women but there was no significant difference in the postprandial responses between the three test meals. The obese women had fasting concentrations of leptin four times greater than the normal-weight women. There were no postprandial changes in the concentrations of leptin. The fasting concentrations of HDL-cholesterol were significantly lower in the obese women than in the normal-weight women, whereas there was no significant difference between the two groups in the concentrations of total cholesterol or LDL-cholesterol. These results provide evidence that obese women have exaggerated lipid and hormone responses compared with normal-weight women but the different contents of saturated and trans monounsaturated fatty acids provided by PO, LD, and PPM have no effect in either group.

  7. Effects on cognitive performance of modulating the postprandial blood glucose profile at breakfast.

    PubMed

    Nilsson, A; Radeborg, K; Björck, I

    2012-09-01

    Considering the importance of glucose as a brain substrate, the postprandial rate of glucose delivery to the blood could be expected to affect cognitive functions. The purpose was to evaluate to what extent the rate of glucose absorption affected measures of cognitive performance in the postprandial period. In addition, cognitive performance was evaluated in relation to individual glucoregulation. A white wheat bread (WWB) enriched with guar gum (G-WWB) with the capacity to produce a low but sustained blood glucose net increment was developed. The G-WWB was evaluated in the postprandial period after breakfast with respect to effects on cognitive function (working memory and selective attention (SA)) in 40 healthy adults (49-71 years, body mass index 20-29 kg/m(2)), using a high glycaemic index WWB for comparison in a randomised crossover design. The G-WWB improved outcome in the cognitive tests (SA test) in the later postprandial period (75-225 min) in comparison with the WWB (P<0.01). Subjects with better glucoregulation performed superior in cognitive tests compared with subjects with worse glucoregulation (P<0.05). Beneficial effects on cognitive performance were observed with the G-WWB in the late postprandial period. The positive effect is suggested to emanate from improved insulin sensitivity, possibly in a combination with an enhanced neural energy supply. The results highlight the importance of carbohydrate foods that induces a low but sustained blood glucose profile in enhancing postprandial cognitive functions.

  8. Docosahexaenoic acid supplementation improves fasting and postprandial lipid profiles in hypertriglyceridemic men.

    PubMed

    Kelley, Darshan S; Siegel, David; Vemuri, Madhuri; Mackey, Bruce E

    2007-08-01

    The effects of docosahexaenoic acid (DHA) on the mean size and concentrations of VLDL, LDL, and HDL subclasses have not been previously studied. We determined the effects of DHA supplementation on the concentrations of apoproteins; large, medium, and small VLDL, LDL, and HDL particles; and the mean diameters of these particles in fasting and postprandial plasma. Hypertriglyceridemic men aged 39-66 y (n = 34) participated in a double-blind, randomized, placebo-controlled parallel study. They received no supplements for the first 8 d and received either 7.5 g DHA oil/d (3 g DHA/d) or olive oil (placebo) for the last 90 d. Lipoprotein particle diameters and concentrations were measured by nuclear magnetic resonance spectroscopy. DHA supplementation for 45 d significantly (P < 0.05) decreased concentrations of fasting triacylglycerol (24%), large VLDL (92%), and intermediate-density lipoproteins (53%) and the mean diameter of VLDL particles (11.1 nm). It elevated concentrations of LDL cholesterol (12.6%), small VLDL particles (133%), and large LDL particles (120%) and the mean diameter of LDL particles (0.6 nm) in fasting plasma. Similar changes were observed for area under the curve for postprandial samples (0-6 h); however, the number of small dense LDL particles decreased significantly (21%), and the change in LDL cholesterol was not significant. Continued supplementation with DHA beyond 45 d caused no further changes; placebo treatment altered none of the responses tested. DHA supplementation may improve cardiovascular health by lowering concentrations of triacylglycerols and small, dense LDL particles.

  9. Effects of variations in the APOA1/C3/A4/A5 gene cluster on different parameters of postprandial lipid metabolism in healthy young men.

    PubMed

    Delgado-Lista, Javier; Perez-Jimenez, Francisco; Ruano, Juan; Perez-Martinez, Pablo; Fuentes, Francisco; Criado-Garcia, Juan; Parnell, Laurence D; Garcia-Rios, Antonio; Ordovas, Jose M; Lopez-Miranda, Jose

    2010-01-01

    The APOA1/C3/A4/A5 gene cluster encodes important regulators of fasting lipids, but the majority of lipid metabolism takes place in the postprandial state and knowledge about gene regulation in this state is scarce. With the aim of characterizing possible regulators of lipid metabolism, we studied the effects of nine single nucleotide polymorphisms (SNPs) during postprandial lipid metabolism. Eighty-eight healthy young men were genotyped for APOA1 -2630 (rs613808), APOA1 -2803 (rs2727784), APOA1 -3012 (rs11216158), APOC3 -640 (rs2542052), APOC3 -2886 (rs2542051), APOC3 G34G (rs4520), APOA4 N147S (rs5104), APOA4 T29T (rs5092), and A4A5_inter (rs1263177) and were fed a saturated fatty acid-rich meal (1g fat/kg of weight with 60% fat, 15% protein and 25% carbohydrate). Serial blood samples were extracted for 11 h after the meal. Total cholesterol and fractions [HDL-cholesterol, LDL-cholesterol, trifacylglycerols (TGs) in plasma, TG-rich lipoproteins (TRLs) (large TRLs and small TRLs), apolipoprotein A-I and apolipoprotein B] were determined. APOA1 -2803 homozygotes for the minor allele and A4A5_inter carriers showed a limited degree of postprandial lipemia. Carriers of the rare alleles of APOA4 N147S and APOA4 T29T had lower APOA1 plasma concentration during this state. APOC3 -640 was associated with altered TG kinetics but not its magnitude. We have identified new associations between SNPs in the APOA1/C3/A4/A5 gene cluster and altered postprandial lipid metabolism.

  10. Postprandial oxidative stress in response to dextrose and lipid meals of differing size

    PubMed Central

    2010-01-01

    We have recently noted that ingestion of dietary lipid (in the form of heavy whipping cream) leads to greater oxidative stress than dietary carbohydrate (in the form of dextrose), when consumed in isocaloric amounts. Objective In the present investigation we attempted to replicate our work and also to determine the oxidative stress response to dextrose and lipid meals of two different kilocalorie (kcal) amounts. Design Nine young (22 ± 2 years), healthy men consumed in a random order, cross-over design one of four meals/drinks: dextrose at 75 g (300 kcals), dextrose at 150 g (600 kcals), lipid at 33 g (300 kcals), lipid at 66 g (600 kcals). Blood samples were collected Pre meal, and at 30 min, 60 min, 120 min, and 180 min post meal. Samples were assayed for glucose, triglycerides (TAG), malondialdehyde (MDA), and hydrogen peroxide (H2O2). Area under the curve (AUC) was calculated for each variable, and a 4 × 5 ANOVA was utilized to further analyze data. Results A meal × time effect (p = 0.0002) and a time effect was noted for glucose (p < 0.0001; 30 min > Pre, 1 hr, 2 hr, and 3 hr). The dextrose meals primarily contributed to this time effect. No other effects were noted for glucose (p > 0.05). A meal effect was noted for TAG (p = 0.01; 66 g lipid meal > 75 g and 150 g dextrose meals). No other effects were noted for TAG (p > 0.05). An AUC effect was noted for MDA (p = 0.04; 66 g lipid meal > 75 g and 150 g dextrose meals). A meal × time effect (p = 0.02) and a meal effect was noted for MDA (p = 0.004; 66 g lipid meal > 75 g and 150 g dextrose meals). No time effect was noted for MDA (p = 0.72). An AUC effect was noted for H2O2 (p = 0.0001; 66 g lipid meal > 33 g lipid meal and 75 g and 150 g dextrose meals). A meal × time effect (p = 0.0002), a meal effect (p < 0.0001; 66 g lipid meal > 33 g lipid meal and 75 g and 150 g dextrose meals), and a time effect was noted for H2O2 (p < 0.0001; 2 hr > Pre, 30 min, and 1 hr; 3 hr > Pre). The time effect for H2O2 was

  11. Effect of meal composition on postprandial lipid concentrations and lipoprotein particle numbers: A randomized cross-over study

    PubMed Central

    Shah, Meena; Jaffery, Manall; Adams-Huet, Beverley; Franklin, Brian; Oliver, Jonathan; Mitchell, Joel

    2017-01-01

    Background It is unclear how high-protein (HP) and high-monounsaturated fat (HMF) meals affect postprandial blood lipids and lipoprotein particle numbers (LPN). Purpose To compare a HP versus a HMF meal on postprandial lipid and LPN responses. Methods Twenty-four participants (age: 36.3±15.0 years; body mass index: 23.6±2.0 kg/m2; 45.8% female) were fed a HP (31.9% energy from protein) and a HMF (35.2% fat and 20.7% monounsaturated fat) meal in a randomized cross-over trial design. Energy and carbohydrate content were the same across meals. Blood samples were drawn in the fasting state and 3 hour postprandial state, and assessed for lipids and LPN. Results Repeated measures analysis showed a significant (p<0.05) treatment by time interaction effect for triglycerides (TG), the primary variable, total high-density lipoprotein particles (T-HDLP) and T-HDLP minus large-buoyant high-density lipoprotein 2b (T-HDLP—LB-HDL2b). HP versus HMF condition led to significantly lower TG at 120 (geometric mean: 90.1 (95% confidence interval (CI): 76.4–106.3) vs. 146.5 (124.2–172.9) mg/dL) and 180 (101.4 (83.1–123.8) vs. 148.7 (121.9–181.4) mg/dL) min and higher T-HDLP at 120 (mean difference: 297.3 (95% CI: 48.6–545.9) nmol/L) and 180 (291.6 (15.8–567.5) nmol/L) min. The difference in T-HDLP by condition was due to the significantly higher small-dense HDLP (T-HDLP—LB-HDL2b) during HP versus HMF condition at 120 (mean difference: 452.6 (95% CI: 177.4–727.9) nmol/L) and 180 (496.8 (263.1–730.6) nmol/L) min. Area under the curve analysis showed that HP versus HMF condition led to significantly lower TG, non-HDLP, and very-low-density lipoprotein particles (VLDLP) responses but significantly less favorable responses in LB-HDL2b particles, T-HDLP—LB-HDL2b, and LB-HDL2b/T-HDLP ratio. Conclusion The HP meal led to lower TG, non-HDLP, and VLDLP but less favorable LB-HDL2b, small-dense HDLP, and LB-HDL2b/T-HDLP ratio responses versus a HMF meal. Further studies are

  12. Ingestion of Casein in a Milk Matrix Modulates Dietary Protein Digestion and Absorption Kinetics but Does Not Modulate Postprandial Muscle Protein Synthesis in Older Men.

    PubMed

    Churchward-Venne, Tyler A; Snijders, Tim; Linkens, Armand M A; Hamer, Henrike M; van Kranenburg, Janneau; van Loon, Luc J C

    2015-07-01

    The slow digestion and amino acid absorption kinetics of isolated micellar casein have been held responsible for its relatively lower postprandial muscle protein synthetic response compared with rapidly digested proteins such as isolated whey. However, casein is normally consumed within a milk matrix. We hypothesized that protein digestion and absorption kinetics and the subsequent muscle protein synthetic response after micellar casein ingestion are modulated by the milk matrix. The aim of this study was to determine the impact of a milk matrix on casein protein digestion and absorption kinetics and postprandial muscle protein synthesis in older men. In a parallel-group design, 32 healthy older men (aged 71 ± 1 y) received a primed continuous infusion of L-[ring-(2)H5]-phenylalanine, L-[ring-3,5-(2)H2]-tyrosine, and L-[1-(13)C]-leucine, and ingested 25 g intrinsically L-[1-(13)C]-phenylalanine and L-[1-(13)C]-leucine labeled casein dissolved in bovine milk serum (Cas+Serum) or water (Cas). Plasma samples and muscle biopsies were collected in the postabsorptive state and for 300 min in the postprandial period to examine whole-body and skeletal muscle protein metabolism. Casein ingestion increased plasma leucine and phenylalanine concentrations and L-[1-(13)C]-phenylalanine enrichments, with a more rapid rise after Cas vs. Cas+Serum. Nonetheless, dietary protein-derived phenylalanine availability did not differ between Cas+Serum (47 ± 2%, mean ± SEM) and Cas (46 ± 3%) when assessed over the 300-min postprandial period (P = 0.80). The milk matrix did not modulate postprandial myofibrillar protein synthesis rates from 0 to 120 min (0.038 ± 0.005 vs. 0.031 ± 0.007%/h) or from 120 to 300 min (0.052 ± 0.004 vs. 0.067 ± 0.005%/h) after Cas+Serum vs. Cas. Similarly, no treatment differences in muscle protein-bound L-[1-(13)C]-phenylalanine enrichments were observed at 120 min (0.003 ± 0.001 vs. 0.002 ± 0.001) or 300 min (0.015 ± 0.002 vs. 0.016 ± 0.002 mole

  13. Postprandial lipid responses do not differ following consumption of butter or vegetable oil when consumed with omega-3 polyunsaturated fatty acids.

    PubMed

    Dias, Cintia B; Phang, Melinda; Wood, Lisa G; Garg, Manohar L

    2015-04-01

    Dietary saturated fat (SFA) intake has been associated with elevated blood lipid levels and increased risk for the development of chronic diseases. However, some animal studies have demonstrated that dietary SFA may not raise blood lipid levels when the diet is sufficient in omega-3 polyunsaturated fatty acids (n-3PUFA). Therefore, in a randomised cross-over design, we investigated the postprandial effects of feeding meals rich in either SFA (butter) or vegetable oil rich in omega-6 polyunsaturated fatty acids (n-6PUFA), in conjunction with n-3PUFA, on blood lipid profiles [total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triacylglycerol (TAG)] and n-3PUFA incorporation into plasma lipids over a 6-h period. The incremental area under the curve for plasma cholesterol, LDL-C, HDL-C, TAG and n-3PUFA levels over 6 h was similar in the n-6PUFA compared to SFA group. The postprandial lipemic response to saturated fat is comparable to that of n-6PUFA when consumed with n-3PUFA; however, sex-differences in response to dietary fat type are worthy of further attention.

  14. Immune modulation by parenteral lipid emulsions.

    PubMed

    Wanten, Geert J A; Calder, Philip C

    2007-05-01

    Total parenteral nutrition is the final option for nutritional support of patients with severe intestinal failure. Lipid emulsions constitute the main source of fuel calories and fatty acids (FAs) in parenteral nutrition formulations. However, adverse effects on patient outcomes have been attributed to the use of lipids, mostly in relation to impaired immune defenses and altered inflammatory responses. Over the years, this issue has remained in the limelight, also because technical advances have provided no safeguard against the most daunting problems, ie, infectious complications. Nevertheless, numerous investigations have failed to produce a clear picture of the immunologic characteristics of the most commonly used soybean oil-derived lipid emulsions, although their high content of n-6 polyunsaturated FAs (PUFAs) has been considered a drawback because of their proinflammatory potential. This concern initiated the development of emulsions in which part of the n-6 FA component is replaced by less bioactive FAs, such as coconut oil (rich in medium-chain saturated FAs) or olive oil (rich in the n-9 monounsaturated FA oleic acid). Another approach has been to use fish oil (rich in n-3 PUFA), the FAs of which have biological activities different from those of n-6 PUFAs. Recent studies on the modulation of host defenses and inflammation by fish-oil emulsions have yielded consistent data, which indicate that these emulsions may provide a tool to beneficially alter the course of immune-mediated conditions. Although most of these lipids have not yet become available on the US market, this review synthesizes available information on immunologic characteristics of the different lipids that currently can be applied via parenteral nutrition support.

  15. The effect of exercise intensity and excess postexercise oxygen consumption on postprandial blood lipids in physically inactive men.

    PubMed

    Littlefield, Laurel A; Papadakis, Zacharias; Rogers, Katie M; Moncada-Jiménez, José; Taylor, J Kyle; Grandjean, Peter W

    2017-09-01

    Reductions in postprandial lipemia have been observed following aerobic exercise of sufficient energy expenditure. Increased excess postexercise oxygen consumption (EPOC) has been documented when comparing high- versus low-intensity exercise. The contribution of EPOC energy expenditure to alterations in postprandial lipemia has not been determined. The purpose of this study was to evaluate the effects of low- and high-intensity exercise on postprandial lipemia in healthy, sedentary, overweight and obese men (age, 43 ± 10 years; peak oxygen consumption, 31.1 ± 7.5 mL·kg(-1)·min(-1); body mass index, 31.8 ± 4.5 kg/m(2)) and to determine the contribution of EPOC to reductions in postprandial lipemia. Participants completed 4 conditions: nonexercise control, low-intensity exercise at 40%-50% oxygen uptake reserve (LI), high-intensity exercise at 70%-80% oxygen uptake reserve (HI), and HI plus EPOC re-feeding (HI+EERM), where the difference in EPOC energy expenditure between LI and HI was re-fed in the form of a sports nutrition bar (Premier Nutrition Corp., Emeryville, Calif., USA). Two hours following exercise participants ingested a high-fat (1010 kcals, 99 g sat fat) test meal. Blood samples were obtained before exercise, before the test meal, and at 2, 4, and 6 h postprandially. Triglyceride incremental area under the curve was significantly reduced following LI, HI, and HI+EERM when compared with nonexercise control (p < 0.05) with no differences between the exercise conditions (p > 0.05). In conclusions, prior LI and HI exercise equally attenuated postprandial triglyceride responses to the test meal. The extra energy expended during EPOC does not contribute significantly to exercise energy expenditure or to reductions in postprandial lipemia in overweight men.

  16. Lipid modulation of neuronal cholinergic activity

    SciTech Connect

    Bottiglieri, D.F.

    1986-01-01

    Phospholipids are the major lipids in the plasma membrane, and it is now evident that the function of phospholipids exceeds that of the role of barrier between different aqueous compartments. Several lines of evidence suggest that a major plasma membrane lipids, phosphatidylcholine, may be a useful compound for modulating presynaptic cholinergic transmission. In order to investigate the effects of PC on cholinergic terminals, rat cortical synaptosomes were preloaded with (/sup 3/H)-ACh and then treated with small unilamellar vesicles (SUV) composed of dipalmitoylphosphatidylcholine (DPPC) at concentrations (0.8-1.5 mg/ml) similar to those found circulating in plasma. The effects of DPPC on levels, hydrolysis, release, and synthesis of (/sup 3/H)-ACh were then examined. Dipalmitoylphosphatidylcholine decreased the levels of (/sup 3/H)-ACh. This decrease does not result from a dilution of the radioactive (/sup 3/H)-choline by nonradioactive choline derived from PC. Specifically, it is the S/sub 3/ (cytoplasmic) level of (/sup 3/H)-ACh that is decreased by DPPC treatment. This decrease appears to be partially due to lipid activation of an intraterminal cholinesterase which results in hydrolysis of nonvesicular (/sup 3/H)-ACh. The ability of the lipid to interfere with exocytosis may account for the blockade of the K/sup +/ induced (/sup 3/H)-ACh release from the P/sub 3/ (vesicular) fraction. The high affinity choline transporter was competitively inhibited by DPPC treatment when synaptosomes were treated with DPPC prior to (/sup 3/H)-choline loading; the ubiquitous low affinity transport was not affected. These effects were specific for cholinergic neurons since the uptake and release of dopamine and norepinephrine from the substantia nigra and the cortex, respectively, were not affected.

  17. Endogenous somatostatin-28 modulates postprandial insulin secretion. Immunoneutralization studies in baboons.

    PubMed Central

    Ensinck, J W; Vogel, R E; Laschansky, E C; Koerker, D J; Prigeon, R L; Kahn, S E; D'Alessio, D A

    1997-01-01

    Somatostatin-28 (S-28), secreted into the circulation from enterocytes after food, and S-14, released mainly from gastric and pancreatic D cells and enteric neurons, inhibit peripheral cellular functions. We hypothesized that S-28 is a humoral regulator of pancreatic B cell function during nutrient absorption. Consistent with this postulate, we observed in baboons a two to threefold increase in portal and peripheral levels of S-28 after meals, with minimal changes in S-14. We attempted to demonstrate a hormonal effect of these peptides by measuring their concentrations before and after infusing a somatostatin-specific monoclonal antibody (mAb) into baboons and comparing glucose, insulin, and glucagon-like peptide-1 levels before and for 4 h after intragastric nutrients during a control study and on 2 d after mAb administration (days 1 and 2). Basal growth hormone (GH) and glucagon levels and parameters of insulin and glucose kinetics were also measured. During immunoneutralization, we found that (a) postprandial insulin levels were elevated on days 1 and 2; (b) GH levels rose immediately and were sustained for 28 h, while glucagon fell; (c) basal insulin levels were unchanged on day 1 but were increased two to threefold on day 2, coincident with decreased insulin sensitivity; and (d) plasma glucose concentrations were similar to control values. We attribute the eventual rise in fasting levels of insulin to its enhanced secretion in compensation for the heightened insulin resistance from increased GH action. Based on the elevated postmeal insulin levels after mAb administration, we conclude that S-28 participates in the enteroinsular axis as a decretin to regulate postprandial insulin secretion. PMID:9410907

  18. How lipids modulate mitochondrial protein import.

    PubMed

    Böttinger, Lena; Ellenrieder, Lars; Becker, Thomas

    2016-04-01

    Mitochondria have to import the vast majority of their proteins, which are synthesized as precursors on cytosolic ribosomes. The translocase of the outer membrane (TOM complex) forms the general entry gate for the precursor proteins, which are subsequently sorted by protein machineries into the mitochondrial subcompartments: the outer and inner membrane, the intermembrane space and the mitochondrial matrix. The transport across and into the inner membrane is driven by the membrane potential, which is generated by the respiratory chain. Recent studies revealed that the lipid composition of mitochondrial membranes is important for the biogenesis of mitochondrial proteins. Cardiolipin and phosphatidylethanolamine exhibit unexpectedly specific functions for the activity of distinct protein translocases. Both phospholipids are required for full activity of respiratory chain complexes and thus to maintain the membrane potential for protein import. In addition, cardiolipin is required to maintain structural integrity of mitochondrial protein translocases. Finally, the low sterol content in the mitochondrial outer membrane may contribute to the targeting of some outer membrane proteins with a single α-helical membrane anchor. Altogether, mitochondrial lipids modulate protein import on various levels involving precursor targeting, membrane potential generation, stability and activity of protein translocases.

  19. Impact of corpulence parameters and haemoglobin A1c on metabolic control in type 2 diabetic patients: comparison of apolipoprotein B/A-I ratio with fasting and postprandial conventional lipid ratios

    PubMed Central

    Diaf, Mustapha; Khaled, Boumediene M.; Sellam, Fériel

    2015-01-01

    Background and objective The incidence of diabetes co-morbidities could probably be better assessed by studying its associations with major corpulence parameters and glycaemic control indicators. We assessed the utility of body mass index (BMI), waist circumference (WC), and glycosylated haemoglobin (HbA1c) levels in metabolic control for type 2 diabetic patients. Methods Fasting and postprandial blood samples were collected from 238 type 2 diabetic patients aged 57.4±11.9 years. The sera were analysed for glucose, HbA1c, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and apolipoproteins (apoA-I and apoB). Ratios of lipids and apolipoproteins were calculated and their associations with BMI, WC, and HbA1c levels were analysed. Results Our investigation showed increases in most fasting and postprandial lipid parameters according to BMI and WC. In men, postprandial HDL-c and TG levels were significantly higher (p<0.05) in overweight and obese patients, respectively, as well as in patients with abdominal obesity. Contrariwise, postprandial TC levels were significantly higher (p<0.01) in overweight and abdominal obese women. However, elevations of apoA-I and apoB levels were according to BMI and WC in both genders. There was a strong influence of BMI, WC, and HbA1c levels on the apoB/apoA-I ratio compared to traditional fasting and postprandial lipid ratios in both men and women. The apoB/apoA-I ratio was more correlated with postprandial TC/HDL and LDL-c/HDL-c ratios in men and with postprandial TG/HDL-c in women. Conclusion The apoB/apoA-I ratio is helpful in assessing metabolic risk caused by overall obesity, abdominal obesity and impaired glycaemia in type 2 diabetic patients. PMID:25959906

  20. Influence of feeding a fish oil-containing diet to young, lean, adult dogs: effects on lipid metabolites, postprandial glycaemia and body weight.

    PubMed

    de Godoy, Maria R C; Conway, Charlotte E; Mcleod, Kyle R; Harmon, David L

    2015-01-01

    The aim of this study was to determine the effect of feeding a fish oil (FO)-containing diet on lipid and protein metabolism, postprandial glycaemia and body weight in young, lean, adult dogs. Eight female Beagles were randomly assigned to one of two isonitrogenous and isoenergetic diets, Control or FO, in a crossover design. At the beginning of the experiment and at 30 and 60 d, a baseline blood sample was collected and the dogs then were fed their daily ration. Nitrogen balance began at 07:00 h on day 63 of each experimental period and ended at 07:00 h on day 69. On day 66 of each period, a single dose (7.5 mg/kg) of (15)N-glycine was administered orally to each dog via gelatin capsule. Postprandial glycaemia did not differ between treatments or among sampling days within treatment. Cholesterol concentration was increased (p<0.05) on the Control treatment throughout the experiment when compared to values of day 0. Dogs fed the FO treatment had higher plasma triglyceride and ghrelin concentrations than those fed the Control treatment. Body weight and food intake did not differ between dietary treatments. Faecal excretion was increased (p<0.05) in the FO treatment. Dry matter digestibility was decreased (p<0.05) and fat digestibility tended (p<0.10) to decrease in the FO treatment. Overall, feeding a FO-containing diet showed a protective effect against the rise of plasma cholesterol and it increased plasma ghrelin concentration. However, FO supplementation did not appear to affect protein metabolism or postprandial glycaemia in adult lean dogs.

  1. Postprandial Spillover of Dietary Lipid into Plasma Is Increased with Moderate Amounts of Ingested Fat and Is Inversely Related to Adiposity in Healthy Older Men123

    PubMed Central

    Puga, Guilherme M.; Meyer, Christian; Mandarino, Lawrence J.; Katsanos, Christos S.

    2012-01-01

    Adverse effects on health mediated by increased plasma FFA concentrations are well established and older individuals are particularly susceptible to these effects. We sought to determine the effects of the amount of dietary fat on increasing the plasma FFA concentrations as a result of “spillover” of dietary fat into the plasma FFA pool during the postprandial period in older men. Healthy, older participants (63–71 y old) were studied in a randomized, crossover design following ingestions of low (LF) and moderate (MF) amounts of [1,1,1-13C]-triolein-labeled fat, corresponding to 0.4 and 0.7 g of fat/kg body weight, respectively. Spillover of dietary fatty acids into plasma during the 8-h postprandial period (AUC; mmol · L−1 · h) after MF ingestion was 1.2 times greater than that after LF ingestion (2.8 ± 0.4 vs. 1.2 ± 0.1; P < 0.05). The spillover of dietary fatty acids following the MF, but not the LF, ingestion was correlated with the percent body fat (rs = −0.89) and percent body fat-free mass (rs = 0.94) of the men (P < 0.05). After adjusting to the amount of ingested fat, the spillover of dietary fatty acids in the MF trial was disproportionally higher than that in the LF trial (P < 0.05), but the corresponding postprandial plasma TG responses did not differ between trials. In conclusion, spillover of dietary lipid into plasma is disproportionally increased at higher doses of dietary fat and this response is inversely related to adiposity in healthy men of advanced age. PMID:22955513

  2. Ovarian Lipid Metabolism Modulates Circulating Lipids in Premenopausal Women.

    PubMed

    Jensen, Jeffrey T; Addis, Ilana B; Hennebold, Jon D; Bogan, Randy L

    2017-09-01

    The premenopausal circulating lipid profile may be linked to the hormonal profile and ovarian lipid metabolism. Assess how estradiol, progesterone, and ovarian lipid metabolism contributes to the premenopausal lipid profile; and evaluate the acute effects of a common hormonal oral contraceptive (OC) on circulating lipids. Experimental crossover with repeated measures. Academic hospitals. Eight healthy, regularly menstruating women. Participants underwent periodic serum sampling during a normal menstrual cycle; a standard 21-day, monophasic combined hormonal OC cycle (30 µg of ethinyl estradiol and 150 µg of levonorgestrel per day); menopause simulated by leuprolide acetate (22.5-mg depot); and an artificial menstrual cycle achieved via transdermal estradiol (50 to 300 µg/d) and vaginal micronized progesterone (100 to 300 mg/d). Primary outcomes included evaluation of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, triglycerides, and the total cholesterol to HDL cholesterol ratio. To estimate the effect of estradiol, progesterone, and ovarian lipid metabolism, all specimens except those from the OC cycle were analyzed. Subgroup analysis was conducted on the follicular and luteal phases. In a separate analysis, the effect of the OC was evaluated relative to the normal menstrual cycle. Estradiol was significantly associated with increased levels of HDL cholesterol throughout the menstrual cycle and in the follicular phase. Ovarian effects were associated with reduced lipid levels, especially during the luteal phase. The OC was associated with an increased total cholesterol to HDL cholesterol ratio and triglycerides. Previously unappreciated factors including ovarian lipid metabolism may contribute to the premenopausal lipid profile.

  3. Postprandial effects of long-term niacin/laropiprant use on glucose and lipid metabolism and on cardiovascular risk in patients with polycystic ovary syndrome.

    PubMed

    Aye, M M; Kilpatrick, E S; Afolabi, P; Wootton, S A; Rigby, A S; Coady, A M; Sandeman, D D; Atkin, S L

    2014-06-01

    This study investigated the effect of long-term niacin/laropiprant therapy on CV risk and IR in obese women with PCOS. In this double-blind randomized placebo-controlled trial, 13 and 12 PCOS women completed a 12 week course of niacin/laropiprant or placebo, respectively. Fasted subjects had an endothelial function test (EndoPat2000) and then consumed a mixed meal with blood sampled postprandially for 6 h before and after intervention. By 12 weeks, niacin/laropiprant lowered low-density lipoprotein cholesterol (LDL-c) (13%) and increased HDL-c (17%). Despite a reduction in fasting triglycerides (21%), the drug had no effect on their postprandial rise (2.69 ± 1.44 vs. 2.49 ± 1.14 mmol/l, p = 0.72). However, following the mixed meal, plasma glucose area under the response curve increased from 13.1 ± 2.9 to 14.0 ± 2.8 mmol/l, p = 0.05, as a consequence of both increased insulin resistance [HOMA-IR: 2.2 (1.2, 4.2) vs. 3.8(1.3, 5.5), p = 0.02] and a reduced acute insulin response to glucose [424 (211, 975) vs. 257(122, 418) pmol/mmol, p = 0.04]. Niacin/laropiprant did not improve RHI (1.97 ± 0.40 vs. 2.05 ± 0.58, p = 0.33) or hsCRP. In PCOS, niacin/laropiprant had a significant negative impact on postprandial glucose and no improvement in postprandial hypertriglyceridaemia, with at least the former mediated through increased IR and reduced β-cell function. This data may help explain why the improvement in fasting lipids has not translated into improved CV risk markers in PCOS. © 2014 John Wiley & Sons Ltd.

  4. A Higher-Complex Carbohydrate Diet in Gestational Diabetes Mellitus Achieves Glucose Targets and Lowers Postprandial Lipids: A Randomized Crossover Study

    PubMed Central

    Hernandez, Teri L.; Van Pelt, Rachael E.; Anderson, Molly A.; Daniels, Linda J.; West, Nancy A.; Donahoo, William T.; Friedman, Jacob E.; Barbour, Linda A.

    2014-01-01

    OBJECTIVE The conventional diet approach to gestational diabetes mellitus (GDM) advocates carbohydrate restriction, resulting in higher fat (HF), also a substrate for fetal fat accretion and associated with maternal insulin resistance. Consequently, there is no consensus about the ideal GDM diet. We hypothesized that, compared with a conventional, lower-carbohydrate/HF diet (40% carbohydrate/45% fat/15% protein), consumption of a higher-complex carbohydrate (HCC)/lower-fat (LF) Choosing Healthy Options in Carbohydrate Energy (CHOICE) diet (60/25/15%) would result in 24-h glucose area under the curve (AUC) profiles within therapeutic targets and lower postprandial lipids. RESEARCH DESIGN AND METHODS Using a randomized, crossover design, we provided 16 GDM women (BMI 34 ± 1 kg/m2) with two 3-day isocaloric diets at 31 ± 0.5 weeks (washout between diets) and performed continuous glucose monitoring. On day 4 of each diet, we determined postprandial (5 h) glucose, insulin, triglycerides (TGs), and free fatty acids (FFAs) following a controlled breakfast meal. RESULTS There were no between-diet differences for fasting or mean nocturnal glucose, but 24-h AUC was slightly higher (∼6%) on the HCC/LF CHOICE diet (P = 0.02). The continuous glucose monitoring system (CGMS) revealed modestly higher 1- and 2-h postprandial glucose on CHOICE (1 h, 115 ± 2 vs. 107 ± 3 mg/dL, P ≤ 0.01; 2 h, 106 ± 3 vs. 97 ± 3 mg/dL, P = 0.001) but well below current targets. After breakfast, 5-h glucose and insulin AUCs were slightly higher (P < 0.05), TG AUC was no different, but the FFA AUC was significantly lower (∼19%; P ≤ 0.01) on the CHOICE diet. CONCLUSIONS This highly controlled study randomizing isocaloric diets and using a CGMS is the first to show that liberalizing complex carbohydrates and reducing fat still achieved glycemia below current treatment targets and lower postprandial FFAs. This diet strategy may have important implications for preventing macrosomia. PMID

  5. Carob pulp preparation rich in insoluble dietary fiber and polyphenols enhances lipid oxidation and lowers postprandial acylated ghrelin in humans.

    PubMed

    Gruendel, Sindy; Garcia, Ada L; Otto, Baerbel; Mueller, Corinna; Steiniger, Jochen; Weickert, Martin O; Speth, Maria; Katz, Norbert; Koebnick, Corinna

    2006-06-01

    Ghrelin is an orexigenic hormone that may affect substrate utilization in humans. Ghrelin is influenced by macronutrients, but the effects of insoluble dietary fiber and polyphenols are unknown. We investigated the effects of a polyphenol-rich insoluble dietary fiber preparation from carob pulp (carob fiber) on postprandial ghrelin responses and substrate utilization. Dose-dependent effects of the consumption of carob fiber were investigated in a randomized, single-blind, crossover study in 20 healthy subjects, aged 22-62 y. Plasma total and acylated ghrelin, triglycerides, and serum insulin and nonesterified fatty acids (NEFA) levels were repeatedly assessed before and after ingestion of an isocaloric standardized liquid meal with 0, 5, 10, or 20 g of carob fiber over a 300-min period. The respiratory quotient (RQ) was determined after consumption of 0 or 20 g of carob fiber. Carob fiber intake lowered acylated ghrelin to 49.1%, triglycerides to 97.2%, and NEFA to 67.2% compared with the control meal (P < 0.001). Total ghrelin and insulin concentrations were not affected by consumption of a carob fiber-enriched liquid meal. Postprandial energy expenditure was increased by 42.3% and RQ was reduced by 99.9% after a liquid meal with carob fiber compared with a control meal (P < 0.001). We showed that the consumption of a carob pulp preparation, an insoluble dietary fiber rich in polyphenols, decreases postprandial responses of acylated ghrelin, triglycerides, and NEFA and alters RQ, suggesting a change toward increased fatty acid oxidation. These results indicate that carob fiber might exert beneficial effects in energy intake and body weight.

  6. Effect of mastication on lipid bioaccessibility of almonds in a randomized human study and its implications for digestion kinetics, metabolizable energy, and postprandial lipemia1234

    PubMed Central

    Grundy, Myriam ML; Grassby, Terri; Mandalari, Giuseppina; Waldron, Keith W; Butterworth, Peter J; Berry, Sarah EE

    2015-01-01

    early stages of digestion. The lipid encapsulation mechanism provides a convincing explanation for why almonds have a low metabolizable energy content and an attenuated impact on postprandial lipemia. This trial was registered at isrctn.org as ISRCTN58438021. PMID:25527747

  7. Interaction between amylose and tea polyphenols modulates the postprandial glycemic response to high-amylose maize starch.

    PubMed

    Chai, Yanwei; Wang, Mingzhu; Zhang, Genyi

    2013-09-11

    High-amylose maize starch (HAM) is a common source material to make resistant starch with its high content of amylose (>70%). In the current investigation, the self-assembly of amylose in the presence of bioactive tea polyphenols (TPLs) and resulting slow digestion property of starch were explored. The experimental results using a mouse model showed a slow digestion property can be achieved with an extended and moderate glycemic response to HAM starch cocooked with TPLs. Further studies using a dilute aqueous amylose solution (0.1%, w/v) revealed an increased hydrodynamic radius of amylose molecules, indicating that TPLs could bridge them together, leading to increased molecular sizes. On the other hand, the bound TPLs interrupted the normal process of amylose recrystallizaiton evidenced by a decreased viscosity and storage modulus (G') of HAM (5%) gel, a rough surface of the cross-section of HAM film, and decreased short-range orders examined by Fourier transform infrared spectral analysis. Single-step degradation curves in the thermal gravimetric profile demonstrated the existence of a self-assembled amylose-TPL complex, which is mainly formed through hydrogen bonding interaction according to the results of iodine binding and X-ray powder diffraction analysis. Collectively, the amylose-TPL complexation influences the normal self-assembling process of amylose, leading to a low-ordered crystalline structure, which is the basis for TPLs' function in modulating the digestion property of HAM starch to produce a slowly digestible starch material that is beneficial to postprandial glycemic control and related health effects.

  8. Lipids modulate the conformational dynamics of a secondary multidrug transporter

    PubMed Central

    Martens, Chloé; Stein, Richard A; Masureel, Matthieu; Roth, Aurélie; Mishra, Smriti; Dawaliby, Rosie; Konijnenberg, Albert; Sobott, Frank; Govaerts, Cédric; Mchaourab, Hassane S

    2017-01-01

    Direct interactions with lipids have emerged as key determinants of the folding, structure and function of membrane proteins, but an understanding of how lipids modulate protein dynamics is still lacking. Here, we systematically explored the effects of lipids on the conformational dynamics of the proton-powered, multidrug transporter LmrP from Lactococcus lactis utilizing the pattern of distances between spin label pairs previously shown to fingerprint alternating access of the protein. We uncover at the molecular level how the lipid headgroups shape the conformational energy landscape of the transporter. The model emerging from our data hypothesizes a direct interaction between lipid headgroups and a conserved motif of charged residues that control the conformational equilibrium through an interplay of electrostatic interactions within the protein. Together, our data lay the foundation for a comprehensive model of secondary multidrug transport in lipid bilayers. PMID:27399258

  9. Comparison of Postprandial Responses to a High-Fat Meal in Hypertriglyceridemic Men and Women before and after Treatment with Fenofibrate in the Genetics and Lipid Lowering Drugs and Diet Network (GOLDN) Study

    PubMed Central

    Glasser, Stephen P.; Wojczynski, Mary K.; Oberman, A. I.; Kabagambe, Edmond K.; Tsai, Michael Y.; Ordovas, Jose M.; Straka, Robert J.; Arnett, Donna K.

    2013-01-01

    Context The fenofibrate effect on the subclass size distribution of lipoproteins before and after a high-fat challenge is not well studied. Objective To characterize the baseline and post-prandial response (PPL) to a high-fat challenge following fenofibrate therapy, on changes in LDL, HDL, and VLDL particle subclasses, number, and size in 271 hypertriglyceridemic participants. Methods Participants from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study who conducted PPL studies both before and after three weeks of fenofibrate (160 mg/d) treatment were analyzed. Particle size distributions were determined using nuclear magnetic resonance imaging, and lipid determinations were measured at fasting (0 hr), 3.5 hours, and 6 hours after ingestion of a standardized high-fat meal. Analyses were stratified by gender. Changes in particle subclass distributions were assessed using repeated measures analysis of variance adjusted for pedigree. Results Before PPL, fenofibrate in men (adjusted for age, field center, smoking status, diabetes, and weight circumference) lowered fasting and postprandial VLDL primarily due to reductions in postprandial levels of large and medium VLDL particles (9 SE +/–0.7 to 4 +/–0.4 and 78 / –4 to 36 / –3 nmol/L both P < .0001, resp.). Fenofibrate also reduced fasting and postprandial total LDL particles, primarily a result of reduced small LDL particles (1497 = / – 37 to 1088 = / – 36 nmol/L, P < .0001). Directional changes were similar in men and women but the magnitude of change was different for some parameters. Conclusion Fenofibrate treatment resulted in a lower triglyceride excursion following a high-fat meal. This investigation provides new knowledge of the magnitude and time course of fenofibrate induced attenuation of Lipoprotein subclass size distribution following a postprandial lipid challenge. PMID:24971173

  10. Small GTPase Rab40c Associates with Lipid Droplets and Modulates the Biogenesis of Lipid Droplets

    PubMed Central

    Tan, Ran; Wang, Weijie; Wang, Shicong; Wang, Zhen; Sun, Lixiang; He, Wei; Fan, Rong; Zhou, Yunhe; Xu, Xiaohui; Hong, Wanjin; Wang, Tuanlao

    2013-01-01

    The subcellular location and cell biological function of small GTPase Rab40c in mammalian cells have not been investigated in detail. In this study, we demonstrated that the exogenously expressed GFP-Rab40c associates with lipid droplets marked by neutral lipid specific dye Oil red or Nile red, but not with the Golgi or endosomal markers. Further examination demonstrated that Rab40c is also associated with ERGIC-53 containing structures, especially under the serum starvation condition. Rab40c is increasingly recruited to the surface of lipid droplets during lipid droplets formation and maturation in HepG2 cells. Rab40c knockdown moderately decreases the size of lipid droplets, suggesting that Rab40c is involved in the biogenesis of lipid droplets. Stimulation for adipocyte differentiation increases the expression of Rab40c in 3T3-L1 cells. Rab40c interacts with TIP47, and is appositionally associated with TIP47-labeled lipid droplets. In addition, over-expression of Rab40c causes the clustering of lipid droplets independent of its GTPase activity, but completely dependent of the intact SOCS box domain of Rab40c. In addition, Rab40c displayed self-interaction as well as interaction with TIP47 and the SOCS box is essential for its ability to induce clustering of lipid droplets. Our results suggest that Rab40c is a novel Rab protein associated with lipid droplets, and is likely involved in modulating the biogenesis of lipid droplets. PMID:23638186

  11. Lipid modulation of thermal transient receptor potential channels.

    PubMed

    Hernández-García, Enrique; Rosenbaum, Tamara

    2014-01-01

    There is a subgroup of transient receptor potential (TRP) ion channels that are responsive to temperature (thermo-TRP channels). These are important to a variety of sensory and physiological phenomena such as pain and taste perception. All thermo-TRP channels known to date are subject to modulation by lipidic molecules of many kinds, from the ubiquitous cholesterol to more specialized molecules such as prostaglandins. Although the mechanisms and sites of binding of lipids on thermo-TRPs are largely unknown, the explosion on research of lipids and ion channels has revealed previously unsuspected roles for them. Diacyl glycerol is a lipid produced by phospholipase C (PLC) and it was discovered to modulate TRP channels in the eye of the fly, and many mammal TRP channels have been found to interact with lipids. While most of the lipids acting on thermo-TRP channels have been found to activate them, there are a few capable of inhibition. Phosphatidylinositol 4,5-bisphosphate is even capable of both inhibition and activation on a couple of thermo-TRPs, depending on the cellular context. More data is required to assess the mechanism through which lipids affect thermo-TRP channel activity and the physiological importance of this interaction.

  12. Acute effects of an oral supplement of (−)-epicatechin on postprandial fat and carbohydrate metabolism in normal and overweight subjects

    PubMed Central

    Gutiérrez-Salmeán, Gabriela; Ortiz-Vilchis, Pilar; Vacaseydel, Claudia M.; Rubio-Gayosso, Ivan; Meaney, Eduardo; Villarreal, Francisco; Ramírez-Sánchez, Israel; Ceballos, Guillermo

    2014-01-01

    Postprandial hyperglycemia, in particular when accompanied by excessive hypertriglyceridemia, is associated with increased cardiovascular risk, mainly in overweight or obese subjects, as it favors oxidative stress, systemic inflammation and endothelial dysfunction. Thus, treatments that favorably modulate metabolism by reducing steep increases in postprandial serum glucose and triglycerides, are of considerable interest. Evidence suggests that (−)-epicatechin (EPI) is responsible for reductions in cardiometabolic risk associated with chocolate consumption these effects may be associated with favorable effects of EPI on postprandial metabolism. The aims of this study were to assess the effects of EPI on postprandial metabolism in normal-weight and overweight/obese subjects. Twenty adult volunteers (normal and overweight) underwent oral metabolic tolerance tests in the absence and presence of oral EPI (1 mg/kg). Metabolic responses were examined using indirect calorimetry and determining blood glucose and triglycerides at 0, 2 and 4 hours after metabolic load ingestion. Results show that EPI increased postprandial lipid catabolism, as evidenced by a significant decrease in the respiratory quotient, which implies an increase in fat oxidation. The effect was associated with significantly lower postprandial plasma glucose and triglycerides concentrations. The effects were more prominent in overweight subjects. In conclusion, EPI modulates postprandial metabolism by enhancing lipid oxidation accompanied by reductions in glycemia and triglyceridemia. PMID:24458104

  13. Habituation to low or high protein intake does not modulate basal or postprandial muscle protein synthesis rates: a randomized trial.

    PubMed

    Gorissen, Stefan Hm; Horstman, Astrid Mh; Franssen, Rinske; Kouw, Imre Wk; Wall, Benjamin T; Burd, Nicholas A; de Groot, Lisette Cpgm; van Loon, Luc Jc

    2017-02-01

    Muscle mass maintenance is largely regulated by basal muscle protein synthesis rates and the ability to increase muscle protein synthesis after protein ingestion. To our knowledge, no previous studies have evaluated the impact of habituation to either low protein intake (LOW PRO) or high protein intake (HIGH PRO) on the postprandial muscle protein synthetic response. We assessed the impact of LOW PRO compared with HIGH PRO on basal and postprandial muscle protein synthesis rates after the ingestion of 25 g whey protein. Twenty-four healthy, older men [age: 62 ± 1 y; body mass index (in kg/m(2)): 25.9 ± 0.4 (mean ± SEM)] participated in a parallel-group randomized trial in which they adapted to either a LOW PRO diet (0.7 g · kg(-1) · d(-1); n = 12) or a HIGH PRO diet (1.5 g · kg(-1) · d(-1); n = 12) for 14 d. On day 15, participants received primed continuous l-[ring-(2)H5]-phenylalanine and l-[1-(13)C]-leucine infusions and ingested 25 g intrinsically l-[1-(13)C]-phenylalanine- and l-[1-(13)C]-leucine-labeled whey protein. Muscle biopsies and blood samples were collected to assess muscle protein synthesis rates as well as dietary protein digestion and absorption kinetics. Plasma leucine concentrations and exogenous phenylalanine appearance rates increased after protein ingestion (P < 0.01) with no differences between treatments (P > 0.05). Plasma exogenous phenylalanine availability over the 5-h postprandial period was greater after LOW PRO than after HIGH PRO (61% ± 1% compared with 56% ± 2%, respectively; P < 0.05). Muscle protein synthesis rates increased from 0.031% ± 0.004% compared with 0.039% ± 0.007%/h in the fasted state to 0.062% ± 0.005% compared with 0.057% ± 0.005%/h in the postprandial state after LOW PRO compared with HIGH PRO, respectively (P < 0.01), with no differences between treatments (P = 0.25). Habituation to LOW PRO (0.7 g · kg(-1) · d(-1)) compared with HIGH PRO (1.5 g · kg(-1) · d(-1)) augments the postprandial

  14. Hydrophobic Moiety of Cationic Lipids Strongly Modulates Their Transfection Activity

    SciTech Connect

    Koynova, Rumiana; Tenchov, Boris; Wang, Li; MacDonald, Robert C.

    2010-01-18

    Synthetic cationic lipids are widely used components of nonviral gene carriers, and the factors regulating their transfection efficiency are the subject of considerable interest. In view of the important role that electrostatic interactions with the polyanionic nucleic acids play in formation of lipoplexes, a common empirical approach to improving transfection has been the synthesis and testing of amphiphiles with new versions of positively charged polar groups, while much less attention has been given to the role of the hydrophobic lipid moieties. On the basis of data for {approx}20 cationic phosphatidylcholine (PC) derivatives, here we demonstrate that hydrocarbon chain variations of these lipids modulate by over 2 orders of magnitude their transfection efficiency. The observed molecular structure-activity relationship manifests in well-expressed dependences of activity on two important molecular characteristics, chain unsaturation and total number of carbon atoms in the lipid chains, which is representative of the lipid hydrophobic volume and hydrophilic-lipophilic ratio. Transfection increases with decrease of chain length and increase of chain unsaturation. Maximum transfection was found for cationic PCs with monounsaturated 14:1 chains. It is of particular importance that the high-transfection lipids strongly promote cubic phase formation in zwitterionic membrane phosphatidylethanolamine (PE). These remarkable correlations point to an alternative, chain-dependent process in transfection, not related to the electrostatic cationic-anionic lipid interactions.

  15. Interdigitation between Triglycerides and Lipids Modulates Surface Properties of Lipid Droplets.

    PubMed

    Bacle, Amélie; Gautier, Romain; Jackson, Catherine L; Fuchs, Patrick F J; Vanni, Stefano

    2017-04-11

    Intracellular lipid droplets (LDs) are the main cellular site of metabolic energy storage. Their structure is unique inside the cell, with a core of esterified fatty acids and sterols, mainly triglycerides and sterol esters, surrounded by a single monolayer of phospholipids. Numerous peripheral proteins, including several that were previously associated with intracellular compartments surrounded by a lipid bilayer, have been recently shown to target the surface of LDs, but how they are able to selectively target this organelle remains largely unknown. Here, we use atomistic and coarse-grained molecular dynamics simulations to investigate the molecular properties of the LD surface and to characterize how it differs from that of a lipid bilayer. Our data suggest that although several surface properties are remarkably similar between the two structures, key differences originate from the interdigitation between surface phospholipids and core neutral lipids that occurs in LDs. This property is extremely sensitive to membrane undulations, unlike in lipid bilayers, and it strongly affects both lipid-packing defects and the lateral pressure profile. We observed a marked change in overall surface properties for surface tensions >10 mN/m, indicative of a bimodal behavior. Our simulations provide a comprehensive molecular characterization of the unique surface properties of LDs and suggest how the molecular properties of the surface lipid monolayer can be modulated by the underlying neutral lipids. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  16. Effect of intragastric acid stability of fat emulsions on gastric emptying, plasma lipid profile and postprandial satiety.

    PubMed

    Marciani, Luca; Faulks, Richard; Wickham, Martin S J; Bush, Debbie; Pick, Barbara; Wright, Jeff; Cox, Eleanor F; Fillery-Travis, Annette; Gowland, Penny A; Spiller, Robin C

    2009-03-01

    Fat is often included in common foods as an emulsion of dispersed oil droplets to enhance the organoleptic quality and stability. The intragastric acid stability of emulsified fat may impact on gastric emptying, satiety and plasma lipid absorption. The aim of the present study was to investigate whether, compared with an acid-unstable emulsion, an acid-stable fat emulsion would empty from the stomach more slowly, cause more rapid plasma lipid absorption and cause greater satiety. Eleven healthy male volunteers received on two separate occasions 500 ml of 15 % (w/w) [13C]palmitate-enriched olive oil-in-water emulsion meals which were either stable or unstable in the acid gastric environment. MRI was used to measure gastric emptying and the intragastric oil fraction of the meals. Blood sampling was used to measure plasma lipids and visual analogue scales were used to assess satiety. The acid-unstable fat emulsion broke and rapidly layered in the stomach. Gastric emptying of meal volume was slower for the acid-stable fat emulsion (P < 0.0001; two-way ANOVA). The rate of energy delivery of fat from the stomach to the duodenum was not different up to t = 110 min. The acid-stable emulsion induced increased fullness (P < 0.05), decreased hunger (P < 0.0002), decreased appetite (P < 0.0001) and increased the concentration of palmitic acid tracer in the chylomicron fraction (P < 0.04). This shows that it is possible to delay gastric emptying and increase satiety by stabilising the intragastric distribution of fat emulsions against the gastric acid environment. This could have implications for the design of novel foods.

  17. Exercise and Dietary-Mediated Reductions in Postprandial Lipemia

    PubMed Central

    Plaisance, Eric P.; Fisher, Gordon

    2014-01-01

    Postprandial hyperlipemia produces long-term derangements in lipid/lipoprotein metabolism, vascular endothelial dysfunction, hypercoagulability, and sympathetic hyperactivity which are strongly linked to atherogenesis. The purpose of this review is to (1) provide a qualitative analysis of the available literature examining the dysregulation of postprandial lipid metabolism in the presence of obesity, (2) inspect the role of adiposity distribution and sex on postprandial lipid metabolism, and (3) examine the role of energy deficit (exercise- and/or energy restriction-mediated), isoenergetic low-carbohydrate diets, and omega-3 (n-3) fatty acid supplementation on postprandial lipid metabolism. We conclude from the literature that central adiposity primarily accounts for sex-related differences in postprandial lipemia and that aerobic exercise attenuates this response in obese or lean men and women to a similar extent through potentially unique mechanisms. In contrast, energy restriction produces only mild reductions in postprandial lipemia suggesting that exercise may be superior to energy restriction alone as a strategy for lowering postprandial lipemia. However, isoenergetic very low-carbohydrate diets and n-3 fatty acid supplementation reduce postprandial lipemia indicating that macronutrient manipulations reduce postprandial lipemia in the absence of energy restriction. Therefore, interactions between exercise/energy restriction and alterations in macronutrient content remain top priorities for the field to identify optimal behavioral treatments to reduce postprandial lipemia. PMID:25061524

  18. Lipids as central modulators of sensory TRP channels.

    PubMed

    Ciardo, Maria Grazia; Ferrer-Montiel, Antonio

    2017-09-01

    The transient receptor potential (TRP) ion channel family is involved in a diversity of physiological processes including sensory and homeostatic functions, as well as muscle contraction and vasomotor control. Their dysfunction contributes to the etiology of several diseases, being validated as therapeutic targets. These ion channels may be activated by physical or chemical stimuli and their function is highly influenced by signaling molecules activated by extracellular signals. Notably, as integral membrane proteins, lipid molecules also modulate their membrane location and function either by direct interaction with the channel structure or by modulating the physico-chemical properties of the cellular membrane. This lipid-based modulatory effect is being considered an alternative and promising approach to regulate TRP channel dysfunction in diseases. Here, we review the current progress in this exciting field highlighting a complex channel regulation by a large diversity of lipid molecules and suggesting some diseases that may benefit from a membrane lipid therapy. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. The impact of the leucine 7 to proline 7 polymorphism of the neuropeptide Y gene on postprandial lipemia and on the response of serum total and lipoprotein lipids to a reduced fat diet.

    PubMed

    Schwab, U S; Agren, J J; Valve, R; Hallikainen, M A; Sarkkinen, E S; Jauhiainen, M; Karvonen, M K; Pesonen, U; Koulu, M; Uusitupa, M I J; Savolainen, M J

    2002-02-01

    The aim of the study was to examine the impact of the leucine7 to proline7 (Leu7Pro) polymorphism of the NPY gene on postprandial (PP) lipemia, post-heparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities, and the response of serum lipids to a reduced fat diet. Seven middle-aged obese subjects with Leu7Pro genotype were matched with seven subjects with Leu7Leu genotype for gender, age, apolipoprotein E phenotype and BMI. These 14 subjects participated in the oral 8 h fat tolerance test. Sixty-eight slightly obese middle-aged subjects (10 with the Leu7Pro genotype) had participated in intervention studies and consumed a reduced fat diet for 8 weeks. There were no statistically significant differences in PP areas under the curve of plasma total triglycerides (TG), chylomicron TG, VLDL-TG or insulin between the genotype groups. The TG-to-cholesterol (C) ratio in VLDL was significantly lower in the subjects with Leu7Pro genotype compared to those with the Leu7Leu genotype at time points 30 min and 1 h in the fat tolerance test. Heparin-induced activities of LPL or HL or the response of serum total or LDL-C to the reduced fat diet did not differ between the groups. The NPY genotype neither affects the magnitude of postprandial lipemia induced by a fat tolerance test nor the response of serum total lipids or lipids in different lipoprotein classes to the reduced fat diet. However, this preliminary study suggests that there might be compositional differences in the lipoprotein particles between the genotype groups that affect postprandial lipid metabolism. The Council for Health Sciences of the Academy of Finland, Kuopio University Hospital and the National Technology Agency, Finland.

  20. Cytoskeletal Modulation of Lipid Interactions Regulates Lck Kinase Activity*

    PubMed Central

    Chichili, Gurunadh R.; Cail, Robert C.; Rodgers, William

    2012-01-01

    The actin cytoskeleton promotes clustering of proteins associated with cholesterol-dependent rafts, but its effect on lipid interactions that form and maintain rafts is not understood. We addressed this question by determining the effect of disrupting the cytoskeleton on co-clustering of dihexadecyl-(C16)-anchored DiO and DiI, which co-enrich in ordered lipid environments such as rafts. Co-clustering was assayed by fluorescence resonance energy transfer (FRET) in labeled T cells, where rafts function in the phosphoregulation of the Src family kinase Lck. Our results show that probe co-clustering was sensitive to depolymerization of actin filaments with latrunculin B (Lat B), inhibition of myosin II with blebbistatin, and treatment with neomycin to sequester phosphatidylinositol 4,5-bisphosphate. Cytoskeletal effects on lipid interactions were not restricted to order-preferring label because co-clustering of C16-anchored DiO with didodecyl (C12)-anchored DiI, which favors disordered lipids, was also reduced by Lat B and blebbistatin. Furthermore, conditions that disrupted probe co-clustering resulted in activation of Lck. These data show that the cytoskeleton globally modulates lipid interactions in the plasma membrane, and this property maintains rafts that function in Lck regulation. PMID:22613726

  1. The postprandial situation as a pro-inflammatory condition.

    PubMed

    de Vries, Marijke A; Klop, Boudewijn; Eskes, Silvia A; van der Loos, Theo L J M; Klessens-Godfroy, Françoise J M; Wiebolt, Janneke; Janssen, Hans W; Westerman, Elsbeth M; Castro Cabezas, Manuel

    2014-01-01

    Postprandial lipemia has been associated with cardiovascular disease. The current pathophysiological concept is that postprandial remnant lipoproteins migrate into the subendothelial space and that remnants activate circulating leukocytes and endothelial cells. Activated monocytes adhere to endothelial adhesion molecules, facilitating subendothelial migration of monocytes. These cells differentiate into macrophages, with the risk of foam cell formation, due to uptake of remnants and modified lipoproteins. Evidence is emerging that specific interventions may reduce the atherogenic postprandial inflammation. Fruits rich in polyphenols, virgin olive oil, carotenoids and exercise have recently been found to reduce postprandial inflammation. Pharmaceutical interventions with fibrates or statins not only improve the overall lipid profile, but reduce postprandial inflammation as well. This review will deal with the current concept of postprandial inflammation in relation to the development of atherosclerosis and potential interventions to reduce postprandial inflammation. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  2. Dietary lipids modulate methylmercury toxicity in Atlantic salmon.

    PubMed

    Olsvik, Pål A; Amlund, Heidi; Torstensen, Bente E

    2011-12-01

    This experiment aimed to study the molecular toxicity of methylmercury (MeHg) in liver, brain and white muscle of Atlantic salmon fed a diet based on fish oil (FO, high dietary n-3/n-6 ratio) compared to an alternative diet mainly based on vegetable oil (VO, low dietary n-3/n-6 ratio). Juvenile salmon were fed decontaminated diets or the FO and VO diets enriched with 5 mg Hg/kg (added as MeHg) for three months. The dietary lipid composition affected the fatty acid composition in the tissues, especially in liver and white muscle. After 84 days of exposure, the liver accumulated three times as much MeHg as the brain and white muscle. Vitamin C content and heme oxygenase, tubulin alpha (TUBA) and Cpt1 transcriptional levels all showed significant effects of MeHg exposure in the liver. TBARS, α-tocopherol, γ-tocopherol, and the transcriptional levels of thioredoxin, heme oxygenase, TUBA, PPARB1, D5D and D6D showed an effect of dietary lipid composition in liver tissue. Effects of dietary lipids were observed in brain tissue for MT-A, HIF1, Bcl-X and TUBA. Interaction effects between MeHg exposure and dietary lipid composition were observed in all tissues. Our data suggest that dietary fats have modulating effects on MeHg toxicity in Atlantic salmon.

  3. Influence of feeding a fish oil-containing diet to mature, overweight dogs: Effects on lipid metabolites, postprandial glycaemia and body weight.

    PubMed

    de Godoy, M R C; McLeod, K R; Harmon, D L

    2017-05-15

    The objective of this study was to determine the effect of feeding a fish oil (FO)-containing diet on lipid and protein metabolism, postprandial glycaemia and body weight (BW) of mature, overweight dogs. Seven female dogs were randomly assigned to one of two isonitrogenous and isocaloric diets, control (CO) or FO (FO), in a crossover design. Experimental periods were 69 day, separated by a washout period of 30 day. At the beginning of the experiment, and at 30 and 60 day of feeding the experimental diets, the dogs were infused with D-glucose (2 g/kg BW) through an intravenous catheter. Blood samples were collected for 3 hr to perform a glucose tolerance test. Nitrogen balance measurements began at 06:30 on d 63 of each experimental period and ended at 06:30 on d 69. On d 66 of each period, a single dose (7.5 mg/kg) of (15) N-glycine was administered orally for determination of protein turnover. Incremental area under the curve and glucose concentration at peak did not differ between treatments or among sampling days within treatment. Glucose half-life tended to decrease (p < .10) in the FO treatment on day 30 when compared to baseline (day 0). β-hydroxybutyrate, non-esterified fatty acid (NEFA) and triglycerides did not differ within or between treatments. Cholesterol decreased (p < .05) on the FO treatment on day 30, 60 and 69 when compared to day 0. High-density lipoprotein (HDL) decreased (p < .05) in the FO treatment on day 69 when compared to day 0. Body weight, food intake, faecal excretion, DM and N digestibilities, N balance and protein turnover were not different between diets. Overall, FO-containing diet decreases cholesterol in mature overweight dogs; however, further research is warranted to verify the effects of FO on glucose metabolism. © 2017 Blackwell Verlag GmbH.

  4. Dietary oleic and palmitic acids modulate the ratio of triacylglycerols to cholesterol in postprandial triacylglycerol-rich lipoproteins in men and cell viability and cycling in human monocytes.

    PubMed

    López, Sergio; Bermúdez, Beatriz; Pacheco, Yolanda M; López-Lluch, Guillermo; Moreda, Wenceslao; Villar, José; Abia, Rocío; Muriana, Francisco J G

    2007-09-01

    The postprandial metabolism of dietary fats produces triacylglycerol (TG)-rich lipoproteins (TRL) that could interact with circulating cells. We investigated whether the ratios of oleic:palmitic acid and monounsaturated fatty acids (MUFA):SFA in the diet affect the ratio of TG:cholesterol (CHOL) in postprandial TRL of healthy men. The ability of postprandial TRL at 3 h (early postprandial period) and 5 h (late postprandial period) to affect cell viability and cycle in the THP-1 human monocytic cell line was also determined. In a randomized, crossover experiment, 14 healthy volunteers (Caucasian men) ate meals enriched (50 g/m(2) body surface area) in refined olive oil, high-palmitic sunflower oil, butter, and a mixture of vegetable and fish oils, which had ratios of oleic:palmitic acid (MUFA:SFA) of 6.83 (5.43), 2.36 (2.42), 0.82 (0.48), and 13.81 (7.08), respectively. The ratio of TG:CHOL in postprandial TRL was inversely correlated (r = -0.89 to -0.99) with the ratio of oleic:palmitic acid and with the MUFA:SFA ratio in the dietary fats (P < 0.05). Postprandial TRL at 3 h preferentially increased the proportion of necrotic cells, whereas postprandial TRL at 5 h increased the proportion of apoptotic cells (P < 0.05). Cell cycle analysis showed that postprandial TRL blocked the human monocytes in S-phase. Our findings suggest that the level of TG and CHOL into postprandial TRL is associated with the ratios of oleic:palmitic acid and MUFA:SFA in dietary fats, which determines the ability of postprandial TRL to induce cytotoxicity and disturb the cell cycle in THP-1 cells.

  5. Epigenome-wide association study of triglyceride postprandial responses to high-fat dietary challenge in the Genetics of Lipid Lowering Drugs and Diet Network study

    USDA-ARS?s Scientific Manuscript database

    Postprandial lipemia (PPL), the increased plasma triglyceride (TG) concentration after consuming a high-fat meal, is an independent risk factor for cardiovascular disease (CVD). Individual responses to a meal high in fat vary greatly, depending on genetic and lifestyle factors. However, only a few ...

  6. Inulin and oligofructose modulate lipid metabolism in animals: review of biochemical events and future prospects.

    PubMed

    Delzenne, N M; Daubioul, C; Neyrinck, A; Lasa, M; Taper, H S

    2002-05-01

    Inulin and oligofructose, besides their effect on the gastro-intestinal tract, are also able to exert 'systemic' effect, namely by modifying the hepatic metabolism of lipids in several animal models. Feeding male Wistar rats on a carbohydrate-rich diet containing 10 % inulin or oligofructose significantly lowers serum triacylglycerol (TAG) and phospholipid concentrations. A lower hepatic lipogenesis, through a coordinate reduction of the activity and mRNA of lipogenic enzymes is a key event in the reduction of very low-density lipoprotein-TAG secretion by oligofructose. Oligofructose is also able to counteract triglyceride metabolism disorder occurring through dietary manipulation in animals, and sometimes independently on lipogenesis modulation: oligofructose reduces post-prandial triglyceridemia by 50 % and avoids the increase in serum free cholesterol level occurring in rats fed a Western-type high fat diet. Oligofructose protects rats against liver TAG accumulation (steatosis) induced by fructose, or occurring in obese Zucker fa/fa rats. The protective effect of dietary inulin and oligofructose on steatosis in animals, would be interesting, if confirmed in humans, since steatosis is one of the most frequent liver disorders, occurring together with the plurimetabolic syndrome, in overweight people. The panel of putative mediators of the systemic effects of inulin and oligofructose consists in either modifications in glucose/insulin homeostasis, the end-products of their colonic fermentation (i.e. propionate) reaching the liver by the portal vein, incretins and/or the availability of other nutrients. The identification of the key mediators of the systemic effects of inulin and oligofructose is the key to identify target function(s) (or dysfunction(s)), and finally individuals who would take an advantage of increasing their dietary intake.

  7. The chronic effects of fish oil with exercise on postprandial lipaemia and chylomicron homeostasis in insulin resistant viscerally obese men

    PubMed Central

    2012-01-01

    Background Visceral obesity and insulin resistance are associated with a postprandial accumulation of atherogenic chylomicron remnants that is difficult to modulate with lipid-lowering therapies. Dietary fish oil and exercise are cardioprotective interventions that can significantly modify the metabolism of TAG-rich lipoproteins. In this study, we investigated whether chronic exercise and fish oil act in combination to affect chylomicron metabolism in obese men with moderate insulin resistance. Methods The single blind study tested the effect of fish oil, exercise and the combined treatments on fasting and postprandial chylomicron metabolism. Twenty nine men with metabolic syndrome were randomly assigned to take fish oil or placebo for four weeks, before undertaking an additional 12 week walking program. At baseline and at the end of each treatment, subjects were tested for concentrations of fasting apo B48, plasma lipids and insulin. Postprandial apo B48 and TAG kinetics were also determined following ingestion of a fat enriched meal. Results Combining fish oil and exercise resulted in a significant reduction in the fasting apo B48 concentration, concomitant with attenuation of fasting TAG concentrations and the postprandial TAGIAUC response (p < 0.05). Fish oil by itself reduced the postprandial TAG response (p < 0.05) but not postprandial apo B48 kinetics. Individual treatments of fish oil and exercise did not correspond with improvements in fasting plasma TAG and apo B48. Conclusion Fish oil was shown to independently improve plasma TAG homeostasis but did not resolve hyper-chylomicronaemia. Instead, combining fish oil with chronic exercise reduced the plasma concentration of pro-atherogenic chylomicron remnants; in addition it reduced the fasting and postprandial TAG response in viscerally obese insulin resistant subjects. PMID:22314022

  8. Changes in macrophage function modulated by the lipid environment

    PubMed Central

    Williams, Michael R; Cauvi, David M; Rivera, Isabel; Hawisher, Dennis; De Maio, Antonio

    2016-01-01

    Macrophages (Mϕs) play a critical role in the defense against pathogens, orchestrating the inflammatory response during injury and maintaining tissue homeostasis. During these processes, macrophages encounter a variety of environmental conditions that are likely to change their gene expression pattern, which modulates their function. In this study, we found that murine Mϕs displayed two different subpopulations characterized by differences in morphologies, expression of surface markers and phagocytic capacity under non-stimulated conditions. These two subpopulations could be recapitulated by changes in the culture conditions. Thus, Mϕs grown in suspension in the presence of serum were highly phagocytic, whereas subtraction of serum resulted in rapid attachment and reduced phagocytic activity. The difference in phagocytosis between these subpopulations was correlated with the expression levels of FcγR. These two cell subpopulations also differed in their responses to LPS and the expression of surface markers, including CD14, CD86, scavenger receptor A1, TLR4 and low-density lipoprotein receptor. Moreover, we found that the lipid/cholesterol content in the culture medium mediated the differences between these two cell subpopulations. Thus, we described a mechanism that modulates Mϕ function depending on the exposure to lipids within their surrounding microenvironment. PMID:26951856

  9. Changes in macrophage function modulated by the lipid environment.

    PubMed

    Williams, Michael R; Cauvi, David M; Rivera, Isabel; Hawisher, Dennis; De Maio, Antonio

    2016-04-01

    Macrophages (Mφs) play a critical role in the defense against pathogens, orchestrating the inflammatory response during injury and maintaining tissue homeostasis. During these processes, macrophages encounter a variety of environmental conditions that are likely to change their gene expression pattern, which modulates their function. In this study, we found that murine Mφs displayed two different subpopulations characterized by differences in morphologies, expression of surface markers and phagocytic capacity under non-stimulated conditions. These two subpopulations could be recapitulated by changes in the culture conditions. Thus, Mφs grown in suspension in the presence of serum were highly phagocytic, whereas subtraction of serum resulted in rapid attachment and reduced phagocytic activity. The difference in phagocytosis between these subpopulations was correlated with the expression levels of FcγR. These two cell subpopulations also differed in their responses to LPS and the expression of surface markers, including CD14, CD86, scavenger receptor A1, TLR4 and low-density lipoprotein receptor. Moreover, we found that the lipid/cholesterol content in the culture medium mediated the differences between these two cell subpopulations. Thus, we described a mechanism that modulates Mφ function depending on the exposure to lipids within their surrounding microenvironment. © The Author(s) 2016.

  10. Weight loss, but not fish oil consumption, improves fasting and postprandial serum lipids, markers of endothelial function, and inflammatory signatures in moderately obese men.

    PubMed

    Plat, Jogchum; Jellema, Annemarie; Ramakers, Julian; Mensink, Ronald P

    2007-12-01

    Overweight persons are at risk for cardiovascular diseases, which may relate to a disturbed endothelial function and pro-inflammatory serum profiles. Indeed, weight loss lowers cardiovascular disease risk, but weight maintenance is difficult. Therefore, dietary supplements such as fish oil, which improve endothelial function, are useful. In this study, we evaluated effects of fish oil and moderate weight loss in the same population. For this, 11 normolipidemic healthy, moderately obese men (BMI 30-35 kg/m2) received in random order 1.1 g/d eicosapentanoic acid (EPA) + docosahexanoic acid (DHA) or oleic acid (control) for 6 wk. In the 3rd period, 8 of the 11 subjects consumed low-energy diets (2 MJ/d) for 4 wk followed by 4 wk weight stabilization. Their body weight was reduced by 9.4 +/- 2.0 kg (P < 0.05). On the final day of all 3 periods, a postprandial test was conducted. Weight loss lowered fasting and postprandial plasma triacylglycerol (TG) responses (P < 0.001), whereas fish oil reduced only postprandial TG (P = 0.006). Fish oil did not affect soluble intercellular adhesion molecule (s-ICAM), whereas weight loss reduced fasting (P = 0.009) and postprandial s-ICAM responses (P < 0.001). Fasting s-ICAM and TG correlated (r = 0.68; P = 0.029), as did changes in fasting s-ICAM and TG during weight loss (r = 0.80; P = 0.029) and fish oil treatment (r = 0.76; P = 0.009). Fasting (P = 0.027) and postprandial (P < 0.001) serum C-reactive protein were lowered by weight loss. The postprandial monocyte chemoattractant protein-1 response was lowered by fish oil and after weight loss (P < 0.001). This indicates that 1.1 g/d EPA+DHA supplied for 6 wk, in contrast to approximately 10 kg weight loss, does not improve markers of endothelial function and inflammation.

  11. The metabolic syndrome in relation to complement component 3 and postprandial lipemia in patients from an outpatient lipid clinic and healthy volunteers.

    PubMed

    van Oostrom, Antonie J H H M; Alipour, Arash; Plokker, Thijs W M; Sniderman, Alan D; Cabezas, Manuel Castro

    2007-01-01

    We investigated the relationship between complement component 3 (C3), fasting and postprandial lipemia and the metabolic syndrome (MetabS). Herefore fasting and postprandial samples after an acute oral fat load were obtained in 40 MetabS+ (50+/-8 years) and 70 MetabS- (48+/-7 years) subjects. Fasting C3 was higher in MetabS+ (1.21+/-0.33g/L versus 0.91+/-0.14g/L, P<0.001). Postprandially, MetabS+ had a higher total and incremental triglyceride response (TG-AUC: +77%; P<0.001 and TG-dAUC: +48%; P<0.05, respectively) and a higher total free fatty acid (FFA-AUC: +13%, P<0.05) and C3 response (C3-AUC: +26%, P<0.001) when compared to MetabS-. In both groups, fasting C3 was strongly associated with fasting TG, TG-AUC, TG-dAUC and insulin sensitivity (HOMA) (R=0.68, 0.67, 0.41 and 0.67, respectively, for the whole group; P<0.001 for each). Fasting C3 showed a dose-dependent relation with the number of MetabS components and, following exclusion of these components, it was after TG-AUC, the second best determinant of the MetabS (adjusted R(2)=0.47, P<0.001). In conclusion, C3 and postprandial lipema are closely associated with the metabolic syndrome and with several metabolic variables linked to insulin resistance. C3 may be a useful marker to identify subjects with the metabolic syndrome.

  12. The association of hs-CRP with fasting and postprandial plasma lipids in patients with type 2 diabetes is disrupted by dietary monounsaturated fatty acids.

    PubMed

    Bozzetto, L; De Natale, C; Di Capua, L; Della Corte, G; Patti, L; Maione, S; Riccardi, G; Rivellese, A A; Annuzzi, G

    2013-04-01

    The aim of the study was to evaluate whether two dietary approaches recommended for diabetes mellitus and cardiovascular prevention-high-MUFA or complex carbohydrates/fiber-differently influence inflammation. A 4-week crossover study in 12 individuals with type 2 diabetes was performed. Fasting and postprandial hs-CRP plasma levels were not significantly different after a high-carbohydrate/high-fiber/low-glycemic index (CHO/fiber) and a high-MUFA diet. Compared with fasting, hs-CRP levels decreased significantly after the MUFA but not after the CHO/fiber meal. Triglyceride-rich lipoproteins were significantly lower after the CHO/fiber than the MUFA diet. At fasting and postprandially, hs-CRP correlated with triglyceride in whole plasma, chylomicrons, small and large VLDL after the CHO/fiber but not after the MUFA diet. In conclusion, a MUFA-rich diet and a carbohydrate/fiber-rich diet induced similar effects on plasma hs-CRP concentrations. However, these dietary approaches seem to influence hs-CRP levels through different mechanisms. i.e., direct acute postprandial effects by MUFA and triglyceride-rich lipoproteins mediated effects by CHO/fiber.

  13. Introduction to the DISRUPT postprandial database: subjects, studies and methodologies.

    PubMed

    Jackson, Kim G; Clarke, Dave T; Murray, Peter; Lovegrove, Julie A; O'Malley, Brendan; Minihane, Anne M; Williams, Christine M

    2010-03-01

    Dysregulation of lipid and glucose metabolism in the postprandial state are recognised as important risk factors for the development of cardiovascular disease and type 2 diabetes. Our objective was to create a comprehensive, standardised database of postprandial studies to provide insights into the physiological factors that influence postprandial lipid and glucose responses. Data were collated from subjects (n = 467) taking part in single and sequential meal postprandial studies conducted by researchers at the University of Reading, to form the DISRUPT (DIetary Studies: Reading Unilever Postprandial Trials) database. Subject attributes including age, gender, genotype, menopausal status, body mass index, blood pressure and a fasting biochemical profile, together with postprandial measurements of triacylglycerol (TAG), non-esterified fatty acids, glucose, insulin and TAG-rich lipoprotein composition are recorded. A particular strength of the studies is the frequency of blood sampling, with on average 10-13 blood samples taken during each postprandial assessment, and the fact that identical test meal protocols were used in a number of studies, allowing pooling of data to increase statistical power. The DISRUPT database is the most comprehensive postprandial metabolism database that exists worldwide and preliminary analysis of the pooled sequential meal postprandial dataset has revealed both confirmatory and novel observations with respect to the impact of gender and age on the postprandial TAG response. Further analysis of the dataset using conventional statistical techniques along with integrated mathematical models and clustering analysis will provide a unique opportunity to greatly expand current knowledge of the aetiology of inter-individual variability in postprandial lipid and glucose responses.

  14. Capsaicin-containing chili improved postprandial hyperglycemia, hyperinsulinemia, and fasting lipid disorders in women with gestational diabetes mellitus and lowered the incidence of large-for-gestational-age newborns.

    PubMed

    Yuan, Li-Jia; Qin, Yu; Wang, Lin; Zeng, Yuan; Chang, Hui; Wang, Jian; Wang, Bin; Wan, Jing; Chen, Shi-Hui; Zhang, Qian-Yong; Zhu, Jun-Dong; Zhou, Yong; Mi, Man-Tian

    2016-04-01

    Gestational diabetes mellitus (GDM) may increase the future health risks of women and their offspring. The aim of this study was to determine the effect of capsaicin supplementation on blood glucose, lipid metabolism and pregnancy outcomes in women with GDM. Forty-four pregnant women with GDM at 22-33 gestational weeks were randomly assigned to the capsaicin group (5 mg/d of capsaicin) or to the placebo group (0 mg/d of capsaicin) for 4 weeks in a randomized, double-blind, placebo-controlled trial. The concentrations of fasting plasma glucose and serum insulin, 2-h postprandial plasma glucose (2-h PG) and serum insulin (2-h INS), and fasting serum lipids, liver and kidney function parameters, and calcitonin gene-related peptide (CGRP) were measured at 0 and 4 weeks. The maternal and neonatal outcomes were also recorded. Forty-two women completed the trial. Compared to the placebo group, 2-h PG and 2-h INS concentrations and 2-h postprandial HOMA-IR (2-h HOMA-IR) levels, and the fasting serum total cholesterol and triglycerides concentrations significantly decreased in the capsaicin group after treatment (P < 0.05). Moreover, the fasting serum apolipoprotein B and CGRP concentrations significantly increased in the capsaicin group (P < 0.05). The changes in the 2-h PG and 2-h INS concentrations and in the 2-h HOMA-IR were negatively correlated with the change in the serum CGRP concentration (P < 0.05). Furthermore, the incidence of large-for-gestational-age (LGA) newborns was significantly lower in the capsaicin group than in the placebo group (P = 0.022). Capsaicin-containing chili supplementation regularly improved postprandial hyperglycemia and hyperinsulinemia as well as fasting lipid metabolic disorders in women with GDM, and it decreased the incidence of LGA newborns. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  15. Dietary supplementation of n-3 PUFA reduces weight gain and improves postprandial lipaemia and the associated inflammatory response in the obese JCR:LA-cp rat.

    PubMed

    Hassanali, Z; Ametaj, B N; Field, C J; Proctor, S D; Vine, D F

    2010-02-01

    Postprandial dyslipidaemia occurs in obesity and insulin resistance (IR), and is associated with an increased risk of developing cardiovascular disease. We have recently established that the JCR:LA-cp rodent model develops postprandial dyslipidaemia concomitant with complications of the metabolic syndrome. Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) are proposed to modulate plasma lipids, serum hormone levels, lipoprotein metabolism and the inflammatory state; however, results remain inconsistent during conditions of IR. To assess the acute metabolic and inflammatory effects of dietary fish oil supplementation on existing postprandial dyslipidaemia in the JCR:LA-cp model. JCR:LA-cp rats (14 weeks of age) were fed either a control, isocaloric, lipid balanced diet (15% w/w total fat, 1.0% cholesterol, P:S ratio 0.4), a lipid balanced diet with 5% n-3 PUFA [fish oil derived eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA)] or a lipid balanced diet with 10% n-3 PUFA for 3 weeks. Fasting plasma lipid, cytokine levels, postprandial chylomicron (apoB48) metabolism and the postprandial inflammatory response [haptoglobin and lipopolysaccharide binding protein (LBP)] were assessed following a standardized 'oral fat challenge'. n-3 PUFA treatment resulted in a significant improvement (i.e. decrease) in the postprandial response for triglyceride (45%) (p < 0.05), apoB48 (45%) (p < 0.03) and LBP (33%) (p < 0.05) compared to controls (measured as area under the clearance curve). In contrast, we observed a significant elevation in postprandial haptoglobin (165%) (p < 0.001) in obese rats supplemented with 10% n-3 PUFA. Treatment with 5% n-3 PUFA in the JCR:LA-cp obese animals resulted in a complementary decrease in total body weight gain (6%) (p < 0.001) and an increase (i.e. improvement) in adiponectin (33%) (p < 0.05) compared to controls, without a concomitant reduction in food intake. Acute dietary n-3 PUFA dietary supplementation can improve fasting as well as

  16. Postprandial Hyperlipidemia and Remnant Lipoproteins

    PubMed Central

    Yamashita, Shizuya

    2017-01-01

    Fasting hypertriglyceridemia is positively associated with the morbidity of coronary heart disease (CHD), and postprandial (non-fasting) hypertriglyceridemia is also correlated with the risk status for CHD, which is related to the increase in chylomicron (CM) remnant lipoproteins produced from the intestine. CM remnant particles, as well as oxidized low density lipoprotein (LDL) or very low density lipoprotein (VLDL) remnants, are highly atherogenic and act by enhancing systemic inflammation, platelet activation, coagulation, thrombus formation, and macrophage foam cell formation. The cholesterol levels of remnant lipoproteins significantly correlate with small, dense LDL; impaired glucose tolerance (IGT) and CHD prevalence. We have developed an assay of apolipoprotein (apo)B-48 levels to evaluate the accumulation of CM remnants. Fasting apoB-48 levels correlate with the morbidity of postprandial hypertriglyceridemia, obesity, type III hyperlipoproteinemia, the metabolic syndrome, hypothyroidism, chronic kidney disease, and IGT. Fasting apoB-48 levels also correlate with carotid intima-media thickening and CHD prevalence, and a high apoB-48 level is a significant predictor of CHD risk, independent of the fasting TG level. Diet interventions, such as dietary fibers, polyphenols, medium-chain fatty acids, diacylglycerol, and long-chain n-3 polyunsaturated fatty acids (PUFA), ameliorate postprandial hypertriglyceridemia, moreover, drugs for dyslipidemia (n-3 PUFA, statins, fibrates or ezetimibe) and diabetes concerning incretins (dipeptidyl-peptidase IV inhibitor or glucagon like peptide-1 analogue) may improve postprandial hypertriglyceridemia. Since the accumulation of CM remnants correlates to impaired lipid and glucose metabolism and atherosclerotic cardiovascular events, further studies are required to investigate the characteristics, physiological activities, and functions of CM remnants for the development of new interventions to reduce atherogenicity. PMID

  17. Postprandial Hyperlipidemia and Remnant Lipoproteins.

    PubMed

    Masuda, Daisaku; Yamashita, Shizuya

    2017-02-01

    Fasting hypertriglyceridemia is positively associated with the morbidity of coronary heart disease (CHD), and postprandial (non-fasting) hypertriglyceridemia is also correlated with the risk status for CHD, which is related to the increase in chylomicron (CM) remnant lipoproteins produced from the intestine. CM remnant particles, as well as oxidized low density lipoprotein (LDL) or very low density lipoprotein (VLDL) remnants, are highly atherogenic and act by enhancing systemic inflammation, platelet activation, coagulation, thrombus formation, and macrophage foam cell formation. The cholesterol levels of remnant lipoproteins significantly correlate with small, dense LDL; impaired glucose tolerance (IGT) and CHD prevalence. We have developed an assay of apolipoprotein (apo)B-48 levels to evaluate the accumulation of CM remnants. Fasting apoB-48 levels correlate with the morbidity of postprandial hypertriglyceridemia, obesity, type III hyperlipoproteinemia, the metabolic syndrome, hypothyroidism, chronic kidney disease, and IGT. Fasting apoB-48 levels also correlate with carotid intima-media thickening and CHD prevalence, and a high apoB-48 level is a significant predictor of CHD risk, independent of the fasting TG level. Diet interventions, such as dietary fibers, polyphenols, medium-chain fatty acids, diacylglycerol, and long-chain n-3 polyunsaturated fatty acids (PUFA), ameliorate postprandial hypertriglyceridemia, moreover, drugs for dyslipidemia (n-3 PUFA, statins, fibrates or ezetimibe) and diabetes concerning incretins (dipeptidyl-peptidase IV inhibitor or glucagon like peptide-1 analogue) may improve postprandial hypertriglyceridemia. Since the accumulation of CM remnants correlates to impaired lipid and glucose metabolism and atherosclerotic cardiovascular events, further studies are required to investigate the characteristics, physiological activities, and functions of CM remnants for the development of new interventions to reduce atherogenicity.

  18. Adenosine receptors: Modulators of lipid availability that are controlled by lipid levels.

    PubMed

    Leiva, Andrea; Guzmán-Gutiérrez, Enrique; Contreras-Duarte, Susana; Fuenzalida, Bárbara; Cantin, Claudette; Carvajal, Lorena; Salsoso, Rocío; Gutiérrez, Jaime; Pardo, Fabián; Sobrevia, Luis

    2017-06-01

    Adenosine as well as agonists and antagonists for the four adenosine receptor subtypes (A1R, A2AR, A2BR and A3R) play a role in several key physiological and pathophysiological processes, including the regulation of vascular tone, thrombosis, immune response, inflammation, and angiogenesis. This review focuses on the adenosine-mediated regulation of lipid availability in the cell and in the systemic circulation as well in humans and animal models. Therefore, adenosine, mainly by acting on A1R, inhibits lipolysis activity, leading to reduction of the circulating fatty acid levels. This nucleoside can also participate in the early development of atherosclerosis by inhibiting the formation of foam cells via stimulation of cholesterol efflux through A2AR expressed on macrophages and reduction of the inflammatory process by activating A2AR and A2BR. Adenosine also appears to modulate intracellular cholesterol availability in Niemann-Pick type C1 disease and Alzheimer disease via A2AR and A3, respectively. Remarkably, the role of adenosine receptors in the regulation of plasma total cholesterol and triglyceride levels has been studied in animal models. Thus, an anti-atherogenic role for A2BR as well as a pro-atherogenic role of A2AR and A1 have been proposed; A3R has not been shown to participate in the control of lipid levels or the development of atherosclerosis. Surprisingly, and despite the role of A2A in the inhibition of foam cell formation among isolated cells, this receptor appears to be pro-atherogenic in mice. Remarkably, the role of adenosine receptors in human dyslipidaemia and atherosclerosis must to be elucidated. Additionally, it has been reported that increased lipid levels impair the effects of adenosine/adenosine receptors in controlling vascular tone, and we speculate on the possibility that this impairment could be due to alterations in the composition of the membrane microdomains where the adenosine receptors are located. Finally, a possible role for

  19. Nifedipine Treatment for Hypertension is Associated with Enhanced Lipolytic Activity and Accelerated Clearance of Postprandial Lipemia.

    PubMed

    Grosskopf, I; Shaish, A; Charach, G; Harats, D; Kamari, Y

    2016-04-01

    Hypertension, advanced age, postprandial hyperlipidemia, and insulin resistance are major risk factors for atherosclerosis. The calcium channel blocker nifedipine is reported to ameliorate insulin resistance possibly by activating PPARγ. This is expected to become accentuated in elderly individuals due to age-related insulin resistance. Insulin resistance modulates lipoprotein metabolism. Therefore, we reasoned that nifedipne offers the potential for improving postprandial lipemia in association with increasing age. We studied the effect of nifedipine on fasting lipids, postprandial lipemia, insulin sensitivity, and plasma lipolytic activity in 24 and 15 hypertensive subjects aged 70-75 years and 40-45 years, respectively. As expected, nifedipine significantly lowered systolic and diastolic blood pressure. Nifedipine decreased fasting triglyceride level (23%) and increased HDL-C (15%) in the elderly group. At baseline, postprandial triglyceride levels were remarkably elevated in elderly compared to younger patients (1 288±798 vs. 501±260 mg·dl(-1)·h, p<0.05), as was retinyl palmitate (surrogate marker for intestinally-derived cholesterol) in the chylomicrons (45.0±26.5 vs. 23.4±10.6 mg·l(-1)·h, p<0.05) and chylomicron remnant (15.2±5.4 vs. 11.7±4.7 mg·l(-1)·h, p<0.05) fractions. Importantly, while the level of chylomicron remnants in the group of younger subjects remained unchanged after treatment, nifedipine was associated with a significantly decreased chylomicron remnants retinyl palmitate in the elderly group, which dropped to levels, observed in younger subjects. This was accompanied by enhanced insulin sensitivity and augmented plasma lipolytic activity. The present work suggests that nifedipine has favorable metabolic effects that are beyond the known enhancement of insulin sensitivity. The improvement in postprandial lipidemia by nifedipine may add to its anti-atherogenic effects in hypertensive patients.

  20. Stratum corneum lipids serve as a bound-water modulator.

    PubMed

    Imokawa, G; Kuno, H; Kawai, M

    1991-06-01

    Stratum corneum lipids have been found to be an important determinant involved in the water-holding function of the stratum corneum. In order to further elucidate the significance of stratum corneum lipids in the water-holding properties, the hydration behavior of the stratum corneum following depletion and replenishment of the lipids has been studied, using an isolated human forearm stratum corneum sheet, by differential scanning calorimetry parallel to ultrastructural changes of intercellular lipids in the stratum corneum. Extraction of the stratum corneum sheet with acetone/ether (1/1) decreased the bound-water content from 33.3% to 19.7%, where the melting temperature of ice remained constant. Further extraction with water, which released a large amount of water-soluble materials such as amino acids, did not change the bound-water content, but definitely raised the melting temperature of ice. The application of the stratum corneum lipids, which were solubilized in squalane containing 1% alpha-monomethyl heptadecyl glyceryl ether to the lipid-depleted stratum corneum sheet, caused a significant recovery of bound-water content to the previous, almost normal level. In accordance with the hydration behavior, electron microscopic analysis of the acetone/ether-treated stratum corneum sheet revealed selective depletion of lipids from the intercellular spaces, accompanied by a marked disruption of multiple lamellar structures. In contrast, the application of stratum corneum lipids into the lipid-depleted stratum corneum sheet resulted in the restoration of the lamellar structure between the stratum corneum cells. These findings strongly suggest that stratum corneum lipids serve a water-holding function through the formation of lamellar structures within the stratum corneum.

  1. Curvature and Lipid Packing Modulate the Elastic Properties of Lipid Assemblies: Comparing HII and Lamellar Phases.

    PubMed

    Johner, Niklaus; Harries, Daniel; Khelashvili, George

    2014-12-04

    Accumulating evidence indicates that membrane reshaping and fusion processes, as well as regulation of membrane protein function, depend on lipid composition. Although it is widely accepted that cell membranes are under considerable stress and frustration and can be locally highly curved, experimental approaches to determine the material properties of lipids usually rely on their study in a relaxed environment or in flat bilayers. Here, we propose a computational method to determine the elastic properties of lipid assemblies of arbitrarily shaped interfaces and apply it to lipidic mixtures in the inverted hexagonal and lamellar phases. We find that the bending rigidity critically depends on the geometry of the system and correlates with the changes in lipid chain order imposed by the specific environment. Our results are relevant for resolving local lipid properties of deformed, stressed, or frustrated membranes that notably emerge around integral membrane proteins or during different membrane remodeling processes.

  2. Nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells

    PubMed Central

    Barbosa, João P; Neves, Ana R; Silva, Andreia M; Barbosa, Mário A; Reis, M Salette; Santos, Susana G

    2016-01-01

    Dendritic cells (DCs) are promising targets for drug delivery, as they can induce immunity or tolerance. The current study aims to examine the potential of using nanostructured lipid carriers (NLC) as delivery systems for human DC by evaluating nanoparticle internalization, cell labeling, and drug activity. NLC were formulated incorporating the fluorochrome fluorescein isothiocyanate (FITC-NLC) or the natural anti-inflammatory molecule resveratrol (rsv-NLC). Primary human DCs were differentiated from peripheral blood monocytes, and the innovative imaging flow cytometry technique was used to examine FITC-NLC internalization. The capacity of rsv-NLC to inhibit DC activation in response to proinflammatory cytokine tumor necrosis factor-α (TNF- α) was investigated by conventional flow cytometry. A combination of imaging and conventional flow cytometry was used to assess NLC cytotoxicity. The results obtained indicate that both NLC formulations were stable over time, with mean diameter <200 nm and highly negative zeta potential (about −30 mV). When DCs were placed in contact with NLC, imaging flow cytometry clearly showed that DCs efficiently internalized FITC-NLC, with nearly 100% of cells internalizing nanoparticles upon 1 hour of incubation. Both immature and mature DCs internalized NLC to high and comparable levels, and without cytotoxicity. Stimulating DC with TNF-α in the presence of rsv-NLC revealed that, using these nanoparticles, very small concentrations of rsv were sufficient to significantly decrease surface expression of activation marker CD83 (5 µM) and major histocompatibility complex-class II molecule human leukocyte antigen – antigen D related (10 µM), both upregulated in response to TNF-α stimulation. Rsv-NLC were compared with free rsv; at 5 µM, rsv-NLC were able to inhibit nuclear factor κ beta phosphorylation and significantly decrease the level of interleukin-12/23, both upregulated in response to TNF-α, while 10 µM free rsv were

  3. Melittin-Induced Lipid Extraction Modulated by the Methylation Level of Phosphatidylcholine Headgroups

    PubMed Central

    Therrien, Alexandre; Lafleur, Michel

    2016-01-01

    Protein- and peptide-induced lipid extraction from membranes is a critical process for many biological events, including reverse cholesterol transport and sperm capacitation. In this work, we examine whether such processes could display specificity for some lipid species. Melittin, the main component of dry bee venom, was used as a model amphipathic α-helical peptide. We specifically determined the modulation of melittin-induced lipid extraction from membranes by the change of the methylation level of phospholipid headgroups. Phosphatidylcholine (PC) bilayers were demethylated either by substitution with phosphatidylethanolamine (PE) or chemically by using mono- and dimethylated PE. It is shown that demethylation reduces the association of melittin with membranes, likely because of the resulting tighter chain packing of the phospholipids, which reduces the capacity of the membranes to accommodate inserted melittin. This reduced binding of the peptide is accompanied by an inhibition of the lipid extraction caused by melittin. We demonstrate that melittin selectively extracts PC from PC/PE membranes. This selectivity is proposed to be a consequence of a PE depletion in the surroundings of bound melittin to minimize disruption of the interphospholipid interactions. The resulting PC-enriched vicinity of melittin would be responsible for the observed formation of PC-enriched lipid/peptide particles resulting from the lipid efflux. These findings reveal that modulating the methylation level of phospholipid headgroups is a simple way to control the specificity of lipid extraction from membranes by peptides/proteins and thereby modulate the lipid composition of the membranes. PMID:26789763

  4. The Tumor Microenvironment Modulates Choline and Lipid Metabolism

    PubMed Central

    Mori, Noriko; Wildes, Flonné; Takagi, Tomoyo; Glunde, Kristine; Bhujwalla, Zaver M.

    2016-01-01

    An increase of cellular phosphocholine (PC) and total choline (tCho)-containing compounds as well as alterations in lipids have been consistently observed in cancer cells and tissue. These metabolic changes are closely related to malignant transformation, invasion, and metastasis. The study of cancer cells in culture plays an important role in understanding mechanisms leading to altered choline (Cho) and lipid metabolism in cancer, as it provides a carefully controlled environment. However, a solid tumor is a complex system with a unique tumor microenvironment frequently containing hypoxic and acidic regions and areas of nutrient deprivation and necrosis. Cancer cell–stromal cell interactions and the extracellular matrix may also alter Cho and lipid metabolism. Human tumor xenograft models in mice are useful to mimic the growth of human cancers and provide insights into the influence of in vivo conditions on metabolism. Here, we have compared metabolites, obtained with high resolution 1H MRS of extracts from human breast and prostate cancer cells in a 2-dimensional (2D) monolayer culture and from solid tumor xenografts derived from these cells, as well as the protein expression of enzymes that regulate Cho and lipid metabolism. Our data demonstrate significant differences in Cho and lipid metabolism and protein expression patterns between human breast and prostate cancer cells in culture and in tumors derived from these cells. These data highlight the influence of the tumor microenvironment on Cho and lipid metabolism. PMID:28066718

  5. The modulating effects of propofol and its lipid carrier on canine neutrophil functions

    PubMed Central

    SATO, Reeko; AOKI, Takuma; KOBAYASHI, Saori; UCHIDA, Naohiro; SIMAMURA, Shunsuke; YAMASAKI, Masahiro

    2016-01-01

    Propofol (2,6-diisopropylphenol), being used as an intravenous sedative and anesthetic agent, influences not only upon nervous system but also for host inflammatory response through modulating neutrophil functions. This study is designed to evaluate the modulating effects of propofol and its lipid carrier administration at clinically relevant rate on canine neutrophil functions. Clinically healthy beagle dogs were received propofol (8.8 mg/kg) from cephalic vein and maintained with propofol dropping infusion (26.4 mg/kg/hr). Blood samples were collected from the dogs before infusion and 30 min after the start of propofol administration, and neutrophil functions were evaluated. The dogs were also administered lipid carrier, and neutrophil functions were evaluated in the same manner as propofol administration. Peripheral white blood cell and neutrophil counts decreased after the propofol or lipid carrier administration. The administration of propofol or lipid carrier significantly reduced neutrophil adherence ability. The superoxide production of neutrophils was measured by luminol-dependent chemiluminescence response using with opsonized zymosan. Peak height of neutrophil chemiluminescence curve was reduced by propofol and lipid carrier administration, on the contrary, peak time of neutrophil chemiluminescence curve was delayed. Administration of propofol or lipid carrier also reduced neutrophil adherence ability to nylon fibers. In the present study, we showed the modulating effects of propofol and its lipid carrier on canine neutrophil functions. However, there was no significant difference in the modulating effects between propofol group and lipid carrier group. Therefore, the modulating effects observed here were deeply concerned in lipid carrier administration. PMID:27665993

  6. Membrane proteins bind lipids selectively to modulate their structure and function

    PubMed Central

    Allison, Timothy M.; Ulmschneider, Martin B.; Degiacomi, Matteo T.; Baldwin, Andrew J.; Robinson, Carol V.

    2014-01-01

    Previous studies have established that the folding, structure and function of membrane proteins are influenced by their lipid environments1-7 and that lipids can bind to specific sites, for example in potassium channels8. Fundamental questions remain however regarding the extent of membrane protein selectivity toward lipids. Here we report a mass spectrometry (MS) approach designed to determine the selectivity of lipid binding to membrane protein complexes. We investigate the mechanosensitive channel of large conductance (MscL), aquaporin Z (AqpZ), and the ammonia channel (AmtB) using ion mobility MS (IM-MS), which reports gas-phase collision cross sections. We demonstrate that folded conformations of membrane protein complexes can exist in the gas-phase. By resolving lipid-bound states we then rank bound lipids based on their ability to resist gas phase unfolding and thereby stabilize membrane protein structure. Results show that lipids bind non-selectively and with high avidity to MscL, all imparting comparable stability, the highest-ranking lipid however is phosphatidylinositol phosphate, in line with its proposed functional role in mechanosensation9. AqpZ is also stabilized by many lipids with cardiolipin imparting the most significant resistance to unfolding. Subsequently, through functional assays, we discover that cardiolipin modulates AqpZ function. Analogous experiments identify AmtB as being highly selective for phosphatidylglycerol prompting us to obtain an X-ray structure in this lipid membrane-like environment. The 2.3Å resolution structure, when compared with others obtained without lipid bound, reveals distinct conformational changes that reposition AmtB residues to interact with the lipid bilayer. Overall our results demonstrate that resistance to unfolding correlates with specific lipid-binding events enabling distinction of lipids that merely bind from those that modulate membrane protein structure and/or function. We anticipate that these

  7. Salt modulates the stability and lipid binding affinity of the adipocyte lipid-binding proteins

    NASA Technical Reports Server (NTRS)

    Schoeffler, Allyn J.; Ruiz, Carmen R.; Joubert, Allison M.; Yang, Xuemei; LiCata, Vince J.

    2003-01-01

    Adipocyte lipid-binding protein (ALBP or aP2) is an intracellular fatty acid-binding protein that is found in adipocytes and macrophages and binds a large variety of intracellular lipids with high affinity. Although intracellular lipids are frequently charged, biochemical studies of lipid-binding proteins and their interactions often focus most heavily on the hydrophobic aspects of these proteins and their interactions. In this study, we have characterized the effects of KCl on the stability and lipid binding properties of ALBP. We find that added salt dramatically stabilizes ALBP, increasing its Delta G of unfolding by 3-5 kcal/mol. At 37 degrees C salt can more than double the stability of the protein. At the same time, salt inhibits the binding of the fluorescent lipid 1-anilinonaphthalene-8-sulfonate (ANS) to the protein and induces direct displacement of the lipid from the protein. Thermodynamic linkage analysis of the salt inhibition of ANS binding shows a nearly 1:1 reciprocal linkage: i.e. one ion is released from ALBP when ANS binds, and vice versa. Kinetic experiments show that salt reduces the rate of association between ANS and ALBP while simultaneously increasing the dissociation rate of ANS from the protein. We depict and discuss the thermodynamic linkages among stability, lipid binding, and salt effects for ALBP, including the use of these linkages to calculate the affinity of ANS for the denatured state of ALBP and its dependence on salt concentration. We also discuss the potential molecular origins and potential intracellular consequences of the demonstrated salt linkages to stability and lipid binding in ALBP.

  8. Salt modulates the stability and lipid binding affinity of the adipocyte lipid-binding proteins

    NASA Technical Reports Server (NTRS)

    Schoeffler, Allyn J.; Ruiz, Carmen R.; Joubert, Allison M.; Yang, Xuemei; LiCata, Vince J.

    2003-01-01

    Adipocyte lipid-binding protein (ALBP or aP2) is an intracellular fatty acid-binding protein that is found in adipocytes and macrophages and binds a large variety of intracellular lipids with high affinity. Although intracellular lipids are frequently charged, biochemical studies of lipid-binding proteins and their interactions often focus most heavily on the hydrophobic aspects of these proteins and their interactions. In this study, we have characterized the effects of KCl on the stability and lipid binding properties of ALBP. We find that added salt dramatically stabilizes ALBP, increasing its Delta G of unfolding by 3-5 kcal/mol. At 37 degrees C salt can more than double the stability of the protein. At the same time, salt inhibits the binding of the fluorescent lipid 1-anilinonaphthalene-8-sulfonate (ANS) to the protein and induces direct displacement of the lipid from the protein. Thermodynamic linkage analysis of the salt inhibition of ANS binding shows a nearly 1:1 reciprocal linkage: i.e. one ion is released from ALBP when ANS binds, and vice versa. Kinetic experiments show that salt reduces the rate of association between ANS and ALBP while simultaneously increasing the dissociation rate of ANS from the protein. We depict and discuss the thermodynamic linkages among stability, lipid binding, and salt effects for ALBP, including the use of these linkages to calculate the affinity of ANS for the denatured state of ALBP and its dependence on salt concentration. We also discuss the potential molecular origins and potential intracellular consequences of the demonstrated salt linkages to stability and lipid binding in ALBP.

  9. The effect of consuming low- versus high-glycemic index meals after exercise on postprandial blood lipid response following a next-day high-fat meal

    PubMed Central

    Kaviani, M; Chilibeck, P D; Yee, P; Zello, G A

    2016-01-01

    Background/Objectives: Exercise performed shortly before (that is, within half a day of) a high-fat meal is beneficial for stimulating fat oxidation after the meal and reducing postprandial triglycerides (TG). This benefit of exercise is unfortunately negated if the after-exercise food choice to replace the calories expended during exercise is one containing high-glycemic index (HGI) carbohydrates. We determined the effect of consuming low-glycemic index (LGI) carbohydrates after an exercise session on fat oxidation and TG after a subsequent high-fat meal. Subjects/Methods: Using a randomized, counterbalanced crossover design, 23 overweight or obese individuals (body mass index ⩾25 kg m−2) performed: walking exercise (90 min) at 1800 h followed by no meal (EX); exercise followed by a meal with LGI carbohydrates (that is, lentils, EX-LGI); exercise followed by a meal with HGI carbohydrates (that is, instant potatoes, white bread, EX-HGI); and a control condition with no exercise or meal. After a 10-h overnight fast, participants were given a standardized high-fat meal. Fat oxidation was estimated before and for 6 h after this meal from respiratory gas measures and TG determined from blood samples. Results: Fat oxidation (mean±s.d.) was higher with EX (6.9±1.7 g h−1) than EX-HGI (6.3±1.6 g h−1; P=0.007) and Control (5.9±1.7 g h−1; P=0.00002), and EX-LGI (6.6±1.7 g h−1) was higher than Control (P=0.002). TG total area under the curve was 18–32% lower with EX and EX-LGI compared with control (P=0.0005 and P=0.0001, respectively) and EX-HGI (P=0.05 and P=0.021, respectively). Conclusions: A meal containing HGI carbohydrates consumed after an evening exercise session cancels the beneficial effect of exercise for stimulating fat oxidation and lowering TG after a subsequent high-fat meal, whereas consuming a post-exercise meal with LGI carbohydrates retains the positive effect of exercise. PMID:27376698

  10. Towards understanding the molecular basis of ion channel modulation by lipids: Mechanistic models and current paradigms.

    PubMed

    Poveda, José A; Marcela Giudici, A; Lourdes Renart, M; Morales, Andrés; González-Ros, José M

    2017-09-01

    Research on ion channel modulation has become a hot topic because of the key roles these membrane proteins play in both prokaryotic and eukaryotic organisms. In this respect, lipid modulation adds to the overall modulatory mechanisms as a potential via to find new pharmacological targets for drug design based on interfering with lipid/channel interactions. However, our knowledge in this field is scarce and often circumscribed to the sites where lipids bind and/or its final functional consequences. To fully understand this process it is necessary to improve our knowledge on its molecular basis, from the binding sites to the signalling pathways that derive in structural and functional effects on the ion channel. In this review, we have compiled information about such mechanisms and established a classification into four different modes of action. Afterwards, we have revised in more detail the lipid modulation of Cys-loop receptors and of the potassium channel KcsA, which were chosen as model channels modulated by specific lipids. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Wolbachia Modulates Lipid Metabolism in Aedes albopictus Mosquito Cells

    PubMed Central

    Molloy, Jennifer C.; Sommer, Ulf; Viant, Mark R.

    2016-01-01

    ABSTRACT Certain strains of the intracellular endosymbiont Wolbachia can strongly inhibit or block the transmission of viruses such as dengue virus (DENV) by Aedes mosquitoes, and the mechanisms responsible are still not well understood. Direct infusion and liquid chromatography-Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry-based lipidomics analyses were conducted using Aedes albopictus Aa23 cells that were infected with the wMel and wMelPop strains of Wolbachia in comparison to uninfected Aa23-T cells. Substantial shifts in the cellular lipid profile were apparent in the presence of Wolbachia. Most significantly, almost all sphingolipid classes were depleted, and some reductions in diacylglycerols and phosphatidylcholines were also observed. These lipid classes have previously been shown to be selectively enriched in DENV-infected mosquito cells, suggesting that Wolbachia may produce a cellular lipid environment that is antagonistic to viral replication. The data improve our understanding of the intracellular interactions between Wolbachia and mosquitoes. IMPORTANCE Mosquitoes transmit a variety of important viruses to humans, such as dengue virus and Zika virus. Certain strains of the intracellular bacterial genus called Wolbachia found in or introduced into mosquitoes can block the transmission of viruses, including dengue virus, but the mechanisms responsible are not well understood. We found substantial shifts in the cellular lipid profiles in the presence of these bacteria. Some lipid classes previously shown to be enriched in dengue virus-infected mosquito cells were depleted in the presence of Wolbachia, suggesting that Wolbachia may produce a cellular lipid environment that inhibits mosquito-borne viruses. PMID:26994075

  12. Membrane lipids are key modulators of the endocannabinoid-hydrolase FAAH.

    PubMed

    Dainese, Enrico; De Fabritiis, Gianni; Sabatucci, Annalaura; Oddi, Sergio; Angelucci, Clotilde Beatrice; Di Pancrazio, Chiara; Giorgino, Toni; Stanley, Nathaniel; Del Carlo, Michele; Cravatt, Benjamin F; Maccarrone, Mauro

    2014-02-01

    Lipid composition is expected to play an important role in modulating membrane enzyme activity, in particular if the substrates are themselves lipid molecules. A paradigmatic case is FAAH (fatty acid amide hydrolase), an enzyme critical in terminating endocannabinoid signalling and an important therapeutic target. In the present study, using a combined experimental and computational approach, we show that membrane lipids modulate the structure, subcellular localization and activity of FAAH. We report that the FAAH dimer is stabilized by the lipid bilayer and shows a higher membrane-binding affinity and enzymatic activity within membranes containing both cholesterol and the natural FAAH substrate AEA (anandamide). Additionally, co-localization of cholesterol, AEA and FAAH in mouse neuroblastoma cells suggests a mechanism through which cholesterol increases the substrate accessibility of FAAH.

  13. Modulation of therapy-induced senescence by reactive lipid aldehydes

    PubMed Central

    Flor, A C; Doshi, A P; Kron, S J

    2016-01-01

    Current understanding points to unrepairable chromosomal damage as the critical determinant of accelerated senescence in cancer cells treated with radiation or chemotherapy. Nonetheless, the potent senescence inducer etoposide not only targets topoisomerase II to induce DNA damage but also produces abundant free radicals, increasing cellular reactive oxygen species (ROS). Toward examining roles for DNA damage and oxidative stress in therapy-induced senescence, we developed a quantitative flow cytometric senescence assay and screened 36 redox-active agents as enhancers of an otherwise ineffective dose of radiation. While senescence failed to correlate with total ROS, the radiation enhancers, etoposide and the other effective topoisomerase inhibitors each produced high levels of lipid peroxidation. The reactive aldehyde 4-hydroxy-2-nonenal, a lipid peroxidation end product, was sufficient to induce senescence in irradiated cells. In turn, sequestering aldehydes with hydralazine blocked effects of etoposide and other senescence inducers. These results suggest that lipid peroxidation potentiates DNA damage from radiation and chemotherapy to drive therapy-induced senescence. PMID:27453792

  14. Modulation of a membrane lipid lamellar-nonlamellar phase transition by cationic lipids: A measure for transfection efficiency

    SciTech Connect

    Tenchov, Boris G; Wang, Li; Koynova, Rumiana; MacDonald, Robert C

    2010-01-18

    Synthetic cationic lipids can be used as DNA carriers and are regarded to be the most promising non-viral gene carriers. For this investigation, six novel phosphatidylcholine (PC) cationic derivatives with various hydrophobic moieties were synthesized and their transfection efficiencies for human umbilical artery endothelial cells (HUAEC) were determined. Three compounds with relatively short, myristoleoyl or myristelaidoyl 14:1 chains exhibited very high activity, exceeding by {approx}10 times that of the reference cationic derivative dioleoyl ethylPC (EDOPC). Noteworthy, cationic lipids with 14:1 hydrocarbon chains have not been tested as DNA carriers in transfection assays previously. The other three lipids, which contained oleoyl 18:1 and longer chains, exhibited moderate to weak transfection activity. Transfection efficiency was found to correlate strongly with the effect of the cationic lipids on the lamellar-to-inverted hexagonal, L{sub {alpha}} {yields} H{sub II}, phase conversion in dipalmitoleoyl phosphatidylethanolamine dispersions (DPoPE). X-ray diffraction on binary DPoPE/cationic lipid mixtures showed that the superior transfection agents eliminated the direct L{sub {alpha}} {yields} H{sub II} phase transition and promoted formation of an inverted cubic phase between the L{sub {alpha}} and H{sub II} phases. In contrast, moderate and weak transfection agents retained the direct L{sub {alpha}} {yields} H{sub II} transition but shifted to higher temperatures than that of pure DPoPE, and induced cubic phase formation at a later stage. On the basis of current models of lipid membrane fusion, promotion of a cubic phase by the high-efficiency agents may be considered as an indication that their high transfection activity results from enhanced lipoplex fusion with cellular membranes. The distinct, well-expressed correlation established between transfection efficiency of a cationic lipid and the way it modulates nonlamellar phase formation of a membrane lipid

  15. The WWOX Gene Modulates HDL and Lipid Metabolism

    PubMed Central

    Iatan, Iulia; Choi, Hong Y.; Ruel, Isabelle; Linga Reddy, M.V. Prasad; Kil, Hyunsuk; Lee, Jaeho; Abu Odeh, Mohammad; Salah, Zaidoun; Abu-Remaileh, Muhannad; Weissglas-Volkov, Daphna; Nikkola, Elina; Civelek, Mete; Awan, Zuhier; Croce, Carlo M.; Aqeilan, Rami I.; Pajukanta, Päivi; Aldaz, C. Marcelo; Genest, Jacques

    2014-01-01

    Background Low high-density lipoprotein-cholesterol (HDL-C) constitutes a major risk factor for atherosclerosis. Recent studies from our group reported a genetic association between the WW domain-containing oxidoreductase (WWOX) gene and HDL-C levels. Here, through next-generation resequencing, in vivo functional studies and gene microarray analyses, we investigated the role of WWOX in HDL and lipid metabolism. Methods and Results Using next-generation resequencing of the WWOX region, we first identified 8 variants significantly associated and perfectly segregating with the low-HDL trait in two multi-generational French Canadian dyslipidemic families. To understand in vivo functions of WWOX, we used liver-specific Wwoxhep−/− and total Wwox−/− mice models, where we found decreased ApoA-I and ABCA1 levels in hepatic tissues. Analyses of lipoprotein profiles in Wwox−/−, but not Wwox hep−/− littermates, also showed marked reductions in serum HDL-C concentrations, concordant with the low-HDL findings observed in families. We next obtained evidence of a gender-specific effect in female Wwoxhep−/− mice, where an increase in plasma triglycerides and altered lipid metabolic pathways by microarray analyses were observed. We further identified a significant reduction in ApoA-I and LPL, and upregulation in Fas, Angptl4 and Lipg, suggesting that the effects of Wwox involve multiple pathways, including cholesterol homeostasis, ApoA-I/ABCA1 pathway, and fatty acid biosynthesis/triglyceride metabolism. Conclusions Our data indicate that WWOX disruption alters HDL and lipoprotein metabolism through several mechanisms and may account for the low-HDL phenotype observed in families expressing the WWOX variants. These findings thus describe a novel gene involved in cellular lipid homeostasis, which effects may impact atherosclerotic disease development. PMID:24871327

  16. Clofazimine modulates the expression of lipid metabolism proteins in Mycobacterium leprae-infected macrophages.

    PubMed

    Degang, Yang; Akama, Takeshi; Hara, Takeshi; Tanigawa, Kazunari; Ishido, Yuko; Gidoh, Masaichi; Makino, Masahiko; Ishii, Norihisa; Suzuki, Koichi

    2012-01-01

    Mycobacterium leprae (M. leprae) lives and replicates within macrophages in a foamy, lipid-laden phagosome. The lipids provide essential nutrition for the mycobacteria, and M. leprae infection modulates expression of important host proteins related to lipid metabolism. Thus, M. leprae infection increases the expression of adipophilin/adipose differentiation-related protein (ADRP) and decreases hormone-sensitive lipase (HSL), facilitating the accumulation and maintenance of lipid-rich environments suitable for the intracellular survival of M. leprae. HSL levels are not detectable in skin smear specimens taken from leprosy patients, but re-appear shortly after multidrug therapy (MDT). This study examined the effect of MDT components on host lipid metabolism in vitro, and the outcome of rifampicin, dapsone and clofazimine treatment on ADRP and HSL expression in THP-1 cells. Clofazimine attenuated the mRNA and protein levels of ADRP in M. leprae-infected cells, while those of HSL were increased. Rifampicin and dapsone did not show any significant effects on ADRP and HSL expression levels. A transient increase of interferon (IFN)-β and IFN-γ mRNA was also observed in cells infected with M. leprae and treated with clofazimine. Lipid droplets accumulated by M. leprae-infection were significantly decreased 48 h after clofazimine treatment. Such effects were not evident in cells without M. leprae infection. In clinical samples, ADRP expression was decreased and HSL expression was increased after treatment. These results suggest that clofazimine modulates lipid metabolism in M. leprae-infected macrophages by modulating the expression of ADRP and HSL. It also induces IFN production in M. leprae-infected cells. The resultant decrease in lipid accumulation, increase in lipolysis, and activation of innate immunity may be some of the key actions of clofazimine.

  17. Postprandial Paraoxonase 1 Activity Following Consumption of Recommended Amounts of Mixed Meals in Healthy Males.

    PubMed

    Kameyama, Noriko; Maruyama, Chizuko; Kotani, Kazuhiko; Caccavello, Russell; Gugliucci, Alejandro; Matsui, Sadako; Araki, Risa; Maruyama, Taro

    2016-01-01

    Postprandial lipid level increases induce oxidative stress, which is involved in atherogenesis. The antioxidant properties of paraoxonase 1 (PON1) have attracted attention. However, changes in postprandial PON1 levels differ across prior studies, and changes in PON1 lactonase activity, potentially relevant to PON1 physiology, after the consumption of ordinary meals are unknown. Herein we evaluated postprandial serum lipid levels and PON1 changes following mixed-meal consumption of the amounts recommended for ordinary meals. Nine healthy male volunteers consumed three different meals in a randomized cross-over design. The test meals were as follows: S, white rice; SMF, S with fat-containing protein-rich main dishes; and SMFV: SMF with vegetable dishes. The serum lipid concentrations and PON1 lactonase and arylesterase activities were determined during a three-hour period after the consumption of these meals. The postprandial triglyceride levels were higher after consuming the SMF and SMFV meals than after consuming the S meal. Despite postprandial high-density lipoprotein cholesterol being unchanged, PON1 lactonase activity was decreased, while PON1 arylesterase activity was increased in the postprandial state after all test meals. Postprandial changes in lactonase and arylesterase activities did not differ among the test meals. Inverse changes in PON1 lactonase and arylesterase activities were observed after consuming recommended ordinary meals. This observation provides useful information for choosing PON1 species as postprandial markers.

  18. Dimethyl fumarate modulates antioxidant and lipid metabolism in oligodendrocytes.

    PubMed

    Huang, He; Taraboletti, Alexandra; Shriver, Leah P

    2015-08-01

    Oxidative stress contributes to pathology associated with inflammatory brain disorders and therapies that upregulate antioxidant pathways may be neuroprotective in diseases such as multiple sclerosis. Dimethyl fumarate, a small molecule therapeutic for multiple sclerosis, activates cellular antioxidant signaling pathways and may promote myelin preservation. However, it is still unclear what mechanisms may underlie this neuroprotection and whether dimethyl fumarate affects oligodendrocyte responses to oxidative stress. Here, we examine metabolic alterations in oligodendrocytes treated with dimethyl fumarate by using a global metabolomic platform that employs both hydrophilic interaction liquid chromatography-mass spectrometry and shotgun lipidomics. Prolonged treatment of oligodendrocytes with dimethyl fumarate induces changes in citric acid cycle intermediates, glutathione, and lipids, indicating that this compound can directly impact oligodendrocyte metabolism. These metabolic alterations are also associated with protection from oxidant challenge. This study provides insight into the mechanisms by which dimethyl fumarate could preserve myelin integrity in patients with multiple sclerosis.

  19. Oleaster oil positively modulates plasma lipids in humans.

    PubMed

    Belarbi, Meriem; Bendimerad, Soraya; Sour, Souad; Soualem, Zoubida; Baghdad, Choukri; Hmimed, Sara; Chemat, Farid; Visioli, Francesco

    2011-08-24

    The olive tree had been domesticated during the early Neolithic in the Near East, and more than 1000 different cultivars have been identified to date. However, examples of wild olive trees (Olea europaea oleaster) can still be found in the Mediterranean basin. Evidence of oleaster use for oil production can be found in historical and sacred texts, such as the Odyssey, the Holey Koran, and the Holey Bible. While the nutritional and healthful properties of olive oil are actively being explored, there are no data on the human actions of oleaster oil. Therefore, we investigated the effect of prolonged, i.e., 1 month, consumption of oleaster oil on the lipid profile of a 40 healthy Algerian subjects (aged 27.9 ± 3.85 years), as compared to nonconsumers from the same area. Plasma urea, creatinine, and uric acid concentrations and glycemia did not significantly differ, at the end of the study, between controls and oleaster-oil-supplemented subjects. Conversely, we recorded significant decreases of plasma triglyceride concentration (-24.8%; p < 0.05), total cholesterol (-12.13%; p < 0.05), and low-density lipoprotein-cholesterol (LDL-C) (-24.39%; p < 0.05) in oleaster-oil-treated subjects. Concomitantly, high-density lipoprotein-cholesterol (HDL-C) concentrations were significantly increased (17.94%; p < 0.05) by oleaster oil administration. In conclusion, we show that oil obtained from feral olive trees, i.e., oleasters, improves the plasma lipid profile of healthy volunteers.

  20. Can exercise minimize postprandial oxidative stress in patients with type 2 diabetes?

    PubMed

    Tucker, Patrick S; Fisher-Wellman, Kelsey; Bloomer, Richard J

    2008-11-01

    It has recently been estimated by the American Diabetes Association that 21 million Americans, or about 7% of the U.S. population, have diabetes, while an additional 54 million Americans have pre-diabetes. The onset and progression of these disorders and related complications are linked to impairments in glucose and lipid metabolism, both of which are associated with increased production of reactive oxygen and nitrogen species (RONS). Increased RONS production coupled with impaired antioxidant defense (a common finding among patients with diabetes) promotes oxidation of specific biomolecules (lipid, protein, DNA), which can lead to an exacerbation of diabetic complications. While bloodborne variables related to these disorders have traditionally been measured in a fasted state, increasing evidence suggests that measurement of postprandial glycemia, lipemia, and oxidative stress may provide more important clinical information concerning an individual's susceptibility to diabetes onset and disease progression. While drugs to treat hyperglycemia and hyperlipidemia have been reported in some studies to promote favorable outcomes related to attenuating the postprandial rise in blood glucose and triglycerides, one non-pharmaceutical approach which may have promise is the performance of regular exercise. Both acute and chronic exercise may aid in attenuating postprandial oxidative stress in three distinct ways. First, exercise stimulates an increase in endogenous antioxidant enzyme activity. Second, exercise improves blood glucose clearance via enhanced GLUT 4 translocation and protein content, as well as enhanced insulin-insulin receptor binding and post-receptor signaling. Third, exercise improves blood triglyceride clearance via a reduced chylomicron-triglyceride half-life and enhanced lipoprotein lipase activity. In this article we provide evidence for the potential role of exercise in modulating postprandial oxidative stress in diabetic and pre-diabetic individuals

  1. Increased Plasma Availability of L-arginine in the Postprandial Period Decreases the Postprandial Lipemia in Older Adults

    PubMed Central

    Puga, Guilherme M.; Meyer, Christian; Mandarino, Lawrence J.; Katsanos, Christos S.

    2012-01-01

    Objective Older adults have exaggerated postprandial lipemia (PPL), which increases their risk for cardiovascular disease. We sought to determine the effects of increased plasma L-arginine availability on the oxidation of ingested fat (enriched with [1,1,1-13C]-triolein) and plasma triglyceride (TG) concentrations during the postprandial period in older subjects. Methods On one day, eight healthy subjects (67.8 ± 1.3 years old) received an intravenous infusion of L-arginine during the first hour of the postprandial period (L-ARG), while on a separate day they received saline (control trial; CON). Results The 8-h area under the curve (AUC0–8h) describing the postprandial plasma TG concentrations was considerably lower in the L-ARG trial than the CON trial (−4 ± 21 vs 104 ± 21 mg·dL−1·h; P < 0.01). The rate of the postprandial oxidation of the ingested lipid was not different between the trials, but the average contribution of ingested-oleate to the oleate of TG of the plasma small TG-rich lipoproteins (TRL; Sf = 20–400) was lower in the L-ARG trial (11 ± 1 vs 18 ± 2%; P < 0.01). L-arginine infusion decreased also the AUC0–8h of the plasma free fatty acid concentrations derived from the ingested fat when compared to the saline infusion (0.77±0.09 vs 1.11 ± 0.08; mmol·L−1·h; P < 0.01). Conclusion Increasing the plasma L-arginine availability during the postprandial period decreases the PPL in older adults, in association with a decrease in the postprandial contribution of ingested lipid into TG of the plasma small TRL. PMID:22959634

  2. Modulation of concentration fluctuations in phase-separated lipid membranes by polypeptide insertion.

    PubMed Central

    Fahsel, S; Pospiech, E-M; Zein, M; Hazlet, T L; Gratton, E; Winter, Roland

    2002-01-01

    The lateral membrane organization and phase behavior of the binary lipid mixture DMPC (1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine) - DSPC (1,2-distearoyl-sn-glycero-3-phosphatidylcholine) without and with incorporated gramicidin D (GD) as a model biomembrane polypeptide was studied by small-angle neutron scattering, Fourier-transform infrared spectroscopy, and by two-photon excitation fluorescence microscopy on giant unilamellar vesicles. The small-angle neutron scattering method allows the detection of concentration fluctuations in the range from 1 to 200 nm. Fluorescence microscopy was used for direct visualization of the lateral lipid organization and domain shapes on a micrometer length scale including information of the lipid phase state. In the fluid-gel coexistence region of the pure binary lipid system, large-scale concentration fluctuations appear. Infrared spectral parameters were used to determine the peptide conformation adopted in the different lipid phases. The data show that the structure of the temperature-dependent lipid phases is significantly altered by the insertion of 2 to 5 mol% GD. At temperatures corresponding to the gel-fluid phase coexistence region the concentration fluctuations drastically decrease, and we observe domains in the giant unilamellar vesicles, which mainly disappear by the incorporation of 2 to 5 mol% GD. Further, the lipid matrix has the ability to modulate the conformation of the inserted polypeptide. The balance between double-helical and helical dimer structures of GD depends on the phospholipid chain length and phase state. A large hydrophobic mismatch, such as in gel phase one-component DSPC bilayers, leads to an increase in population of double-helical structures. Using an effective molecular sorting mechanism, a large hydrophobic mismatch can be avoided in the DMPC-DSPC lipid mixture, which leads to significant changes in the heterogeneous lipid structure and in polypeptide conformation. PMID:12080124

  3. Methanothermobacter thermautotrophicus modulates its membrane lipids in response to hydrogen and nutrient availability

    PubMed Central

    Yoshinaga, Marcos Y.; Gagen, Emma J.; Wörmer, Lars; Broda, Nadine K.; Meador, Travis B.; Wendt, Jenny; Thomm, Michael; Hinrichs, Kai-Uwe

    2015-01-01

    Methanothermobacter thermautotrophicus strain ΔH is a model hydrogenotrophic methanogen, for which extensive biochemical information, including the complete genome sequence, is available. Nevertheless, at the cell membrane lipid level, little is known about the responses of this archaeon to environmental stimuli. In this study, the lipid composition of M. thermautotrophicus was characterized to verify how this archaeon modulates its cell membrane components during growth phases and in response to hydrogen depletion and nutrient limitation (potassium and phosphate). As opposed to the higher abundance of phospholipids in the stationary phase of control experiments, cell membranes under nutrient, and energy stress were dominated by glycolipids that likely provided a more effective barrier against ion leakage. We also identified particular lipid regulatory mechanisms in M. thermautotrophicus, which included the accumulation of polyprenols under hydrogen-limited conditions and an increased content of sodiated adducts of lipids in nutrient-limited cells. These findings suggest that M. thermautotrophicus intensely modulates its cell membrane lipid composition to cope with energy and nutrient availability in dynamic environments. PMID:25657645

  4. A Two-Stage Model for Lipid Modulation of the Activity of Integral Membrane Proteins

    PubMed Central

    Dodes Traian, Martín M.; Cattoni, Diego I.; Levi, Valeria; González Flecha, F. Luis

    2012-01-01

    Lipid-protein interactions play an essential role in the regulation of biological function of integral membrane proteins; however, the underlying molecular mechanisms are not fully understood. Here we explore the modulation by phospholipids of the enzymatic activity of the plasma membrane calcium pump reconstituted in detergent-phospholipid mixed micelles of variable composition. The presence of increasing quantities of phospholipids in the micelles produced a cooperative increase in the ATPase activity of the enzyme. This activation effect was reversible and depended on the phospholipid/detergent ratio and not on the total lipid concentration. Enzyme activation was accompanied by a small structural change at the transmembrane domain reported by 1-aniline-8-naphtalenesulfonate fluorescence. In addition, the composition of the amphipilic environment sensed by the protein was evaluated by measuring the relative affinity of the assayed phospholipid for the transmembrane surface of the protein. The obtained results allow us to postulate a two-stage mechanistic model explaining the modulation of protein activity based on the exchange among non-structural amphiphiles at the hydrophobic transmembrane surface, and a lipid-induced conformational change. The model allowed to obtain a cooperativity coefficient reporting on the efficiency of the transduction step between lipid adsorption and catalytic site activation. This model can be easily applied to other phospholipid/detergent mixtures as well to other membrane proteins. The systematic quantitative evaluation of these systems could contribute to gain insight into the structure-activity relationships between proteins and lipids in biological membranes. PMID:22723977

  5. Protein type and caloric density of protein supplements modulate postprandial amino acid profile through changes in gastrointestinal behaviour: A randomized trial.

    PubMed

    Luiking, Yvette C; Abrahamse, Evan; Ludwig, Thomas; Boirie, Yves; Verlaan, Sjors

    2016-02-01

    The requirement of leucine and essential amino acids (EAA) to stimulate muscle protein synthesis increases with age. To target muscle anabolism it is suggested that higher postprandial blood levels of leucine and EAA are needed in older people. The aim was to evaluate the impact of oral nutritional supplements with distinct protein source and energy density, resembling mixed meals, on serum amino acid profiles and on gastrointestinal behaviour. Four iso-nitrogenous protein (21 g) supplements were studied containing leucine-enriched whey protein with 150/320 kcal (W150/W320) or casein protein with 150/320 kcal (C150/C320); all products contained carbohydrates (10 or 32 g) and fat (3 or 12 g). Postprandial serum AA profiles were evaluated in twelve healthy, older subjects who participated in a randomized, controlled, single blind, cross-over study. Gastrointestinal behaviour was studied in vitro by looking at gastric coagulation and cumulative intestinal protein digestion over time. The peak serum leucine concentration was twofold higher for W150 vs. C150 (521 ± 15 vs. 260 ± 15 μmol/L, p < 0.001), higher for W320 vs. C320 (406 ± 15 vs. 228 ± 15 μmol/L, p < 0.001), and higher for low-caloric vs. high-caloric products (p < 0.001 for pooled analyses; p < 0.001 for interaction protein source*caloric density). Similar effects were observed for the peak concentrations of EAA and total AA (TAA). In vitro gastric coagulation was observed only for the casein protein supplements. Intestinal digestion for 90 min resulted in higher levels of free TAA, EAA, and leucine for W150 vs. C150, for W150 vs. W320, and for C150 vs. C320 (p < 0.0125). A low caloric leucine-enriched whey protein nutritional supplement provides a higher rise in serum levels of TAA, EAA and leucine compared to casein protein or high caloric products in healthy, elderly subjects. These differences appear to be mediated in part by the gastrointestinal behaviour of these products. ClinicalTrials.gov: NCT

  6. Dictyostelium discoideum lipids modulate cell-cell cohesion and cyclic AMP signaling.

    PubMed Central

    Fontana, D R; Luo, C S; Phillips, J C

    1991-01-01

    During Dictyostelium discoideum development, cell-cell communication is mediated through cyclic AMP (cAMP)-induced cAMP synthesis and secretion (cAMP signaling) and cell-cell contact. Cell-cell contact elicits cAMP secretion and modulates the magnitude of a subsequent cAMP signaling response (D. R. Fontana and P. L. Price, Differentiation 41:184-192, 1989), demonstrating that cell-cell contact and cAMP signaling are not independent events. To identify components involved in the contact-mediated modulation of cAMP signaling, amoebal membranes were added to aggregation-competent amoebae in suspension. The membranes from aggregation-competent amoebae inhibited cAMP signaling at all concentrations tested, while the membranes from vegetative amoebae exhibited a concentration-dependent enhancement or inhibition of cAMP signaling. Membrane lipids inhibited cAMP signaling at all concentrations tested. The lipids abolished cAMP signaling by blocking cAMP-induced adenylyl cyclase activation. The membrane lipids also inhibited amoeba-amoeba cohesion at concentrations comparable to those which inhibited cAMP signaling. The phospholipids and neutral lipids decreased cohesion and inhibited the cAMP signaling response. The glycolipid/sulfolipid fraction enhanced cohesion and cAMP signaling. Caffeine, a known inhibitor of cAMP-induced adenylyl cyclase activation, inhibited amoeba-amoeba cohesion. These studies demonstrate that endogenous lipids are capable of modulating amoeba-amoeba cohesion and cAMP-induced activation of the adenylyl cyclase. These results suggest that cohesion may modulate cAMP-induced adenylyl cyclase activation. Because the complete elimination of cohesion is accompanied by the complete elimination of cAMP signaling, these results further suggest that cohesion may be necessary for cAMP-induced adenylyl cyclase activation in D. discoideum. PMID:1846024

  7. Simvastatin Attenuates Astrogliosis after Traumatic Brain Injury through the Modulation of EGFR in Lipid Rafts

    PubMed Central

    Wu, Hongtao; Mahmood, Asim; Lu, Dunyue; Jiang, Hao; Xiong, Ye; Zhou, Dong; Chopp, Michael

    2010-01-01

    Objective Our previous studies demonstrated that simvastatin treatment promotes neuronal survival and reduces inflammatory cytokine release from astrocytes after traumatic brain injury (TBI) in rats. Since reactive astrocytes produce inflammation mediators, in the current study we investigated the effect of simvastatin on astrocyte activation after TBI and its underlying signaling mechanisms. Methods Saline or simvastatin (1 mg/kg) was orally administered to rats starting at Day 1 after TBI and then daily for 14 days. Rats were sacrificed at 1, 3, 7, 14 days after treatment. Brain sections and tissues were prepared for immunohistochemical staining and Western blot analysis, respectively. Cultured astrocytes were subjected to oxygen-glucose deprivation (OGD) and followed by immunocytochemical staining with GFAP/caveolin-1 and Western blot analysis. Lipid rafts were isolated from the cell lysate and Western blot was carried out to detect the changes in epidermal growth factor receptor (EGFR) expression and phosphorylation in the lipid rafts. Results Simvastatin significantly promoted neuronal survival after TBI and attenuated activation of astrocytes. Simvastatin modified the caveolin-1 expression in lipid rafts in astrocyte cell membrane, suppressed the phosphorylation of EGFR in lipid rafts of astrocytes after OGD, and inhibited the OGD-induced interleukin-1 (IL-1) production. Conclusions These data suggest that simvastatin reduces reactive astrogliosis and rescues neuronal cells after TBI. These beneficial effects of simvastatin may be mediated by inhibiting astrocyte activation after TBI through modifying the caveolin-1 expression in lipid rafts and the subsequent modulation of EGFR phosphorylation in lipid rafts. PMID:19895202

  8. Postprandial Oxidative Stress in Exercise Trained and Sedentary Cigarette Smokers

    PubMed Central

    Bloomer, Richard J.; Fisher-Wellman, Kelsey H.

    2009-01-01

    Cigarette smokers experience an exaggerated triglyceride (TAG) and oxidative stress response to high fat feeding. Exercise training may serve to attenuate the rise in these variables, by improving TAG clearance and antioxidant defense. We compared blood TAG, antioxidant capacity, and oxidative stress biomarkers in exercise trained (>2 hrs per wk) and untrained smokers matched for age, in response to a high fat test meal. We report here that low volume exercise training can attenuate postprandial lipid peroxidation, but has little impact on blood TAG and other markers of oxidative stress. Higher volumes of exercise may be needed to allow for clinically meaningful adaptations in postprandial lipemia and oxidative stress. PMID:19440401

  9. C-terminal interactions of apolipoprotein E4 respond to the postprandial state.

    PubMed

    Tetali, Sarada D; Budamagunta, Madhu S; Voss, John C; Rutledge, John C

    2006-07-01

    Increased triglyceride-rich lipoproteins (TGRLs) in the postprandial state are associated with atherosclerosis. We investigated whether the postprandial state induced structural changes at the apolipoprotein E4 (apoE4) C terminus, its principal lipid binding domain, using electron paramagnetic resonance (EPR) spectroscopy of a site-directed spin label attached to the cysteine of apoE4-W264C. Spin coupling between labels located in the C termini was followed after mixing with preprandial and postprandial human plasma samples. Our results indicate that postprandial plasma triggers a reorganization of the protein such that the dipolar broadening is diminished, indicating a reduction in C-terminal interaction. The loss of spectral broadening was directly correlated with an increase in postprandial plasma triglycerides and was reduced with delipidated plasma. The spin-labeled apoE4 displayed a lipid preference of VLDL > LDL > HDL in the preprandial and postprandial states. The apoE4 shift to VLDL during the postprandial state was accompanied by a loss in spectral broadening of the protein. These findings suggest that apoE4 associated with LDL maintains self-association via its C terminus and that this association is diminished in VLDL-associated protein. Lipolyzed TGRL reflected a depletion of the C-terminal interaction of apoE4. Addition of palmitate to VLDL gave a similar response as lipolyzed TGRL, suggesting that lipolysis products play a major role in reorganizing apoE4 during the postprandial state.

  10. Dietary rapeseed/canola-oil supplementation reduces serum lipids and liver enzymes and alters postprandial inflammatory responses in adipose tissue compared to olive-oil supplementation in obese men.

    PubMed

    Kruse, Michael; von Loeffelholz, Christian; Hoffmann, Daniela; Pohlmann, Antje; Seltmann, Anne-Cathrin; Osterhoff, Martin; Hornemann, Silke; Pivovarova, Olga; Rohn, Sascha; Jahreis, Gerhard; Pfeiffer, Andreas F H

    2015-03-01

    Obesity is associated with hyperlipidemia, hepatic steatosis, and low-grade inflammation. Studies have shown that MUFA as well as PUFA have beneficial effects on blood lipids and the inflammatory state. This study investigates the effects of a daily supplementation of either 50 g of rapeseed/canola (RA) or olive (OL) oil over 4 wk on serum lipids, serum liver enzymes, and inflammatory gene expression in subcutaneous (s. c.) adipose tissue in obese men. Consuming RA resulted in increased serum n-3 fatty acids and a reduction in total cholesterol, LDL cholesterol, and serum aspartate aminotransferase compared to OL. In s. c. adipose tissue, gene expression of the pro-inflammatory cytokine IL6 was reduced in RA compared to OL. However, after 4 h after a test meal, containing the appropriate oil, white bread, and 400 mL of liquid diet drink (835 kcal in total), gene expression of IL6, IL1B, and EMR1 (egf-like module containing Mucin-like hormone receptor-like 1) was increased in RA and of monocyte chemoattractant protein-1 (CCL2) in both RA and OL. This demonstrates that consuming RA for 4 wk improves serum lipids, liver enzymes, and basal inflammation in s. c. adipose tissue, but it mediates an acute pro-inflammatory response in adipose tissue upon consuming a meal. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Hedgehog Pathway Modulation by Multiple Lipid Binding Sites on the Smoothened Effector of Signal Response

    PubMed Central

    Myers, Benjamin R.; Sever, Navdar; Chong, Yong Chun; Kim, James; Belani, Jitendra D.; Rychnovsky, Scott; Bazan, J. Fernando; Beachy, Philip A.

    2014-01-01

    Summary Hedgehog (Hh) signaling during development and in postembryonic tissues requires activation of the 7TM oncoprotein Smoothened (Smo), by mechanisms that may involve endogenous lipidic modulators. Exogenous Smo ligands previously identified include the plant sterol cyclopamine (and its therapeutically useful synthetic mimics) and hydroxylated cholesterol derivatives (oxysterols); Smo is also highly sensitive to cellular sterol levels. The relationships between these effects are unclear because the relevant Smo structural determinants are unknown. We identify the conserved extracellular cysteine rich domain (CRD) as the site of action for oxysterols on Smo, involving residues structurally analogous to those contacting the Wnt lipid adduct in the homologous Frizzled CRD; this modulatory effect is distinct from that of cyclopamine mimics, from Hh-mediated regulation, and from the permissive action of cellular sterol pools. These results imply that Hh pathway activity is sensitive to lipid binding at several Smo sites, suggesting mechanisms for tuning by multiple physiological inputs. PMID:23954590

  12. Stratum corneum modulation by chemical enhancers and lipid nanostructures: implications for transdermal drug delivery.

    PubMed

    Kapoor, Mudra Saurabh; GuhaSarkar, Shruti; Banerjee, Rinti

    2017-07-01

    Skin is the outermost and largest protective covering of the body. The uppermost layer of the skin, stratum corneum also called the horny layer is composed of keratin-filled cells covered by a lipid matrix which shields the skin from physical and chemical entrants. The lipid lamellar structure comprises of ceramides, cholesterol, fatty acids and proteins. Chemical enhancers that mimic the lamellar chemistry, reversibly fluidize the latter can be utilized for enhancing transport of cargo across the epidermis into the dermis. This review deals with the stratum corneum chemistry, mechanisms to modulate its packing with the aid of chemical enhancers, biophysical techniques for characterization and applications in the design of nature-inspired biocompatible lipid nanostructures for transdermal delivery of drugs and bioactive agents.

  13. Postprandial lipemia is not increased in patients with previous unprovoked venous thromboembolism.

    PubMed

    Hald, Erin M; Brækkan, Sigrid K; Vik, Anders; Brodin, Ellen E; Hansen, John-Bjarne

    2013-01-01

    Patients with arterial cardiovascular disease have increased postprandial lipemia, and plasma levels of postprandial remnants are related to the progression of atherosclerosis. Studies have shown that patients with unprovoked venous thromboembolism have increased risk of arterial cardiovascular disease. To investigate whether patients with a history of unprovoked venous thromboembolism have increased postprandial lipemia. A population-based case-control study was performed in 20 patients with a history of unprovoked venous thromboembolism and 20 age- and gender-matched healthy controls. Participants were subjected to a standard fat tolerance test (1 g/kilo body weight) with subsequent blood sampling every second hour for 8 hours. Lipids were measured by traditional methods and lipoprotein subclasses by proton nuclear magnetic resonance. Fasting lipids and lipoprotein subclasses did not differ between groups. The postprandial lipemia, assessed by the incremental area under the triglyceride curve, was not different in venous thromboembolism patients and healthy controls (5.0 ± 3.6 mmol/L∗h vs 5.3 ± 4.4 mmol/L∗h, P = .81). Similarly, the distribution and size of the lipoprotein subclasses obtained 4 hours postprandially did not differ between groups. Patients with a history of unprovoked venous thromboembolism had similar lipoprotein subclasses size, distribution, and postprandial lipemia as healthy controls. Our findings indicate that postprandial lipemia is not a link between unprovoked venous thromboembolism and arterial cardiovascular disease. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  14. Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity

    SciTech Connect

    Pols, Thijs W.H.; Ottenhoff, Roelof; Vos, Mariska; Levels, Johannes H.M.; Quax, Paul H.A.; Meijers, Joost C.M.; Pannekoek, Hans; Groen, Albert K.; Vries, Carlie J.M. de

    2008-02-22

    NR4A nuclear receptors are induced in the liver upon fasting and regulate hepatic gluconeogenesis. Here, we studied the role of nuclear receptor Nur77 (NR4A1) in hepatic lipid metabolism. We generated mice expressing hepatic Nur77 using adenoviral vectors, and demonstrate that these mice exhibit a modulation of the plasma lipid profile and a reduction in hepatic triglyceride. Expression analysis of >25 key genes involved in lipid metabolism revealed that Nur77 inhibits SREBP1c expression. This results in decreased SREBP1c activity as is illustrated by reduced expression of its target genes stearoyl-coA desaturase-1, mitochondrial glycerol-3-phosphate acyltransferase, fatty acid synthase and the LDL receptor, and provides a mechanism for the physiological changes observed in response to Nur77. Expression of LXR target genes Abcg5 and Abcg8 is reduced by Nur77, and may suggest involvement of LXR in the inhibitory action of Nur77 on SREBP1c expression. Taken together, our study demonstrates that Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity.

  15. Wine lees modulate lipid metabolism and induce fatty acid remodelling in zebrafish.

    PubMed

    Caro, M; Sansone, A; Amezaga, J; Navarro, V; Ferreri, C; Tueros, I

    2017-03-21

    This study investigates the ability of a polyphenolic extract obtained from a wine lees by-product to modulate zebrafish lipid metabolism. Lees from a Spanish winery were collected and the polyphenolic extract was chemically characterised in terms of antioxidant capacity, total phenolic content and the individual main phenolic compounds. The effects of the extract on lipid metabolism were evaluated using a zebrafish animal model. Lees are rich in polyphenols (42.33 mg gallic acid equivalent per g dry matter) with high antioxidant capacity (56.04 mg Trolox equivalent per g dry matter), rutin and quercetin being their main identified polyphenols. The biological effects of lees extract included (i) a reduction in zebrafish embryos' fat reserve (40%), (ii) changes in the expression of lipid metabolism key genes, (iii) remodelling of the fatty acid content in phospholipid and triglyceride fractions of zebrafish embryos and (iv) reduction in the trans fatty acid content. On the whole, wine lees polyphenolic extract was effective at modulating zebrafish lipid metabolism evidencing remodelling effects and antioxidant properties that can be further developed for food innovation.

  16. Postprandial hemodynamics in the conscious rat

    SciTech Connect

    Anzueto Hernandez, L.; Kvietys, P.R.; Granger, D.N.

    1986-07-01

    The postprandial intestinal hyperemia was studied in conscious and anesthetized rats using the radioactive microsphere technique. Carbohydrate, protein, lipid, and mixed meals, and the vehicle (Tyrode's solution), were placed in the stomach via a gastrostomy tube. In conscious rats, blood flow increased by 40-80% in the duodenum and jejunum 1 h after either a carbohydrate, lipid, protein, or mixed meal. Tyrode's solution produced a comparable hyperemia. Blood flow in the distal bowel segments (ileum, cecum, and colon) was significantly increased only by Tyrode's solution and the carbohydrate meal. The proximal intestinal hyperemia produced by the mixed meal in conscious animals was significantly attenuated by vagotomy yet unaltered by atropine pretreatment. In contrast to the results obtained from conscious rats, the mixed meal did not significantly alter intestinal blood flow in anesthetized animals. The results of this study indicate that the postprandial intestinal hyperemia is much greater in conscious than anesthetized animals. This difference may result from the higher resting blood flows in the latter group. The hyperemic response in conscious animals may be mediated by the vagus nerve.

  17. Identification and metabolomic analysis of chemical modulators for lipid accumulation in Crypthecodinium cohnii.

    PubMed

    Li, Jinghan; Niu, Xiangfeng; Pei, Guangsheng; Sui, Xiao; Zhang, Xiaoqing; Chen, Lei; Zhang, Weiwen

    2015-09-01

    In the study, fourteen chemical modulators from five groups (i.e., auxin, gibberellin, cytokinin, signal transducer and amine) were evaluated for their effects on lipid accumulation in Crypthecodinium cohnii. The results showed that naphthoxyacetic acid (BNOA), 2-chlorodracylicacid, salicylic acid (SA), abscisic acid (ABA) and ethanolamine (ETA), increased lipid accumulation in C. cohnii by 10.00-18.78%. In addition, the combined uses of the above chemicals showed that two combinations, 1.0mg/L SA & 152.7 mg/L ETA and 4.0mg/L BNOA & 152.7 mg/L ETA, increased lipid accumulation by 22.45% and 20.54%, respectively. Moreover, a targeted metabolomic approach was employed to decipher the possible mechanisms responsible for the increased lipid accumulation, and the results showed that the enhanced metabolism in glycolysis and TCA cycle as well as the decreased metabolism in PPP pathway could be important for the stimulatory roles of BNOA & ETA and SA & ETA on lipid accumulation in C. cohnii.

  18. The effect of IL6-174C/G polymorphisms on postprandial triglycerides metabolism in the GOLDN study

    USDA-ARS?s Scientific Manuscript database

    Chronically elevated IL-6 affects lipid and lipoprotein metabolism. Individuals genetically predisposed to higher IL-6 secretion may be at risk of dyslipidemia, especially during the postprandial phase. We investigated the effect of genetic variants at the IL6 locus on postprandial lipemia in US Whi...

  19. Kinetic analysis of apolipoproteins in postprandial hypertriglyceridaemia rabbits.

    PubMed

    Hata, M; Ito, T; Ohwada, K

    2009-04-01

    The postprandial hypertriglyceridaemia (PHT) rabbit, developed as a new animal model of metabolic syndrome, is characterized by PHT, central obesity and glucose intolerance. For detailed investigation of lipid metabolism characteristics in PHT rabbit, the plasma levels of apolipoproteins A-I, B, C-II, C-III and E were measured. Movements of apolipoproteins B100 and B48 were investigated using sodium dodecyl sulphate-polyacrylamide gel electrophoresis to determine whether postprandially increased triglyceride is exogenous or endogenous. The level of apolipoproteins A-I, B, C-II and E were increased in PHT rabbit after feeding. Apolipoproteins B100 and B48 were detected in the plasma fraction of d < 1.006 g/mL of the PHT rabbit. The postprandial increase in apolipoprotein B in the PHT rabbit reflects a numerical increase in lipoprotein particles in the blood; the increase in apolipoproteins C-II and E suggests some disturbance in lipoprotein catabolism. Apolipoprotein B48 was detected postprandially in PHT rabbits. These results suggest that delayed catabolism of exogenous lipids caused the retention of chylomicron remnants in the blood. Results also suggest that activities of the lipolytic enzyme lipoprotein lipase and hepatic triglyceride lipase were deficient and that the hepatic uptake of exogenous lipoproteins was delayed in the PHT rabbit. Especially, for examining remnant hyperlipoproteinaemia in humans, PHT rabbit is an excellent animal model for hypertriglyceridaemia research.

  20. Lipid Geometry and Bilayer Curvature Modulate LC3/GABARAP-Mediated Model Autophagosomal Elongation

    PubMed Central

    Landajuela, Ane; Hervás, Javier H.; Antón, Zuriñe; Montes, L. Ruth; Gil, David; Valle, Mikel; Rodriguez, J. Francisco; Goñi, Felix M.; Alonso, Alicia

    2016-01-01

    Autophagy, an important catabolic pathway involved in a broad spectrum of human diseases, implies the formation of double-membrane-bound structures called autophagosomes (AP), which engulf material to be degraded in lytic compartments. How APs form, especially how the membrane expands and eventually closes upon itself, is an area of intense research. Ubiquitin-like ATG8 has been related to both membrane expansion and membrane fusion, but the underlying molecular mechanisms are poorly understood. Here, we used two minimal reconstituted systems (enzymatic and chemical conjugation) to compare the ability of human ATG8 homologs (LC3, GABARAP, and GATE-16) to mediate membrane fusion. We found that both enzymatically and chemically lipidated forms of GATE-16 and GABARAP proteins promote extensive membrane tethering and fusion, whereas lipidated LC3 does so to a much lesser extent. Moreover, we characterize the GATE-16/GABARAP-mediated membrane fusion as a phenomenon of full membrane fusion, independently demonstrating vesicle aggregation, intervesicular lipid mixing, and intervesicular mixing of aqueous content, in the absence of vesicular content leakage. Multiple fusion events give rise to large vesicles, as seen by cryo-electron microscopy observations. We also show that both vesicle diameter and selected curvature-inducing lipids (cardiolipin, diacylglycerol, and lyso-phosphatidylcholine) can modulate the fusion process, smaller vesicle diameters and negative intrinsic curvature lipids (cardiolipin, diacylglycerol) facilitating fusion. These results strongly support the hypothesis of a highly bent structural fusion intermediate (stalk) during AP biogenesis and add to the growing body of evidence that identifies lipids as important regulators of autophagy. PMID:26789764

  1. Mitochondrial modulators improve lipid composition and attenuate memory deficits in experimental model of Huntington's disease.

    PubMed

    Mehrotra, Arpit; Sood, Abhilasha; Sandhir, Rajat

    2015-12-01

    3-Nitropropionic acid (3-NP) is an irreversible inhibitor of succinate dehydrogenase and induces neuropathological changes similar to those observed in Huntington's disease (HD). The objective of the present study was to investigate neuroprotective effect of mitochondrial modulators; alpha-lipoic acid (ALA) and acetyl-L-carnitine (ALCAR) on 3-NP-induced alterations in mitochondrial lipid composition, mitochondrial structure and memory functions. Experimental model of HD was developed by administering 3-NP at sub-chronic doses, twice daily for 17 days. The levels of conjugated dienes, cholesterol and glycolipids were significantly increased, whereas the levels of phospholipids (phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine) including cardiolipin were significantly decreased in the mitochondria isolated from the striatum of 3-NP-treated animals. In addition, the difference in molecular composition of each phospholipid class was also evaluated using mass spectrometry. Mitochondria lipid from 3-NP-treated animals showed increased cholesterol to phospholipid ratio, suggesting decreased mitochondrial membrane fluidity. 3-NP administration also resulted in ultra-structural changes in mitochondria, accompanied by swelling as assessed by transmission electron microscopy. The 3-NP administered animals had impaired spatial memory evaluated using elevated plus maze test. However, combined supplementation with ALA + ALCAR for 21 days normalized mitochondrial lipid composition, improved mitochondrial structure and ameliorated memory impairments in 3-NP-treated animals, suggesting an imperative role of these two modulators in combination in the management of HD.

  2. Membrane lipids tune synaptic transmission by direct modulation of presynaptic potassium channels.

    PubMed

    Carta, Mario; Lanore, Frederic; Rebola, Nelson; Szabo, Zsolt; Da Silva, Silvia Viana; Lourenço, Joana; Verraes, Agathe; Nadler, André; Schultz, Carsten; Blanchet, Christophe; Mulle, Christophe

    2014-02-19

    Voltage-gated potassium (Kv) channels are involved in action potential (AP) repolarization in excitable cells. Exogenous application of membrane-derived lipids, such as arachidonic acid (AA), regulates the gating of Kv channels. Whether membrane-derived lipids released under physiological conditions have an impact on neuronal coding through this mechanism is unknown. We show that AA released in an activity-dependent manner from postsynaptic hippocampal CA3 pyramidal cells acts as retrograde messenger, inducing a robust facilitation of mossy fiber (Mf) synaptic transmission over several minutes. AA acts by broadening presynaptic APs through the direct modulation of Kv channels. This form of short-term plasticity can be triggered when postsynaptic cell fires with physiologically relevant patterns and sets the threshold for the induction of the presynaptic form of long-term potentiation (LTP) at hippocampal Mf synapses. Hence, direct modulation of presynaptic Kv channels by activity-dependent release of lipids serves as a physiological mechanism for tuning synaptic transmission.

  3. Biopolymer-Lipid Bilayer Interaction Modulates the Physical Properties of Liposomes: Mechanism and Structure.

    PubMed

    Tan, Chen; Zhang, Yating; Abbas, Shabbar; Feng, Biao; Zhang, Xiaoming; Xia, Wenshui; Xia, Shuqin

    2015-08-19

    This study was conducted to elucidate the conformational dependence of the modulating ability of chitosan, a positively charged biopolymer, on a new type of liposome composed of mixed lipids including egg yolk phosphatidylcholine (EYPC) and nonionic surfactant (Tween 80). Analysis of the dynamic and structure of bilayer membrane upon interaction with chitosan by fluorescence and electron paramagnetic resonance techniques demonstrated that, in addition to providing a physical barrier for the membrane surface, the adsorption of chitosan extended and crimped chains rigidified the lipid membrane. However, the decrease in relative microviscosity and order parameter suggested that the presence of chitosan coils disturbed the membrane organization. It was also noted that the increase of fluidity in the lipid bilayer center was not pronounced, indicating the shallow penetration of coils into the hydrophobic interior of bilayer. Microscopic observations revealed that chitosan adsorption not only affected the morphology of liposomes but also modulated the particle aggregation and fusion. Especially, a number of very heterogeneous particles were visualized, which tended to confirm the role of chitosan coils as a "polymeric surfactant". In addition to particle deformation, the membrane permeability was also tuned. These findings may provide a new perspective to understand the physiological functionality of biopolymer and design biopolymer-liposome composite structures as delivery systems for bioactive components.

  4. Diacylglycerol kinase ε deficiency preserves glucose tolerance and modulates lipid metabolism in obese mice.

    PubMed

    Mannerås-Holm, Louise; Schönke, Milena; Brozinick, Joseph T; Vetterli, Laurène; Bui, Hai-Hoang; Sanders, Philip; Nascimento, Emmani B M; Björnholm, Marie; Chibalin, Alexander V; Zierath, Juleen R

    2017-05-01

    Diacylglycerol kinases (DGKs) catalyze the phosphorylation and conversion of diacylglycerol (DAG) into phosphatidic acid. DGK isozymes have unique primary structures, expression patterns, subcellular localizations, regulatory mechanisms, and DAG preferences. DGKε has a hydrophobic segment that promotes its attachment to membranes and shows substrate specificity for DAG with an arachidonoyl acyl chain in the sn-2 position of the substrate. We determined the role of DGKε in the regulation of energy and glucose homeostasis in relation to diet-induced insulin resistance and obesity using DGKε-KO and wild-type mice. Lipidomic analysis revealed elevated unsaturated and saturated DAG species in skeletal muscle of DGKε KO mice, which was paradoxically associated with increased glucose tolerance. Although skeletal muscle insulin sensitivity was unaltered, whole-body respiratory exchange ratio was reduced, and abundance of mitochondrial markers was increased, indicating a greater reliance on fat oxidation and intracellular lipid metabolism in DGKε KO mice. Thus, the increased intracellular lipids in skeletal muscle from DGKε KO mice may undergo rapid turnover because of increased mitochondrial function and lipid oxidation, rather than storage, which in turn may preserve insulin sensitivity. In conclusion, DGKε plays a role in glucose and energy homeostasis by modulating lipid metabolism in skeletal muscle. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  5. Lipids as modulators of membrane fusion mediated by viral fusion proteins.

    PubMed

    Teissier, Elodie; Pécheur, Eve-Isabelle

    2007-11-01

    Enveloped viruses infect host cells by fusion of viral and target membranes. This fusion event is triggered by specific glycoproteins in the viral envelope. Fusion glycoproteins belong to either class I, class II or the newly described third class, depending upon their arrangement at the surface of the virion, their tri-dimensional structure and the location within the protein of a short stretch of hydrophobic amino acids called the fusion peptide, which is able to induce the initial lipid destabilization at the onset of fusion. Viral fusion occurs either with the plasma membrane for pH-independent viruses, or with the endosomal membranes for pH-dependent viruses. Although, viral fusion proteins are parted in three classes and the subcellular localization of fusion might vary, these proteins have to act, in common, on lipid assemblies. Lipids contribute to fusion through their physical, mechanical and/or chemical properties. Lipids can thus play a role as chemically defined entities, or through their preferential partitioning into membrane microdomains called "rafts", or by modulating the curvature of the membranes involved in the fusion process. The purpose of this review is to make a state of the art on recent findings on the contribution of cholesterol, sphingolipids and glycolipids in cell entry and membrane fusion of a number of viral families, whose members bear either class I or class II fusion proteins, or fusion proteins of the recently discovered third class.

  6. Polychlorinated biphenyl 153 in lipid medium modulates differentiation of human adipocytes.

    PubMed

    Mullerova, D; Pesta, M; Dvorakova, J; Cedikova, M; Kulda, V; Dvorak, P; Bouchalová, V; Kralickova, M; Babuska, V; Kuncova, J; Langmajerova, J; Muller, L

    2017-04-12

    Emerging evidence indicates that polychlorinated biphenyls (PCBs) are involved in the development of diabetes mellitus in the obese. The purpose of this study was to determine mechanisms by which PCB 153 (2,2´,4,4´,5,5´-hexachlorobiphenyl) could influence diet-induced obesity and insulin resistance during adipogenesis. Lineage of h-ADMSCs was differentiated either as control (differentiation medium only), or with lipid vehicle modelling high fat nutrition (NuTRIflex) or lipid free vehicle (dimethylsulfoxide) for 28 days with or without PCB 153 daily co-exposure (in three concentrations 0.1, 1, and 10 microM). Gene expression analyses were performed using RT-qPCR at days 4, 10, 21, 24, 28; protein levels Akt and phosphorylated Akt (Phospho-Akt) by Western blot at days 4, and 21. PCB 153 treatment of h-ADMSCs only in lipid vehicle was associated with down regulation of key master genes of adipogenesis: PPARgamma, SREBP-1, PPARGC1B, and PLIN2 during the whole process of differentiation; and with increased Akt and decreased Phospho-Akt protein level at day 21. We have shown that PCB 153, in concentration 0.1 microM, has a potential in lipid rich environment to modulate differentiation of adipocytes. Because European and U.S. adults have been exposed to PCB 153, this particular nutrient-toxicant interaction potentially impacts human obesity and insulin sensitivity.

  7. Monitoring and modulating ion traffic in hybrid lipid/polymer vesicles.

    PubMed

    Paxton, Walter F; McAninch, Patrick T; Achyuthan, Komandoor E; Shin, Sun Hae Ra; Monteith, Haley L

    2017-08-01

    Controlling the traffic of molecules and ions across membranes is a critical feature in a number of biologically relevant processes and highly desirable for the development of technologies based on membrane materials. In this paper, ion transport behavior of hybrid lipid/polymer membranes was studied in the absence and presence of ion transfer agents. A pH-sensitive fluorophore was used to investigate ion (H(+)/OH(-)) permeability across hybrid lipid/polymer membranes as a function of the fraction of amphiphilic block copolymer. It was observed that vesicles with intermediate lipid/polymer ratios tend to be surprisingly more permeable to ion transport than the pure lipid or pure polymer vesicles. Hybrid vesicle permeability could be further modulated with valinomycin, nigericin, or gramicidin A, which significantly expedite the dissipation of externally-imposed pH gradients by facilitating the transport of the rate-limiting co-ions (e.g. K(+)) ions across the membrane. For gramicidin A, ion permeability decreased with increasing polymer mole fraction, and the method of introduction of gramicidin A into the membrane played an important role. Strategies to incorporate biofunctional molecules and facilitate their activity in synthetic systems are highly desirable for developing artificial organelles or other synthetic compartmentalized structures requiring control over molecular traffic across biomimetic membranes. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. The modulation of biodistribution of stem cells by anchoring lipid-conjugated heparin on the cell surface.

    PubMed

    Kim, Jong Chul; Tae, Giyoong

    2015-11-10

    Heparin is a bioactive glycosaminoglycan that can interact with various extracellular matrix (ECM) proteins and growth factors. Lipid-conjugated heparin was synthesized, and was used to coat adipose-derived stem cells (ADSCs) by physical insertion on the cell membrane. Coating of lipid-conjugated heparin with two lipid moieties on ADSCs was stable for 24h in vitro. Biodistribution of heparin-coated ADSCs upon intravenous injection in mice was analyzed by In-Vivo Imaging System (IVIS), and showed enhanced accumulation in the liver and spleen while reduced entrapment in the lung. Thus, the coating of ADSCs with lipid-conjugated heparin could significantly modulate the biodistribution of cells.

  9. Specific Ions Modulate Diffusion Dynamics of Hydration Water on Lipid Membrane Surfaces

    PubMed Central

    2015-01-01

    Effects of specific ions on the local translational diffusion of water near large hydrophilic lipid vesicle surfaces were measured by Overhauser dynamic nuclear polarization (ODNP). ODNP relies on an unpaired electron spin-containing probe located at molecular or surface sites to report on the dynamics of water protons within ∼10 Å from the spin probe, which give rise to spectral densities for electron–proton cross-relaxation processes in the 10 GHz regime. This pushes nuclear magnetic resonance relaxometry to more than an order of magnitude higher frequencies than conventionally feasible, permitting the measurement of water moving with picosecond to subnanosecond correlation times. Diffusion of water within ∼10 Å of, i.e., up to ∼3 water layers around the spin probes located on hydrophilic lipid vesicle surfaces is ∼5 times retarded compared to the bulk water translational diffusion. This directly reflects on the activation barrier for surface water diffusion, i.e., how tightly water is bound to the hydrophilic surface and surrounding waters. We find this value to be modulated by the presence of specific ions in solution, with its order following the known Hofmeister series. While a molecular description of how ions affect the hydration structure at the hydrophilic surface remains to be answered, the finding that Hofmeister ions directly modulate the surface water diffusivity implies that the strength of the hydrogen bond network of surface hydration water is directly modulated on hydrophilic surfaces. PMID:24456096

  10. Sensing small molecule interactions with lipid membranes by local pH modulation.

    PubMed

    Huang, Da; Zhao, Tao; Xu, Wei; Yang, Tinglu; Cremer, Paul S

    2013-11-05

    Herein, we utilized a label-free sensing platform based on pH modulation to detect the interactions between tetracaine, a positively charged small molecule used as a local anesthetic, and planar supported lipid bilayers (SLBs). The SLBs were patterned inside a flow cell, allowing for various concentrations of tetracaine to be introduced over the surface in a buffer solution. Studies with membranes containing POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) yielded an equilibrium dissociation constant value of Kd = 180 ± 47 μm for this small molecule-membrane interaction. Adding cholesterol to the SLBs decreased the affinity between tetracaine and the bilayers, while this interaction tightened when POPE (1-hexadecanoyl-2-(9-Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine) was added. Studies were also conducted with three negatively charged membrane lipids, POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt)), POPS (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (sodium salt)), and ganglioside GM1. All three measurements gave rise to a similar tightening of the apparent Kd value compared with pure POPC membranes. The lack of chemical specificity with the identity of the negatively charged lipid indicated that the tightening was largely electrostatic. Through a direct comparison with ITC measurements, it was found that the pH modulation sensor platform offers a facile, inexpensive, highly sensitive, and rapid method for the detection of interactions between putative drug candidates and lipid bilayers. As such, this technique may potentially be exploited as a screen for drug development and analysis.

  11. Amyloid fibril formation of peptides derived from the C-terminus of CETP modulated by lipids

    SciTech Connect

    García-González, Victor; Mas-Oliva, Jaime

    2013-04-26

    Highlights: •The secondary structure of a C-terminal peptide derived from CETP was studied. •Lipids modulate secondary structure changes of a C-terminal peptide derived from CETP. •Lysophosphatidic acid maintains a functional α-helix and prevents fibril formation. •Transfer of lipids by CETP is related to the presence of an α-helix at its C-end. -- Abstract: Cholesteryl-ester transfer protein (CETP) is a plasmatic protein involved in neutral lipid transfer between lipoproteins. Focusing on the last 12 C-terminus residues we have previously shown that mutation D{sub 470}N promotes a conformational change towards a β-secondary structure. In turn, this modification leads to the formation of oligomers and fibrillar structures, which cause cytotoxic effects similar to the ones provoked by amyloid peptides. In this study, we evaluated the role of specific lipid arrangements on the structure of peptide helix-Z (D{sub 470}N) through the use of thioflavin T fluorescence, peptide bond absorbance, circular dichroism and electron microscopy. The results indicate that the use of micelles formed with lysophosphatidylcholine and lysophosphatidic acid (LPA) under neutral pH induce a conformational transition of peptide helix-Z containing a β-sheet conformation to a native α-helix structure, therefore avoiding the formation of amyloid fibrils. In contrast, incubation with phosphatidic acid does not change the profile for the β-sheet conformation. When the electrostatic charge at the surface of micelles or vesicles is regulated through the use of lipids such as phospholipid and LPA, minimal changes and the presence of β-structures were recorded. Mixtures with a positive net charge diminished the percentage of β-structure and the amount of amyloid fibrils. Our results suggest that the degree of solvation determined by the presence of a free hydroxyl group on lipids such as LPA is a key condition that can modulate the secondary structure and the consequent formation of

  12. Acute metabolic response to fasted and postprandial exercise

    PubMed Central

    de Lima, Filipe Dinato; Correia, Ana Luiza Matias; Teixeira, Denilson da Silva; da Silva Neto, Domingos Vasco; Fernandes, Ítalo Sávio Gonçalves; Viana, Mário Boratto Xavier; Petitto, Mateus; da Silva Sampaio, Rodney Antônio; Chaves, Sandro Nobre; Alves, Simone Teixeira; Dantas, Renata Aparecida Elias; Mota, Márcio Rabelo

    2015-01-01

    The aim of this study was to analyze the acute metabolic response to exercise in fasting and postprandial. For this, ten individuals were submitted to an incremental treadmill test, with an initial speed of 5 and 1 km/h increments every minute, with no inclination, and a body composition assessment. After this 1st day, all volunteers were submitted to two experimental procedures (fasting and postprandial), with an aerobic exercise performed for 36 minutes at 65% of maximal oxygen consumption. At postprandial procedure, all subjects ingested a breakfast containing 59.3 g of carbohydrate (76.73%), 9.97 g of protein (12.90%), 8.01 g of lipids (10.37%), with a total energy intake of 349.17 kcal. An analysis of plasma concentration of triglycerides, lactate, and glucose was performed in two stages: before and after exercise. The Shapiro–Wilk test was used to verify the normality of the data. For analysis of glucose concentration, plasma lactate, and triglycerides, we used a repeated measures analysis of variance factorial 2×2, with Bonferroni multiple comparison test. The significance level of P<0.05 was adopted. The results indicated a maintenance level of glucose at fasting and a decrease in glucose concentration at postprandial exercise. Both conditions increase plasma lactate. Triglycerides also increased in the two experimental conditions; however, after exercise fasting, the increase was significantly higher than in the postprandial exercise. These data suggest that both exercises could increase plasma lactate and triglycerides. However, exercise performed in fasting condition decreases glucose concentration and increases triglycerides, even more than postprandial exercise. PMID:26316800

  13. Red wine prevents the postprandial increase in plasma cholesterol oxidation products: a pilot study.

    PubMed

    Natella, F; Macone, A; Ramberti, A; Forte, M; Mattivi, F; Matarese, R M; Scaccini, C

    2011-06-28

    Moderate wine consumption has been shown to lower cardiovascular risk. One of the mechanisms could involve the control of postprandial hyperlipaemia, a well-defined risk factor for atherosclerosis, reasonably by reducing the absorption of lipid oxidised species from the meal. The objective of the present study was to investigate whether wine consumption with the meal is able to reduce the postprandial increase in plasma lipid hydroperoxides and cholesterol oxidation products, in human subjects. In two different study sessions, twelve healthy volunteers consumed the same test meal rich in oxidised and oxidisable lipids (a double cheeseburger), with 300 ml of water (control) or with 300 ml of red wine (wine). The postprandial plasma concentration of cholesterol oxidation products was measured by GC-MS. The control meal induced a significant increase in the plasma concentration of lipid hydroperoxides and of two cholesterol oxidation products, 7-β-hydroxycholesterol and 7-ketocholesterol. The postprandial increase in lipid hydroperoxides and cholesterol oxidation products was fully prevented by wine when consumed with the meal. In conclusion, the present study provides evidence that consumption of wine with the meal could prevent the postprandial increase in plasma cholesterol oxidation products.

  14. Clinical considerations and mechanistic determinants of postprandial lipemia in older adults.

    PubMed

    Katsanos, Christos S

    2014-05-01

    The typical diet of individuals in Western societies results in metabolic responses associated with fed-state fat metabolism for most of the daily life of the individual. This fat metabolism is characterized specifically by an increase in the concentration of plasma lipids, primarily triglycerides. Increased postprandial lipemia, which is typically observed in older individuals (i.e., >65 y old), has now emerged as an important correlate of cardiovascular disease risk. An understanding of the mechanisms contributing to the increased postprandial lipemia in older individuals becomes, therefore, of particular clinical importance in any effort to explain and address the well-documented increase in cardiovascular disease risk as individuals age. Current evidence points to an increase in the accumulation of ingested lipid in lipoprotein particles of hepatic origin, together with an overall accumulation of lipid in these lipoproteins during the postprandial period, as primary contributors to the postprandial lipemia in older persons. When this evidence is considered together with the evidence suggesting large atherogenic potential of lipoproteins of hepatic origin, this can, at least in part, explain the increased risk of cardiovascular disease in older individuals. Understanding changes in the metabolism of ingested fat in the immediate postprandial period with advancing age, and how lifestyle interventions such as diet and physical exercise can ameliorate the increase in postprandial lipemia in older individuals, is important in order to address the increased cardiovascular disease risk in this particularly affected and growing segment of the population.

  15. Clinical Considerations and Mechanistic Determinants of Postprandial Lipemia in Older Adults12

    PubMed Central

    Katsanos, Christos S.

    2014-01-01

    The typical diet of individuals in Western societies results in metabolic responses associated with fed-state fat metabolism for most of the daily life of the individual. This fat metabolism is characterized specifically by an increase in the concentration of plasma lipids, primarily triglycerides. Increased postprandial lipemia, which is typically observed in older individuals (i.e., >65 y old), has now emerged as an important correlate of cardiovascular disease risk. An understanding of the mechanisms contributing to the increased postprandial lipemia in older individuals becomes, therefore, of particular clinical importance in any effort to explain and address the well-documented increase in cardiovascular disease risk as individuals age. Current evidence points to an increase in the accumulation of ingested lipid in lipoprotein particles of hepatic origin, together with an overall accumulation of lipid in these lipoproteins during the postprandial period, as primary contributors to the postprandial lipemia in older persons. When this evidence is considered together with the evidence suggesting large atherogenic potential of lipoproteins of hepatic origin, this can, at least in part, explain the increased risk of cardiovascular disease in older individuals. Understanding changes in the metabolism of ingested fat in the immediate postprandial period with advancing age, and how lifestyle interventions such as diet and physical exercise can ameliorate the increase in postprandial lipemia in older individuals, is important in order to address the increased cardiovascular disease risk in this particularly affected and growing segment of the population. PMID:24829469

  16. Postprandial sleep mechanics in Drosophila

    PubMed Central

    Murphy, Keith R; Deshpande, Sonali A; Yurgel, Maria E; Quinn, James P; Weissbach, Jennifer L; Keene, Alex C; Dawson-Scully, Ken; Huber, Robert; Tomchik, Seth M; Ja, William W

    2016-01-01

    Food consumption is thought to induce sleepiness. However, little is known about how postprandial sleep is regulated. Here, we simultaneously measured sleep and food intake of individual flies and found a transient rise in sleep following meals. Depending on the amount consumed, the effect ranged from slightly arousing to strongly sleep inducing. Postprandial sleep was positively correlated with ingested volume, protein, and salt—but not sucrose—revealing meal property-specific regulation. Silencing of leucokinin receptor (Lkr) neurons specifically reduced sleep induced by protein consumption. Thermogenetic stimulation of leucokinin (Lk) neurons decreased whereas Lk downregulation by RNAi increased postprandial sleep, suggestive of an inhibitory connection in the Lk-Lkr circuit. We further identified a subset of non-leucokininergic cells proximal to Lkr neurons that rhythmically increased postprandial sleep when silenced, suggesting that these cells are cyclically gated inhibitory inputs to Lkr neurons. Together, these findings reveal the dynamic nature of postprandial sleep. DOI: http://dx.doi.org/10.7554/eLife.19334.001 PMID:27873574

  17. Biophysical Insights into How Surfaces, Including Lipid Membranes, Modulate Protein Aggregation Related to Neurodegeneration

    PubMed Central

    Burke, Kathleen A.; Yates, Elizabeth A.; Legleiter, Justin

    2013-01-01

    There are a vast number of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), associated with the rearrangement of specific proteins to non-native conformations that promotes aggregation and deposition within tissues and/or cellular compartments. These diseases are commonly classified as protein-misfolding or amyloid diseases. The interaction of these proteins with liquid/surface interfaces is a fundamental phenomenon with potential implications for protein-misfolding diseases. Kinetic and thermodynamic studies indicate that significant conformational changes can be induced in proteins encountering surfaces, which can play a critical role in nucleating aggregate formation or stabilizing specific aggregation states. Surfaces of particular interest in neurodegenerative diseases are cellular and subcellular membranes that are predominately comprised of lipid components. The two-dimensional liquid environments provided by lipid bilayers can profoundly alter protein structure and dynamics by both specific and non-specific interactions. Importantly for misfolding diseases, these bilayer properties can not only modulate protein conformation, but also exert influence on aggregation state. A detailed understanding of the influence of (sub)cellular surfaces in driving protein aggregation and/or stabilizing specific aggregate forms could provide new insights into toxic mechanisms associated with these diseases. Here, we review the influence of surfaces in driving and stabilizing protein aggregation with a specific emphasis on lipid membranes. PMID:23459674

  18. Heat shock protein coinducers with no effect on protein denaturation specifically modulate the membrane lipid phase

    PubMed Central

    Török, Zsolt; Tsvetkova, Nelly M.; Balogh, Gábor; Horváth, Ibolya; Nagy, Enikő; Pénzes, Zoltán; Hargitai, Judit; Bensaude, Olivier; Csermely, Péter; Crowe, John H.; Maresca, Bruno; Vígh, László

    2003-01-01

    The hydroxylamine derivative bimoclomol (BM) has been shown to activate natural cytoprotective homeostatic responses by enhancing the capability of cells to cope with various pathophysiological conditions. It exerts its effect in synergy with low levels of stress to induce the synthesis of members of major stress protein families. We show here that the presence of BM does not influence protein denaturation in the cells. BM and its derivatives selectively interact with acidic lipids and modulate their thermal and dynamic properties. BM acts as a membrane fluidizer at normal temperature, but it is a highly efficient membrane stabilizer, inhibiting the bilayer–nonbilayer phase transitions during severe heat shock. We suggest that BM and the related compounds modify those domains of membrane lipids where the thermally or chemically induced perturbation of lipid phase is sensed and transduced into a cellular signal, leading to enhanced activation of heat shock genes. BM may be a prototype for clinically safe membrane-interacting drug candidates that rebalance the level and composition of heat shock proteins. PMID:12615993

  19. MODULATING LPS SIGNAL TRANSDUCTION AT THE LPS RECEPTOR COMPLEX WITH SYNTHETIC LIPID A ANALOGUES

    PubMed Central

    White, Aileen F. B.; Demchenko, Alexei V.

    2015-01-01

    Sepsis, defined as a clinical syndrome brought about by an amplified and dysregulated inflammatory response to infections, is one of the leading causes of death worldwide. Despite persistent attempts to develop treatment strategies to manage sepsis in the clinical setting, the basic elements of treatment have not changed since the 1960s. As such, the development of effective therapies for reducing inflammatory reactions and end-organ dysfunction in critically ill patients with sepsis remains a global priority. Advances in understanding of the immune response to sepsis provide the opportunity to develop more effective pharmaceuticals. This article details current information on the modulation of the lipopolysaccharide (LPS) receptor complex with synthetic Lipid A mimetics. As the initial and most critical event in sepsis pathophysiology, the LPS receptor provides an attractive target for antisepsis agents. One of the well-studied approaches to sepsis therapy involves the use of derivatives of Lipid A, the membrane-anchor portion of an LPS, which is largely responsible for its endotoxic activity. This article describes the structural and conformational requirements influencing the ability of Lipid A analogues to compete with LPS for binding to the LPS receptor complex and to inhibit the induction of the signal transduction pathway by impairing LPS-initiated receptor dimerization. PMID:25480508

  20. Monitoring lipid accumulation in the green microalga Botryococcus braunii with frequency-modulated stimulated Raman scattering

    NASA Astrophysics Data System (ADS)

    Wang, Chun-Chin; Chandrappa, Dayananda; Smirnoff, Nicholas; Moger, Julian

    2015-03-01

    The potential of microalgae as a source of renewable energy has received considerable interest because they can produce lipids (fatty acids and isoprenoids) that can be readily converted into biofuels. However, significant research in this area is required to increase yields to make this a viable renewable source of energy. An analytical tool that could provide quantitative in situ spectroscopic analysis of lipids synthesis in individual microalgae would significantly enhance our capability to understand the synthesis process at the cellular level and lead to the development of strategies for increasing yield. Stimulated Raman scattering (SRS) microscopy has great potential in this area however, the pump-probe signal from two-color two-photon absorption of pigments (chlorophyll and carotenoids) overwhelm the SRS signal and prevent its application. Clearly, the development of a background suppression technique is of significant value for this important research area. To overcome the limitation of SRS in pigmented specimens, we establish a frequency-modulated stimulated Raman scattering (FM-SRS) microscopy that eliminates the non-Raman background by rapidly toggling on-and-off the targeted Raman resonance. Moreover, we perform the background-free imaging and analysis of intracellular lipid droplets and extracellular hydrocarbons in a green microalga with FM-SRS microscopy. We believe that FM-SRS microscopy demonstrates the potential for many applications in pigmented cells and provides the opportunity for improved selective visualization of the chemical composition of algae and plants

  1. Biochemical Modulation of Lipid Pathway in Microalgae Dunaliella sp. for Biodiesel Production

    PubMed Central

    Talebi, Ahmad Farhad; Tohidfar, Masoud; Mousavi Derazmahalleh, Seyedeh Mahsa; Sulaiman, Alawi; Baharuddin, Azhari Samsu; Tabatabaei, Meisam

    2015-01-01

    Exploitation of renewable sources of energy such as algal biodiesel could turn energy supplies problem around. Studies on a locally isolated strain of Dunaliella sp. showed that the mean lipid content in cultures enriched by 200 mg L−1 myoinositol was raised by around 33% (1.5 times higher than the control). Similarly, higher lipid productivity values were achieved in cultures treated by 100 and 200 mg L−1 myoinositol. Fluorometry analyses (microplate fluorescence and flow cytometry) revealed increased oil accumulation in the Nile red-stained algal samples. Moreover, it was predicted that biodiesel produced from myoinositol-treated cells possessed improved oxidative stability, cetane number, and cloud point values. From the genomic point of view, real-time analyses revealed that myoinositol negatively influenced transcript abundance of AccD gene (one of the key genes involved in lipid production pathway) due to feedback inhibition and that its positive effect must have been exerted through other genes. The findings of the current research are not to interprete that myoinositol supplementation could answer all the challenges faced in microalgal biodiesel production but instead to show that “there is a there there” for biochemical modulation strategies, which we achieved, increased algal oil quantity and enhanced resultant biodiesel quality. PMID:26146623

  2. Formulation, Characterization and Evaluation of Paclitaxel loaded Solid Lipid Nanoparticles Prepared by Temperature Modulated Solidification Technique

    NASA Astrophysics Data System (ADS)

    Deshpande, Ameya Abhay

    The aim of this research was to formulate, characterize, and evaluate the paclitaxel loaded solid lipid nanoparticles (SLNs) prepared by a temperature modulated solidification technique developed and optimized in our laboratory. The particle size analysis through dynamic light scattering (DLS) and transmission electron microscopy (TEM) revealed and confirmed the spherical shape and nanometer size range of the formulated nanoparticles. Zeta potential measurements confirmed the physical stability of the SLNs with a negative surface charge. Atomic force microscopy (AFM) studies were done to study the surface topography and particle size and shape. AFM data showed minimal aggregation and more or less spherical SLNs. Differential scanning calorimetry (DSC), powder X-ray diffraction (P-XRD) and Fourier transform infrared spectroscopy (ATR-FTIR) confirmed the conversion of bulk lipid into SLNs and high entrapment of paclitaxel into the lipid matrix. The optimized formulation had an entrapment efficiency of approximately 62%. The in-vitro drug release depicted a sustained release of paclitaxel from the SLNs over duration of one week. The drug release data was found to best fit and hence followed the Higuchi drug-release model.

  3. Biochemical Modulation of Lipid Pathway in Microalgae Dunaliella sp. for Biodiesel Production.

    PubMed

    Talebi, Ahmad Farhad; Tohidfar, Masoud; Mousavi Derazmahalleh, Seyedeh Mahsa; Sulaiman, Alawi; Baharuddin, Azhari Samsu; Tabatabaei, Meisam

    2015-01-01

    Exploitation of renewable sources of energy such as algal biodiesel could turn energy supplies problem around. Studies on a locally isolated strain of Dunaliella sp. showed that the mean lipid content in cultures enriched by 200 mg L(-1) myoinositol was raised by around 33% (1.5 times higher than the control). Similarly, higher lipid productivity values were achieved in cultures treated by 100 and 200 mg L(-1) myoinositol. Fluorometry analyses (microplate fluorescence and flow cytometry) revealed increased oil accumulation in the Nile red-stained algal samples. Moreover, it was predicted that biodiesel produced from myoinositol-treated cells possessed improved oxidative stability, cetane number, and cloud point values. From the genomic point of view, real-time analyses revealed that myoinositol negatively influenced transcript abundance of AccD gene (one of the key genes involved in lipid production pathway) due to feedback inhibition and that its positive effect must have been exerted through other genes. The findings of the current research are not to interprete that myoinositol supplementation could answer all the challenges faced in microalgal biodiesel production but instead to show that "there is a there there" for biochemical modulation strategies, which we achieved, increased algal oil quantity and enhanced resultant biodiesel quality.

  4. Dynamic Modulation of the Glycosphingolipid Content in Supported Lipid Bilayers by Glycolipid Transfer Protein

    PubMed Central

    Carton, Ixaskun; Lucy Malinina; Richter, Ralf P.

    2010-01-01

    Supported lipid bilayers (SLBs) are popular models of cell membranes. Owing to the importance of glycosphingolipids (GSLs) in modulating structure and function of membranes and membrane proteins, methods to tune the GSL content in SLBs would be desirable. Glycolipid transfer protein (GLTP) can selectively transfer GSLs between membrane compartments. Using the ganglioside GM1 as a model GSL, and two mass-sensitive and label-free characterization techniques—quartz crystal microbalance with dissipation monitoring and ellipsometry—we demonstrate that GLTP is an efficient and robust biochemical tool to dynamically modulate the GSL content of SLBs up to 10 mol % GM1, and to quantitatively control the GSL content in the bulk-facing SLB leaflet. By exploiting what we believe to be a novel tool, we provide evidence that GM1 distributes highly asymmetrically in silica-supported lipid bilayers, with ∼85% of the ganglioside being present in the bulk-facing membrane leaflet. We report also that the pentameric B-subunit of cholera toxin binds with close-to-maximal stoichiometry to GM1 in SLBs over a large range of GM1 concentrations. Furthermore, we quantify the liganding affinity of GLTP for GM1 in an SLB context to be 1.5 μM. PMID:21044592

  5. Dynamic modulation of the glycosphingolipid content in supported lipid bilayers by glycolipid transfer protein.

    PubMed

    Carton, Ixaskun; Malinina, Lucy; Richter, Ralf P

    2010-11-03

    Supported lipid bilayers (SLBs) are popular models of cell membranes. Owing to the importance of glycosphingolipids (GSLs) in modulating structure and function of membranes and membrane proteins, methods to tune the GSL content in SLBs would be desirable. Glycolipid transfer protein (GLTP) can selectively transfer GSLs between membrane compartments. Using the ganglioside GM1 as a model GSL, and two mass-sensitive and label-free characterization techniques-quartz crystal microbalance with dissipation monitoring and ellipsometry-we demonstrate that GLTP is an efficient and robust biochemical tool to dynamically modulate the GSL content of SLBs up to 10 mol % GM1, and to quantitatively control the GSL content in the bulk-facing SLB leaflet. By exploiting what we believe to be a novel tool, we provide evidence that GM1 distributes highly asymmetrically in silica-supported lipid bilayers, with ∼85% of the ganglioside being present in the bulk-facing membrane leaflet. We report also that the pentameric B-subunit of cholera toxin binds with close-to-maximal stoichiometry to GM1 in SLBs over a large range of GM1 concentrations. Furthermore, we quantify the liganding affinity of GLTP for GM1 in an SLB context to be 1.5 μM. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  6. Postprandial Oxidative Stress and Gastrointestinal Hormones: Is There a Link?

    PubMed Central

    Malinska, Hana; Kahleova, Hana; Topolcan, Ondrej; Vrzalova, Jindra; Oliyarnyk, Olena; Kazdova, Ludmila; Belinova, Lenka; Hill, Martin; Pelikanova, Terezie

    2014-01-01

    Background Abnormal postprandial elevation of plasma glucose and lipids plays an important role in the pathogenesis of diabetes and strongly predicts cardiovascular mortality. In patients suffering from type 2 diabetes (T2D) postprandial state is associated with oxidative stress, cardiovascular risk and, probably, with impairment of both secretion and the effect of gastrointestinal peptides. Evaluating postprandial changes of gastrointestinal hormones together with changes in oxidative stress markers may help to understand the mechanisms behind the postprandial state in diabetes as well as suggest new preventive and therapeutical strategies. Methods A standard meal test has been used for monitoring the postprandial concentrations of gastrointestinal hormones and oxidative stress markers in patients with T2D (n = 50) compared to healthy controls (n = 50). Blood samples were drawn 0, 30, 60, 120 and 180 minutes after the standard meal. Results Both basal and postprandial plasma concentrations of glucose and insulin proved to be significantly higher in patients with T2D, whereas plasma concentrations of ghrelin showed significantly lower values during the whole meal test. In comparison with healthy controls, both basal and postprandial concentrations of almost all other gastrointestinal hormones and lipoperoxidation were significantly increased while ascorbic acid, reduced glutathione and superoxide dismutase activity were decreased in patients with T2D. A positive relationship was found between changes in GIP and those of glucose and immunoreactive insulin in diabetic patients (p<0.001 and p<0.001, respectively) and between changes in PYY and those of glucose (p<0.01). There was a positive correlation between changes in GIP and PYY and changes in ascorbic acid in patients with T2D (p<0.05 and p<0.001, respectively). Conclusion/Interpretation Apart from a positive relationship of postprandial changes in GIP and PYY with changes in ascorbic acid, there was no

  7. Carbon Monoxide Modulates Connexin Function through a Lipid Peroxidation-Dependent Process: A Hypothesis

    PubMed Central

    Retamal, Mauricio A.

    2016-01-01

    Hemichannels are ion channels composed of six connexins (Cxs), and they have the peculiarity to be permeable not only to ions, but also to molecules such as ATP and glutamate. Under physiological conditions they present a low open probability, which is sufficient to enable them to participate in several physiological functions. However, massive and/or prolonged hemichannel opening induces or accelerates cell death. Therefore, the study of the molecular mechanisms that control hemichannel activity appears to be essential for understanding several physiological and pathological processes. Carbon monoxide (CO) is a gaseous transmitter that modulates many cellular processes, some of them through modulation of ion channel activity. CO exerts its biological actions through the activation of guanylate cyclase and/or inducing direct carbonylation of proline, threonine, lysine, and arginine. It is well accepted that guanylate cyclase dependent pathway and direct carbonylation, are not sensitive to reducing agents. However, it is important to point out that CO—through a lipid peroxide dependent process—can also induce a secondary carbonylation in cysteine groups, which is sensitive to reducing agents. Recently, in our laboratory we demonstrated that the application of CO donors to the bath solution inhibited Cx46 hemichannel currents in Xenopus laevis oocytes, a phenomenon that was fully reverted by reducing agents. Therefore, a plausible mechanism of CO-induced Cx46 hemichannel inhibition is through Cx46-lipid oxidation. In this work, I will present current evidence and some preliminary results that support the following hypothesis: Carbon monoxide inhibits Cx46 HCs through a lipid peroxidation-dependent process. The main goal of this paper is to broaden the scientific community interest in studying the relationship between CO-Fatty acids and hemichannels, which will pave the way to more research directed to the understanding of the molecular mechanism(s) that control

  8. The Vascular Implications of Post-prandial Lipoprotein Metabolism

    PubMed Central

    Sullivan, David R; Celermajer, David S; Le Couteur, David G; Lam, Christopher W K

    2004-01-01

    Impaired lipoprotein metabolism is one of the major aetiological factors for the pathogenesis of atherosclerosis and cardiovascular disease (CVD). Assessment is usually made in the fasting state, and particular attention is directed towards the measurement of the cholesterol content of both the low and high-density lipoprotein fractions. By comparison, a massive amount of lipid fluxes through the intra-vascular compartment during the post-prandial period. This has led to the hypothesis that atherosclerosis could be partially, or even predominantly, due to the pathological effects of this flux of post-prandial lipoproteins on the vessel wall. This justifies efforts to systematically study the relationship between the lipoprotein responses to food (particularly fat) ingestion and cardiovascular disease or its surrogate markers. This review will consider the mechanisms by which post-prandial metabolism might affect the risk of CVD. It will examine the evidence for and against such an association. It will also consider the practical and methodological issues that are likely to determine the future utility of post-prandial lipoprotein assessment. PMID:18516208

  9. Arabidopsis SEIPIN Proteins Modulate Triacylglycerol Accumulation and Influence Lipid Droplet Proliferation[OPEN

    PubMed Central

    2015-01-01

    The lipodystrophy protein SEIPIN is important for lipid droplet (LD) biogenesis in human and yeast cells. In contrast with the single SEIPIN genes in humans and yeast, there are three SEIPIN homologs in Arabidopsis thaliana, designated SEIPIN1, SEIPIN2, and SEIPIN3. Essentially nothing is known about the functions of SEIPIN homologs in plants. Here, a yeast (Saccharomyces cerevisiae) SEIPIN deletion mutant strain and a plant (Nicotiana benthamiana) transient expression system were used to test the ability of Arabidopsis SEIPINs to influence LD morphology. In both species, expression of SEIPIN1 promoted accumulation of large-sized lipid droplets, while expression of SEIPIN2 and especially SEIPIN3 promoted small LDs. Arabidopsis SEIPINs increased triacylglycerol levels and altered composition. In tobacco, endoplasmic reticulum (ER)-localized SEIPINs reorganized the normal, reticulated ER structure into discrete ER domains that colocalized with LDs. N-terminal deletions and swapping experiments of SEIPIN1 and 3 revealed that this region of SEIPIN determines LD size. Ectopic overexpression of SEIPIN1 in Arabidopsis resulted in increased numbers of large LDs in leaves, as well as in seeds, and increased seed oil content by up to 10% over wild-type seeds. By contrast, RNAi suppression of SEIPIN1 resulted in smaller seeds and, as a consequence, a reduction in the amount of oil per seed compared with the wild type. Overall, our results indicate that Arabidopsis SEIPINs are part of a conserved LD biogenesis machinery in eukaryotes and that in plants these proteins may have evolved specialized roles in the storage of neutral lipids by differentially modulating the number and sizes of lipid droplets. PMID:26362606

  10. β2-Adrenergic receptor ablation modulates hepatic lipid accumulation and glucose tolerance in aging mice.

    PubMed

    Shi, Yun; Shu, Zhen-Ju; Xue, Xiaoling; Yeh, Chih-Ko; Katz, Michael S; Kamat, Amrita

    2016-06-01

    Catecholamines acting through β-adrenergic receptors (β(1)-, β(2)-, β(3)-AR subtypes) modulate important biological responses in various tissues. Our previous studies suggest a role for increased hepatic β-AR-mediated signaling during aging as a mediator of hepatic steatosis, liver glucose output, and insulin resistance in rodents. In the current study, we have utilized β(2)-AR knockout (KO) and wildtype (WT) control mice to define further the role of β(2)-AR signaling during aging on lipid and glucose metabolism. Our results demonstrate for the first time that age-related increases in hepatic triglyceride accumulation and body weight are attenuated upon β(2)-AR ablation. Although no differences in plasma triglyceride, non-esterified fatty acids or insulin levels were detected between old WT and KO animals, an age-associated increase in hepatic expression of lipid homeostasis regulator Cidea was significantly reduced in old KO mice. Interestingly, we also observed a shift from reduced glucose tolerance in young adult KO animals to significantly improved glucose tolerance in old KO when compared to age-matched WT mice. These results provide evidence for an important role played by β(2)-ARs in the regulation of lipid and glucose metabolism during aging. The effect of β(2)-AR ablation on caloric intake during aging is currently not known and requires investigation. Future studies are also warranted to delineate the β(2)-AR-mediated mechanisms involved in the control of lipid and glucose homeostasis, especially in the context of a growing aging population. Published by Elsevier Inc.

  11. Arabidopsis SEIPIN Proteins Modulate Triacylglycerol Accumulation and Influence Lipid Droplet Proliferation.

    PubMed

    Cai, Yingqi; Goodman, Joel M; Pyc, Michal; Mullen, Robert T; Dyer, John M; Chapman, Kent D

    2015-09-01

    The lipodystrophy protein SEIPIN is important for lipid droplet (LD) biogenesis in human and yeast cells. In contrast with the single SEIPIN genes in humans and yeast, there are three SEIPIN homologs in Arabidopsis thaliana, designated SEIPIN1, SEIPIN2, and SEIPIN3. Essentially nothing is known about the functions of SEIPIN homologs in plants. Here, a yeast (Saccharomyces cerevisiae) SEIPIN deletion mutant strain and a plant (Nicotiana benthamiana) transient expression system were used to test the ability of Arabidopsis SEIPINs to influence LD morphology. In both species, expression of SEIPIN1 promoted accumulation of large-sized lipid droplets, while expression of SEIPIN2 and especially SEIPIN3 promoted small LDs. Arabidopsis SEIPINs increased triacylglycerol levels and altered composition. In tobacco, endoplasmic reticulum (ER)-localized SEIPINs reorganized the normal, reticulated ER structure into discrete ER domains that colocalized with LDs. N-terminal deletions and swapping experiments of SEIPIN1 and 3 revealed that this region of SEIPIN determines LD size. Ectopic overexpression of SEIPIN1 in Arabidopsis resulted in increased numbers of large LDs in leaves, as well as in seeds, and increased seed oil content by up to 10% over wild-type seeds. By contrast, RNAi suppression of SEIPIN1 resulted in smaller seeds and, as a consequence, a reduction in the amount of oil per seed compared with the wild type. Overall, our results indicate that Arabidopsis SEIPINs are part of a conserved LD biogenesis machinery in eukaryotes and that in plants these proteins may have evolved specialized roles in the storage of neutral lipids by differentially modulating the number and sizes of lipid droplets. © 2015 American Society of Plant Biologists. All rights reserved.

  12. SEPP1 polymorphisms modulate serum glucose and lipid response to Brazil nut supplementation.

    PubMed

    Donadio, Janaina L S; Rogero, Marcelo M; Guerra-Shinohara, Elvira M; Desmarchelier, Charles; Borel, Patrick; Cozzolino, Silvia M F

    2017-05-13

    The consumption of Brazil nuts has been associated with benefits to lipid metabolism and reductions in total cholesterol and LDL concentrations. They are the richest natural source of selenium which has essential functions in human physiology. Genetic polymorphisms in Selenoprotein P could impair lipid and glucose metabolisms. The aim of this work was to verify the influence of polymorphisms in genes for selenoproteins on blood lipid levels after dietary supplementation with Brazil nuts in healthy adults. The study included 130 healthy volunteers selected at the University of São Paulo, Brazil. They were supplemented with one nut a day for 8 weeks, followed by 8 weeks without intervention. The following analyses were performed: anthropometric measurements, serum fasting glucose, lipid profile, C-reactive protein and plasma MDA levels. The volunteers were genotyped for SNPs rs1050450, rs3811699, rs1800699, rs713041, rs3877899, rs7579, rs34713741, and rs5845 in genes for selenoproteins. The concentrations of total cholesterol and fasting glucose levels decreased after 8 weeks of supplementation (p < 0.05). Glucose levels were modulated by rs3877899 in SEPP1, with significantly lower levels observed for individuals with the GA + AA genotype (p = 0.025). In addition, rs7579 was associated with cholesterol concentrations, which were significantly lower for individuals with the GG genotype (p = 0.053). Supplementation with one Brazil nut a day for 8 weeks reduced total cholesterol and glucose levels. Furthermore, our results suggest that rs3877899 might be associated with glucose concentrations and rs7579 with cholesterol concentrations. Therefore, the effect of genetic variations should be considered in future nutritional interventions evaluating the response to Brazil nut supplementation.

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

    PubMed Central

    Frank, Daniel N.; Bales, Elise S.; Monks, Jenifer; Jackman, Matthew J.; MacLean, Paul S.; Ir, Diana; Robertson, Charles E.; Orlicky, David J.; McManaman, James L.

    2015-01-01

    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. PMID:26147095

  14. Membranes as programmable matter: modulating physical-chemical behavior in lipid ensembles derived from archaea and eukaryotes

    NASA Astrophysics Data System (ADS)

    Gilmore, Sean Fitzpatrick

    Lipid membranes are of general interest to the scientific community due to their roles as cellular membranes, and because of their interesting material properties, such as tendencies to self-assemble into two- and three-dimensional structures. Further, there is interest in using lipid membranes as a self-assembling template or substrate for other materials, such as membrane proteins. The work presented here explores the physical-chemical interactions in and around artificial lipid membranes. In the first two chapters, lipid membranes are investigated as a form of programmable matter that responds to environmental changes. These responses manifest as two- and three-dimensional reorganization. In the subsequent chapters, the lipids of an extremophilic archaeon are examined in synthetic configurations to 1) identify how ensembles of lipids originating from organisms of different domains on the tree of life may behave in similar ways, and 2) to examine how the lipids of a desiccation-tolerant organism may be used to create robust lipid (bilayer) membranes that do not rely on liquid water to retain their structure. These collected findings expand how living membranes may be modulated or reorganized in vivo, and also suggest new ways to create programmable lipid-based materials.

  15. Postprandial Plasma Phospholipids in Men Are Influenced by the Source of Dietary Fat.

    PubMed

    Meikle, Peter J; Barlow, Christopher K; Mellett, Natalie A; Mundra, Piyushkumar A; Bonham, Maxine P; Larsen, Amy; Cameron-Smith, David; Sinclair, Andrew; Nestel, Paul J; Wong, Gerard

    2015-09-01

    Postprandial lipemia represents a risk factor for chronic diseases, including type 2 diabetes. Little is known about the effect of dietary fat on the plasma lipidome in the postprandial period. The objective of this study was to assess the effect of dairy fat and soy oil on circulating postprandial lipids in men. Men (40-60 y old, nonsmokers; n = 16) were randomly assigned in a crossover design to consume 2 breakfast meals of dairy-based or soy oil-based foods. The changes in the plasma lipidome during the 4-h postprandial period were analyzed with electrospray ionization tandem mass spectrometry and included 316 lipid species in 23 classes and subclasses, representing sphingolipids, phospholipids, glycerolipids, and sterols. Nonparametric Friedman tests showed significant changes in multiple plasma lipid classes, subclasses, and species in the postprandial period after both dairy and soy meals. No difference was found in triglyceridemia after each meal. However, 6 endogenous lipid classes increased after dairy but decreased after soy (P < 0.05), including ether-linked phospholipids and plasmalogens and sphingomyelin (not present in soy), dihexosylceramide, and GM3 ganglioside. Phosphatidylcholine and phosphatidylinositol were not affected by the soy meal but were significantly elevated after the dairy meal (8.3% and 16%, respectively; P < 0.05). The changes in postprandial plasma phospholipids in men relate to the diet composition and the relative size of the endogenous phospholipid pools. Despite similar lipemic responses as measured by changes in triglyceride concentrations, the differential responses to dairy and soy meals derived through lipidomic analysis of phospholipids suggest differences in the metabolism of soybean oil and dairy fat. The increased concentrations of plasmalogens, with potential antioxidant capacity, in the postprandial period after dairy but not soy meals may represent a further important difference in the response to these sources of fat

  16. Ouabain Modulates the Lipid Composition of Hippocampal Plasma Membranes from Rats with LPS-induced Neuroinflammation.

    PubMed

    Garcia, Israel José Pereira; Kinoshita, Paula Fernanda; Scavone, Cristoforo; Mignaco, Julio Alberto; Barbosa, Leandro Augusto de Oliveira; Santos, Hérica de Lima

    2015-12-01

    The effects of ouabain (OUA) and lipopolysaccharide (LPS) in vivo on hippocampal membranes (RHM) of Wistar male rats aged 3 months were analyzed. After intraperitoneal (i.p.) injection of OUA only, LPS only, OUA plus LPS, or saline, the content of proteins, phospholipids, cholesterol and gangliosides from RHM was analyzed. The total protein and cholesterol contents of RHM were not significantly affected by OUA or LPS for the experimentally paired groups. In contrast, total phospholipids and gangliosides were strongly modulated by either OUA or LPS treatments. LPS reduced the total phospholipids (roughly 23 %) and increased the total gangliosides (approximately 40 %). OUA alone increased the total phospholipids (around 23 %) and also the total gangliosides (nearly 34 %). OUA pretreatment compensated the LPS-induced changes, preserving the total phospholipids and gangliosides around the same levels of the control. Thus, an acute treatment with OUA not only modulated the composition of hippocampal membranes from 3-month-old rats, but also was apparently able to counteract membrane alterations resulting from LPS-induced neuroinflammation. This study demonstrates for the first time that the OUA capacity modulates the lipid composition of hippocampal plasma membranes from rats with LPS-induced neuroinflammation.

  17. Human plasma lipid modulation in schistosomiasis mansoni depends on apolipoprotein E polymorphism.

    PubMed

    Martins da Fonseca, Caíque Silveira; Pimenta Filho, Adenor Almeida; dos Santos, Bianka Santana; da Silva, César Augusto; Domingues, Ana Lúcia Coutinho; Owen, James Stuart; Lima, Vera Lúcia de Menezes

    2014-01-01

    Schistosomiasis mansoni is a parasitic liver disease, which causes several metabolic disturbances. Here, we evaluate the influence of Apolipoprotein E (APOE) gene polymorphism, a known modulator of lipid metabolism, on plasma lipid levels in patients with hepatosplenic schistosomiasis. Blood samples were used for APOE genotyping and to measure total cholesterol (TC), LDL-C, HDL-C and triglycerides. Schistosomiasis patients had reduced TC, LDL-C and triglycerides (25%, 38% and 32% lower, respectively; P<0.0001) compared to control individuals, whereas HDL-C was increased (10% higher; P = 0.0136). Frequency of the common alleles, ε2, ε3 and ε4, was similar (P = 0.3568) between controls (n = 108) and patients (n = 84), implying that APOE genotype did not affect susceptibility to the advanced stage of schistosomiasis. Nevertheless, while patient TC and LDL-C levels were significantly reduced for each allele (except TC in ε2 patients), changes in HDL-C and triglycerides were noted only for the less common ε2 and ε4 alleles. The most striking finding, however, was that accepted regulation of plasma lipid levels by APOE genotype was disrupted by schistosomiasis. Thus, while ε2 controls had higher TC and LDL-C than ε3 carriers, these parameters were lower in ε2 versus ε3 patients. Similarly, the inverse relationship of TG levels in controls (ε2>ε3>ε4) was absent in patients (ε2 or ε4>ε3), and the increase in HDL-C of ε2 or ε4 patients compared to ε3 patients was not seen in the control groups. We confirm that human schistosomiasis causes dyslipidemia and report for the first time that certain changes in plasma lipid and lipoprotein levels depend on APOE gene polymorphism. Importantly, we also concluded that S. mansoni disrupts the expected regulation of plasma lipids by the different ApoE isoforms. This finding suggests ways to identify new metabolic pathways affected by schistosomiasis and also potential molecular targets to treat

  18. Postprandial elevation of remnant lipoprotein leads to endothelial dysfunction.

    PubMed

    Funada, Jun-ichi; Sekiya, Michihito; Hamada, Mareomi; Hiwada, Kunio

    2002-02-01

    Recent studies have demonstrated that elevated levels of cholesterol in the form of remnant-like particles (RLP-C) induce deterioration of endothelial function during the fasting state, but it is not known whether postprandial RLP-C elevation has the same effect. The objective of this study was to assess the effect of postprandial RLP-C elevation on endothelial function in 24 fasting normolipidemic subjects. Flow-mediated dilatation (FMD) during reactive hyperemia in the brachial artery was investigated. Serum lipids and lipoproteins during fasting and 4h after regular fat-loading were measured. Subjects were divided into 2 groups: the high responders (postprandial RLP-C level >7.5mg/dl, n=8) and the normal responders (postprandial RLP-C level < or =7.5mg/dl, n=16). Significant increases in the level of both triglycerides and RLP-C were observed in the high responders. Basal FMD in the high responders (4.3+/-3.0%) was significantly lower than that in the normal responders (8.3+/-2.4%) (p<0.01), but FMD after the fat-loading in both groups did not change significantly. The change in RLP-C levels during the fat-loading test correlated significantly with basal FMD (r=-0.588, p<0.01). Multiple regression analysis showed a significant correlation between basal FMD and the change in RLP-C levels (r=-0.488, p<0.02). The results of this study suggest that postprandial RLP-C elevation could be associated with atherosclerotic progression even in normolipidemic subjects.

  19. Effect of Spirulina maxima on postprandial lipemia in young runners: a preliminary report.

    PubMed

    Torres-Durán, Patricia Victoria; Ferreira-Hermosillo, Aldo; Ramos-Jiménez, Arnulfo; Hernández-Torres, Rosa Patricia; Juárez-Oropeza, Marco Antonio

    2012-08-01

    Trained people exhibit low plasma concentrations of triacylglcyerols in both fasting and postprandial states. Exercise practice is commonly believed to improve postprandial lipemia. In addition, elevated postprandial lipemia is an indicator of poor lipid clearance, and it has been associated with atherosclerosis, insulin resistance, and obesity. Spirulina maxima is an edible microorganism with a high nutritional value. When it is consumed, beneficial properties to health have been demonstrated, such as hypolipemic and antihypertensive properties in human beings. This work evaluates the effects of orally administrated S. maxima on postprandial lipemia in a young Mexican sporting population after 15 days of consumption, as a possible alternative treatment to improve their lipid clearance. Forty-one runners (10-26 years old; 21 men and 20 women) volunteered to participate in the study. All of them were physically active for at least 1 year before the study and were not undergoing training during the study. The subjects consumed 5 g of Spirulina during 15 days. Before and after the treatment with Spirulina, they consumed (12 h fasting) a standardized meal with high fat content (53.2% total calories). Postprandial lipemia was measured at 1.5, 3, and 4.5 h after the fatty meal. Fasting plasma triacylglycerol (TAG) concentrations were lower after Spirulina treatment than before treatment. In addition, the postprandial area under the curve of TAG concentrations was lower after the treatment with Spirulina. Sixty-two percent of the youngest runners (10-16 years) studied exhibited the best response to the treatment. Orally administered S. maxima decreased postprandial lipemia in sporting teenagers. The youngest people were the most responsive to the beneficial effects of Spirulina on postprandial lipemia.

  20. Effect of Spirulina maxima on Postprandial Lipemia in Young Runners: A Preliminary Report

    PubMed Central

    Torres-Durán, Patricia Victoria; Ferreira-Hermosillo, Aldo; Ramos-Jiménez, Arnulfo; Hernández-Torres, Rosa Patricia

    2012-01-01

    Abstract Trained people exhibit low plasma concentrations of triacylglcyerols in both fasting and postprandial states. Exercise practice is commonly believed to improve postprandial lipemia. In addition, elevated postprandial lipemia is an indicator of poor lipid clearance, and it has been associated with atherosclerosis, insulin resistance, and obesity. Spirulina maxima is an edible microorganism with a high nutritional value. When it is consumed, beneficial properties to health have been demonstrated, such as hypolipemic and antihypertensive properties in human beings. This work evaluates the effects of orally administrated S. maxima on postprandial lipemia in a young Mexican sporting population after 15 days of consumption, as a possible alternative treatment to improve their lipid clearance. Forty-one runners (10–26 years old; 21 men and 20 women) volunteered to participate in the study. All of them were physically active for at least 1 year before the study and were not undergoing training during the study. The subjects consumed 5 g of Spirulina during 15 days. Before and after the treatment with Spirulina, they consumed (12 h fasting) a standardized meal with high fat content (53.2% total calories). Postprandial lipemia was measured at 1.5, 3, and 4.5 h after the fatty meal. Fasting plasma triacylglycerol (TAG) concentrations were lower after Spirulina treatment than before treatment. In addition, the postprandial area under the curve of TAG concentrations was lower after the treatment with Spirulina. Sixty-two percent of the youngest runners (10–16 years) studied exhibited the best response to the treatment. Orally administered S. maxima decreased postprandial lipemia in sporting teenagers. The youngest people were the most responsive to the beneficial effects of Spirulina on postprandial lipemia. PMID:22738038

  1. Liver Med23 ablation improves glucose and lipid metabolism through modulating FOXO1 activity

    PubMed Central

    Chu, Yajing; Rosso, Leonardo Gómez; Huang, Ping; Wang, Zhichao; Xu, Yichi; Yao, Xiao; Bao, Menghan; Yan, Jun; Song, Haiyun; Wang, Gang

    2014-01-01

    Mediator complex is a molecular hub integrating signaling, transcription factors, and RNA polymerase II (RNAPII) machinery. Mediator MED23 is involved in adipogenesis and smooth muscle cell differentiation, suggesting its role in energy homeostasis. Here, through the generation and analysis of a liver-specific Med23-knockout mouse, we found that liver Med23 deletion improved glucose and lipid metabolism, as well as insulin responsiveness, and prevented diet-induced obesity. Remarkably, acute hepatic Med23 knockdown in db/db mice significantly improved the lipid profile and glucose tolerance. Mechanistically, MED23 participates in gluconeogenesis and cholesterol synthesis through modulating the transcriptional activity of FOXO1, a key metabolic transcription factor. Indeed, hepatic Med23 deletion impaired the Mediator and RNAPII recruitment and attenuated the expression of FOXO1 target genes. Moreover, this functional interaction between FOXO1 and MED23 is evolutionarily conserved, as the in vivo activities of dFOXO in larval fat body and in adult wing can be partially blocked by Med23 knockdown in Drosophila. Collectively, our data revealed Mediator MED23 as a novel regulator for energy homeostasis, suggesting potential therapeutic strategies against metabolic diseases. PMID:25223702

  2. Modulation of human lipids and lipoproteins by dietary palm oil and palm olein: a review.

    PubMed

    Sundram, K

    1997-03-01

    Several human clinical trials have now evaluated palm oil's effects on blood lipids and lipoproteins. These studies suggest that palm oil and palm olein diets do not raise plasma TC and LDL-cholesterol levels to the extent expected from its fatty acid composition. With maximum substitution of palm oil in a Western type diet some coronary heart disease risk factors were beneficially modulated: HDL2-cholesterol was significantly increased while the apolipoprotein B/A1 ratio was beneficially lowered by palm oil. Comparison of palm olein with a variety of monounsaturated edible oils including rapeseed, canola, and olive oils has shown that plasma and LDL-cholesterol were not elevated by palm olein. To focus these findings, specific fatty acid effects have been evaluated. Myristic acid may be the most potent cholesterol raising saturated fatty acid. Palmitic acid effects were largely comparable to the monounsaturated oleic acid in normolipidaemic subjects while trans fatty acids detrimentally increased plasma cholesterol, LDL-cholesterol, lipoprotein Lp(a) and lowered the beneficial HDL-cholesterol. Apart from these fatty acids there is evidence that the tocotrienols in palm oil products may have a hypocholesterolaemic effect. This is mediated by the ability of the tocotrienols to suppress HMG-CoA reductase. These new findings on palm oil merit a scientific reexamination of the classical saturated fat-lipid hypothesis and its role in lipoprotein regulation.

  3. Exported Epoxide Hydrolases Modulate Erythrocyte Vasoactive Lipids during Plasmodium falciparum Infection

    PubMed Central

    Dalmia, Varun K.

    2016-01-01

    ABSTRACT Erythrocytes are reservoirs of important epoxide-containing lipid signaling molecules, including epoxyeicosatrienoic acids (EETs). EETs function as vasodilators and anti-inflammatory modulators in the bloodstream. Bioactive EETs are hydrolyzed to less active diols (dihydroxyeicosatrienoic acids) by epoxide hydrolases (EHs). The malaria parasite Plasmodium falciparum infects host red blood cells (RBCs) and exports hundreds of proteins into the RBC compartment. In this study, we show that two parasite epoxide hydrolases, P. falciparum epoxide hydrolases 1 (PfEH1) and 2 (PfEH2), both with noncanonical serine nucleophiles, are exported to the periphery of infected RBCs. PfEH1 and PfEH2 were successfully expressed in Escherichia coli, and they hydrolyzed physiologically relevant erythrocyte EETs. Mutations in active site residues of PfEH1 ablated the ability of the enzyme to hydrolyze an epoxide substrate. Overexpression of PfEH1 or PfEH2 in parasite-infected RBCs resulted in a significant alteration in the epoxide fatty acids stored in RBC phospholipids. We hypothesize that the parasite disruption of epoxide-containing signaling lipids leads to perturbed vascular function, creating favorable conditions for binding and sequestration of infected RBCs to the microvascular endothelium. PMID:27795395

  4. Temperature induced modulation of lipid oxidation and lipid accumulation in palmitate-mediated 3T3-L1 adipocytes and 3T3-L1 adipocytes.

    PubMed

    Lin, Xiaofen; Li, Yi; Leung, Polly Hangmei; Li, Jiashen; Hu, Junyan; Liu, Xuan; Li, Zhi

    2016-05-01

    Human skin temperature can vary widely depending on anatomical location and ambient temperature. It is also known that local changes in skin and subcutaneous temperature can affect fat metabolism. This study aimed to explore the potential effects of surrounding thermal environment on fat by investigating cell viability, lipid oxidation, and lipid accumulation in 3T3-L1 adipocytes and palmitate-treated adipocytes after 4h incubation. No significant differences of viability in 3T3-L1 adipocytes were detected under different temperature conditions. Despite no significant increase being observed under warm temperature (39°C) conditions, a similarly significant suppression of intracellular reactive oxygen species (ROS) and lipid peroxidation were found in 3T3-L1 adipocytes and palmitate-treated adipocytes under 4h exposure to cooler temperatures of 31-33°C (P<0.01). ROS, chemically reactive molecules containing oxygen, are currently understood to be a major contributor to oxidantive stress in obesity. Additionally, cooler temperatures (31-33°C) could improve the size of lipid droplets in 3T3-L1 adipocytes (P<0.01), but no significant effect was generated by temperature change on lipid droplets in palmitate-treated adipocytes. In the palmitate-induced adiposity model, although excessive ROS and lipid peroxidation has been attenuated by temperature decrease (P<0.01), it still does not positively modulate lipid droplet size (P>0.05) and remedy the palmitate damage induced cell death (P<0.01). These findings provide preliminary support for potential interventions based on temperature manipulation for cell metabolism of adipocytes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Effects of roux-en-Y gastric bypass surgery on postprandial fructose metabolism.

    PubMed

    Surowska, Anna; De Giorgi, Sara; Theytaz, Fanny; Campos, Vanessa; Hodson, Leanne; Stefanoni, Nathalie; Rey, Valentine; Schneiter, Philippe; Laville, Martine; Giusti, Vittorio; Gabert, Laure; Tappy, Luc

    2016-03-01

    Fructose is partly metabolized in small bowel enterocytes, where it can be converted into glucose or fatty acids. It was therefore hypothesized that Roux-en-Y gastric bypass (RYGB) may significantly alter fructose metabolism. We performed a randomized clinical study in eight patients 12-17 months after RYGB and eight control (Ctrl) subjects. Each participant was studied after ingestion of a protein and lipid meal (PL) and after ingestion of a protein+lipid+fructose+glucose meal labeled with (13) C-fructose (PLFG). Postprandial blood glucose, fructose, lactate, apolipoprotein B48 (apoB48), and triglyceride (TG) concentrations, (13) C-palmitate concentrations in chylomicron-TG and VLDL-TG, fructose oxidation ((13) CO2 production), and gluconeogenesis from fructose (GNGf) were measured over 6 hours. After ingestion of PLFG, postprandial plasma fructose, glucose, insulin, and lactate concentrations increased earlier and reached higher peak values in RYGB than in Ctrl. GNGf was 33% lower in RYGB than Ctrl (P = 0.041), while fructose oxidation was unchanged. Postprandial incremental areas under the curves for total TG and chylomicrons-TG were 72% and 91% lower in RYGB than Ctrl (P = 0.064 and P = 0.024, respectively). ApoB48 and (13) C-palmitate concentrations were not significantly different. Postprandial fructose metabolism was not grossly altered, but postprandial lipid concentrations were markedly decreased in subjects having had RYGB surgery. © 2015 The Obesity Society.

  6. Isolated Polar Amino Acid Residues Modulate Lipid Binding in the Large Hydrophobic Cavity of CD1d.

    PubMed

    Inuki, Shinsuke; Aiba, Toshihiko; Hirata, Natsumi; Ichihara, Osamu; Yoshidome, Daisuke; Kita, Shunsuke; Maenaka, Katsumi; Fukase, Koichi; Fujimoto, Yukari

    2016-11-18

    The CD1d protein is a nonpolymorphic MHC class I-like protein that controls the activation of natural killer T (NKT) cells through the presentation of self- and foreign-lipid ligands, glycolipids, or phospholipids, leading to the secretion of various cytokines. The CD1d contains a large hydrophobic lipid binding pocket: the A' pocket of CD1d, which recognizes hydrophobic moieties of the ligands, such as long fatty acyl chains. Although lipid-protein interactions typically rely on hydrophobic interactions between lipid chains and the hydrophobic sites of proteins, we showed that the small polar regions located deep inside the hydrophobic A' pocket could be used for the modulation of the lipid binding. A series of the ligands, α-galactosyl ceramide (α-GalCer) derivatives containing polar groups in the acyl chain, was synthesized, and the structure-activity relationship studies demonstrated that simple modification from a methylene to an amide group in the long fatty acyl chain, when introduced at optimal positions, enhanced the CD1d recognition of the glycolipid ligands. Formation of hydrogen bonds between the amide group and the polar residues was supported by molecular dynamics (MD) simulations and WaterMap calculations. The computational studies suggest that localized hydrating water molecules may play an important role in the ligand recognition. Here, the results showed that confined polar residues in the large hydrophobic lipid binding pockets of the proteins could be potential targets to modulate the affinity for its ligands.

  7. The Herbal Bitter Drug Gentiana lutea Modulates Lipid Synthesis in Human Keratinocytes In Vitro and In Vivo

    PubMed Central

    Haarhaus, Birgit; Seiwerth, Jasmin; Cawelius, Anja; Schwabe, Kay; Quirin, Karl-Werner; Schempp, Christoph M.

    2017-01-01

    Gentiana lutea is a herbal bitter drug that is used to enhance gastrointestinal motility and secretion. Recently we have shown that amarogentin, a characteristic bitter compound of Gentiana lutea extract (GE), binds to the bitter taste receptors TAS2R1 and TAS2R38 in human keratinocytes, and stimulates the synthesis of epidermal barrier proteins. Here, we wondered if GE also modulates lipid synthesis in human keratinocytes. To address this issue, human primary keratinocytes were incubated for 6 days with GE. Nile Red labeling revealed that GE significantly increased lipid synthesis in keratinocytes. Similarly, gas chromatography with flame ionization detector indicated that GE increases the amount of triglycerides in keratinocytes. GE induced the expression of epidermal ceramide synthase 3, but not sphingomyelinase. Lipid synthesis, as well as ceramide synthase 3 expression, could be specifically blocked by inhibitors of the p38 MAPK and PPARγ signaling pathway. To assess if GE also modulates lipid synthesis in vivo, we performed a proof of concept half side comparison on the volar forearms of 33 volunteers. In comparison to placebo, GE significantly increased the lipid content of the treated skin areas, as measured with a sebumeter. Thus, GE enhances lipid synthesis in human keratinocytes that is essential for building an intact epidermal barrier. Therefore, GE might be used to improve skin disorders with an impaired epidermal barrier, e.g., very dry skin and atopic eczema. PMID:28829355

  8. The Herbal Bitter Drug Gentiana lutea Modulates Lipid Synthesis in Human Keratinocytes In Vitro and In Vivo.

    PubMed

    Wölfle, Ute; Haarhaus, Birgit; Seiwerth, Jasmin; Cawelius, Anja; Schwabe, Kay; Quirin, Karl-Werner; Schempp, Christoph M

    2017-08-22

    Gentiana lutea is a herbal bitter drug that is used to enhance gastrointestinal motility and secretion. Recently we have shown that amarogentin, a characteristic bitter compound of Gentiana lutea extract (GE), binds to the bitter taste receptors TAS2R1 and TAS2R38 in human keratinocytes, and stimulates the synthesis of epidermal barrier proteins. Here, we wondered if GE also modulates lipid synthesis in human keratinocytes. To address this issue, human primary keratinocytes were incubated for 6 days with GE. Nile Red labeling revealed that GE significantly increased lipid synthesis in keratinocytes. Similarly, gas chromatography with flame ionization detector indicated that GE increases the amount of triglycerides in keratinocytes. GE induced the expression of epidermal ceramide synthase 3, but not sphingomyelinase. Lipid synthesis, as well as ceramide synthase 3 expression, could be specifically blocked by inhibitors of the p38 MAPK and PPARγ signaling pathway. To assess if GE also modulates lipid synthesis in vivo, we performed a proof of concept half side comparison on the volar forearms of 33 volunteers. In comparison to placebo, GE significantly increased the lipid content of the treated skin areas, as measured with a sebumeter. Thus, GE enhances lipid synthesis in human keratinocytes that is essential for building an intact epidermal barrier. Therefore, GE might be used to improve skin disorders with an impaired epidermal barrier, e.g., very dry skin and atopic eczema.

  9. Modulating effect of lipid bilayer-carotenoid interactions on the property of liposome encapsulation.

    PubMed

    Xia, Shuqin; Tan, Chen; Zhang, Yating; Abbas, Shabbar; Feng, Biao; Zhang, Xiaoming; Qin, Fang

    2015-04-01

    Liposomes have become an attractive alternative to encapsulate carotenoids to improve their solubility, stability and bioavailability. The interaction mechanism of carotenoid with lipid bilayer is one of the major concerns in improving the delivery efficiency of liposomes. In this study, the microstructure and carotenoid encapsulation efficiency of liposomes composed of native phospholipid (egg yolk phosphatidylcholine, EYPC) and nonionic surfactant Tween 80 were investigated by atomic force microscopy, dynamic light scattering, and Raman spectroscopy, respectively. Subsequently, the effects of carotenoid incorporation on the physical properties of liposomal membrane were performed by Raman spectroscopy, fluorescence polarization, and electron paramagnetic resonance. Results showed that the incorporation of carotenoids affected the liposomes morphology, size and size distribution to various extents. Analysis on the Raman characteristic peaks of carotenoids revealed that lutein exhibited the strongest incorporating ability into liposomes, followed by β-carotene, lycopene, and canthaxanthin. Furthermore, it was demonstrated that carotenoids modulated the dynamics, structure and hydrophobicity of liposomal membrane, highly depending on their molecular structures and incorporated concentration. These modulations were closely correlated with the stabilization of liposomes, including mediating particle aggregation and fusion. These findings should guide the rationale designing for liposomal encapsulation technology to efficiently deliver carotenoids in pharmaceutics, nutraceuticals and functional foods.

  10. Modulation of endotoxicity of Shigella generalized modules for membrane antigens (GMMA) by genetic lipid A modifications: relative activation of TLR4 and TLR2 pathways in different mutants.

    PubMed

    Rossi, Omar; Pesce, Isabella; Giannelli, Carlo; Aprea, Susanna; Caboni, Mariaelena; Citiulo, Francesco; Valentini, Sara; Ferlenghi, Ilaria; MacLennan, Calman Alexander; D'Oro, Ugo; Saul, Allan; Gerke, Christiane

    2014-09-05

    Outer membrane particles from Gram-negative bacteria are attractive vaccine candidates as they present surface antigens in their natural context. We previously developed a high yield production process for genetically derived particles, called generalized modules for membrane antigens (GMMA), from Shigella. As GMMA are derived from the outer membrane, they contain immunostimulatory components, especially lipopolysaccharide (LPS). We examined ways of reducing their reactogenicity by modifying lipid A, the endotoxic part of LPS, through deletion of late acyltransferase genes, msbB or htrB, in GMMA-producing Shigella sonnei and Shigella flexneri strains. GMMA with resulting penta-acylated lipid A from the msbB mutants showed a 600-fold reduced ability, and GMMA from the S. sonnei ΔhtrB mutant showed a 60,000-fold reduced ability compared with GMMA with wild-type lipid A to stimulate human Toll-like receptor 4 (TLR4) in a reporter cell line. In human peripheral blood mononuclear cells, GMMA with penta-acylated lipid A showed a marked reduction in induction of inflammatory cytokines (S. sonnei ΔhtrB, 800-fold; ΔmsbB mutants, 300-fold). We found that the residual activity of these GMMA is largely due to non-lipid A-related TLR2 activation. In contrast, in the S. flexneri ΔhtrB mutant, a compensatory lipid A palmitoleoylation resulted in GMMA with hexa-acylated lipid A with ∼10-fold higher activity to stimulate peripheral blood mononuclear cells than GMMA with penta-acylated lipid A, mostly due to retained TLR4 activity. Thus, for use as vaccines, GMMA will likely require lipid A penta-acylation. The results identify the relative contributions of TLR4 and TLR2 activation by GMMA, which need to be taken into consideration for GMMA vaccine development.

  11. The synaptic recruitment of lipid rafts is dependent on CD19-PI3K module and cytoskeleton remodeling molecules.

    PubMed

    Xu, Liling; Auzins, Arturs; Sun, Xiaolin; Xu, Yinsheng; Harnischfeger, Fiona; Lu, Yun; Li, Zhanguo; Chen, Ying-Hua; Zheng, Wenjie; Liu, Wanli

    2015-08-01

    Sphingolipid- and cholesterol-rich lipid raft microdomains are important in the initiation of BCR signaling. Although it is known that lipid rafts promote the coclustering of BCR and Lyn kinase microclusters within the B cell IS, the molecular mechanism of the recruitment of lipid rafts into the B cell IS is not understood completely. Here, we report that the synaptic recruitment of lipid rafts is dependent on the cytoskeleton-remodeling proteins, RhoA and Vav. Such an event is also efficiently regulated by motor proteins, myosin IIA and dynein. Further evidence suggests the synaptic recruitment of lipid rafts is, by principle, an event triggered by BCR signaling molecules and second messenger molecules. BCR-activating coreceptor CD19 potently enhances such an event depending on its cytoplasmic Tyr421 and Tyr482 residues. The enhancing function of the CD19-PI3K module in synaptic recruitment of lipid rafts is also confirmed in human peripheral blood B cells. Thus, these results improve our understanding of the molecular mechanism of the recruitment of lipid raft microdomains in B cell IS.

  12. Docosahexaenoic acid modulates the enterocyte Caco-2 cell expression of microRNAs involved in lipid metabolism.

    PubMed

    Gil-Zamorano, Judit; Martin, Roberto; Daimiel, Lidia; Richardson, Kris; Giordano, Elena; Nicod, Nathalie; García-Carrasco, Belén; Soares, Sara M A; Iglesias-Gutiérrez, Eduardo; Lasunción, Miguel A; Sala-Vila, Aleix; Ros, Emilio; Ordovás, Jose M; Visioli, Francesco; Dávalos, Alberto

    2014-05-01

    Consumption of the long-chain ω-3 (n-3) polyunsaturated fatty acid docosahexaenoic acid (DHA) is associated with a reduced risk of cardiovascular disease and greater chemoprevention. However, the mechanisms underlying the biologic effects of DHA remain unknown. It is well known that microRNAs (miRNAs) are versatile regulators of gene expression. Therefore, we aimed to determine if the beneficial effects of DHA may be modulated in part through miRNAs. Loss of dicer 1 ribonuclease type III (DICER) in enterocyte Caco-2 cells supplemented with DHA suggested that several lipid metabolism genes are modulated by miRNAs. Analysis of miRNAs predicted to target these genes revealed several miRNA candidates that are differentially modulated by fatty acids. Among the miRNAs modulated by DHA were miR-192 and miR-30c. Overexpression of either miR-192 or miR-30c in enterocyte and hepatocyte cells suggested an effect on the expression of genes related to lipid metabolism, some of which were confirmed by endogenous inhibition of these miRNAs. Our results show in enterocytes that DHA exerts its biologic effect in part by regulating genes involved in lipid metabolism and cancer. Moreover, this response is mediated through miRNA activity. We validate novel targets of miR-30c and miR-192 related to lipid metabolism and cancer including nuclear receptor corepressor 2, isocitrate dehydrogenase 1, DICER, caveolin 1, ATP-binding cassette subfamily G (white) member 4, retinoic acid receptor β, and others. We also present evidence that in enterocytes DHA modulates the expression of regulatory factor X6 through these miRNAs. Alteration of miRNA levels by dietary components in support of their pharmacologic modulation might be valuable in adjunct therapy for dyslipidemia and other related diseases.

  13. Lean-seafood intake reduces cardiovascular lipid risk factors in healthy subjects: results from a randomized controlled trial with a crossover design.

    PubMed

    Aadland, Eli Kristin; Lavigne, Charles; Graff, Ingvild Eide; Eng, Øyvin; Paquette, Martine; Holthe, Asle; Mellgren, Gunnar; Jacques, Hélène; Liaset, Bjørn

    2015-09-01

    Observational studies have strongly indicated an association between fish consumption and reduced risk of cardiovascular disease, but data from randomized controlled trials have been inconclusive. Our primary outcome in this study was to elucidate the potentials of the 2 main dietary protein sources lean seafood and nonseafood to modulate fasting and postprandial lipids in healthy subjects. We hypothesized that lean-seafood intake would reduce cardiovascular lipid risk factors in healthy subjects more than would the intake of nonseafood protein sources. This study was a randomized controlled trial with a crossover design. After 3-wk run-in periods and separated by a 5-wk washout period, 20 healthy subjects (7 men and 13 women) consumed 2 balanced diets that varied in main protein sources (60% of total dietary proteins from lean-seafood or nonseafood sources for 4 wk). At days 1 and 28 of each intervention, fasting and postprandial blood samples were collected before and after consumption, respectively, of test meals with cod or lean beef. Relative to the nonseafood intervention, the lean-seafood intervention reduced fasting (relative difference by diets: 0.31 mmol/L; P = 0.03) and postprandial (P = 0.01) serum triacylglycerol concentrations. The lower serum triacylglycerol concentration was associated with reduced fasting triacylglycerol in chylomicrons and very-low-density lipoproteins (VLDLs) (P = 0.004), reduced fasting VLDL particle size (P = 0.04), and a reduced postprandial concentration of medium-sized VLDL particles (P = 0.02). The lean-seafood intervention prevented the elevated ratio of total cholesterol to HDL cholesterol in the fasted serum (P = 0.03) and postprandial serum (P = 0.01) that was observed after the nonseafood intervention. The dietary protein source determines fasting and postprandial lipids in healthy individuals in a manner that may have an effect on the long-term development of cardiovascular disease. This study was registered at

  14. A Conserved Circular Network of Coregulated Lipids Modulates Innate Immune Responses.

    PubMed

    Köberlin, Marielle S; Snijder, Berend; Heinz, Leonhard X; Baumann, Christoph L; Fauster, Astrid; Vladimer, Gregory I; Gavin, Anne-Claude; Superti-Furga, Giulio

    2015-07-02

    Lipid composition affects the biophysical properties of membranes that provide a platform for receptor-mediated cellular signaling. To study the regulatory role of membrane lipid composition, we combined genetic perturbations of sphingolipid metabolism with the quantification of diverse steps in Toll-like receptor (TLR) signaling and mass spectrometry-based lipidomics. Membrane lipid composition was broadly affected by these perturbations, revealing a circular network of coregulated sphingolipids and glycerophospholipids. This evolutionarily conserved network architecture simultaneously reflected membrane lipid metabolism, subcellular localization, and adaptation mechanisms. Integration of the diverse TLR-induced inflammatory phenotypes with changes in lipid abundance assigned distinct functional roles to individual lipid species organized across the network. This functional annotation accurately predicted the inflammatory response of cells derived from patients suffering from lipid storage disorders, based solely on their altered membrane lipid composition. The analytical strategy described here empowers the understanding of higher-level organization of membrane lipid function in diverse biological systems.

  15. Nutritional and Lipid Modulation of PCSK9: Effects on Cardiometabolic Risk Factors.

    PubMed

    Krysa, Jacqueline A; Ooi, Teik Chye; Proctor, Spencer D; Vine, Donna F

    2017-04-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease involved in the regulation of LDL receptor (LDLR) expression and apolipoprotein B lipoprotein cholesterol metabolism. Hepatic PCSK9 protein expression, activity, and secretion have been shown to affect cholesterol homeostasis. An upregulation of hepatic PSCK9 protein leads to increased LDLR degradation, resulting in decreased uptake of apoB lipoproteins and a consequent increase in the plasma concentration of these lipoproteins, including LDL and chylomicron remnants. Hence, PCSK9 has become a novel target for lipid-lowering therapies. The aim of this review is to outline current findings on the metabolic and dietary regulation of PCSK9 and effects on cholesterol, apoB lipoprotein metabolism, and cardiovascular disease (CVD) risk. PCSK9 gene and protein expression have been shown to be regulated by metabolic status and the diurnal pattern. In the fasting state, plasma PCSK9 is reduced via modulation of the nuclear transcriptional factors, including sterol regulatory element-binding protein (SREBP) 1c, SREBP2, and hepatocyte nuclear factor 1α. Plasma PCSK9 concentrations are also known to be positively associated with plasma insulin and homeostasis model assessment of insulin resistance, and appear to be regulated by SREBP1c independently of glucose status. Plasma PCSK9 concentrations are stable in response to high-fat or high-protein diets in healthy individuals; however, this response may differ in altered metabolic conditions. Dietary n-3 polyunsaturated fatty acids have been shown to reduce plasma PCSK9 concentration and hepatic PCSK9 mRNA expression, consistent with their lipid-lowering effects, whereas dietary fructose appears to upregulate PCSK9 mRNA expression and plasma PCSK9 concentrations. Further studies are needed to elucidate the mechanisms of how dietary components regulate PCSK9 and effects on cholesterol and apoB lipoprotein metabolism, as well as to delineate the clinical

  16. Cytokine modulation (IL-6, IL-8, IL-10) by human breast milk lipids on intestinal epithelial cells (Caco-2).

    PubMed

    Barrera, Girolamo J; Sánchez, Gabriela

    2016-01-01

    Human breast milk is the best form of nourishment for infants during the first year of life. It is composed by a complex mixture of carbohydrates, proteins and fats. Breast milk provides nutrients and bioactive factors that themselves modulate maturation and development of the gastrointestinal tract. Many studies have shown that it provides protection against gastrointestinal tract inflammation. In this sense, this study aimed to evaluate the effect of human breast milk lipids on epithelial intestinal cells (Caco-2) cytokine regulation and the fatty acid transporter protein (FATP) involved in this process. Caco-2 cells were cultivated and stimulated with different concentration of human milk lipids from healthy human mothers (18-30-year-olds) or single commercial lipids for 48 h. We measured the concentrations and mRNA levels of IL-6, IL-8 and IL-10 cytokines by immunoassay (ELISA) and quantitative-PCR (qRT-PCR) technique, respectively. We observed a two to three times decrease in pro-inflammatory cytokine levels (p < 0.01) as well as an increase in anti-inflammatory IL-10 levels in cells stimulated with increasing concentrations of breast milk lipids. These results suggest that human breast milk lipids could have an important role on the cytokine modulation in the newborn bowel.

  17. Modulation of lipid metabolism by deep-sea water in cultured human liver (HepG2) cells.

    PubMed

    He, Shan; Hao, Jiejie; Peng, Weibing; Qiu, Peiju; Li, Chunxia; Guan, Huashi

    2014-04-01

    It has been found that deep-sea water was associated with lower serum lipid in animal model studies. Herein, we investigated whether DSW exerted a hypolipidemic activity and further elucidated how DSW modulated lipid metabolism in HepG2 cells. Preliminary animal studies showed that DSW exhibited potency to decrease serum total cholesterol, triglycerides, and LDL cholesterol, and increase HDL cholesterol, and the hepatic lipid contents were also significantly lower in the DSW group. When DSW was added to HepG2 cells, it decreased the lipid contents of hepatocyte through the activation of AMP-activated protein kinase, thus inhibiting the synthesis of cholesterol and fatty acid. Besides, LDL receptor was upregulated by activation of sterol regulatory element-binding protein-2. In addition, the levels of apolipoprotein AI and cholesterol 7-alpha-hydroxylase were also raised. Our investigation provided mechanisms by which DSW modulated lipid metabolism and indicated that DSW was worthy of further investigation and could be developed as functional drinking water in the prevention and treatment of hypolipidemic and other lifestyle-related diseases.

  18. Sesamin modulation of lipid class and fatty acid profile in early juvenile teleost, Lates calcarifer, fed different dietary oils.

    PubMed

    Alhazzaa, Ramez; Bridle, Andrew R; Carter, Chris G; Nichols, Peter D

    2012-10-15

    Sesamin, a major sesame seed lignan, has diverse biological functions including the modulation of molecular actions in lipid metabolic pathways and reducing cholesterol levels. Vertebrates have different capacities to biosynthesize long-chain PUFA from dietary precursors and sesamin can enhance the biosynthesis of ALA to EPA and DHA in marine teleost. Early juvenile barramundi, Lates calcarifer, were fed for two weeks on diets rich in ALA or SDA derived from linseed or Echium plantagineum, respectively. Both diets contained phytosterols and less cholesterol compared with a standard fish oil-based diet. The growth rates were reduced in the animals receiving sesamin regardless of the dietary oil. However, the relative levels of n-3 LC-PUFA in total lipid, but not the phospholipid, increased in the whole body by up to 25% in animals fed on sesamin with ALA or SDA. Sesamin reduced the relative levels of triacylglycerols and increased polar lipid, and did not affect the relative composition of phospholipid subclasses or sterols. Sesamin is a potent modulator for LC-PUFA biosynthesis in animals, but probably will have more effective impact at advanced ages. By modulating certain lipid metabolic pathways, sesamin has probably disrupted the body growth and development of organs and tissues in early juvenile barramundi.

  19. A20 modulates lipid metabolism and energy production to promote liver regeneration.

    PubMed

    Damrauer, Scott M; Studer, Peter; da Silva, Cleide G; Longo, Christopher R; Ramsey, Haley E; Csizmadia, Eva; Shrikhande, Gautam V; Scali, Salvatore T; Libermann, Towia A; Bhasin, Manoj K; Ferran, Christiane

    2011-03-17

    Liver regeneration is clinically of major importance in the setting of liver injury, resection or transplantation. We have demonstrated that the NF-κB inhibitory protein A20 significantly improves recovery of liver function and mass following extended liver resection (LR) in mice. In this study, we explored the Systems Biology modulated by A20 following extended LR in mice. We performed transcriptional profiling using Affymetrix-Mouse 430.2 arrays on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20) and rAd.βgalactosidase treated livers, before and 24 hours after 78% LR. A20 overexpression impacted 1595 genes that were enriched for biological processes related to inflammatory and immune responses, cellular proliferation, energy production, oxidoreductase activity, and lipid and fatty acid metabolism. These pathways were modulated by A20 in a manner that favored decreased inflammation, heightened proliferation, and optimized metabolic control and energy production. Promoter analysis identified several transcriptional factors that implemented the effects of A20, including NF-κB, CEBPA, OCT-1, OCT-4 and EGR1. Interactive scale-free network analysis captured the key genes that delivered the specific functions of A20. Most of these genes were affected at basal level and after resection. We validated a number of A20's target genes by real-time PCR, including p21, the mitochondrial solute carriers SLC25a10 and SLC25a13, and the fatty acid metabolism regulator, peroxisome proliferator activated receptor alpha. This resulted in greater energy production in A20-expressing livers following LR, as demonstrated by increased enzymatic activity of cytochrome c oxidase, or mitochondrial complex IV. This Systems Biology-based analysis unravels novel mechanisms supporting the pro-regenerative function of A20 in the liver, by optimizing energy production through improved lipid/fatty acid metabolism, and down-regulated inflammation. These findings support pursuit of A

  20. Single administration of vildagliptin attenuates postprandial hypertriglyceridemia and endothelial dysfunction in normoglycemic individuals.

    PubMed

    Noguchi, Kaoru; Hirota, Minoru; Miyoshi, Toru; Tani, Yoshinori; Noda, Yoko; Ito, Hiroshi; Nanba, Seiji

    2015-01-01

    Postprandial hypertriglyceridemia impairs endothelial function and plays an important role in the development of atherosclerosis. The aim of the present study was to examine the postprandial effects of the dipeptidyl peptidase-4 inhibitor vildagliptin and the α-glucosidase inhibitor voglibose on endothelial dysfunction and lipid profiles following a single administration. A randomized cross-over trial using 11 normoglycemic individuals was performed. The postprandial effects of a single administration of vildagliptin (50 mg) or voglibose (0.3 mg) on endothelial function were analyzed using brachial artery flow-mediated dilation (FMD) and lipid profiles during fasting and 1.5 and 3 h after an oral cookie-loading test. Compared with voglibose, vildagliptin significantly suppressed postprandial endothelial dysfunction, (%FMD, -1.6±0.9 vildagliptin vs. -4.0±0.7 voglibose; P=0.01) and the postprandial incremental increase in the triglyceride level (28±18 vildagliptin vs. 51±26 mg/dl voglibose; P=0.01) 3 h after a cookie-loading test. In addition, vildagliptin significantly increased the levels of glucagon-like peptide-1 compared with voglibose 3 h after a loading cookie test (4.4±0.6 vs. 2.9±0.7 pmol/l, respectively; P=0.04). No significant differences in the levels of glucose, apolipoprotein B-48, glucagon or insulin were observed between vildagliptin and voglibose treatments. In conclusion, a single administration of vildagliptin attenuated postprandial endothelial dysfunction and postprandial hypertriglyceridemia, suggesting that vildagliptin may be a promising antiatherogenic agent.

  1. The interaction of eugenol with cell membrane models at the air-water interface is modulated by the lipid monolayer composition.

    PubMed

    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.

  2. Synaptic and extrasynaptic NMDA receptors differentially modulate neuronal COX-2 function, lipid peroxidation, and neuroprotection

    PubMed Central

    Stark, David T.; Bazan, Nicolas G.

    2011-01-01

    Stimulation of synaptic NMDA receptors (NMDARs) induces neuroprotection, while extrasynaptic NMDARs promote excitotoxic cell death. Neuronal expression of cyclooxygenase-2 (COX-2) is enhanced by synaptic NMDARs, and although this enzyme mediates neuronal functions, COX-2 is also regarded as a key modulator of neuroinflammation and is thought to exacerbate excitotoxicity via overproduction of prostaglandins. This raises an apparent paradox: synaptic NMDARs are pro-survival yet are essential for robust neuronal COX-2 expression. We hypothesized that stimulation of extrasynaptic NMDARs converts COX-2 signaling from a physiological to a potentially pathological process. We combined HPLC-ESI-MS/MS-based mediator lipidomics and unbiased image analysis in mouse dissociated and organotypic cortical cultures to uncover that synaptic and extrasynaptic NMDARs differentially modulate neuronal COX-2 expression and activity. We show that synaptic NMDARs enhance neuronal COX-2 expression, while sustained synaptic stimulation limits COX-2 activity by suppressing cellular levels of the primary COX-2 substrate, arachidonic acid (AA). In contrast, extrasynaptic NMDARs suppress COX-2 expression while activating phospholipase A2 (PLA2), which enhances AA levels by hydrolysis of membrane phospholipids. Thus, sequential activation of synaptic then extrasynaptic NMDARs maximizes COX-2-dependent prostaglandin synthesis. We also show that excitotoxic events only drive induction of COX-2 expression through abnormal synaptic network excitability. Finally, we show that non-enzymatic lipid peroxidation of arachidonic and other polyunsaturated fatty acids is a function of network activity history. A new paradigm emerges from our results suggesting that pathological COX-2 signaling associated with models of stroke, epilepsy, and neurodegeneration requires specific spatio-temporal NMDAR stimulation. PMID:21957234

  3. Genetic ablation of carotene oxygenases and consumption of lycopene or tomato powder diets modulates carotenoid and lipid metabolism in mice

    PubMed Central

    Ford, Nikki A.; Elsen, Amy C.; Erdman, John W.

    2013-01-01

    Carotene-15,15'-monooxygenase (CMO-I) cleaves β-carotene to form vitamin A while carotene-9’,10’-monooxygenase (CMO-II) preferentially cleaves non-provitamin A carotenoids. Recent reports indicate that beta-carotene metabolites regulate dietary lipid uptake while lycopene regulates peroxisome-proliferated activator receptor (PPAR) expression. To determine the physiologic consequences of carotenoids and their interactions with CMO-I and CMO-II, we characterized mammalian carotenoid metabolism, metabolic perturbations and lipid metabolism in female CMO-I−/− and CMO-II−/− mice fed lycopene or tomato-containing diets for 30 days. We hypothesized that there would be significant interactions between diet and genotype on carotenoid accumulation and lipid parameters. CMO-I−/− mice had higher levels of leptin, insulin and hepatic lipidosis, but lower levels of serum cholesterol. CMO-II−/− mice had increased tissue lycopene and phytofluene accumulation, reduced IGF-1 levels and cholesterol levels, but elevated liver lipids and cholesterol compared with WT mice. The diets did not modulate these genotypic perturbations, but lycopene and tomato powder did significantly decrease serum insulin-like growth factor-I. Tomato powder also reduced hepatic PPAR expression, independent of genotype. These data point to the pleiotropic actions of CMO-I and CMO-II supporting a strong role of these proteins in regulating tissue carotenoid accumulation and the lipid metabolic phenotype, as well as tomato carotenoid-independent regulation of lipid metabolism. PMID:24034573

  4. Proteomic Analysis of Lipid Droplets from Caco-2/TC7 Enterocytes Identifies Novel Modulators of Lipid Secretion

    PubMed Central

    Beilstein, Frauke; Bouchoux, Julien; Rousset, Monique; Demignot, Sylvie

    2013-01-01

    In enterocytes, the dynamic accumulation and depletion of triacylglycerol (TAG) in lipid droplets (LD) during fat absorption suggests that cytosolic LD-associated TAG contribute to TAG-rich lipoprotein (TRL) production. To get insight into the mechanisms controlling the storage/secretion balance of TAG, we used as a tool hepatitis C virus core protein, which localizes onto LDs, and thus may modify their protein coat and decrease TRL secretion. We compared the proteome of LD fractions isolated from Caco-2/TC7 enterocytes expressing or not hepatitis C virus core protein by a differential proteomic approach (isobaric tag for relative and absolute quantitation (iTRAQ) labeling coupled with liquid chromatography and tandem mass spectrometry). We identified 42 proteins, 21 being involved in lipid metabolism. Perilipin-2/ADRP, which is suggested to stabilize long term-stored TAG, was enriched in LD fractions isolated from Caco-2/TC7 expressing core protein while perilipin-3/TIP47, which is involved in LD synthesis from newly synthesized TAG, was decreased. Endoplasmic reticulum-associated proteins were strongly decreased, suggesting reduced interactions between LD and endoplasmic reticulum, where TRL assembly occurs. For the first time, we show that 17β-hydroxysteroid dehydrogenase 2 (DHB2), which catalyzes the conversion of 17-keto to 17 β-hydroxysteroids and which was the most highly enriched protein in core expressing cells, is localized to LD and interferes with TAG secretion, probably through its capacity to inactivate testosterone. Overall, we identified potential new players of lipid droplet dynamics, which may be involved in the balance between lipid storage and secretion, and may be altered in enterocytes in pathological conditions such as insulin resistance, type II diabetes and obesity. PMID:23301014

  5. Constituents of chyme responsible for postprandial intestinal hyperemia.

    PubMed

    Chou, C C; Kvietys, P; Post, J; Sit, S P

    1978-12-01

    While local venous outflow was measured in anesthetized dogs, various constituents of intestinal chyme were placed in the jejunal lumen to identify those responsible for postprandial intestinal hyperemia. Digested food and its supernatant increased local blood flow, whereas its precipitate, undigested food, and pancreatic enzymes did not. In the jejunum bile alone had no effect, but it markedly enhanced the hyperemic effect of digested food. Bile in the ileal lumen, however, increased local blood flow. At physiological postprandial concentrations in the jejunum, glucose, and micellar solutions of oleic acid and monoolein increased flow, but taurocholate and 16 common dietary amino acids did not. The hyperemic effect of lipids required the presence of taurocholate. Of the 16 amino acids, only Glu and Asp increased flow at 10 times the physiological concentrations (28 and 20 mM, respectively). The study indicates that the constituents of chyme responsible for postprandial intestinal hyperemia are the hydrolytic products of food, especially those of carbohydrates and fats and that bile plays an important role in the hyperemia.

  6. Hypertriglyceridaemia, postprandial lipaemia and non-HDL cholesterol.

    PubMed

    Stefanutti, Claudia; Labbadia, Giancarlo; Athyros, Vasilios G

    2014-01-01

    Maintaining total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels within healthy limits decreases the risk of atherosclerotic vascular disease (AVD) and cardiovascular (CV) events. The predictive value of elevated TG levels for coronary artery disease (CAD) seen in univariate analysis tends to disappear on multivariate analyses, especially when correction is made for HDL-C. The relationship between TG and HDL-C is complex and not fully understood. Hydrolysis of TG by lipoprotein lipase converts HDL subclass 3 to a larger lipoprotein enriched in both phospholipid and TG. This process occurs in postprandial lipaemia (PPL). An additional factor for the complex relationship between TGs and CV risk is that the lipoproteins which transport plasma TG (chylomicrons, very low density lipoproteins and their remnants) are heterogeneous particles. Therefore, they may differ in their level of atherogenicity. PPL is a physiological process during which plasma lipoproteins and their subclasses undergo variations in concentration and composition following consumption of food, particularly fatty food. "Postprandial hyperlipidaemia" is the quantitative/qualitative alteration of this normal process. These lipoprotein alterations could play a role in the development of CV disease (CVD). However, lipid levels used to evaluate CV risk are usually measured in the fasting state. This review focuses on TG, PPL, postprandial hyperlipidaemia and non-HDL-C, their relationships and potential predictive role in atherogenesis and CVD.

  7. Postprandial lipoproteins and the molecular regulation of vascular homeostasis.

    PubMed

    Botham, Kathleen M; Wheeler-Jones, Caroline P D

    2013-10-01

    Blood levels of triglyceride-rich lipoproteins (TRL) increase postprandially, and a delay in their clearance results in postprandial hyperlipidemia, an important risk factor in atherosclerosis development. Atherosclerosis is a multifactorial inflammatory disease, and its initiation involves endothelial dysfunction, invasion of the artery wall by leukocytes and subsequent formation of foam cells. TRL are implicated in several of these inflammatory processes, including the formation of damaging free radicals, leukocyte activation, endothelial dysfunction and foam cell formation. Recent studies have provided insights into the mechanisms of uptake and the signal transduction pathways mediating the interactions of TRL with leukocytes and vascular cells, and how they are modified by dietary lipids. Multiple receptor and non-receptor mediated pathways function in macrophage uptake of TRL. TRL also induce expression of adhesion molecules, cyclooxygenase-2 and heme-oxygenase-1 in endothelial cells, and activate intracellular signaling pathways involving mitogen-activated protein kinases, NF-κB and Nrf2. Many of these effects are strongly influenced by dietary components carried in TRL. There is extensive evidence indicating that raised postprandial TRL levels are a risk factor for atherosclerosis, but the molecular mechanisms involved are only now becoming appreciated. Here, we review current understanding of the mechanisms by which TRL influence vascular cell function. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Fasting and Feeding Signals Control the Oscillatory Expression of Angptl8 to Modulate Lipid Metabolism

    PubMed Central

    Dang, Fabin; Wu, Rong; Wang, Pengfei; Wu, Yuting; Azam, Md. Shofiul; Xu, Qian; Chen, Yaqiong; Liu, Yi

    2016-01-01

    Emerging evidence implies a key role of angiopoietin-like protein 8 (Angptl8) in the metabolic transition between fasting and feeding, whereas much less is known about the mechanism of its own expression. Here we show that hepatic Angptl8 is rhythmically expressed, which involving the liver X receptor alpha (LXRα) and glucocorticoid receptor (GR) modulation during feeding and fasting periods, respectively. In addition, Angptl8 mRNA is very unstable, which contributes to the nature of its daily rhythmicity by rapidly responding to fasting/feeding transition. To explore its pathological function in dexamethasone (DEX)-induced fatty liver, we reversed its suppression by glucocorticoids through adenoviral delivery of Angptl8 gene in mouse liver. Surprisingly, hepatic overexpression of Angptl8 dramatically elevated plasma triglyceride (TG) and non-esterified fatty acid (NEFA) levels in DEX-treated mice, suggesting a metabolic interaction between Angptl8 and glucocorticoid signaling. Moreover, intracellular hepatic Angptl8 is implicated in the regulation of lipid homeostasis by the experiments with ectopic expression of a nonsecreted Angptl8 mutant (Δ25-Angptl8). Altogether, our data demonstrate the molecular mechanism of the diurnal rhythm of Angptl8 expression regulated by glucocorticoid signaling and LXRα pathway, and provide new evidence to understand the role of Angptl8 in maintaining plasma TG homeostasis. PMID:27845381

  9. Polarization-modulated FTIR spectroscopy of lipid/gramicidin monolayers at the air/water interface.

    PubMed Central

    Ulrich, W P; Vogel, H

    1999-01-01

    Monolayers of gramicidin A, pure and in mixtures with dimyristoylphosphatidylcholine (DMPC), were studied in situ at the air/H2O and air/D2O interfaces by polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). Simulations of the entire set of amide I absorption modes were also performed, using complete parameter sets for different conformations based on published normal mode calculations. The structure of gramicidin A in the DMPC monolayer could clearly be assigned to a beta6.3 helix. Quantitative analysis of the amide I bands revealed that film pressures of up to 25-30 mN/m the helix tilt angle from the vertical in the pure gramicidin A layer exceeded 60 degrees. A marked dependence of the peptide orientation on the applied surface pressure was observed for the mixed lipid-peptide monolayers. At low pressure the helix lay flat on the surface, whereas at high pressures the helix was oriented almost parallel to the surface normal. PMID:10049344

  10. Omega-3 fatty acids improve postprandial lipemia and associated endothelial dysfunction in healthy individuals - a randomized cross-over trial.

    PubMed

    Miyoshi, Toru; Noda, Yoko; Ohno, Yuko; Sugiyama, Hiroki; Oe, Hiroki; Nakamura, Kazufumi; Kohno, Kunihisa; Ito, Hiroshi

    2014-10-01

    Postprandial elevation of triglycerides impairs endothelial function and contributes to the development of atherosclerosis. We investigated the effects of omega-3 fatty acids on postprandial endothelial function and lipid profiles. Healthy volunteers [10] were given supplementation at 4g/day omega-3 fatty acids (or were not treated) for 4 weeks in a randomised crossover study. Postprandial levels of various lipids were monitored and endothelial function assessed by brachial artery flow-mediated dilation during fasting and after a standard cookie test. Omega-3 fatty acids reduced postprandial endothelial dysfunction compared with the control diet (flow-mediated dilation at 4h=-0.5±1.2 vs. -2.0±1.6%, P=0.03). Postprandial levels of triglycerides, apolipoprotein B-48, and remnant lipoprotein-cholesterol increased in untreated subjects, peaked at 2-4h, and returned to baseline at 8h, whereas low-density lipoprotein-cholesterol levels did not change. Supplementation with omega-3 fatty acids significantly suppressed postprandial elevation of triglycerides (incremental area under the curve=220±209 vs. 374±216mg/h/dL, P=0.04) and remnant lipoprotein-cholesterol (incremental area under the curve=21.7±13.8 vs. 13.3±12.9mg/h/dL, P=0.04). Supplementation with omega-3 fatty acids significantly suppressed the increase in triglyceride content in chylomicrons as well as in very-low-density lipoproteins from baseline to 4h after the cookie test. Omega-3 fatty acids significantly decreased postprandial triglyceride elevation and postprandial endothelial dysfunction, suggesting that omega-3 fatty acids may have vascular protective effects in postprandial state. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  11. Cell type-specific modulation of lipid mediator's formation in murine adipose tissue by omega-3 fatty acids.

    PubMed

    Kuda, Ondrej; Rombaldova, Martina; Janovska, Petra; Flachs, Pavel; Kopecky, Jan

    2016-01-15

    Mutual interactions between adipocytes and immune cells in white adipose tissue (WAT) are involved in modulation of lipid metabolism in the tissue and also in response to omega-3 polyunsaturated fatty acids (PUFA), which counteract adverse effects of obesity. This complex interplay depends in part on in situ formed anti- as well as pro-inflammatory lipid mediators, but cell types engaged in the synthesis of the specific mediators need to be better characterized. We used tissue fractionation and metabolipidomic analysis to identify cells producing lipid mediators in epididymal WAT of mice fed for 5 weeks obesogenic high-fat diet (lipid content 35% wt/wt), which was supplemented or not by omega-3 PUFA (4.3 mg eicosapentaenoic acid and 14.7 mg docosahexaenoic acid per g of diet). Our results demonstrate selective increase in levels of anti-inflammatory lipid mediators in WAT in response to omega-3, reflecting either their association with adipocytes (endocannabinoid-related N-docosahexaenoylethanolamine) or with stromal vascular cells (pro-resolving lipid mediator protectin D1). In parallel, tissue levels of obesity-associated pro-inflammatory endocannabinoids were suppressed. Moreover, we show that adipose tissue macrophages (ATMs), which could be isolated using magnetic force from the stromal vascular fraction, are not the major producers of protectin D1 and that omega-3 PUFA lowered lipid load in ATMs while promoting their less-inflammatory phenotype. Taken together, these results further document specific roles of various cell types in WAT in control of WAT inflammation and metabolism and they suggest that also other cells but ATMs are engaged in production of pro-resolving lipid mediators in response to omega-3 PUFA.

  12. PIP2 regulation of KCNQ channels: biophysical and molecular mechanisms for lipid modulation of voltage-dependent gating.

    PubMed

    Zaydman, Mark A; Cui, Jianmin

    2014-01-01

    Voltage-gated potassium (Kv) channels contain voltage-sensing (VSD) and pore-gate (PGD) structural domains. During voltage-dependent gating, conformational changes in the two domains are coupled giving rise to voltage-dependent opening of the channel. In addition to membrane voltage, KCNQ (Kv7) channel opening requires the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2). Recent studies suggest that PIP2 serves as a cofactor to mediate VSD-PGD coupling in KCNQ1 channels. In this review, we put these findings in the context of the current understanding of voltage-dependent gating, lipid modulation of Kv channel activation, and PIP2-regulation of KCNQ channels. We suggest that lipid-mediated coupling of functional domains is a common mechanism among KCNQ channels that may be applicable to other Kv channels and membrane proteins.

  13. PIP2 regulation of KCNQ channels: biophysical and molecular mechanisms for lipid modulation of voltage-dependent gating

    PubMed Central

    Zaydman, Mark A.; Cui, Jianmin

    2014-01-01

    Voltage-gated potassium (Kv) channels contain voltage-sensing (VSD) and pore-gate (PGD) structural domains. During voltage-dependent gating, conformational changes in the two domains are coupled giving rise to voltage-dependent opening of the channel. In addition to membrane voltage, KCNQ (Kv7) channel opening requires the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2). Recent studies suggest that PIP2 serves as a cofactor to mediate VSD-PGD coupling in KCNQ1 channels. In this review, we put these findings in the context of the current understanding of voltage-dependent gating, lipid modulation of Kv channel activation, and PIP2-regulation of KCNQ channels. We suggest that lipid-mediated coupling of functional domains is a common mechanism among KCNQ channels that may be applicable to other Kv channels and membrane proteins. PMID:24904429

  14. Modulation of keratinocyte expression of antioxidants by 4-hydroxynonenal, a lipid peroxidation end product

    SciTech Connect

    Zheng, Ruijin; Heck, Diane E.; Mishin, Vladimir; Black, Adrienne T.; Shakarjian, Michael P.; Kong, Ah-Ng Tony; Laskin, Debra L.; Laskin, Jeffrey D.

    2014-03-01

    4-Hydroxynonenal (4-HNE) is a lipid peroxidation end product generated in response to oxidative stress in the skin. Keratinocytes contain an array of antioxidant enzymes which protect against oxidative stress. In these studies, we characterized 4-HNE-induced changes in antioxidant expression in mouse keratinocytes. Treatment of primary mouse keratinocytes and PAM 212 keratinocytes with 4-HNE increased mRNA expression for heme oxygenase-1 (HO-1), catalase, NADPH:quinone oxidoreductase (NQO1) and glutathione S-transferase (GST) A1-2, GSTA3 and GSTA4. In both cell types, HO-1 was the most sensitive, increasing 86–98 fold within 6 h. Further characterization of the effects of 4-HNE on HO-1 demonstrated concentration- and time-dependent increases in mRNA and protein expression which were maximum after 6 h with 30 μM. 4-HNE stimulated keratinocyte Erk1/2, JNK and p38 MAP kinases, as well as PI3 kinase. Inhibition of these enzymes suppressed 4-HNE-induced HO-1 mRNA and protein expression. 4-HNE also activated Nrf2 by inducing its translocation to the nucleus. 4-HNE was markedly less effective in inducing HO-1 mRNA and protein in keratinocytes from Nrf2 −/− mice, when compared to wild type mice, indicating that Nrf2 also regulates 4-HNE-induced signaling. Western blot analysis of caveolar membrane fractions isolated by sucrose density centrifugation demonstrated that 4-HNE-induced HO-1 is localized in keratinocyte caveolae. Treatment of the cells with methyl-β-cyclodextrin, which disrupts caveolar structure, suppressed 4-HNE-induced HO-1. These findings indicate that 4-HNE modulates expression of antioxidant enzymes in keratinocytes, and that this can occur by different mechanisms. Changes in expression of keratinocyte antioxidants may be important in protecting the skin from oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a reactive aldehyde. • 4-HNE induces antioxidant proteins in mouse keratinocytes. • Induction of

  15. Postprandial glucose regulation and diabetic complications.

    PubMed

    Ceriello, Antonio; Hanefeld, Markolf; Leiter, Lawrence; Monnier, Louis; Moses, Alan; Owens, David; Tajima, Naoko; Tuomilehto, Jaakko

    2004-10-25

    Atherosclerotic disease accounts for much of the increased mortality and morbidity associated with type 2 diabetes. Epidemiological studies support the potential of improved glycemic control to reduce cardiovascular complications. An association between glycosylated hemoglobin (HbA(1c)) level and the risk for cardiovascular complications has frequently been reported. Most epidemiological data implicate postprandial hyperglycemia in the development of cardiovascular disease, whereas the link between fasting glycemia and diabetic complications is inconclusive. Moreover, in many studies, postprandial glycemia is a better predictor of cardiovascular risk than HbA(1c) level. Postprandial glucose may have a direct toxic effect on the vascular endothelium, mediated by oxidative stress that is independent of other cardiovascular risk factors such as hyperlipidemia. Postprandial hyperglycemia also may exert its effects through its substantial contribution to total glycemic exposure. The present review examines the hypothesis that controlling postprandial glucose level is an important strategy in the prevention of cardiovascular complications associated with diabetes.

  16. MALDI mass spectrometry reveals that cumulus cells modulate the lipid profile of in vitro-matured bovine oocytes.

    PubMed

    Vireque, Alessandra A; Tata, Alessandra; Belaz, Katia Roberta A; Grázia, João Gabriel V; Santos, Fábio N; Arnold, Daniel R; Basso, Andrea C; Eberlin, Marcos N; Silva-de-Sá, Marcos Felipe; Ferriani, Rui A; Sá Rosa-E-Silva, Ana Carolina J

    2017-04-01

    The influence of cumulus cells (CC) on the lipid profile of bovine oocytes matured in two different lipid sources was investigated. Cumulus-oocyte complexes (COC) or denuded oocytes (DO) were matured in tissue culture medium (TCM) supplemented with fetal bovine serum (FBS) or serum substitute supplement (SSS). Lipid profiles of TCM, serum supplements, immature CC and oocyte (IO), and in vitro-matured oocytes from COC and DO were then analyzed by matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) and submitted to partial least squares-discriminant analysis (PLS-DA). The developmental competence of such oocytes was also assessed. Differences in lipid composition were observed between two types of sera and distinctly influenced the lipid profile of CC. As revealed by PLS-DA, the abundance of specific ions corresponding to triacylglycerols (TAG) or phospholipids (PL) were higher in COC compared to DO both supplemented with FBS or SSS and to some extent affected the subsequent DO in vitro embryo development. DO exposed to SSS had however a marked diminished ability to develop to the blastocyst stage. These results indicate a modulation by CC of the oocyte TAG and PL profiles associated with a specific cell response to the serum supplement used for in vitro maturation.

  17. Non-neuronal cell modulation relieves neuropathic pain: efficacy of the endogenous lipid palmitoylethanolamide.

    PubMed

    Bettoni, Isabella; Comelli, Francesca; Colombo, Anita; Bonfanti, Patrizia; Costa, Barbara

    2013-02-01

    We have previously shown that the endogenous lipid palmitoylethanolamide (PEA) induced relief of neuropathic pain through an action upon receptors located on the nociceptive pathway. Recently, it has been proposed that immune cells, in particular mast cells, and microglia, by releasing algogen mediators interact with neurons to alter pain sensitivity thereby contributing to the development and maintenance of chronic pain states. The aim of this work was to explore whether the anti-nociceptive properties of PEA might be accompanied by modulation of these non-neuronal cells. Mice were subjected to a chronic constriction injury model of neuropathic pain and treated with PEA. The data show that at the earlier (3 days) time-point after nerve injury there was a substantial recruitment of mast cells whose activation was not yet pronounced. In contrast, at the later time point (8 days) there was no further increase in mast cell number, but rather a marked activation of these cells. An up-regulation of activated microglia was found in the spinal cord of neuropathic pain mice. PEA delayed mast cell recruitment, protected mast cells against degranulation and abolished the nerve growth factor increase in sciatic nerve concomitantly preserving the nerve from degeneration, while reducing microglia activation in the spinal cord. These findings support the idea that non-neuronal cells may be a valuable pharmacological target to treat neuropathic pain since the current neuronal-direct drugs are still unsatisfactory. In this context PEA could represent an innovative molecule, combining a dual analgesic activity, both on neurons and on nonneuronal cells.

  18. Modulation of keratinocyte expression of antioxidants by 4-hydroxynonenal, a lipid peroxidation end product.

    PubMed

    Zheng, Ruijin; Heck, Diane E; Mishin, Vladimir; Black, Adrienne T; Shakarjian, Michael P; Kong, Ah-Ng Tony; Laskin, Debra L; Laskin, Jeffrey D

    2014-03-01

    4-Hydroxynonenal (4-HNE) is a lipid peroxidation end product generated in response to oxidative stress in the skin. Keratinocytes contain an array of antioxidant enzymes which protect against oxidative stress. In these studies, we characterized 4-HNE-induced changes in antioxidant expression in mouse keratinocytes. Treatment of primary mouse keratinocytes and PAM 212 keratinocytes with 4-HNE increased mRNA expression for heme oxygenase-1 (HO-1), catalase, NADPH:quinone oxidoreductase (NQO1) and glutathione S-transferase (GST) A1-2, GSTA3 and GSTA4. In both cell types, HO-1 was the most sensitive, increasing 86-98 fold within 6h. Further characterization of the effects of 4-HNE on HO-1 demonstrated concentration- and time-dependent increases in mRNA and protein expression which were maximum after 6h with 30 μM. 4-HNE stimulated keratinocyte Erk1/2, JNK and p38 MAP kinases, as well as PI3 kinase. Inhibition of these enzymes suppressed 4-HNE-induced HO-1 mRNA and protein expression. 4-HNE also activated Nrf2 by inducing its translocation to the nucleus. 4-HNE was markedly less effective in inducing HO-1 mRNA and protein in keratinocytes from Nrf2-/- mice, when compared to wild type mice, indicating that Nrf2 also regulates 4-HNE-induced signaling. Western blot analysis of caveolar membrane fractions isolated by sucrose density centrifugation demonstrated that 4-HNE-induced HO-1 is localized in keratinocyte caveolae. Treatment of the cells with methyl-β-cyclodextrin, which disrupts caveolar structure, suppressed 4-HNE-induced HO-1. These findings indicate that 4-HNE modulates expression of antioxidant enzymes in keratinocytes, and that this can occur by different mechanisms. Changes in expression of keratinocyte antioxidants may be important in protecting the skin from oxidative stress. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Genistein reduced insulin resistance index through modulating lipid metabolism in ovariectomized rats.

    PubMed

    Choi, Joo Sun; Koh, In-Uk; Song, Jihyun

    2012-11-01

    Postmenopausal women are at higher risk for obesity and insulin resistance due to the decline of estrogen, but genistein, a phytoestrogen, may reduce the risks of these diet-related diseases. In this study, we hypothesized that supplemental genistein has beneficial effects on insulin resistance in an ovariectomized rat model by modulating lipid metabolism. Three weeks after a sham surgery (sham) or an ovariectomy (OVX), ovariectomized Sprague-Dawley rats were placed on a diet containing 0 (OVX group) or 0.1% genistein for 4 weeks. The sham rats were fed a high-fat diet containing 0% genistein and served as the control group (sham group). The ovariectomized rats showed increases in body weight and insulin resistance index, but genistein reduced insulin resistance index and the activity of hepatic fatty acid synthetase. Genistein was also associated with increased activity of succinate dehydrogenase and carnitine palmitoyltransferase and the rate of β-oxidation in the fat tissue of rats. The ovariectomized rats given genistein had smaller-sized adipocytes. Using gene-set enrichment analysis (GSEA) of microarray data, we found that a number of gene sets of fatty acid metabolism, insulin resistance, and oxidative stress were differentially expressed by OVX and reversed by genistein. This systemic approach of GSEA enables the identification of such consensus between the gene expression changes and phenotypic changes caused by OVX and genistein supplementation. Genistein treatment could help reduce insulin resistance through the amelioration of OVX-induced metabolic dysfunction, and the GSEA approach may be useful in proposing putative targets related to insulin resistance. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Expression of genes of lipid synthesis and altered lipid composition modulates L-glutamate efflux of Corynebacterium glutamicum.

    PubMed

    Nampoothiri, K M; Hoischen, C; Bathe, B; Möckel, B; Pfefferle, W; Krumbach, K; Sahm, H; Eggeling, L

    2002-01-01

    L-Glutamate is made with Corynebacterium glutamicum on a scale of more than 106 tons/year. Nevertheless, formation of this amino acid is enigmatic and there is very limited molecular information available to unravel the apparently complex conditions leading to L-glutamate efflux. Here, we report the isolation and overexpression of the genes involved in lipid synthesis: acp, fadD 15, cma, cls, pgsA2, cdsA, gpsA, and plsC, and the inactivation of cma and cls. In addition, the consequences for phospholipid content, temperature sensitivity, as well as detergent-independent and detergent-dependent L-glutamate efflux were quantified. An in part strong alteration of the phospholipid composition was achieved; for instance, overexpression offadD15 encoding an acyl-CoA ligase resulted in an increase of phosphatidyl inositol from 12.6 to 30.2%. All strains, except that overexpressing acp (acyl carrier protein), exhibited increased temperature sensitivity, with the strongest sensitivity present upon cls (cardiolipin synthetase) inactivation. As a consequence of the genetically modified lipid synthesis, L-glutamate efflux changed quite dramatically; for instance, overexpression of plsC (acylglycerolacyl transferase) resulted in a detergent-triggered increase of L-glutamate accumulation from 92 mM to 108 mM, whereas acp overexpression reduced the accumulation to 24 mM. With some of the overexpressed genes, substantial L-glutamate excretion even without detergent addition was obtained when the fermentation temperature was elevated. These data show that the chemical and physical properties of the cytoplasmic membrane are altered and suggest that this is a necessary precondition to achieve L-glutamate efflux.

  1. A Conserved Circular Network of Coregulated Lipids Modulates Innate Immune Responses

    PubMed Central

    Köberlin, Marielle S.; Snijder, Berend; Heinz, Leonhard X.; Baumann, Christoph L.; Fauster, Astrid; Vladimer, Gregory I.; Gavin, Anne-Claude; Superti-Furga, Giulio

    2015-01-01

    Summary Lipid composition affects the biophysical properties of membranes that provide a platform for receptor-mediated cellular signaling. To study the regulatory role of membrane lipid composition, we combined genetic perturbations of sphingolipid metabolism with the quantification of diverse steps in Toll-like receptor (TLR) signaling and mass spectrometry-based lipidomics. Membrane lipid composition was broadly affected by these perturbations, revealing a circular network of coregulated sphingolipids and glycerophospholipids. This evolutionarily conserved network architecture simultaneously reflected membrane lipid metabolism, subcellular localization, and adaptation mechanisms. Integration of the diverse TLR-induced inflammatory phenotypes with changes in lipid abundance assigned distinct functional roles to individual lipid species organized across the network. This functional annotation accurately predicted the inflammatory response of cells derived from patients suffering from lipid storage disorders, based solely on their altered membrane lipid composition. The analytical strategy described here empowers the understanding of higher-level organization of membrane lipid function in diverse biological systems. PMID:26095250

  2. pH modulation of transport properties of alamethicin oligomers inserted in zwitterionic-based artificial lipid membranes.

    PubMed

    Chiriac, Roxana; Luchian, Tudor

    2007-11-01

    Electric features of biological membranes are major determinants of the function and physiological manifestation of membrane-penetrating peptides, and such features are prone to be modulated by the properties of the surrounding aqueous medium. In this work, we demonstrate that pH plays crucial roles in modulating electric characteristics of zwitterionic-based artificial lipid membranes. The effect of pH on electrical properties of such membranes was probed by evaluating the transport properties of embedded alamethicin oligomers over a wide range of pH values (i.e., 0.65, 2.08, 2.94, 7 and 10.1). Our data strongly support the paradigm of a pH-dependent variation of the surface and membrane dipole potential which, in conjunction with possible lateral pressure effects within the lipid membrane, lead to a non-monotonic modulation of the electrical conductance of alamethicin oligomers. As expected, pH modulation of transport properties through the alamethicin oligomer is more visible for narrower pores (that is, the 1st conductive state) with slightly better cation selectivity as compared to larger oligomers.

  3. Olive oil and postprandial hyperlipidemia: implications for atherosclerosis and metabolic syndrome.

    PubMed

    Montserrat-de la Paz, Sergio; Bermudez, Beatriz; Cardelo, Magdalena P; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G

    2016-12-07

    Olive oil is the primary source of fat in the Mediterranean diet, which is associated with a significant improvement in health status, as measured by reduced mortality from several chronic diseases. The current pandemic of obesity, metabolic syndrome, and type 2 diabetes is intimately associated with an atherogenic dyslipidemic phenotype. The core components of the dyslipidemia of the metabolic syndrome, which most likely initiate atherosclerosis, are the "lipid triad" consisting of high plasma triglycerides, low levels of high-density lipoproteins, and a preponderance of small, dense low-density lipoproteins at fasting. However, postprandial (non-fasting) TGs (postprandial hyperlipidemia) are also recognized as an important component for atherosclerosis. Herein, the purpose of this review was to provide an update on the effects and mechanisms related to olive oil on postprandial hyperlipidemia and its implications for the onset and progression of atherosclerosis and metabolic syndrome.

  4. Assessment and clinical relevance of non-fasting and postprandial triglycerides: an expert panel statement.

    PubMed

    Kolovou, Genovefa D; Mikhailidis, Dimitri P; Kovar, Jan; Lairon, Dennis; Nordestgaard, Børge G; Ooi, Teik Chye; Perez-Martinez, Pablo; Bilianou, Helen; Anagnostopoulou, Katherine; Panotopoulos, George

    2011-05-01

    An Expert Panel group of scientists and clinicians met to consider several aspects related to non-fasting and postprandial triglycerides (TGs) and their role as risk factors for cardiovascular disease (CVD). In this context, we review recent epidemiological studies relevant to elevated non-fasting TGs as a risk factor for CVD and provide a suggested classification of non-fasting TG concentration. Secondly, we sought to describe methodologies to evaluate postprandial TG using a fat tolerance test (FTT) in the clinic. Thirdly, we discuss the role of non-fasting lipids in the treatment of postprandial hyperlipemia. Finally, we provide a series of clinical recommendations relating to non-fasting TGs based on the consensus of the Expert Panel: 1). Elevated non-fasting TGs are a risk factor for CVD. 2). The desirable non-fasting TG concentration is <2 mmol/l (<180 mg/dl). 3). For standardized postprandial testing, a single FTT meal should be given after an 8 h fast and should consist of 75 g of fat, 25 g of carbohydrates and 10 g of protein. 4). A single TG measurement 4 h after a FTT meal provides a good evaluation of the postprandial TG response. 5). Preferably, subjects with non-fasting TG levels of 1-2 mmol/l (89-180 mg/dl) should be tested with a FTT. 6). TG concentration ≤ 2.5 mmol/l (220 mg/dl) at any time after a FTT meal should be considered as a desirable postprandial TG response. 7). A higher and undesirable postprandial TG response could be treated by aggressive lifestyle modification (including nutritional supplementation) and/or TG lowering drugs like statins, fibrates and nicotinic acid.

  5. Effects of Fuscoporia obliqua on postprandial glucose excursion and endothelial dysfunction in type 2 diabetic patients.

    PubMed

    Maenaka, Toshihiro; Oshima, Masami; Itokawa, Yuka; Masubuchi, Takashi; Takagi, Yasuyuki; Choi, Jung-Sook; Ishida, Torao; Gu, Yeunhwa

    2008-03-01

    Postprandial hyperglycemia has been reported to elicit endothelial dysfunction and provoke future cardiovascular complications. A reduction of postprandial blood glucose levels by the glucosidase inhibitor Fuscoporia obliqua was associated with a risk reduction of cardiovascular complications, but the effects of Fuscoporia obliqua on endothelial function have never been elucidated. This study is aimed to assess the efficacy of Fuscoporia obliqua on postprandial metabolic parameters and endothelial function in type 2 diabetic patients. Postprandial peak glucose (14.47 +/- 1.27 vs. 8.50 +/- 0.53 mmol/liter), plasma glucose excursion (PPGE), and change in the area under the curve (AUC) glucose after a single loading of test meal (total 450 kcal; protein 15.3%; fat 32.3%; carbohydrate 51.4%) were significantly higher in the diet-treated type 2 diabetic patients (n=14) than the age- and sex-matched controls (n=12). The peak forearm blood flow response and total reactive hyperemic flow (flow debt repayment) during reactive hyperemia, indices of resistance artery endothelial function on strain-gauge plethysmography, were unchanged before and after meal loading in the controls. But those of the diabetics were significantly decreased 120 and 240 min after the test meal. A prior administration of Fuscoporia obliqua decreased postprandial peak glucose, PPGE, and AUC glucose. The peak forearm blood flow and flow debt repayment were inversely well correlated with peak glucose, PPGE, and AUC glucose, but not with AUC insulin or the other lipid parameters. Even a single loading of the test meal was shown to impair the endothelial function in type 2 diabetic patients, and the postprandial endothelial dysfunction was improved by a prior use of Fuscoporia obliqua. Fuscoporia obliqua might reduce macrovascular complication by avoiding endothelial injury in postprandial hyperglycemic status.

  6. The PPARα agonist fenofibrate suppresses B-cell lymphoma in mice by modulating lipid metabolism.

    PubMed

    Huang, Jianfeng; Das, Suman Kumar; Jha, Pooja; Al Zoughbi, Wael; Schauer, Silvia; Claudel, Thierry; Sexl, Veronika; Vesely, Paul; Birner-Gruenberger, Ruth; Kratky, Dagmar; Trauner, Michael; Hoefler, Gerald

    2013-10-01

    Obesity is associated with an increased risk for malignant lymphoma development. We used Bcr/Abl transformed B cells to determine the impact of aggressive lymphoma formation on systemic lipid mobilization and turnover. In wild-type mice, tumor size significantly correlated with depletion of white adipose tissues (WAT), resulting in increased serum free fatty acid (FFA) concentrations which promote B-cell proliferation in vitro. Moreover, B-cell tumor development induced hepatic lipid accumulation due to enhanced hepatic fatty acid (FA) uptake and impaired FA oxidation. Serum triglyceride, FFA, phospholipid and cholesterol levels were significantly elevated. Consistently, serum VLDL/LDL-cholesterol and apolipoprotein B levels were drastically increased. These findings suggest that B-cell tumors trigger systemic lipid mobilization from WAT to the liver and increase VLDL/LDL release from the liver to promote tumor growth. Further support for this concept stems from experiments where we used the peroxisome proliferator-activated receptor α (PPARα) agonist and lipid-lowering drug fenofibrate that significantly suppressed tumor growth independent of angiogenesis and inflammation. In addition to WAT depletion, fenofibrate further stimulated FFA uptake by the liver and restored hepatic FA oxidation capacity, thereby accelerating the clearance of lipids released from WAT. Furthermore, fenofibrate blocked hepatic lipid release induced by the tumors. In contrast, lipid utilization in the tumor tissue itself was not increased by fenofibrate which correlates with extremely low expression levels of PPARα in B-cells. Our data show that fenofibrate associated effects on hepatic lipid metabolism and deprivation of serum lipids are capable to suppress B-cell lymphoma growth which may direct novel treatment strategies. This article is part of a Special Issue entitled Lipid Metabolism in Cancer. Copyright © 2013 The Author. Published by Elsevier B.V. All rights reserved.

  7. Reduction in generation of reactive oxygen species and endothelial dysfunction during postprandial state.

    PubMed

    Sodré, F L; Paim, B A; Urban, A; Vercesi, A E; Faria, E C

    2011-10-01

    To characterise changes in generation of cellular reactive oxygen species (ROS) in healthy males during the postprandial state, and to analyse the influence of the postprandial state on endothelial ROS generation and endothelial dysfunction. Seventeen healthy subjects were recruited. Blood samples were collected in the fasting state and 2, 4, 6 and 8h after liquid-meal intake (composition: 25% fat, 55% dextromaltose and 14% protein), providing 40 gfat m(-2) body surface. Plasma lipids, apolipoproteins, glucose and insulin were measured during this period. Peripheral blood mononuclear cells (PBMCs) were isolated by density-gradient centrifugation. The influence of postprandial state on intracellular ROS generation was measured by two different methods in PBMCs and in a human immortalised endothelial cell line (ECV 304). Artery flow-mediated vasodilation (FMD) was used to evaluate the endothelial function, and oxygen consumption by PBMCs was measured. Reduced ROS generation was observed in all methods and cells during the postprandial period. FMD was impaired 8h after meal intake (23±6 vs. 13±2, P<0.05 vs. baseline). The consumption of oxygen was reduced in PBMCs (-14% into 2h, P<0.05 vs. baseline and -27% after 4h, P<0.01 vs. baseline). ROS generation was correlated with plasma lipids, insulin, apolipoproteins and oxygen consumption. In contrast to the previously reported elevation of postprandial oxidative stress, this study shows reduced ROS generation in PBMCs and in ECV 304. Data obtained in both cellular models suggest the existence of a protective response against plasma postprandial oxidative stress. Copyright © 2009 Elsevier B.V. All rights reserved.

  8. A mitochondrial-targeted ubiquinone modulates muscle lipid profile and improves mitochondrial respiration in obesogenic diet-fed rats.

    PubMed

    Coudray, Charles; Fouret, Gilles; Lambert, Karen; Ferreri, Carla; Rieusset, Jennifer; Blachnio-Zabielska, Agnieszka; Lecomte, Jérôme; Ebabe Elle, Raymond; Badia, Eric; Murphy, Michael P; Feillet-Coudray, Christine

    2016-04-14

    The prevalence of the metabolic syndrome components including abdominal obesity, dyslipidaemia and insulin resistance is increasing in both developed and developing countries. It is generally accepted that the development of these features is preceded by, or accompanied with, impaired mitochondrial function. The present study was designed to analyse the effects of a mitochondrial-targeted lipophilic ubiquinone (MitoQ) on muscle lipid profile modulation and mitochondrial function in obesogenic diet-fed rats. For this purpose, twenty-four young male Sprague-Dawley rats were divided into three groups and fed one of the following diets: (1) control, (2) high fat (HF) and (3) HF+MitoQ. After 8 weeks, mitochondrial function markers and lipid metabolism/profile modifications in skeletal muscle were measured. The HF diet was effective at inducing the major features of the metabolic syndrome--namely, obesity, hepatic enlargement and glucose intolerance. MitoQ intake prevented the increase in rat body weight, attenuated the increase in adipose tissue and liver weights and partially reversed glucose intolerance. At the muscle level, the HF diet induced moderate TAG accumulation associated with important modifications in the muscle phospholipid classes and in the fatty acid composition of total muscle lipid. These lipid modifications were accompanied with decrease in mitochondrial respiration. MitoQ intake corrected the lipid alterations and restored mitochondrial respiration. These results indicate that MitoQ protected obesogenic diet-fed rats from some features of the metabolic syndrome through its effects on muscle lipid metabolism and mitochondrial activity. These findings suggest that MitoQ is a promising candidate for future human trials in the metabolic syndrome prevention.

  9. Postprandial antioxidant effect of the Mediterranean diet supplemented with coenzyme Q10 in elderly men and women.

    PubMed

    Yubero-Serrano, Elena M; Delgado-Casado, Nieves; Delgado-Lista, Javier; Perez-Martinez, Pablo; Tasset-Cuevas, Inmaculada; Santos-Gonzalez, Monica; Caballero, Javier; Garcia-Rios, Antonio; Marin, Carmen; Gutierrez-Mariscal, Francisco M; Fuentes, Francisco; Villalba, Jose M; Tunez, Isaac; Perez-Jimenez, Francisco; Lopez-Miranda, Jose

    2011-12-01

    Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. We have investigated whether the quality of dietary fat alters postprandial cellular oxidative stress and whether the supplementation with coenzyme Q(10) (CoQ) lowers postprandial oxidative stress in an elderly population. In this randomized crossover study, 20 participants were assigned to receive three isocaloric diets for periods of 4 week each: (1) Mediterranean diet supplemented with CoQ (Med+CoQ diet), (2) Mediterranean diet (Med diet), and (3) saturated fatty acid-rich diet (SFA diet). After a 12-h fast, the volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. CoQ, lipid peroxides (LPO), oxidized low-density lipoprotein (oxLDL), protein carbonyl (PC), total nitrite, nitrotyrosine plasma levels, catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and ischemic reactive hyperaemia (IRH) were determined. Med diet produced a lower postprandial GPx activity and a lower decrease in total nitrite level compared to the SFA diet. Med and Med+CoQ diets induced a higher postprandial increase in IRH and a lower postprandial LPO, oxLDL, and nitrotyrosine plasma levels than the SFA diet. Moreover, the Med+CoQ diet produced a lower postprandial decrease in total nitrite and a greater decrease in PC levels compared to the other two diets and lower SOD, CAT, and GPx activities than the SFA diet.In conclusion, Med diet reduces postprandial oxidative stress by reducing processes of cellular oxidation and increases the action of the antioxidant system in elderly persons and the administration of CoQ further improves this redox balance.

  10. Influence of acute exercise of varying intensity and duration on postprandial oxidative stress.

    PubMed

    Canale, Robert E; Farney, Tyler M; McCarthy, Cameron G; Bloomer, Richard J

    2014-09-01

    Aerobic exercise can reduce postprandial lipemia, and possibly oxidative stress, when performed prior to a lipid-rich meal. To compare the impact of acute exercise on postprandial oxidative stress. We compared aerobic and anaerobic exercise bouts of different intensities and durations on postprandial blood triglycerides (TAG), oxidative stress biomarkers (malondialdehyde, hydrogen peroxide, advanced oxidation protein products), and antioxidant status (trolox equivalent antioxidant capacity, superoxide dismutase, catalase, glutathione peroxidase). Twelve trained men (21-35 years) underwent four conditions: (1) No exercise rest; (2) 60-min aerobic exercise at 70% heart rate reserve; (3) five 60-s sprints at 100% max capacity; and (4) ten 15-s sprints at 200% max capacity. All exercise bouts were performed on a cycle ergometer. A high-fat meal was consumed 1 h after exercise cessation. Blood samples were collected pre-meal and 2 and 4 h post-meal and analyzed for TAG, oxidative stress biomarkers, and antioxidant status. No significant interaction or condition effects were noted for any variable (p > 0.05), with acute exercise having little to no effect on the magnitude of postprandial oxidative stress. In a sample of healthy, well-trained men, neither aerobic nor anaerobic exercise attenuates postprandial oxidative stress in response to a high-fat meal.

  11. Glucokinase regulatory protein (GCKR) gene polymorphism affects postprandial lipemic response in a dietary intervention study

    PubMed Central

    Shen, Haiqing; Pollin, Toni I.; Damcott, Coleen M.; McLenithan, John C.; Mitchell, Braxton D.; Shuldiner, Alan R.

    2010-01-01

    Postprandial triglyceridemia is an emerging risk factor for cardiovascular disease. However, most of the genes that influence postprandial triglyceridemia are not known. We evaluated whether a common nonsynonymous SNP rs1260326/P446L in the glucokinase regulatory protein (GCKR) gene influenced variation in the postprandial lipid response after a high-fat challenge in seven hundred and seventy participants in the Amish HAPI Heart Study who underwent an oral high-fat challenge and had blood samples taken in the fasting state and during the postprandial phase at 1, 2, 3, 4, and 6 hours. We found that the minor T allele at rs1260326 was associated with significantly higher fasting TG levels after adjusting for age, sex, and family structure (Pa = 0.06 for additive model, and Pr=0.0003 for recessive model). During the fat challenge, the T allele was associated with significantly higher maximum TG level (Pa = 0.006), incremental maximum TG level (Pa = 0.006), TG area under the curve (Pa = 0.02) and incremental TG area under the curve (Pa = 0.03). Our data indicate that the rs1260326 T allele of GCKR is associated with both higher fasting levels of TG as well as the postprandial TG response, which may result in higher atherogenic risk. PMID:19526250

  12. Adaptation Independent Modulation of Auditory Hair Cell Mechanotransduction Channel Open Probability Implicates a Role for the Lipid Bilayer.

    PubMed

    Peng, Anthony W; Gnanasambandam, Radhakrishnan; Sachs, Frederick; Ricci, Anthony J

    2016-03-09

    The auditory system is able to detect movement down to atomic dimensions. This sensitivity comes in part from mechanisms associated with gating of hair cell mechanoelectric transduction (MET) channels. MET channels, located at the tops of stereocilia, are poised to detect tension induced by hair bundle deflection. Hair bundle deflection generates a force by pulling on tip-link proteins connecting adjacent stereocilia. The resting open probability (P(open)) of MET channels determines the linearity and sensitivity to mechanical stimulation. Classically, P(open) is regulated by a calcium-sensitive adaptation mechanism in which lowering extracellular calcium or depolarization increases P(open). Recent data demonstrated that the fast component of adaptation is independent of both calcium and voltage, thus requiring an alternative explanation for the sensitivity of P(open) to calcium and voltage. Using rat auditory hair cells, we characterize a mechanism, separate from fast adaptation, whereby divalent ions interacting with the local lipid environment modulate resting P(open). The specificity of this effect for different divalent ions suggests binding sites that are not an EF-hand or calmodulin model. GsMTx4, a lipid-mediated modifier of cationic stretch-activated channels, eliminated the voltage and divalent sensitivity with minimal effects on adaptation. We hypothesize that the dual mechanisms (lipid modulation and adaptation) extend the dynamic range of the system while maintaining adaptation kinetics at their maximal rates.

  13. Lipid modulation of early G protein-coupled receptor signalling events.

    PubMed

    Dijkman, Patricia M; Watts, Anthony

    2015-11-01

    Upon binding of extracellular ligands, G protein coupled-receptors (GPCRs) initiate signalling cascades by activating heterotrimeric G proteins through direct interactions with the α subunit. While the lipid dependence of ligand binding has previously been studied for one class A GPCR, the neurotensin receptor 1 (NTS1), the role the lipid environment plays in the interaction of activated GPCRs with G proteins is less well understood. It is therefore of interest to understand the balance of lipid interactions required to support both ligand binding and G protein activation, not least since some receptors have multiple locations, and may experience different membrane environments when signalling in the plasma membrane or during endocytosis. Here, using the sensitive biophysical technique of microscale thermophoresis in conjunction with nanodisc lipid bilayer reconstitution, we show that in more native lipid environments rich in phosphatidyl ethanolamine (PE), the Gαi1 subunit has a ~4-fold higher affinity for NTS1 than in the absence of native lipids. The G protein-receptor affinity was further shown to be dependent on the ligand-binding state of the receptor, with potential indication of biased signalling for the known antagonist SR142948A. Gαi1 also showed preferential interaction with empty nanodiscs of native lipid mixtures rich in PE by around 2- to 4-fold over phosphatidyl choline (PC)/phosphatidyl glycerol (PG) lipid mixtures. The lipid environment may therefore play a role in creating favourable micro-environments for efficient GPCR signalling. Our approach combining nanodiscs with microscale thermophoresis will be useful in future studies to elucidate further the complexity of the GPCR interactome.

  14. Consumption of low doses of fat prevents the postprandial rise in chylomicron particle concentration and remnant accumulation in healthy normolipidaemic males

    PubMed Central

    James, Anthony P.; Mamo, John C.

    2012-01-01

    Chylomicron particles are continually synthesised and secreted from the intestine even in the absence of ingested fat. It is possible that following consumption of low doses of fat the basal level of chylomicron secretion and subsequent metabolism are sufficient to metabolise this fat without an increase in postprandial chylomicron concentrations. To test this hypothesis, healthy male subjects were randomised to receive, on three separate occasions, meals containing a range of doses of fat (average 8·1–19 g) and effects on postprandial lipaemia and chylomicron concentration were determined. Furthermore, to delineate the effect on lipid-rich v. lipid-poor (remnant) forms lipid levels were also determined in a density <1·006 g/ml fraction. Following consumption of the very low dose of fat the postprandial concentration of chylomicrons was unaltered, whereas following the medium dose postprandial chylomicron concentrations were significantly increased. Interestingly, this increase was only detected in the lipid-rich chylomicron fraction, with postprandial levels of chylomicron remnants remaining unchanged. In conclusion, it appears that consumption of what would be considered low to medium doses of fat are not associated with transient postprandial increases in chylomicron remnants in healthy male subjects. PMID:25191552

  15. The modulation of gap-junctional intercellular communication by lipid rafts.

    PubMed

    Defamie, Norah; Mesnil, Marc

    2012-08-01

    Lipid rafts are specific microdomains of plasma membrane which are enriched in cholesterol and sphingolipids. These domains seem to favour the interactions of particular proteins and the regulation of signalling pathways in the cells. Recent data have shown that among the proteins, which are preferentially localized in lipid rafts, are connexins that are the structural proteins of gap junctions. Since gap junctional intercellular communication is involved in various cellular processes and pathologies such as cancer, we were interested to review the various observations concerning this specific localization of connexins in lipid rafts and its consequences on gap junctional intercellular communication capacity. In particular, we will focus our discussion on the role of the lipid raft-connexin connection in cancer progression. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.

  16. Electrostatic interactions at the microscale modulate dynamics and distribution of lipids in bilayers.

    PubMed

    Mangiarotti, Agustín; Wilke, Natalia

    2017-01-18

    For decades, it has been assumed that electrostatic long-range (micron distances) repulsions in lipid bilayers are negligible due to screening from the aqueous milieu. This concept, mostly derived from theoretical calculations, is broadly accepted in the biophysical community. Here we present experimental evidence showing that domain-domain electrostatic repulsions in charged and also in neutral lipid bilayers regulate the diffusion, in-plane structuring and merging of lipid domains in the micron range. All the experiments were performed on both, lipid monolayers and bilayers, and the remarkable similarity in the results found in bilayers compared to monolayers led us to propose that inter-domain repulsions occur mainly within the plane of the membrane. Finally, our results indicate that electrostatic interactions between the species inserted in a cell membrane are not negligible, not only at nanometric but also at larger distances, suggesting another manner for regulating the membrane properties.

  17. Dynamic Lipid-dependent Modulation of Protein Topology by Post-translational Phosphorylation.

    PubMed

    Vitrac, Heidi; MacLean, David M; Karlstaedt, Anja; Taegtmeyer, Heinrich; Jayaraman, Vasanthi; Bogdanov, Mikhail; Dowhan, William

    2017-02-03

    Membrane protein topology and folding are governed by structural principles and topogenic signals that are recognized and decoded by the protein insertion and translocation machineries at the time of initial membrane insertion and folding. We previously demonstrated that the lipid environment is also a determinant of initial protein topology, which is dynamically responsive to post-assembly changes in membrane lipid composition. However, the effect on protein topology of post-assembly phosphorylation of amino acids localized within initially cytoplasmically oriented extramembrane domains has never been investigated. Here, we show in a controlled in vitro system that phosphorylation of a membrane protein can trigger a change in topological arrangement. The rate of change occurred on a scale of seconds, comparable with the rates observed upon changes in the protein lipid environment. The rate and extent of topological rearrangement were dependent on the charges of extramembrane domains and the lipid bilayer surface. Using model membranes mimicking the lipid compositions of eukaryotic organelles, we determined that anionic lipids, cholesterol, sphingomyelin, and membrane fluidity play critical roles in these processes. Our results demonstrate how post-translational modifications may influence membrane protein topology in a lipid-dependent manner, both along the organelle trafficking pathway and at their final destination. The results provide further evidence that membrane protein topology is dynamic, integrating for the first time the effect of changes in lipid composition and regulators of cellular processes. The discovery of a new topology regulatory mechanism opens additional avenues for understanding unexplored structure-function relationships and the development of optimized topology prediction tools.

  18. Adaptation Independent Modulation of Auditory Hair Cell Mechanotransduction Channel Open Probability Implicates a Role for the Lipid Bilayer

    PubMed Central

    Gnanasambandam, Radhakrishnan; Sachs, Frederick

    2016-01-01

    The auditory system is able to detect movement down to atomic dimensions. This sensitivity comes in part from mechanisms associated with gating of hair cell mechanoelectric transduction (MET) channels. MET channels, located at the tops of stereocilia, are poised to detect tension induced by hair bundle deflection. Hair bundle deflection generates a force by pulling on tip-link proteins connecting adjacent stereocilia. The resting open probability (Popen) of MET channels determines the linearity and sensitivity to mechanical stimulation. Classically, Popen is regulated by a calcium-sensitive adaptation mechanism in which lowering extracellular calcium or depolarization increases Popen. Recent data demonstrated that the fast component of adaptation is independent of both calcium and voltage, thus requiring an alternative explanation for the sensitivity of Popen to calcium and voltage. Using rat auditory hair cells, we characterize a mechanism, separate from fast adaptation, whereby divalent ions interacting with the local lipid environment modulate resting Popen. The specificity of this effect for different divalent ions suggests binding sites that are not an EF-hand or calmodulin model. GsMTx4, a lipid-mediated modifier of cationic stretch-activated channels, eliminated the voltage and divalent sensitivity with minimal effects on adaptation. We hypothesize that the dual mechanisms (lipid modulation and adaptation) extend the dynamic range of the system while maintaining adaptation kinetics at their maximal rates. SIGNIFICANCE STATEMENT Classically, changes in extracellular calcium and voltage affect open probability (Popen) through mechanoelectric transduction adaptation, and this mechanism is the only means of controlling the set point of the channel. Here, we further characterize the effects of extracellular calcium and voltage on the channel and for the first time determine that these manipulations occur through a mechanism that is independent of fast adaptation

  19. Maternal omega-3 fatty acids and micronutrients modulate fetal lipid metabolism: A review.

    PubMed

    Khaire, Amrita A; Kale, Anvita A; Joshi, Sadhana R

    2015-07-01

    It is well established that alterations in the mother's diet or metabolism during pregnancy has long-term adverse effects on the lipid metabolism in the offspring. There is growing interest in the role of specific nutrients especially omega-3 fatty acids in the pathophysiology of lipid disorders. A series of studies carried out in humans and rodents in our department have consistently suggested a link between omega-3 fatty acids especially docosahexaenoic acid and micronutrients (vitamin B12 and folic acid) in the one carbon metabolic cycle and its effect on the fatty acid metabolism, hepatic transcription factors and DNA methylation patterns. However the association of maternal intake or metabolism of these nutrients with fetal lipid metabolism is relatively less explored. In this review, we provide insights into the role of maternal omega-3 fatty acids and vitamin B12 and their influence on fetal lipid metabolism through various mechanisms which influence phosphatidylethanolamine-N-methyltransferase activity, peroxisome proliferator activated receptor, adiponectin signaling pathway and epigenetic process like chromatin methylation. This will help understand the possible mechanisms involved in fetal lipid metabolism and may provide important clues for the prevention of lipid disorders in the offspring.

  20. Light Remodels Lipid Biosynthesis in Nannochloropsis gaditana by Modulating Carbon Partitioning between Organelles1[OPEN

    PubMed Central

    Vitulo, Nicola; Diretto, Gianfranco; Block, Maryse; Jouhet, Juliette; Meneghesso, Andrea; Valle, Giorgio; Giuliano, Giovanni; Maréchal, Eric

    2016-01-01

    The seawater microalga Nannochloropsis gaditana is capable of accumulating a large fraction of reduced carbon as lipids. To clarify the molecular bases of this metabolic feature, we investigated light-driven lipid biosynthesis in Nannochloropsis gaditana cultures combining the analysis of photosynthetic functionality with transcriptomic, lipidomic and metabolomic approaches. Light-dependent alterations are observed in amino acid, isoprenoid, nucleic acid, and vitamin biosynthesis, suggesting a deep remodeling in the microalgal metabolism triggered by photoadaptation. In particular, high light intensity is shown to affect lipid biosynthesis, inducing the accumulation of diacylglyceryl-N,N,N-trimethylhomo-Ser and triacylglycerols, together with the up-regulation of genes involved in their biosynthesis. Chloroplast polar lipids are instead decreased. This situation correlates with the induction of genes coding for a putative cytosolic fatty acid synthase of type 1 (FAS1) and polyketide synthase (PKS) and the down-regulation of the chloroplast fatty acid synthase of type 2 (FAS2). Lipid accumulation is accompanied by the regulation of triose phosphate/inorganic phosphate transport across the chloroplast membranes, tuning the carbon metabolic allocation between cell compartments, favoring the cytoplasm, mitochondrion, and endoplasmic reticulum at the expense of the chloroplast. These results highlight the high flexibility of lipid biosynthesis in N. gaditana and lay the foundations for a hypothetical mechanism of regulation of primary carbon partitioning by controlling metabolite allocation at the subcellular level. PMID:27325666

  1. Postprandial lymphatic pump function after a high-fat meal: a characterization of contractility, flow, and viscosity.

    PubMed

    Kassis, Timothy; Yarlagadda, Sri Charan; Kohan, Alison B; Tso, Patrick; Breedveld, Victor; Dixon, J Brandon

    2016-05-15

    Dietary lipids are transported from the intestine through contractile lymphatics. Chronic lipid loads can adversely affect lymphatic function. However, the acute lymphatic pump response in the mesentery to a postprandial lipid meal has gone unexplored. In this study, we used the rat mesenteric collecting vessel as an in vivo model to quantify the effect of lipoproteins on vessel function. Lipid load was continuously monitored by using the intensity of a fluorescent fatty-acid analog, which we infused along with a fat emulsion through a duodenal cannula. The vessel contractility was simultaneously quantified. We demonstrated for the first time that collecting lymphatic vessels respond to an acute lipid load by reducing pump function. High lipid levels decreased contraction frequency and amplitude. We also showed a strong tonic response through a reduction in the end-diastolic and systolic diameters. We further characterized the changes in flow rate and viscosity and showed that both increase postprandially. In addition, shear-mediated Ca(2+) signaling in lymphatic endothelial cells differed when cultured with lipoproteins. Together these results show that the in vivo response could be both shear and lipid mediated and provide the first evidence that high postprandial lipid has an immediate negative effect on lymphatic function even in the acute setting. Copyright © 2016 the American Physiological Society.

  2. Molecular resolution of a dioleoyl-Sn-glycero-phosphocholine lipid bilayer in liquid by phase modulation atomic force microscopy

    NASA Astrophysics Data System (ADS)

    Hoel, Antonin; Osaki, Toshihisa; Takeuchi, Shoji; Volz, Sebastian; Kawakatsu, Hideki

    2012-08-01

    We present a molecular resolved image of a supported lipid bilayer using atomic force microscopy in liquid conditions. Due to the well-known molecular diffusion processes with velocities of a few nm/s occurring in free-standing membranes, this type of mapping is difficult to achieve. We have obtained a sub-nanometer scale resolution of a dioleoyl-sn-glycero-phosphocholine membrane because of the high sensitivity of our phase modulated microscope and the slowed down diffusion due to the interaction with the substrate. A pair function analysis has revealed local disordered and gel phases with an order range limited to the first neighbour.

  3. Modulation of the spontaneous curvature and bending rigidity of lipid membranes by interfacially adsorbed amphipathic peptides.

    PubMed

    Zemel, Assaf; Ben-Shaul, Avinoam; May, Sylvio

    2008-06-12

    Amphipathic alpha-helical peptides are often ascribed an ability to induce curvature stress in lipid membranes. This may lead directly to a bending deformation of the host membrane, or it may promote the formation of defects that involve highly curved lipid layers present in membrane pores, fusion intermediates, and solubilized peptide-micelle complexes. The driving force is the same in all cases: peptides induce a spontaneous curvature in the host lipid layer, the sign of which depends sensitively on the peptide's structural properties. We provide a quantitative account for this observation on the basis of a molecular-level method. To this end, we consider a lipid membrane with peptides interfacially adsorbed onto one leaflet at high peptide-to-lipid ratio. The peptides are modeled generically as rigid cylinders that interact with the host membrane through a perturbation of the conformational properties of the lipid chains. Through the use of a molecular-level chain packing theory, we calculate the elastic properties, that is, the spontaneous curvature and bending stiffness, of the peptide-decorated lipid membrane as a function of the peptide's insertion depth. We find a positive spontaneous curvature (preferred bending of the membrane away from the peptide) for small penetration depths of the peptide. At a penetration depth roughly equal to half-insertion into the hydrocarbon core, the spontaneous curvature changes sign, implying negative spontaneous curvature (preferred bending of the membrane toward the peptide) for large penetration depths. Despite thinning of the membrane upon peptide insertion, we find an increase in the bending stiffness. We discuss these findings in terms of how the peptide induces elastic stress.

  4. Postprandial hypertriglyceridemia as a coronary risk factor.

    PubMed

    Borén, Jan; Matikainen, Niina; Adiels, Martin; Taskinen, Marja-Riitta

    2014-04-20

    Postprandial hypertriglyceridemia is now established as an important risk factor for cardiovascular disease (CVD). This metabolic abnormality is principally initiated by overproduction and/or decreased catabolism of triglyceride-rich lipoproteins (TRLs) and is a consequence of predisposing genetic variations and medical conditions such as obesity and insulin resistance. Accumulation of TRLs in the postprandial state promotes the retention of remnant particles in the artery wall. Because of their size, most remnant particles cannot cross the endothelium as efficiently as smaller low-density lipoprotein (LDL) particles. However, since each remnant particle contains approximately 40 times more cholesterol compared with LDL, elevated levels of remnants may lead to accelerated atherosclerosis and CVD. The recognition of postprandial hypertriglyceridemia in the clinical setting has been severely hampered by technical difficulties and the lack of established clinical protocols for investigating postprandial lipemia. In addition, there are currently no internationally agreed management guidelines for this type of dyslipidemia. Here we review the mechanism for and consequences of excessive postprandial hypertriglyceridemia, epidemiological evidence in support of high triglycerides and remnant particles as risk factors for CVD, the definition of hypertriglyceridemia, methods to measure postprandial hypertriglyceridemia and apolipoproteins and, finally, current and future treatment opportunities.

  5. Postprandial lipemia enhances the capacity of large HDL2 particles to mediate free cholesterol efflux via SR-BI and ABCG1 pathways in type IIB hyperlipidemia.

    PubMed

    Julia, Zélie; Duchene, Emilie; Fournier, Natalie; Bellanger, Natacha; Chapman, M John; Le Goff, Wilfried; Guerin, Maryse

    2010-11-01

    Lipid and cholesterol metabolism in the postprandial phase is associated with both quantitative and qualitative remodeling of HDL particle subspecies that may influence their anti-atherogenic functions in the reverse cholesterol transport pathway. We evaluated the capacity of whole plasma or isolated HDL particles to mediate cellular free cholesterol (FC) efflux, cholesteryl ester transfer protein (CETP)-mediated cholesteryl ester (CE) transfer, and selective hepatic CE uptake during the postprandial phase in subjects displaying type IIB hyperlipidemia (n = 16). Postprandial, large HDL2 displayed an enhanced capacity to mediate FC efflux via both scavenger receptor class B type I (SR-BI)-dependent (+12%; P < 0.02) and ATP binding cassette transporter G1 (ABCG1)-dependent (+31%; P < 0.008) pathways in in vitro cell systems. In addition, the capacity of whole postprandial plasma (4 h and 8 h postprandially) to mediate cellular FC efflux via the ABCA1-dependent pathway was significantly increased (+19%; P < 0.0003). Concomitantly, postprandial lipemia was associated with elevated endogenous CE transfer rates from HDL2 to apoB lipoproteins and with attenuated capacity (-17%; P < 0.02) of total HDL to deliver CE to hepatic cells. Postprandial lipemia enhanced SR-BI and ABCG1-dependent efflux to large HDL2 particles. However, postprandial lipemia is equally associated with deleterious features by enhancing formation of CE-enriched, triglyceride-rich lipoprotein particles through the action of CETP and by reducing the direct return of HDL-CE to the liver.

  6. Fat taste and lipid metabolism in humans.

    PubMed

    Mattes, Richard D

    2005-12-15

    Dietary and body fat are essential for life. Fatty acids modulate fat detection, ingestion, digestion, absorption and elimination. Though direct effects occur throughout the body, much of this regulation stems from signals originating in the oral cavity. The predominant orosensory cue for dietary fat is textural, but accumulating electrophysiological, behavioral and clinical evidence supports olfactory and gustatory components. Orosensory stimulation with long-chain unsaturated, but possibly also saturated, fatty acids elicits an array of cephalic phase responses including release of gastric lipase, secretion of pancreatic digestive enzymes, mobilization of lipid stored in the intestine from the prior meal, pancreatic endocrine secretion and, probably indirectly, altered lipoprotein lipase activity. Combined, these processes influence postprandial lipemia. There is preliminary evidence of marked individual variability in fat "taste" with uncertain health implications. The possibility that fat taste sensitivity reflects systemic reactivity to fat warrants further evaluation.

  7. Basal and postprandial change in serum fibroblast growth factor-21 concentration in type 1 diabetic mellitus and in healthy controls.

    PubMed

    Zibar, Karin; Blaslov, Kristina; Bulum, Tomislav; Ćuća, Jadranka Knežević; Smirčić-Duvnjak, Lea

    2015-04-01

    Fibroblast growth factor-21 (FGF-21) appears to have an important role in glucose and lipid metabolism. FGF-21 secretion is mainly determined by nutritional status. The aim of this study was to measure basal and postprandial FGF-21 and postprandial change of FGF-21 concentration in type 1 diabetes mellitus (T1DM) patients and in healthy controls, and to investigate the differences between the groups. The cross-sectional study included 30 C-peptide negative T1DM patients, median age 37 years (20-59), disease duration 22 years (3-45), and nine healthy controls, median age 30 years (27-47). Basal and postprandial FGF-21 concentrations were measured by ELISA. The associations of FGF-21 with glucose, lipids, and insulin were analyzed. Individuals with T1DM showed significantly lower basal FGF-21 concentration (P=0.046) when compared with healthy controls (median value 28.2 vs 104 pg/mL) and had significantly different postprandial change (∆ 30'-0') of FGF-21 (P=0.006) in comparison with healthy controls (median value -1.1 vs -20.5 pg/mL). The glucose and lipid status did not correlate with FGF-21. In healthy controls, postprandial insulin level correlated with basal FGF-21 (ρ=0.7, P=0.036). Multiple regression analysis showed that they are independently associated after adjustment for confounding factors (β=1.824, P=0.04). We describe the pathological pattern of basal and postprandial change of FGF-21 secretion not associated with glucose, lipid levels, or insulin therapy in patients with T1DM. Since FGF-21 has numerous protective metabolic effects in the experimental model, the lower basal FGF-21 concentration in T1DM patients opens the question about the potential role of recombinant FGF-21 therapy.

  8. Dopaminergic Neurons Respond to Iron-Induced Oxidative Stress by Modulating Lipid Acylation and Deacylation Cycles

    PubMed Central

    Sánchez Campos, Sofía; Rodríguez Diez, Guadalupe; Oresti, Gerardo Martín; Salvador, Gabriela Alejandra

    2015-01-01

    Metal-imbalance has been reported as a contributor factor for the degeneration of dopaminergic neurons in Parkinson Disease (PD). Specifically, iron (Fe)-overload and copper (Cu) mis-compartmentalization have been reported to be involved in the injury of dopaminergic neurons in this pathology. The aim of this work was to characterize the mechanisms of membrane repair by studying lipid acylation and deacylation reactions and their role in oxidative injury in N27 dopaminergic neurons exposed to Fe-overload and Cu-supplementation. N27 dopaminergic neurons incubated with Fe (1mM) for 24 hs displayed increased levels of reactive oxygen species (ROS), lipid peroxidation and elevated plasma membrane permeability. Cu-supplemented neurons (10, 50 μM) showed no evidence of oxidative stress markers. A different lipid acylation profile was observed in N27 neurons pre-labeled with [3H] arachidonic acid (AA) or [3H] oleic acid (OA). In Fe-exposed neurons, AA uptake was increased in triacylglycerols (TAG) whereas its incorporation into the phospholipid (PL) fraction was diminished. TAG content was 40% higher in Fe-exposed neurons than in controls. This increase was accompanied by the appearance of Nile red positive lipid bodies. Contrariwise, OA incorporation increased in the PL fractions and showed no changes in TAG. Lipid acylation profile in Cu-supplemented neurons showed AA accumulation into phosphatidylserine and no changes in TAG. The inhibition of deacylation/acylation reactions prompted an increase in oxidative stress markers and mitochondrial dysfunction in Fe-overloaded neurons. These findings provide evidence about the participation of lipid acylation mechanisms against Fe-induced oxidative injury and postulate that dopaminergic neurons cleverly preserve AA in TAG in response to oxidative stress. PMID:26076361

  9. Bread making technology influences postprandial glucose response: a review of the clinical evidence.

    PubMed

    Stamataki, Nikoleta S; Yanni, Amalia E; Karathanos, Vaios T

    2017-04-01

    Lowering postprandial glucose and insulin responses may have significant beneficial implications for prevention and treatment of metabolic disorders. Bread is a staple food consumed worldwide in a daily basis, and the use of different baking technologies may modify the glucose and insulin response. The aim of this review was to critically record the human studies examining the application of different bread making processes on postprandial glucose and insulin response to bread. Literature is rich of results which show that the use of sourdough fermentation instead of leavening with Saccharomyces cerevisiae is able to modulate glucose response to bread, whereas evidence regarding its efficacy on lowering postprandial insulin response is less clear. The presence of organic acids is possibly involved, but the exact mechanism of action is still to be confirmed. The reviewed data also revealed that the alteration of other processing conditions (method of cooking, proofing period, partial baking freezing technology) can effectively decrease postprandial glucose response to bread, by influencing physical structure and retrogradation of starch. The development of healthier bread products that benefit postprandial metabolic responses is crucial and suggested baking conditions can be used by the bread industry for the promotion of public health.

  10. Mechanisms of incretin effects on plasma lipids and implications for the cardiovascular system.

    PubMed

    Xiao, Changting; Dash, Satya; Lewis, Gary F

    2012-12-01

    Dyslipidemia is a prominent feature of type 2 diabetes and insulin resistance that contributes to increased atherosclerosis and cardiovascular disease (CVD) risks under these conditions. Incretin-based therapies (GLP-1 receptor agonists and DPP-4 inhibitors) have recently been developed and are approved for clinical use for treatment of type 2 diabetes. Besides improved glycemic control, other benefits are being increasingly appreciated, one of which is improved plasma lipid profile. This review aims to summarize the evidence and potential mechanism of such agents in humans in modulating fasting and postprandial lipoprotein metabolism.

  11. Panax red ginseng extract regulates energy expenditures by modulating PKA dependent lipid mobilization in adipose tissue.

    PubMed

    Cho, Hae-Mi; Kang, Young-Ho; Yoo, Hanju; Yoon, Seung-Yong; Kang, Sang-Wook; Chang, Eun-Ju; Song, Youngsup

    2014-05-16

    Regulation of balance between lipid accumulation and energy consumption is a critical step for the maintenance of energy homeostasis. Here, we show that Panax red ginseng extract treatments increased energy expenditures and prevented mice from diet induced obesity. Panax red ginseng extracts strongly activated Hormone Specific Lipase (HSL) via Protein Kinase A (PKA). Since activation of HSL induces lipolysis in WAT and fatty acid oxidation in brown adipose tissue (BAT), these results suggest that Panax red ginseng extracts reduce HFD induced obesity by regulating lipid mobilization.

  12. Novel Nanostructured Solid Materials for Modulating Oral Drug Delivery from Solid-State Lipid-Based Drug Delivery Systems.

    PubMed

    Dening, Tahnee J; Rao, Shasha; Thomas, Nicky; Prestidge, Clive A

    2016-01-01

    Lipid-based drug delivery systems (LBDDS) have gained significant attention in recent times, owing to their ability to overcome the challenges limiting the oral delivery of poorly water-soluble drugs. Despite the successful commercialization of several LBDDS products over the years, a large discrepancy exists between the number of poorly water-soluble drugs displaying suboptimal in vivo performances and the application of LBDDS to mitigate their various delivery challenges. Conventional LBDDS, including lipid solutions and suspensions, emulsions, and self-emulsifying formulations, suffer from various drawbacks limiting their widespread use and commercialization. Accordingly, solid-state LBDDS, fabricated by adsorbing LBDDS onto a chemically inert solid carrier material, have attracted substantial interest as a viable means of stabilizing LBDDS whilst eliminating some of the various limitations. This review describes the impact of solid carrier choice on LBDDS performance and highlights the importance of appropriate solid carrier material selection when designing hybrid solid-state LBDDS. Specifically, emphasis is placed on discussing the ability of the specific solid carrier to modulate drug release, control lipase action and lipid digestion, and enhance biopharmaceutical performance above the original liquid-state LBDDS. To encourage the interested reader to consider their solid carrier choice on a higher level, various novel materials with the potential for future use as solid carriers for LBDDS are described. This review is highly significant in guiding future research directions in the solid-state LBDDS field and fostering the translation of these delivery systems to the pharmaceutical marketplace.

  13. Chlorogenic acid from honeysuckle improves hepatic lipid dysregulation and modulates hepatic fatty acid composition in rats with chronic endotoxin infusion.

    PubMed

    Zhou, Yan; Ruan, Zheng; Wen, Yanmei; Yang, Yuhui; Mi, Shumei; Zhou, Lili; Wu, Xin; Ding, Sheng; Deng, Zeyuan; Wu, Guoyao; Yin, Yulong

    2016-03-01

    Chlorogenic acid as a natural hydroxycinnamic acid has protective effect for liver. Endotoxin induced metabolic disorder, such as lipid dysregulation and hyperlipidemia. In this study, we investigated the effect of chlorogenic acid in rats with chronic endotoxin infusion. The Sprague-Dawley rats with lipid metabolic disorder (LD group) were intraperitoneally injected endotoxin. And the rats of chlorogenic acid-LD group were daily received chlorogenic acid by intragastric administration. In chlorogenic acid-LD group, the area of visceral adipocyte was decreased and liver injury was ameliorated, as compared to LD group. In chlorogenic acid-LD group, serum triglycerides, free fatty acids, hepatic triglycerides and cholesterol were decreased, the proportion of C20:1, C24:1 and C18:3n-6, Δ9-18 and Δ6-desaturase activity index in the liver were decreased, and the proportion of C18:3n-3 acid was increased, compared to the LD group. Moreover, levels of phosphorylated AMP-activated protein kinase, carnitine palmitoyltransferase-I, and fatty acid β-oxidation were increased in chlorogenic acid-LD group compared to LD rats, whereas levels of fatty acid synthase and acetyl-CoA carboxylase were decreased. These findings demonstrate that chlorogenic acid effectively improves hepatic lipid dysregulation in rats by regulating fatty acid metabolism enzymes, stimulating AMP-activated protein kinase activation, and modulating levels of hepatic fatty acids.

  14. Vegetable oil blends with α-linolenic acid rich Garden cress oil modulate lipid metabolism in experimental rats.

    PubMed

    Umesha, S S; Naidu, K Akhilender

    2012-12-15

    Vegetable oil blends with modified fatty acid profile are being developed to improve n-6/n-3 polyunsaturated fatty acid (PUFAs) ratio in edible oils. The objective of this study is to develop vegetable oil blends with α-linolenic acid (ALA) rich Garden cress oil (GCO) and assess their modulatory effect on lipid metabolism. Sunflower oil (SFO), Rice bran oil (RBO), Sesame oil (SESO) were blended with GCO at different ratios to obtain n-6/n-3 PUFA ratio of 2.3-2.6. Native and GCO blended oils were fed to Wistar rats at 10% level in the diet for 60 days. Serum and liver lipids showed significant decrease in Total cholesterol (TC), Triglyceride (TG), LDL-C levels in GCO and GCO blended oil fed rats compared to native oil fed rats. ALA, EPA, DHA contents were significantly increased while linoleic acid (LA), arachidonic acid (AA) levels decreased in different tissues of GCO and GCO blended oils fed rats. In conclusion, blending of vegetable oils with GCO increases ALA, decreases n-6 to n-3 PUFA ratio and beneficially modulates lipid profile.

  15. Fasting and postprandial levels of a novel anorexigenic peptide nesfatin in childhood obesity.

    PubMed

    Anık, Ahmet; Çatlı, Gönül; Abacı, Ayhan; Küme, Tuncay; Bober, Ece

    2014-07-01

    Nesfatin-1, a recently discovered anorexigenic peptide, is expressed in several tissues, including pancreatic islet cells and central nervous system. However, its pathophysiological role in the development of obesity and insulin resistance remains unknown. To investigate the possible involvement of nesfatin-1 in the pathogenesis of childhood obesity, we examined the relationship between fasting and postprandial nesfatin-1 concentrations and metabolic/antropometric parameters in obese children. The study included obese children with a body mass index >95th percentile. Fasting serum glucose, insulin, lipid profile, fasting and postprandial (120th min) nesfatin-1 levels were measured to evaluate the metabolic parameters. Different cutoff values for prepubertal and pubertal stages were used to determine the status of insulin resistance (HOMA-IR) (prepubertal >2.5, pubertal >4). The percentage of body fat was measured using bioelectric impedance analysis. Seventy-one obese children were included in this study. There was no statistically significant difference between fasting and postprandial nesfatin-1 levels in obese subjects (0.70 ± 0.15 and 0.69 ± 0.14 ng/mL, p>0.05, respectively). Insulin resistance was observed in 58% (41/71) of the cases. There was no significant difference in either fasting or postprandial serum nesfatin-1 levels between the insulin-resistant and non-resistant groups (p>0.05). There was no correlation between fasting and postprandial serum nesfatin-1 levels and anthropometric and metabolic parameters in insulin-resistant and non-resistant groups. In this study, there was no significant increase in the postprandial level of nesfatin-1. This observation suggested that oral glucose load in obese children may not be sufficient for nesfatin-1 response and that nesfatin-1 may not have an effect as a short-term regulator of food intake.

  16. Apolipoprotein E polymorphism influences postprandial retinyl palmitate but not triglyceride concentrations

    SciTech Connect

    Boerwinkle, E. ); Brown, S.; Patsch, W. ); Sharrett, A.R. ); Heiss, G. )

    1994-02-01

    To quantify the effect of the apolipoprotein (apo) E polymorphism on the magnitude of postprandial lipemia, the authors have defined its role in determining the response to a single high-fat meal in a large sample of (N = 474) individuals taking part in the biethnic Atherosclerosis Risk in Communities Study. The profile of postprandial response in plasma was monitored over 8 h by triglyceride, triglyceride-rich lipoprotein (TGRL)-triglyceride, apo B-48/apo B-100 ratio, and retinyl palmitate concentrations, and the apo E polymorphism was determined by DNA amplification and digestion. The frequency of the apo E alleles and their effects on fasting lipid levels in this sample with vitamin A was significantly different among apo E genotypes, with delayed clearance in individuals with an [var epsilon]2 allele, compared with [var epsilon]3/3 and [var epsilon]3/4 individuals. In the sample of 397 Caucasians, average retinyl palmitate response was 1,489 [mu]g/dl in [var epsilon]2/3 individuals, compared with 1,037 [mu]g/dl in [var epsilon]3/3 individuals and 1,108 [mu]g/dl in [var epsilon]3/4 individuals. The apo E polymorphism accounted for 7.1% of the interindividual variation in postprandial retinyl palmitate response, a contribution proportionally greater than its well-known effect on fasting LDL-cholesterol. However, despite this effect on postprandial retinyl palmitate, the profile of postprandial triglyceride response was not significantly different among apo E genotypes. The profile of postprandial response was consistent between the sample of Caucasians and a smaller sample of black subjects. While these data indicate that the removal of remnant particles from circulation is delayed in subjects with the [var epsilon]2/3 genotype, there is no reported evidence that the [var epsilon]2 allele predisposes to coronary artery disease (CAD). 82 refs., 6 figs., 4 tabs.

  17. Green Tea Extract Improves the Postprandial Overproduction of Intestinal Apolipoprotein B-containing Lipoproteins in Fructose-Fed Hamsters

    USDA-ARS?s Scientific Manuscript database

    Green tea has putative medicinal properties that may be useful in preventing the metabolic syndrome since increased consumption of green tea extract (GTE) is associated with improved lipid and glucose homeostasis in human and animals. The acute effect of GTE on postprandial intestinal apoB48 product...

  18. Modulation of radiation induced lipid peroxidation by phospholipase A 2 and calmodulin antagonists: Relevance to detoxification

    NASA Astrophysics Data System (ADS)

    Varshney, Rajeev; Kale, R. K.

    1995-04-01

    Ghost membranes prepared from erythrocytes of Swiss albino mice were irradiated with 0.9 Gy s -1. Lipid peroxidation initiated by ionizing radiation was enhanced by phospholipase A 2, and required both phospholipase A 2 and GSH-peroxidase for consecutive action to convert fatty acid peroxides into corresponding alcohols. The ability of phospholipase A 2 to enhance lipid peroxidation was increased in presence of Ca 2+. However, in combination, phospholipase A 2 and GSH-peroxidase were effective in inhibiting lipid peroxidation. These findings show that free fatty acid peroxides considerably increase the peroxidation. Calmodulin antagonists inhibit lipid peroxidation and decrease the radiation induced release of Ca 2+ from the membranes. Our results suggest the importance of Ca 2+ dependent phospholipase A 2 in detoxification of fatty acid peroxides in the membranes. It is quite possible that scavenging of free radicals by calmodulin antagonists lower the formation of hydroperoxides, resulting in the decrease in activity of phospholipase A 2. Alternatively, decrease in Ca 2+ release due to the calmodulin antagonists might have affected the activity of phospholipase A 2. Our observations might be of considerable significance in the understanding of post irradiation effect on biological membranes.

  19. Modulation of Lipid Metabolism and Spiramycin Biosynthesis in Streptomyces ambofaciens Unstable Mutants

    PubMed Central

    Schauner, Catherine; Dary, Annie; Lebrihi, Ahmed; Leblond, Pierre; Decaris, Bernard; Germain, Pierre

    1999-01-01

    Streptomyces ambofaciens is prone to genetic instability involving genomic rearrangements at the extremities of the chromosomal DNA. An amplified DNA sequence (ADS205), including an open reading frame (orfPS), is responsible for the reversible loss of spiramycin production in the mutant strain NSA205 (ADS205+ Spi−). The product of orfPS is homologous to polyketide synthase systems (PKSs) involved in the biosynthesis of erythromycin and rapamycin and is overexpressed in strain NSA205 compared with the parental strain RP181110. As PKSs and fatty acid synthase systems have the same precursors, we tested the possibility that overexpression of orfPS also affects lipid metabolism in strain NSA205. This report focuses on comparative analysis of lipids in strain RP181110, the mutant strain NSA205, and a derivative, NSA228 (ADS205− Spi+). NSA205 showed a dramatically depressed lipid content consisting predominantly of phospholipids and triacylglycerols. This lipid content was globally restored in strain NSA228, which had lost ADS205. Furthermore, strains RP181110 and NSA205 presented similar phospholipid and triacylglycerol compositions. No abnormal fatty acids were detected in NSA205. PMID:10347068

  20. Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors.

    PubMed

    Goto, Tsuyoshi; Kim, Young-Il; Takahashi, Nobuyuki; Kawada, Teruo

    2013-01-01

    Obesity causes excess fat accumulation in various tissues, most notoriously in the adipose tissue, along with other insulin-responsive organs such as skeletal muscle and the liver, which predisposes an individual to the development of metabolic abnormalities. The molecular mechanisms underlying obesity-induced metabolic abnormalities have not been completely elucidated; however, in recent years, the search for therapies to prevent the development of obesity and obesity-associated metabolic disorders has increased. It is known that several nuclear receptors, when activated by specific ligands, regulate carbohydrate and lipid metabolism at the transcriptional level. The expression of lipid metabolism-related enzymes is directly regulated by the activity of various nuclear receptors via their interaction with specific response elements in promoters of those genes. Many natural compounds act as ligands of nuclear receptors and regulate carbohydrate and lipid metabolism by regulating the activities of these nuclear receptors. In this review, we describe our current knowledge of obesity, the role of lipid-sensing nuclear receptors in energy metabolism, and several examples of food factors that act as agonists or antagonists of nuclear receptors, which may be useful for the management of obesity and the accompanying energy metabolism abnormalities.

  1. Modulation of hexa-acyl pyrophosphate lipid A population under Escherichia coli phosphate (Pho) regulon activation.

    PubMed

    Lamarche, Martin G; Kim, Sang-Hyun; Crépin, Sébastien; Mourez, Michael; Bertrand, Nicolas; Bishop, Russell E; Dubreuil, J Daniel; Harel, Josée

    2008-08-01

    Environmental phosphate is an important signal for microorganism gene regulation, and it has recently been shown to trigger some key bacterial virulence mechanisms. In many bacteria, the Pho regulon is the major circuit involved in adaptation to phosphate limitation. The Pho regulon is controlled jointly by the two-component regulatory system PhoR/PhoB and by the phosphate-specific transport (Pst) system, which both belong to the Pho regulon. We showed that a pst mutation results in virulence attenuation in extraintestinal pathogenic Escherichia coli (ExPEC) strains. Our results indicate that the bacterial cell surface of the pst mutants is altered. In this study, we show that pst mutants of ExPEC strains display an increased sensitivity to different cationic antimicrobial peptides and vancomycin. Remarkably, the hexa-acylated 1-pyrophosphate form of lipid A is significantly less abundant in pst mutants. Among differentially expressed genes in the pst mutant, lpxT coding for an enzyme that transfers a phosphoryl group to lipid A, forming the 1-diphosphate species, was found to be downregulated. Our results strongly suggest that the Pho regulon is involved in lipid A modifications, which could contribute to bacterial surface perturbations. Since the Pho regulon and the Pst system are conserved in many bacteria, such a lipid A modification mechanism could be widely distributed among gram-negative bacterial species.

  2. Lipid-Modulated Sequence-Specific Association of Glycophorin A in Membranes

    PubMed Central

    Janosi, Lorant; Prakash, Anupam; Doxastakis, Manolis

    2010-01-01

    Abstract Protein association in lipid membranes is a complex process with thermodynamics directed by a multitude of different factors. Amino-acid sequence is a molecular parameter that affects dimerization as shown by limited directed mutations along the transmembrane domains. Membrane-mediated interactions are also important although details of such contributions remain largely unclear. In this study, we probe directly the free energy of association of Glycophorin A by means of extensive parallel Monte Carlo simulations with recently developed methods and a model that accounts for sequence-specificity while representing lipid membranes faithfully. We find that lipid-induced interactions are significant both at short and intermediate separations. The ability of molecules to tilt in a specific hydrophobic environment extends their accessible interfaces, leading to intermittent contacts during protein recognition. The dimer with the lowest free energy is largely determined by the favorable lipid-induced attractive interactions at the closest distance. Finally, the coarse-grained model employed herein, together with the extensive sampling performed, provides estimates of the free energy of association that are in excellent agreement with existing data. PMID:20655857

  3. Arabidopsis SEIPIN proteins modulate triacylglycerol accumulation and influence lipid droplet proliferation

    USDA-ARS?s Scientific Manuscript database

    The lipodystrophy protein SEIPIN is important for lipid droplet (LD) biogenesis in human and yeast cells. By contrast to the single SEIPIN genes in humans and yeast, there are three SEIPIN homologues in Arabidopsis thaliana, designated At-SEIPIN1, At-SEIPIN2 and At-SEIPIN3. Here, a yeast (Saccharomy...

  4. The gut microbiota modulates host energy and lipid metabolism in mice[S

    PubMed Central

    Velagapudi, Vidya R.; Hezaveh, Rahil; Reigstad, Christopher S.; Gopalacharyulu, Peddinti; Yetukuri, Laxman; Islam, Sama; Felin, Jenny; Perkins, Rosie; Borén, Jan; Orešič, Matej; Bäckhed, Fredrik

    2010-01-01

    The gut microbiota has recently been identified as an environmental factor that may promote metabolic diseases. To investigate the effect of gut microbiota on host energy and lipid metabolism, we compared the serum metabolome and the lipidomes of serum, adipose tissue, and liver of conventionally raised (CONV-R) and germ-free mice. The serum metabolome of CONV-R mice was characterized by increased levels of energy metabolites, e.g., pyruvic acid, citric acid, fumaric acid, and malic acid, while levels of cholesterol and fatty acids were reduced. We also showed that the microbiota modified a number of lipid species in the serum, adipose tissue, and liver, with its greatest effect on triglyceride and phosphatidylcholine species. Triglyceride levels were lower in serum but higher in adipose tissue and liver of CONV-R mice, consistent with increased lipid clearance. Our findings show that the gut microbiota affects both host energy and lipid metabolism and highlights its role in the development of metabolic diseases. PMID:20040631

  5. Exercise-induced modulation of cardiac lipid content in healthy lean young men.

    PubMed

    Bilet, L; van de Weijer, T; Hesselink, M K C; Glatz, J F C; Lamb, H J; Wildberger, J; Kooi, M E; Schrauwen, P; Schrauwen-Hinderling, V B

    2011-03-01

    Cardiac lipid accumulation is associated with decreased cardiac function and energy status (PCr/ATP). It has been suggested that elevated plasma fatty acid (FA) concentrations are responsible for the cardiac lipid accumulation. Therefore, the aim of the present study was to investigate if elevating plasma FA concentrations by exercise results in an increased cardiac lipid content, and if this influences cardiac function and energy status. Eleven male subjects (age 25.4 ± 1.1 years, BMI 23.6 ± 0.8 kg/m²) performed a 2-h cycling protocol, once while staying fasted and once while ingesting glucose, to create a state of high versus low plasma FA concentrations, respectively. Cardiac lipid content was measured by proton magnetic resonance spectroscopy (¹H-MRS) at baseline, directly after exercise and again 4 h post-exercise, together with systolic function (by multi-slice cine-MRI) and cardiac energy status (by ³¹P-MRS). Plasma FA concentrations were increased threefold during exercise and ninefold during recovery in the fasted state compared with the glucose-fed state (p < 0.01). Cardiac lipid content was elevated at the end of the fasted test day (from 0.26 ± 0.04 to 0.44 ± 0.04%, p = 0.003), while it did not change with glucose supplementation (from 0.32 ± 0.03 to 0.26 ± 0.05%, p = 0.272). Furthermore, PCr/ATP was decreased by 32% in the high plasma FA state compared with the low FA state (n = 6, p = 0.014). However, in the high FA state, the ejection fraction 4 h post-exercise was higher compared with the low FA state (63 ± 2 vs. 59 ± 2%, p = 0.018). Elevated plasma FA concentrations, induced by exercise in the fasted state, lead to increased cardiac lipid content, but do not acutely hamper systolic function. Although the lower cardiac energy status is in line with a lipotoxic action of cardiac lipid content, a causal relationship cannot be proven.

  6. The emerging role of peptides and lipids as antimicrobial epidermal barriers and modulators of local inflammation

    PubMed Central

    Brogden, N.K.; Mehalick, L.; Fischer, C.L.; Wertz, P.W.; Brogden, K.A.

    2012-01-01

    Skin is complex and comprised of distinct layers, each layer with unique architecture and immunologic functions. Cells within these layers produce differing amounts of antimicrobial peptides and lipids (sphingoid bases and sebaceous fatty acids) that limit colonization of commensal and opportunistic microorganisms. Furthermore, antimicrobial peptides and lipids have distinct, concentration-dependent ancillary innate and adaptive immune functions. At 0.1-2.0 μM, antimicrobial peptides induce cell migration and adaptive immune responses to co-administered antigens. At 2.0-6.0 μM, they induce cell proliferation and enhance wound healing. At 6.0-12.0 μM, antimicrobial peptides can regulate chemokine and cytokine production and at their highest concentrations of 15.0-30.0 μM, antimicrobial peptides can be cytotoxic. At 1-100 nM, lipids enhance cell migration induced by chemokines, suppress apoptosis, and optimize T cell cytotoxicity and at 0.3-1.0 μM, they inhibit cell migration and attenuate chemokine and pro-inflammatory cytokine responses. Recently many antimicrobial peptides and lipids at 0.1-2.0 μM have been found to attenuate the production of chemokines and pro-inflammatory cytokines to microbial antigens. Together, both the antimicrobial and the anti-inflammatory activities of these peptides and lipids may serve to create a strong, overlapping immunologic barrier that not only controls the concentrations of cutaneous commensal flora but also the extent to which they induce a localized inflammatory response. PMID:22538862

  7. Modulation of lipid peroxidation and antioxidant defense systems in rat intestine by subchronic fluoride and ethanol administration.

    PubMed

    Chauhan, Shailender Singh; Ojha, Sudarshan; Mahmood, Akhtar

    2011-11-01

    Excessive consumption of fluoride and ethanol has been identified as injurious to human health. Fluoride and ethanol co-exposures are commonly seen among the alcoholics residing in endemic fluoride areas worldwide. This study was undertaken to examine the modulation of lipid peroxidation and antioxidant defense systems in rat intestine by subchronic fluoride and ethanol administration. Female Sprague-Dawley rats were divided into four groups: group I (control), group II (fluoride was given orally at a dose of 25 mg/kg body weight), group III (30% ethanol was given orally at a dose of 1 mL/kg body weight), and group IV (a combination of fluoride and ethanol was administered orally at the dose described for groups II and III). Lipid peroxidation was elevated (P<.05) in intestine of rats by fluoride or ethanol treatments for 20 or 40 days. However, glutathione content was reduced by fluoride (32 and 44%) and ethanol (21 and 40%) treatments after 20 and 40 days, respectively. Fluoride-exposed animals showed reduction (P<.05) in the activities of superoxide dismutase (22 and 42%), catalase (30 and 37%), glutathione peroxidase (22 and 35%), glutathione reductase (32 and 34%), and glutathione-S-transferase (24 and 30%) after 20 and 40 days. A similar decrease (P<.05) in the activities of these enzymes was also noticed in animals exposed to ethanol for 20 or 40 days. The observed changes in lipid peroxidation, reduced glutathione levels, and enzyme systems were further augmented in intestine of rats exposed to fluoride and ethanol together. Intestinal histology showed large reactive lymphoid follicles along with mild excess of lymphocytes in lamina propria of villi, villous edema, focal ileitis, and necrosis of villi in animals exposed to fluoride and ethanol for 40 days. These findings suggest that fluoride and ethanol exposure induces considerable changes in lipid peroxidation, antioxidant defense, and morphology of rat intestine, which may affect its functions.

  8. Postprandial decrease in LDL-cholesterol in men with metabolic syndrome

    PubMed Central

    Turczyn, Barbara; Wojakowska, Anna; Kreczyńska, Bogusława; Skoczyńska, Marta; Wojtas, Kamila

    2015-01-01

    Background In some epidemiological studies, blood lipids are determined at non-fasting state, which may impact cardiovascular risk estimation. The aim of this study was to evaluate postprandial LDL-C changes in men with newly diagnosed metabolic syndrome (MetSy). Methods 36 male patients were examined: 12 men with and 24 men without MetSy. The fat tolerance test was performed before and after a three-month hypolipidemic treatment. Serum lipids were measured using routine methods, lipid peroxides (LPO) colorimetrically, apolipoproteins A-I, B, and hsCRP immunoturbidimetrically. Results The postprandial increase in triglycerides was associated with a decrease in LDL-C and a small decrease in apo B. In men with MetSy, the mean change in LDL-C (−19.5 ± 2.3 mg/dl) was greater than in healthy men (−5.7 ± 3.8 mg/dl). All lipid changes (ΔTG, ΔLDL-C and ΔLPO) were linearly dependent on the postprandial non-LDL-cholesterol. After three months of hypolipidemic treatment, in all men with MetSy, the apoB/apoA-I ratio remained the same as before the therapy. Conclusion In men diagnosed with MetSy, postprandial decreases in LDL-cholesterol may cause underestimation of cardiovascular risk. After three months of hypolipidemic treatment, there was only a partial reduction in this risk, as the apoB/apoA-I ratio remained the same.

  9. Hypertriglyceridemia Influences the Degree of Postprandial Lipemic Response in Patients with Metabolic Syndrome and Coronary Artery Disease: From the Cordioprev Study

    PubMed Central

    Alcala-Diaz, Juan F.; Delgado-Lista, Javier; Perez-Martinez, Pablo; Garcia-Rios, Antonio; Marin, Carmen; Quintana-Navarro, Gracia M.; Gomez-Luna, Purificacion; Camargo, Antonio; Almaden, Yolanda; Caballero, Javier; Tinahones, Francisco J.; Ordovas, Jose M.

    2014-01-01

    Objective To determine whether metabolic syndrome traits influence the postprandial lipemia response of coronary patients, and whether this influence depends on the number of MetS criteria. Materials and Methods 1002 coronary artery disease patients from the CORDIOPREV study were submitted to an oral fat load test meal with 0.7 g fat/kg body weight (12% saturated fatty acids, 10% polyunsaturated fatty acids, 43% monounsaturated fatty acids), 10% protein and 25% carbohydrates. Serial blood test analyzing lipid fractions were drawn at 0, 1, 2, 3 and 4 hours during the postprandial state. Total and incremental area under the curves of the different postprandial parameters were calculated following the trapezoid rule to assess the magnitude of change during the postprandial state Results Postprandial lipemia response was directly related to the presence of metabolic syndrome. We found a positive association between the number of metabolic syndrome criteria and the response of postprandial plasma triglycerides (p<0.001), area under the curve of triglycerides (p<0.001) and incremental area under the curve of triglycerides (p<0.001). However, the influence of them on postprandial triglycerides remained statistically significant only in those patients without basal hypertriglyceridemia. Interestingly, in stepwise multiple linear regression analysis with the AUC of triglycerides as the dependent variable, only fasting triglycerides, fasting glucose and waist circumference appeared as significant independent (P<0.05) contributors. The multiple lineal regression (R) was 0.77, and fasting triglycerides showed the greatest effect on AUC of triglycerides with a standardized coefficient of 0.75. Conclusions Fasting triglycerides are the major contributors to the postprandial triglycerides levels. MetS influences the postprandial response of lipids in patients with coronary heart disease, particularly in non-hypertriglyceridemic patients. PMID:24802225

  10. Consumption of a liquid high-fat meal increases triglycerides but decreases high-density lipoprotein cholesterol in abdominally obese subjects with high postprandial insulin resistance.

    PubMed

    Wang, Feng; Lu, Huixia; Liu, Fukang; Cai, Huizhen; Xia, Hui; Guo, Fei; Xie, Yulan; Huang, Guiling; Miao, Miao; Shu, Guofang; Sun, Guiju

    2017-07-01

    Abdominal obesity is associated with an increased risk of insulin resistance, which may be a potential contributor to dyslipidemia. However, the relationship between postprandial insulin resistance and lipid metabolism in abdominally obese subjects remains unknown. We hypothesized that postprandial dyslipidemia would be exaggerated in abdominally obese subjects with high postprandial insulin resistance. To test this hypothesis, serum glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B were measured at baseline and postprandial state at 0.5, 1, 2, 4, 6, and 8 hours after a liquid high-fat meal in non-abdominally obese controls (n=44) and abdominally obese subjects with low (AO-LPIR, n=40), middle (n=40), and high postprandial insulin resistance (AO-HPIR, n=40) based on the tertiles ratio of the insulin to glucose areas under the curve (AUC). Their serum adipokines were tested at baseline only. Fasting serum leptin was higher (P<.05) in AO-HPIR than that in AO-LPIR and controls. Postprandial triglycerides AUC was higher (P<.05), whereas high-density lipoprotein cholesterol AUC was lower (P<.05), in AO-HPIR than those in AO-LPIR and controls. Postprandial AUCs for total cholesterol and apolipoprotein B were similar in abdominally obese subjects with different degrees of postprandial insulin resistance and controls. The present study indicated that the higher degree of postprandial insulin resistance, the more adverse lipid profiles in abdominally obese subjects, which provides insight into opportunity for screening in health. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Approach to the patient with postprandial hypoglycemia.

    PubMed

    Galati, Sandi-Jo; Rayfield, Elliot J

    2014-04-01

    Postprandial hypoglycemia in a nondiabetic patient is a frequent chief complaint across all medical specialties and represents a significant diagnostic challenge. We conducted an electronic and print literature search using PubMed for articles published in the last 40 years using the key words "postprandial hypoglycemia," "reactive hypoglycemia," and "hyperinsulinemic hypoglycemia." All available sources were reviewed, and publications were included based on clinical relevance. Over the last century, the classification, etiologies, diagnosis, and management of hypoglycemia have evolved considerably. In the contemporary literature, the evaluation of hypoglycemia is divided into well-appearing and ill-appearing patients. Symptoms of hypoglycemia in the well-appearing patient may result from insulinoma, noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS), postbariatric surgery hypoglycemia, dumping syndrome, insulin autoimmunity, or postprandial syndrome. For each of these, the literature is lacking in randomized clinical trials investigating optimal diagnostic and treatment modalities, and this is due to the relatively recent description of some diseases and the rarity of cases. This review provides an overview of postprandial hypoglycemia and summarizes the proposed pathophysiologic mechanisms of postprandial hypoglycemia, with special attention paid to some of the more recently described syndromes, such as NIPHS and postbariatric surgery hypoglycemia. Diagnostic and management strategies are also discussed.

  12. Trimerization of the HIV Transmembrane Domain in Lipid Bilayers Modulates Broadly Neutralizing Antibody Binding.

    PubMed

    Reichart, Timothy M; Baksh, Michael M; Rhee, Jin-Kyu; Fiedler, Jason D; Sligar, Stephen G; Finn, M G; Zwick, Michael B; Dawson, Philip E

    2016-02-18

    The membrane-proximal external region (MPER) of HIV gp41 is an established target of antibodies that neutralize a broad range of HIV isolates. To evaluate the role of the transmembrane (TM) domain, synthetic MPER-derived peptides were incorporated into lipid nanoparticles using natural and designed TM domains, and antibody affinity was measured using immobilized and solution-based techniques. Peptides incorporating the native HIV TM domain exhibit significantly stronger interactions with neutralizing antibodies than peptides with a monomeric TM domain. Furthermore, a peptide with a trimeric, three-helix bundle TM domain recapitulates the binding profile of the native sequence. These studies suggest that neutralizing antibodies can bind the MPER when the TM domain is a three-helix bundle and this presentation could influence the binding of neutralizing antibodies to the virus. Lipid-bilayer presentation of viral antigens in Nanodiscs is a new platform for evaluating neutralizing antibodies.

  13. Cocoa extract intake for 4 weeks reduces postprandial systolic blood pressure response of obese subjects, even after following an energy-restricted diet

    PubMed Central

    Ibero-Baraibar, Idoia; Suárez, Manuel; Arola-Arnal, Anna; Zulet, M. Angeles; Martinez, J. Alfredo

    2016-01-01

    Background Cardiometabolic profile is usually altered in obesity. Interestingly, the consumption of flavanol-rich foods might be protective against those metabolic alterations. Objective To evaluate the postprandial cardiometabolic effects after the acute consumption of cocoa extract before and after 4 weeks of its daily intake. Furthermore, the bioavailability of cocoa extract was investigated. Design Twenty-four overweight/obese middle-aged subjects participated in a 4-week intervention study. Half of the volunteers consumed a test meal enriched with 1.4 g of cocoa extract (415 mg flavanols), while the rest of the volunteers consumed the same meal without the cocoa extract (control group). Glucose and lipid profile, as well as blood pressure and cocoa metabolites in plasma, were assessed before and at 60, 120, and 180 min post-consumption, at the beginning of the study (Postprandial 1) and after following a 4-week 15% energy-restricted diet including meals containing or not containing the cocoa extract (Postprandial 2). Results In the Postprandial 1 test, the area under the curve (AUC) of systolic blood pressure (SBP) was significantly higher in the cocoa group compared with the control group (p=0.007), showing significant differences after 120 min of intake. However, no differences between groups were observed at Postprandial 2. Interestingly, the reduction of postprandial AUC of SBP (AUC_Postprandial 2-AUC_Postprandial 1) was higher in the cocoa group (p=0.016). Furthermore, cocoa-derived metabolites were detected in plasma of the cocoa group, while the absence or significantly lower amounts of metabolites were found in the control group. Conclusions The daily consumption of cocoa extract within an energy-restricted diet for 4 weeks resulted in a greater reduction of postprandial AUC of SBP compared with the effect of energy-restricted diet alone and independently of body weight loss. These results suggest the role of cocoa flavanols on postprandial blood

  14. Cell mechanisms of gustatory lipids perception and modulation of the dietary fat preference.

    PubMed

    Dramane, Gado; Akpona, Simon; Besnard, Philippe; Khan, Naim A

    2014-12-01

    Dietary lipids are usually responsible of several metabolic disorders. Recent compelling evidences suggest that there is a sixth taste modality, destined for the detection of oro-gustatory fats. The lipid-binding glycoprotein CD36, expressed by circumvallate papillae (CVP) of the mouse tongue, has been shown to be implicated in oro-gustatory perception of dietary lipids. We demonstrate that linoleic acid (LA) by activating sPLA2, cPLA2 and iPLA2 via CD36, produced arachidonic acid (AA) and lyso-phosphatidylcholine (Lyso-PC) which triggered Ca(2+) influx in CD36-positive taste bud cells (TBC), purified from mouse CVP. LA induced the production of Ca(2+) influx factor (CIF). CIF, AA and Lyso-PC exerted different actions on the opening of store-operated Ca2+ (SOC) channels, constituted of Orai proteins and regulated by STIM1, a sensor of Ca(2+) depletion in the endoplasmic reticulum. We observed that CIF and Lyso-PC opened Orai1 channels whereas AA-opened Ca(2+) channels were composed of Orai1/Orai3. STIM1 was found to regulate LA-induced CIF production and opening of both kinds of Ca(2+) channels. Furthermore, Stim1(-/-) mice lost the spontaneous preference for fat, observed in wild-type animals. Our results suggest that fatty acid-induced Ca(2+) signaling, regulated by STIM1 via CD36, might be implicated in oro-gustatory perception of dietary lipids and the spontaneous preference for fat. Other cell types are involved in, and external factors can influence this preference. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. The lipid composition of Legionella dumoffii membrane modulates the interaction with Galleria mellonella apolipophorin III.

    PubMed

    Palusińska-Szysz, Marta; Zdybicka-Barabas, Agnieszka; Reszczyńska, Emilia; Luchowski, Rafał; Kania, Magdalena; Gisch, Nicolas; Waldow, Franziska; Mak, Paweł; Danikiewicz, Witold; Gruszecki, Wiesław I; Cytryńska, Małgorzata

    2016-07-01

    Apolipophorin III (apoLp-III), an insect homologue of human apolipoprotein E (apoE), is a widely used model protein in studies on protein-lipid interactions, and anti-Legionella activity of Galleria mellonella apoLp-III has been documented. Interestingly, exogenous choline-cultured Legionella dumoffii cells are considerably more susceptible to apoLp-III than non-supplemented bacteria. In order to explain these differences, we performed, for the first time, a detailed analysis of L. dumoffii lipids and a comparative lipidomic analysis of membranes of bacteria grown without and in the presence of exogenous choline. (31)P NMR analysis of L. dumoffii phospholipids (PLs) revealed a considerable increase in the phosphatidylcholine (PC) content in bacteria cultured on choline medium and a decrease in the phosphatidylethanolamine (PE) content in approximately the same range. The interactions of G. mellonella apoLp-III with lipid bilayer membranes prepared from PLs extracted from non- and choline-supplemented L. dumoffii cells were examined in detail by means of attenuated total reflection- and linear dichroism-Fourier transform infrared spectroscopy. Furthermore, the kinetics of apoLp-III binding to liposomes formed from L. dumoffii PLs was analysed by fluorescence correlation spectroscopy and fluorescence lifetime imaging microscopy using fluorescently labelled G. mellonella apoLp-III. Our results indicated enhanced binding of apoLp-III to and deeper penetration into lipid membranes formed from PLs extracted from the choline-supplemented bacteria, i.e. characterized by an increased PC/PE ratio. This could explain, at least in part, the higher susceptibility of choline-cultured L. dumoffii to G. mellonella apoLp-III.

  16. MicroRNA modulation of lipid metabolism and oxidative stress in cardiometabolic diseases

    PubMed Central

    Aranda, Juan F.; Madrigal-Matute, Julio; Rotllan, Noemi; Fernández-Hernando, Carlos

    2014-01-01

    The regulation of cholesterol metabolism is one of the most studied biological processes since its first isolation from gallstones in 1784. High levels of plasma low-density lipoprotein (LDL) cholesterol and reduced levels of plasma high-density lipoprotein (HDL) cholesterol are widely recognized as major risk factors of cardiovascular disease. An imbalance in the production of reactive oxygen species (ROS) can oxidize LDL particles increasing the levels of the highly pro-atherogenic oxidized LDLs (ox-LDLs). Furthermore, under pathological scenarios, numerous molecules can function as pro-oxidants, such as iron or high-glucose levels. In addition to the classical mechanisms regulating lipid homeostasis, recent studies have demonstrated the important role of microRNAs (miRNAs) as regulators of lipoprotein metabolism, its oxidative derivatives and redox balance. Here, we summarize the recent findings in the field, highlighting the contribution of some miRNAs in lipid and oxidative-associated pathologies. We also discuss how therapeutic intervention of miRNAs may be a promising strategy to decrease LDL, increase HDL and ameliorate lipid and oxidative related disorders, including atherosclerosis, non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome. PMID:23871755

  17. Protein, lipid, and DNA radicals to measure skin UVA damage and modulation by melanin.

    PubMed

    Haywood, Rachel; Rogge, Fabrice; Lee, Martin

    2008-03-15

    Afro-Caribbeans have a lower incidence of skin cancer than Caucasians, but the effectiveness of melanin as a photoprotective pigment is debated. We investigated the UVA and solar irradiation of ex vivo human skin and DMPO using electron spin resonance spectroscopy, to determine whether pigmented skin is protected by melanin against free radical damage. Initial ascorbate radicals in Caucasian skin were superseded by lipid and/or protein radical adducts with isotropic (a(H)=1.8 mT) and anisotropic spectra comparable to spectra in irradiated pig fat (a(H)=1.9 mT) and BSA. DNA carbon-centered radical adducts (a(H)=2.3 mT) and a broad singlet were detected in genomic DNA/melanin but were not distinguishable in irradiated Caucasian skin. Protein and lipid radicals (n=6 in Caucasian skin) were minimal in Afro-Caribbean skin (n=4) and intermediate skin pigmentations were variable (n=3). In irradiated Afro-Caribbean skin a shoulder to the melanin radical (also in UVA-irradiated pigmented melanoma cells and genomic DNA/melanin and intrinsic to pheomelanin) was detected. In this sample group, protein (but not lipid) radical adducts decreased directly with pigmentation. ESR/spin trapping methodology has potential for screening skin susceptibility to aging and cancer-related radical damage and for measuring protection afforded by melanin, sunscreens, and antiaging creams.

  18. Maternal chromium restriction modulates miRNA profiles related to lipid metabolism disorder in mice offspring.

    PubMed

    Zhang, Qian; Xiao, Xinhua; Zheng, Jia; Li, Ming; Yu, Miao; Ping, Fan; Wang, Zhixin; Qi, Cuijuan; Wang, Tong; Wang, Xiaojing

    2017-08-01

    Increasing evidence shows that maternal nutrition status has a vital effect on offspring susceptibility to obesity. MicroRNAs are related to lipid metabolism processes. This study aimed to evaluate whether maternal chromium restriction could affect miRNA expression involved in lipid metabolism in offspring. Weaning C57BL/6J mice born from mothers fed with normal control diet or chromium-restricted diet were fed for 13 weeks. The adipose miRNA expression profile was analyzed by miRNA array analysis. At 16 weeks old, pups from dams fed with chromium-restricted diet exhibit higher body weight, fat weight, and serum TC, TG levels. Six miRNAs were identified as upregulated in the RC group compared with the CC group, whereas eight miRNAs were lower than the threshold level set in the RC group. In the validated target genes of these differentially expressed miRNA, the MAPK signaling pathway serves an important role in the influence of early life chromium-restricted diet on lipid metabolism through miRNA. Long-term programming on various specific miRNA and MAPK signaling pathway may be involved in maternal chromium restriction in the adipose of female offspring. Impact statement For the first time, our study demonstrates important miRNA differences in the effect of maternal chromium restriction in offspring. These miRNAs may serve as "bridges" between the mother and the offspring by affecting the MAPK pathway.

  19. An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption.

    PubMed

    Iqbal, Jahangir; Li, Xiaosong; Chang, Benny Hung-Junn; Chan, Lawrence; Schwartz, Gary J; Chua, Streamson C; Hussain, M Mahmood

    2010-07-01

    Fat is delivered to tissues by apoB-containing lipoproteins synthesized in the liver and intestine with the help of an intracellular chaperone, microsomal triglyceride transfer protein (MTP). Leptin, a hormone secreted by adipose tissue, acts in the brain and on peripheral tissues to regulate fat storage and metabolism. Our aim was to identify the role of leptin signaling in MTP regulation and lipid absorption using several mouse models deficient in leptin receptor (LEPR) signaling and downstream effectors. Mice with spontaneous LEPR B mutations or targeted ablation of LEPR B in proopiomelanocortin (POMC) or agouti gene related peptide (AGRP) expressing cells had increased triglyceride in plasma, liver, and intestine. Furthermore, melanocortin 4 receptor (MC4R) knockout mice expressed a similar triglyceride phenotype, suggesting that leptin might regulate intestinal MTP expression through the melanocortin pathway. Mechanistic studies revealed that the accumulation of triglyceride in the intestine might be secondary to decreased expression of MTP and lipid absorption in these mice. Surgical and chemical blockade of vagal efferent outflow to the intestine in wild-type mice failed to alter the triglyceride phenotype, demonstrating that central neural control mechanisms were likely not involved in the observed regulation of intestinal MTP. Instead, we found that enterocytes express LEPR, POMC, AGRP, and MC4R. We propose that a peripheral, local gut signaling mechanism involving LEPR B and MC4R regulates intestinal MTP and controls intestinal lipid absorption.

  20. Adsorption of alpha-synuclein on lipid bilayers: modulating the structure and stability of protein assemblies.

    PubMed

    Haque, Farzin; Pandey, Anjan P; Cambrea, Lee R; Rochet, Jean-Christophe; Hovis, Jennifer S

    2010-03-25

    The interaction of alpha-synuclein with phospholipid membranes has been examined using supported lipid bilayers and epi-fluorescence microscopy. The membranes contained phosphatidylcholine (PC) and phosphatidic acid (PA), which mix at physiological pH. Upon protein adsorption, the lipids undergo fluid-fluid phase separation into PC-rich and PA-rich regions. The protein preferentially adsorbs to the PA-rich regions. The adsorption and subsequent aggregation of alpha-synuclein was probed by tuning several parameters: the charge on the lipids, the charge on the protein, and the screening environment. Conditions which promoted the greatest extent of adsorption resulted in structurally heterogeneous aggregates, while comparatively homogeneous aggregates were observed under conditions whereby adsorption did not occur as readily. Our observation that different alterations to the system lead to different degrees of aggregation and different aggregate structures poses a challenge for drug discovery. Namely, therapies aimed at neutralizing alpha-synuclein must target a broad range of potentially toxic, membrane-bound assemblies.

  1. Genetic modulation of lipid profiles following lifestyle modification or metformin treatment: the Diabetes Prevention Program.

    PubMed

    Pollin, Toni I; Isakova, Tamara; Jablonski, Kathleen A; de Bakker, Paul I W; Taylor, Andrew; McAteer, Jarred; Pan, Qing; Horton, Edward S; Delahanty, Linda M; Altshuler, David; Shuldiner, Alan R; Goldberg, Ronald B; Florez, Jose C; Franks, Paul W

    2012-01-01

    Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04-1 × 10(-17)). Except for total HDL particles (r = -0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial |r| = 0.07-0.17, P = 5 × 10(-5)-1 10(-19)). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE ± 0.22 mg/dl/allele, P = 8 × 10(-5), P(interaction) = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE ± 0.22 mg/dl/allele, P = 0.35) or metformin (β = -0.03, SEE ± 0.22 mg/dl/allele, P = 0.90; P(interaction) = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE ± 0.012 ln nmol/L/allele, P = 0.01, P(interaction) = 0.01) but not in the placebo (β = -0.002, SEE ± 0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE ± 0.008 nmol/L/allele, P = 0.12; P(interaction) = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.

  2. Modulation of gluconeogenesis and lipid production in an engineered oleaginous Saccharomyces cerevisiae transformant.

    PubMed

    Kamisaka, Yasushi; Kimura, Kazuyoshi; Uemura, Hiroshi; Ledesma-Amaro, Rodrigo

    2016-09-01

    We previously created an oleaginous Saccharomyces cerevisiae transformant as a dga1 mutant overexpressing Dga1p lacking 29 amino acids at the N-terminal (Dga1∆Np). Because we have already shown that dga1 disruption decreases the expression of ESA1, which encodes histone acetyltransferase, the present study was aimed at exploring how Esa1p was involved in lipid accumulation. We based our work on the previous observation that Esa1p acetylates and activates phosphoenolpyruvate carboxykinase (PEPCK) encoded by PCK1, a rate-limiting enzyme in gluconeogenesis, and subsequently evaluated the activation of Pck1p by yeast growth with non-fermentable carbon sources, thus dependent on gluconeogenesis. This assay revealed that the ∆dga1 mutant overexpressing Dga1∆Np had much lower growth in a glycerol-lactate (GL) medium than the wild-type strain overexpressing Dga1∆Np. Moreover, overexpression of Esa1p or Pck1p in mutants improved the growth, indicating that the ∆dga1 mutant overexpressing Dga1∆Np had lower activities of Pck1p and gluconeogenesis due to lower expression of ESA1. In vitro PEPCK assay showed the same trend in the culture of the ∆dga1 mutant overexpressing Dga1∆Np with 10 % glucose medium, indicating that Pck1p-mediated gluconeogenesis decreased in this oleaginous transformant under the lipid-accumulating conditions introduced by the glucose medium. The growth of the ∆dga1 mutant overexpressing Dga1∆Np in the GL medium was also improved by overexpression of acetyl-CoA synthetase, Acs1p or Acs2p, indicating that supply of acetyl-CoA was crucial for Pck1p acetylation by Esa1p. In addition, the ∆dga1 mutant without Dga1∆Np also showed better growth in the GL medium, indicating that decreased lipid accumulation was enhancing Pck1p-mediated gluconeogenesis. Finally, we found that overexpression of Ole1p, a fatty acid ∆9-desaturase, in the ∆dga1 mutant overexpressing Dga1∆Np improved its growth in the GL medium. Although the exact

  3. Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment: The Diabetes Prevention Program

    PubMed Central

    Jablonski, Kathleen A.; de Bakker, Paul I. W.; Taylor, Andrew; McAteer, Jarred; Pan, Qing; Horton, Edward S.; Delahanty, Linda M.; Altshuler, David; Shuldiner, Alan R.; Goldberg, Ronald B.; Florez, Jose C.; Bray, George A.; Culbert, Iris W.; Champagne, Catherine M.; Eberhardt, Barbara; Greenway, Frank; Guillory, Fonda G.; Herbert, April A.; Jeffirs, Michael L.; Kennedy, Betty M.; Lovejoy, Jennifer C.; Morris, Laura H.; Melancon, Lee E.; Ryan, Donna; Sanford, Deborah A.; Smith, Kenneth G.; Smith, Lisa L.; Amant, Julia A. St.; Tulley, Richard T.; Vicknair, Paula C.; Williamson, Donald; Zachwieja, Jeffery J.; Polonsky, Kenneth S.; Tobian, Janet; Ehrmann, David; Matulik, Margaret J.; Clark, Bart; Czech, Kirsten; DeSandre, Catherine; Hilbrich, Ruthanne; McNabb, Wylie; Semenske, Ann R.; Caro, Jose F.; Watson, Pamela G.; Goldstein, Barry J.; Smith, Kellie A.; Mendoza, Jewel; Liberoni, Renee; Pepe, Constance; Spandorfer, John; Donahue, Richard P.; Goldberg, Ronald B.; Prineas, Ronald; Rowe, Patricia; Calles, Jeanette; Cassanova-Romero, Paul; Florez, Hermes J.; Giannella, Anna; Kirby, Lascelles; Larreal, Carmen; McLymont, Valerie; Mendez, Jadell; Ojito, Juliet; Perry, Arlette; Saab, Patrice; Haffner, Steven M.; Montez, Maria G.; Lorenzo, Carlos; Martinez, Arlene; Hamman, Richard F.; Nash, Patricia V.; Testaverde, Lisa; Anderson, Denise R.; Ballonoff, Larry B.; Bouffard, Alexis; Calonge, B. Ned; Delve, Lynne; Farago, Martha; Hill, James O.; Hoyer, Shelley R.; Jortberg, Bonnie T.; Lenz, Dione; Miller, Marsha; Price, David W.; Regensteiner, Judith G.; Seagle, Helen; Smith, Carissa M.; Steinke, Sheila C.; VanDorsten, Brent; Horton, Edward S.; Lawton, Kathleen E.; Arky, Ronald A.; Bryant, Marybeth; Burke, Jacqueline P.; Caballero, Enrique; Callaphan, Karen M.; Ganda, Om P.; Franklin, Therese; Jackson, Sharon D.; Jacobsen, Alan M.; Jacobsen, Alan M.; Kula, Lyn M.; Kocal, Margaret; Malloy, Maureen A.; Nicosia, Maryanne; Oldmixon, Cathryn F.; Pan, Jocelyn; Quitingon, Marizel; Rubtchinsky, Stacy; Seely, Ellen W.; Schweizer, Dana; Simonson, Donald; Smith, Fannie; Solomon, Caren G.; Warram, James; Kahn, Steven E.; Montgomery, Brenda K.; Fujimoto, Wilfred; Knopp, Robert H.; Lipkin, Edward W.; Marr, Michelle; Trence, Dace; Kitabchi, Abbas E.; Murphy, Mary E.; Applegate, William B.; Bryer-Ash, Michael; Frieson, Sandra L.; Imseis, Raed; Lambeth, Helen; Lichtermann, Lynne C.; Oktaei, Hooman; Rutledge, Lily M.K.; Sherman, Amy R.; Smith, Clara M.; Soberman, Judith E.; Williams-Cleaves, Beverly; Metzger, Boyd E.; Johnson, Mariana K.; Behrends, Catherine; Cook, Michelle; Fitzgibbon, Marian; Giles, Mimi M.; Heard, Deloris; Johnson, Cheryl K.H.; Larsen, Diane; Lowe, Anne; Lyman, Megan; McPherson, David; Molitch, Mark E.; Pitts, Thomas; Reinhart, Renee; Roston, Susan; Schinleber, Pamela A.; Nathan, David M.; McKitrick, Charles; Turgeon, Heather; Abbott, Kathy; Anderson, Ellen; Bissett, Laurie; Cagliero, Enrico; Florez, Jose C.; Delahanty, Linda; Goldman, Valerie; Poulos, Alexandra; Olefsky, Jerrold M.; Carrion-Petersen, Mary Lou; Barrett-Connor, Elizabeth; Edelman, Steven V.; Henry, Robert R.; Horne, Javiva; Janesch, Simona Szerdi; Leos, Diana; Mudaliar, Sundar; Polonsky, William; Smith, Jean; Vejvoda, Karen; Pi-Sunyer, F. Xavier; Lee, Jane E.; Allison, David B.; Aronoff, Nancy J.; Crandall, Jill P.; Foo, Sandra T.; Pal, Carmen; Parkes, Kathy; Pena, Mary Beth; Rooney, Ellen S.; Wye, Gretchen E.H. Van; Viscovich, Kristine A.; Marrero, David G.; Prince, Melvin J.; Kelly, Susie M.; Dotson, Yolanda F.; Fineberg, Edwin S.; Guare, John C; Hadden, Angela M.; Ignaut, James M.; Jackson, Marcia L.; Kirkman, Marion S.; Mather, Kieren J.; Porter, Beverly D.; Roach, Paris J.; Rowland, Nancy D.; Wheeler, Madelyn L.; Ratner, Robert E.; Youssef, Gretchen; Shapiro, Sue; Bavido-Arrage, Catherine; Boggs, Geraldine; Bronsord, Marjorie; Brown, Ernestine; Cheatham, Wayman W.; Cola, Susan; Evans, Cindy; Gibbs, Peggy; Kellum, Tracy; Levatan, Claresa; Nair, Asha K.; Passaro, Maureen; Uwaifo, Gabriel; Saad, Mohammed F.; Budget, Maria; Jinagouda, Sujata; Akbar, Khan; Conzues, Claudia; Magpuri, Perpetua; Ngo, Kathy; Rassam, Amer; Waters, Debra; Xapthalamous, Kathy; Santiago, Julio V.; Dagogo-Jack, Samuel; White, Neil H.; Das, Samia; Santiago, Ana; Brown, Angela; Fisher, Edwin; Hurt, Emma; Jones, Tracy; Kerr, Michelle; Ryder, Lucy; Wernimont, Cormarie; Saudek, Christopher D.; Bradley, Vanessa; Sullivan, Emily; Whittington, Tracy; Abbas, Caroline; Brancati, Frederick L.; Clark, Jeanne M.; Charleston, Jeanne B.; Freel, Janice; Horak, Katherine; Jiggetts, Dawn; Johnson, Deloris; Joseph, Hope; Loman, Kimberly; Mosley, Henry; Rubin, Richard R.; Samuels, Alafia; Stewart, Kerry J.; Williamson, Paula; Schade, David S.; Adams, Karwyn S.; Johannes, Carolyn; Atler, Leslie F.; Boyle, Patrick J.; Burge, Mark R.; Canady, Janene L.; Chai, Lisa; Gonzales, Ysela; Hernandez-McGinnis, Doris A.; Katz, Patricia; King, Carolyn; Rassam, Amer; Rubinchik, Sofya; Senter, Willette; Waters, Debra; Shamoon, Harry; Brown, Janet O.; Adorno, Elsie; Cox, Liane; Crandall, Jill; Duffy, Helena; Engel, Samuel; Friedler, Allison; Howard-Century, Crystal J.; Kloiber, Stacey; Longchamp, Nadege; Martinez, Helen; Pompi, Dorothy; Scheindlin, Jonathan; Violino, Elissa; Walker, Elizabeth; Wylie-Rosett, Judith; Zimmerman, Elise; Zonszein, Joel; Orchard, Trevor; Wing, Rena R.; Koenning, Gaye; Kramer, M. Kaye; Barr, Susan; Boraz, Miriam; Clifford, Lisa; Culyba, Rebecca; Frazier, Marlene; Gilligan, Ryan; Harrier, Susan; Harris, Louann; Jeffries, Susan; Kriska, Andrea; Manjoo, Qurashia; Mullen, Monica; Noel, Alicia; Otto, Amy; Semler, Linda; Smith, Cheryl F.; Smith, Marie; Venditti, Elizabeth; Weinzierl, Valarie; Williams, Katherine V.; Wilson, Tara; Arakaki, Richard F.; Latimer, Renee W.; Baker-Ladao, Narleen K.; Beddow, Ralph; Dias, Lorna; Inouye, Jillian; Mau, Marjorie K.; Mikami, Kathy; Mohideen, Pharis; Odom, Sharon K.; Perry, Raynette U.; Knowler, William C.; Cooeyate, Norman; Hoskin, Mary A.; Percy, Carol A.; Acton, Kelly J.; Andre, Vickie L.; Barber, Rosalyn; Begay, Shandiin; Bennett, Peter H.; Benson, Mary Beth; Bird, Evelyn C.; Broussard, Brenda A.; Chavez, Marcella; Dacawyma, Tara; Doughty, Matthew S.; Duncan, Roberta; Edgerton, Cyndy; Ghahate, Jacqueline M.; Glass, Justin; Glass, Martia; Gohdes, Dorothy; Grant, Wendy; Hanson, Robert L.; Horse, Ellie; Ingraham, Louise E.; Jackson, Merry; Jay, Priscilla; Kaskalla, Roylen S.; Kessler, David; Kobus, Kathleen M.; Krakoff, Jonathan; Manus, Catherine; Michaels, Sara; Morgan, Tina; Nashboo, Yolanda; Nelson, Julie A.; Poirier, Steven; Polczynski, Evette; Reidy, Mike; Roumain, Jeanine; Rowse, Debra; Sangster, Sandra; Sewenemewa, Janet; Tonemah, Darryl; Wilson, Charlton; Yazzie, Michelle; Bain, Raymond; Fowler, Sarah; Brenneman, Tina; Abebe, Solome; Bamdad, Julie; Callaghan, Jackie; Edelstein, Sharon L.; Gao, Yuping; Grimes, Kristina L.; Grover, Nisha; Haffner, Lori; Jones, Steve; Jones, Tara L.; Katz, Richard; Lachin, John M.; Mucik, Pamela; Orlosky, Robert; Rochon, James; Sapozhnikova, Alla; Sherif, Hanna; Stimpson, Charlotte; Temprosa, Marinella; Walker-Murray, Fredricka; Marcovina, Santica; Strylewicz, Greg; Aldrich, F. Alan; O'Leary, Dan; Stamm, Elizabeth; Rautaharju, Pentti; Prineas, Ronald J.; Alexander, Teresa; Campbell, Charles; Hall, Sharon; Li, Yabing; Mills, Margaret; Pemberton, Nancy; Rautaharju, Farida; Zhang, Zhuming; Mayer-Davis, Elizabeth; Moran, Robert R.; Ganiats, Ted; David, Kristin; Sarkin, Andrew J.; Eastman, R.; Fradkin, Judith; Garfield, Sanford; Gregg, Edward; Zhang, Ping; Herman, William; Florez, Jose C.; Altshuler, David; de Bakker, Paul I.W.; Franks, Paul W.; Hanson, Robert L.; Jablonski, Kathleen; Knowler, William C.; McAteer, Jarred B.; Pollin, Toni I.; Shuldiner, Alan R.

    2012-01-01

    Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04–1×10−17). Except for total HDL particles (r = −0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial |r| = 0.07–0.17, P = 5×10−5–1×10−19). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10−5, P interaction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = −0.03, SEE±0.22 mg/dl/allele, P = 0.90; P interaction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, P interaction = 0.01) but not in the placebo (β = −0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; P interaction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss. PMID:22951888

  4. DHA attenuates postprandial hyperlipidemia via activating PPARα in intestinal epithelial cells[S

    PubMed Central

    Kimura, Rino; Takahashi, Nobuyuki; Lin, Shan; Goto, Tsuyoshi; Murota, Kaeko; Nakata, Rieko; Inoue, Hiroyasu; Kawada, Teruo

    2013-01-01

    It is known that peroxisome proliferator-activated receptor (PPAR)α, whose activation reduces hyperlipidemia, is highly expressed in intestinal epithelial cells. Docosahexaenoic acid (DHA) could improve postprandial hyperlipidemia, however, its relationship with intestinal PPARα activation is not revealed. In this study, we investigated whether DHA can affect postprandial hyperlipidemia by activating intestinal PPARα using Caco-2 cells and C57BL/6 mice. The genes involved in fatty acid (FA) oxidation and oxygen consumption rate were increased, and the secretion of triacylglyceride (TG) and apolipoprotein B (apoB) was decreased in DHA-treated Caco-2 cells. Additionally, intestinal FA oxidation was induced, and TG and apoB secretion from intestinal epithelial cells was reduced, resulting in the attenuation of plasma TG and apoB levels after oral administration of olive oil in DHA-rich oil-fed mice compared with controls. However, no increase in genes involved in FA oxidation was observed in the liver. Furthermore, the effects of DHA on intestinal lipid secretion and postprandial hyperlipidemia were abolished in PPARα knockout mice. In conclusion, the present work suggests that DHA can inhibit the secretion of TG from intestinal epithelial cells via PPARα activation, which attenuates postprandial hyperlipidemia. PMID:24133194

  5. Acute Glucagon Induces Postprandial Peripheral Insulin Resistance

    PubMed Central

    Patarrão, Rita S.; Lautt, W. Wayne; Macedo, M. Paula

    2015-01-01

    Glucagon levels are often moderately elevated in diabetes. It is known that glucagon leads to a decrease in hepatic glutathione (GSH) synthesis that in turn is associated with decreased postprandial insulin sensitivity. Given that cAMP pathway controls GSH levels we tested whether insulin sensitivity decreases after intraportal (ipv) administration of a cAMP analog (DBcAMP), and investigated whether glucagon promotes insulin resistance through decreasing hepatic GSH levels.Insulin sensitivity was determined in fed male Sprague-Dawley rats using a modified euglycemic hyperinsulinemic clamp in the postprandial state upon ipv administration of DBcAMP as well as glucagon infusion. Glucagon effects on insulin sensitivity was assessed in the presence or absence of postprandial insulin sensitivity inhibition by administration of L-NMMA. Hepatic GSH and NO content and plasma levels of NO were measured after acute ipv glucagon infusion. Insulin sensitivity was assessed in the fed state and after ipv glucagon infusion in the presence of GSH-E. We founf that DBcAMP and glucagon produce a decrease of insulin sensitivity, in a dose-dependent manner. Glucagon-induced decrease of postprandial insulin sensitivity correlated with decreased hepatic GSH content and was restored by administration of GSH-E. Furthermore, inhibition of postprandial decrease of insulin sensitivity L-NMMA was not overcome by glucagon, but glucagon did not affect hepatic and plasma levels of NO. These results show that glucagon decreases postprandial insulin sensitivity through reducing hepatic GSH levels, an effect that is mimicked by increasing cAMP hepatic levels and requires physiological NO levels. These observations support the hypothesis that glucagon acts via adenylate cyclase to decrease hepatic GSH levels and induce insulin resistance. We suggest that the glucagon-cAMP-GSH axis is a potential therapeutic target to address insulin resistance in pathological conditions. PMID:25961284

  6. Acute glucagon induces postprandial peripheral insulin resistance.

    PubMed

    Patarrão, Rita S; Lautt, W Wayne; Macedo, M Paula

    2015-01-01

    Glucagon levels are often moderately elevated in diabetes. It is known that glucagon leads to a decrease in hepatic glutathione (GSH) synthesis that in turn is associated with decreased postprandial insulin sensitivity. Given that cAMP pathway controls GSH levels we tested whether insulin sensitivity decreases after intraportal (ipv) administration of a cAMP analog (DBcAMP), and investigated whether glucagon promotes insulin resistance through decreasing hepatic GSH levels.Insulin sensitivity was determined in fed male Sprague-Dawley rats using a modified euglycemic hyperinsulinemic clamp in the postprandial state upon ipv administration of DBcAMP as well as glucagon infusion. Glucagon effects on insulin sensitivity was assessed in the presence or absence of postprandial insulin sensitivity inhibition by administration of L-NMMA. Hepatic GSH and NO content and plasma levels of NO were measured after acute ipv glucagon infusion. Insulin sensitivity was assessed in the fed state and after ipv glucagon infusion in the presence of GSH-E. We founf that DBcAMP and glucagon produce a decrease of insulin sensitivity, in a dose-dependent manner. Glucagon-induced decrease of postprandial insulin sensitivity correlated with decreased hepatic GSH content and was restored by administration of GSH-E. Furthermore, inhibition of postprandial decrease of insulin sensitivity L-NMMA was not overcome by glucagon, but glucagon did not affect hepatic and plasma levels of NO. These results show that glucagon decreases postprandial insulin sensitivity through reducing hepatic GSH levels, an effect that is mimicked by increasing cAMP hepatic levels and requires physiological NO levels. These observations support the hypothesis that glucagon acts via adenylate cyclase to decrease hepatic GSH levels and induce insulin resistance. We suggest that the glucagon-cAMP-GSH axis is a potential therapeutic target to address insulin resistance in pathological conditions.

  7. Effect of moderate-intensity exercise session on preprandial and postprandial responses of circulating ghrelin and appetite.

    PubMed

    Malkova, D; McLaughlin, R; Manthou, E; Wallace, A M; Nimmo, M A

    2008-06-01

    Responses of plasma total ghrelin and appetite were investigated during preprandial and postprandial stages of recovery from a moderate-intensity cycling session. Healthy recreationally active men underwent one exercise and one control trial. In the exercise trial, subjects exercised for approximately 60 minutes, while in the control trial they rested quietly for the same duration. After the intervention, subjects rested for 120 minutes and then consumed a test meal. Measurements were obtained immediately and 120 minutes after the intervention and then during 180 minutes of the postprandial period. The post-intervention concentration of total ghrelin was lower (p<0.05) in the exercise than in the control trial. The modulating effect of exercise was related to the reduction in the postprandial rather than preprandial concentration. Post-intervention scores of appetite were not different between the two trials, but when preprandial and postprandial responses were considered separately, postprandial hunger and desire to eat was higher (p<0.05) in the exercise trial. In summary, during recovery from moderate-intensity exercise, total ghrelin does not respond in a compensatory manner to disturbances in energy balance. Thus, an exercise-induced increase in appetite during the later stages of recovery coinciding with the postprandial state cannot be explained by changes in the plasma concentration of total ghrelin.

  8. Modulation of lipid homeostasis in response to continuous or intermittent high-fat diet in pigs.

    PubMed

    Puccinelli, E; Gervasi, P G; Trivella, M G; Vornoli, A; Viglione, F; Pelosi, G; Parodi, O; Sampietro, T; Puntoni, M

    2015-06-01

    A high-fat diet is known to induce atherosclerosis in animal models. Dietary factors and timing of atherogenic food delivery may affect plasma lipoprotein content composition and its potential atherogenic effect. Increasingly often, humans spend periods/days eating in a completely unregulated way, ingesting excessive amounts of food rich in oils and fats, alternating with periods/days when food intake is more or less correct. We investigate the effect on lipid homeostasis of a high-fat diet administered either continuously or intermittently. We investigated control pigs receiving standard diet (C, n=7), pigs receiving a high-fat diet every day for 10 weeks (CHF, n=5), and pigs receiving a high-fat diet every other week for 10 weeks (IHF, n=7). IHF animals were shown to have a different lipid profile compared with CHF animals, with a significant increase in high-density lipoproteins (HDL) levels with respect to C and CHF groups. CHF also showed significantly higher values of TC/HDL cholesterol compared with C and IHF. Hepatic expression analysis of genes involved in lipid homeostasis showed an increasing trend of nuclear receptor LXRα along with its target genes in the CHF group and in the IHF group, whereas SREBP2 and LDLr were significantly inhibited. A significant correlation was found between ABCA1 expression and circulating levels of HDL-C. Periodic withdrawals of a high-fat atherogenic diet compared with a regular administration results in a different adaptive response of lipoprotein metabolism, which leads to a significantly higher plasma level of HDL-C and lower TC/HDL-C.

  9. Altering Pyrroloquinoline Quinone Nutritional Status Modulates Mitochondrial, Lipid, and Energy Metabolism in Rats

    PubMed Central

    Bauerly, Kathryn; Harris, Calliandra; Chowanadisai, Winyoo; Graham, James; Havel, Peter J.; Tchaparian, Eskouhie; Satre, Mike; Karliner, Joel S.; Rucker, Robert B.

    2011-01-01

    We have reported that pyrroloquinoline quinone (PQQ) improves reproduction, neonatal development, and mitochondrial function in animals by mechanisms that involve mitochondrial related cell signaling pathways. To extend these observations, the influence of PQQ on energy and lipid relationships and apparent protection against ischemia reperfusion injury are described herein. Sprague-Dawley rats were fed a nutritionally complete diet with PQQ added at either 0 (PQQ−) or 2 mg PQQ/Kg diet (PQQ+). Measurements included: 1) serum glucose and insulin, 2) total energy expenditure per metabolic body size (Wt3/4), 3) respiratory quotients (in the fed and fasted states), 4) changes in plasma lipids, 5) the relative mitochondrial amount in liver and heart, and 6) indices related to cardiac ischemia. For the latter, rats (PQQ− or PQQ+) were subjected to left anterior descending occlusions followed by 2 h of reperfusion to determine PQQ's influence on infarct size and myocardial tissue levels of malondialdehyde, an indicator of lipid peroxidation. Although no striking differences in serum glucose, insulin, and free fatty acid levels were observed, energy expenditure was lower in PQQ− vs. PQQ+ rats and energy expenditure (fed state) was correlated with the hepatic mitochondrial content. Elevations in plasma di- and triacylglyceride and β-hydroxybutryic acid concentrations were also observed in PQQ− rats vs. PQQ+ rats. Moreover, PQQ administration (i.p. at 4.5 mg/kg BW for 3 days) resulted in a greater than 2-fold decrease in plasma triglycerides during a 6-hour fast than saline administration in a rat model of type 2 diabetes. Cardiac injury resulting from ischemia/reperfusion was more pronounced in PQQ− rats than in PQQ+ rats. Collectively, these data demonstrate that PQQ deficiency impacts a number of parameters related to normal mitochondrial function. PMID:21814553

  10. [Characteristics of interaction of adenylate cyclase modulators and phosphoinositide cell signaling systems with lipid langmuir monolayers].

    PubMed

    Liakhov, O M; Prokopenko, V V; Prokopenko, R A; Mohylevych, S Ie

    2006-01-01

    Interaction of two groups of bioregulators, which oppositely affect activity of adenylate cyclase and phosphoinositide cellular signaling systems, with the Langmuir monolayer films made of natural lecithin was studied. Most significant influence on the structural and energy characteristics of lipid monolayers was revealed for the group of bioregulators, which inhibit polyphosphoinositide signaling system or/and activate adenylate cyclase signaling system. It is shown, that using the cluster analysis the bioregulators can be divided into two groups according to general orientation of their action on the considered systems of transduction of a signal.

  11. Rosiglitazone modulates pigeon atherosclerotic lipid accumulation and gene expression in vitro.

    PubMed

    Anderson, J L; Keeley, M C; Smith, S C; Smith, E C; Taylor, R L

    2014-06-01

    Atherosclerosis is a major contributor to the overall United States mortality rate, primarily in the form of heart attacks and stroke. Unlike the human disease, which is believed to be multifactorial, pigeon atherosclerosis is due to a single gene autosomal recessive trait. The White Carneau (WC-As) strain develops atherosclerotic plaques without the presence of known environmental risk factors such as diet and classic predictors such as blood pressure or blood cholesterol levels. With similar parameters, the Show Racer (SR-Ar) is resistant to plaque development. Thiazolidinediones, including rosiglitazone, activate the peroxisome proliferator-activated receptor gamma (PPARγ) raising cellular sensitivity to insulin. The effect of rosiglitazone was evaluated in aortic smooth muscle cells (SMC) from these 2 pigeon breeds. Primary SMC cultures were prepared from WC-As and SR-Ar squabs. Cell monolayers, which achieved confluence in 7 d, were treated with 0 or 4 µM rosiglitazone for 24 h. Cellular lipid accumulation was evaluated by oil red O staining. Control WC-As cells had significantly higher vacuole scores and lipid content than did the SR-Ar control cells. Rosiglitazone treatment decreased WC-As lipid vacuoles significantly compared with the control cells. On the other hand, lipid vacuoles in the treated and untreated SR-Ar cells did not differ significantly. The effect of rosiglitazone on WC-As SMC gene expression was compared with control SMC using representational difference analysis. Significant transcript increases were found for caveolin and RNA binding motif in the control cells compared with the rosiglitazone-treated cells as well as cytochrome p450 family 17 subfamily A polypeptide 1 (CYP171A) in the rosiglitazone-treated cells compared with the control cells. Although rosiglitazone was selected for these experiments because of its role as a PPARγ agonist, it appears that the drug also tempers c-myc expression, as genes related to this second

  12. Maternal obesity modulates intracellular lipid turnover in the human term placenta.

    PubMed

    Hirschmugl, B; Desoye, G; Catalano, P; Klymiuk, I; Scharnagl, H; Payr, S; Kitzinger, E; Schliefsteiner, C; Lang, U; Wadsack, C; Hauguel-de Mouzon, S

    2017-02-01

    Obesity before pregnancy is associated with impaired metabolic status of the mother and the offspring later in life. These adverse effects have been attributed to epigenetic changes in utero, but little is known about the role of placental metabolism and its contribution to fetal development. We examined the impact of maternal pre-pregnancy obesity on the expression of genes involved in placental lipid metabolism in lean and obese women. Seventy-three lean and obese women with healthy pregnancy were recruited at term elective cesarean delivery. Metabolic parameters were measured on maternal venous blood samples. Expression of 88 genes involved in lipid metabolism was measured in whole placenta tissue. Proteins of genes differently expressed in response to maternal obesity were quantified, correlated with maternal parameters and immunolocalized in placenta sections. Isolated primary trophoblasts were used for in vitro assays. Triglyceride (TG) content was increased in placental tissue of obese (1.10, CI 1.04-1.24 mg g(-1), P<0.05) vs lean (0.84, CI 0.72-1.02 mg g(-1)) women. Among target genes examined, six showed positive correlation (P<0.05) with maternal pre-pregnancy BMI, namely ATGL (PNPLA2), FATP1 (SLC27A1), FATP3 (SLC27A3), PLIN2, PPARG and CGI-58 (ABHD5). CGI-58 protein abundance was twofold higher (P<0.001) in placentas of obese vs lean women. CGI-58 protein levels correlated positively with maternal insulin levels and pre-pregnancy body mass index (R=0.63, P<0.001 and R=0.64, P<0.001, respectively). CGI-58 and PLIN2 were primarily located in the syncytiotrophoblast and, were upregulated (1.38- and 500-fold, respectively) upon oleic acid and insulin treatment of cultured trophoblast cells. Pre-gravid obesity significantly modifies the expression of placental genes related to transport and storage of neutral lipids. We propose that the upregulation of CGI-58, a master regulator of TG hydrolysis, contributes to the turnover of intracellular lipids in

  13. Maternal obesity modulates intracellular lipid turnover in the human term placenta

    PubMed Central

    Hirschmugl, B; Desoye, G; Catalano, P; Klymiuk, I; Scharnagl, H; Payr, S; Kitzinger, E; Schliefsteiner, C; Lang, U; Wadsack, C; Hauguel-de Mouzon, S

    2017-01-01

    Background: Obesity before pregnancy is associated with impaired metabolic status of the mother and the offspring later in life. These adverse effects have been attributed to epigenetic changes in utero, but little is known about the role of placental metabolism and its contribution to fetal development. Objectives: We examined the impact of maternal pre-pregnancy obesity on the expression of genes involved in placental lipid metabolism in lean and obese women. Subjects/Methods: Seventy-three lean and obese women with healthy pregnancy were recruited at term elective cesarean delivery. Metabolic parameters were measured on maternal venous blood samples. Expression of 88 genes involved in lipid metabolism was measured in whole placenta tissue. Proteins of genes differently expressed in response to maternal obesity were quantified, correlated with maternal parameters and immunolocalized in placenta sections. Isolated primary trophoblasts were used for in vitro assays. Results: Triglyceride (TG) content was increased in placental tissue of obese (1.10, CI 1.04–1.24 mg g−1, P<0.05) vs lean (0.84, CI 0.72–1.02 mg g−1) women. Among target genes examined, six showed positive correlation (P<0.05) with maternal pre-pregnancy BMI, namely ATGL (PNPLA2), FATP1 (SLC27A1), FATP3 (SLC27A3), PLIN2, PPARG and CGI-58 (ABHD5). CGI-58 protein abundance was twofold higher (P<0.001) in placentas of obese vs lean women. CGI-58 protein levels correlated positively with maternal insulin levels and pre-pregnancy body mass index (R=0.63, P<0.001 and R=0.64, P<0.001, respectively). CGI-58 and PLIN2 were primarily located in the syncytiotrophoblast and, were upregulated (1.38- and 500-fold, respectively) upon oleic acid and insulin treatment of cultured trophoblast cells. Conclusion: Pre-gravid obesity significantly modifies the expression of placental genes related to transport and storage of neutral lipids. We propose that the upregulation of CGI-58, a master regulator of TG

  14. Egg consumption modulates HDL lipid composition and increases the cholesterol-accepting capacity of serum in metabolic syndrome.

    PubMed

    Andersen, Catherine J; Blesso, Christopher N; Lee, Jiyoung; Barona, Jacqueline; Shah, Dharika; Thomas, Michael J; Fernandez, Maria Luz

    2013-06-01

    We recently demonstrated that daily whole egg consumption during moderate carbohydrate restriction leads to greater increases in plasma HDL-cholesterol (HDL-C) and improvements in HDL profiles in metabolic syndrome (MetS) when compared to intake of a yolk-free egg substitute. We further investigated the effects of this intervention on HDL composition and function, hypothesizing that the phospholipid species present in egg yolk modulate HDL lipid composition to increase the cholesterol-accepting capacity of subject serum. Men and women classified with MetS were randomly assigned to consume either three whole eggs (EGG, n = 20) per day or the equivalent amount of egg substitute (SUB, n = 17) throughout a 12-week moderate carbohydrate-restricted (25-30 % of energy) diet. Relative to other HDL lipids, HDL-cholesteryl ester content increased in all subjects, with greater increases in the SUB group. Further, HDL-triacylglycerol content was reduced in EGG group subjects with normal baseline plasma HDL-C, resulting in increases in HDL-CE/TAG ratios in both groups. Phospholipid analysis by mass spectrometry revealed that HDL became enriched in phosphatidylethanolamine in the EGG group, and that EGG group HDL better reflected sphingomyelin species present in the whole egg product at week 12 compared to baseline. Further, macrophage cholesterol efflux to EGG subject serum increased from baseline to week 12, whereas no changes were observed in the SUB group. Together, these findings suggest that daily egg consumption promotes favorable shifts in HDL lipid composition and function beyond increasing plasma HDL-C in MetS.

  15. Orally Administered Berberine Modulates Hepatic Lipid Metabolism by Altering Microbial Bile Acid Metabolism and the Intestinal FXR Signaling Pathway.

    PubMed

    Sun, Runbin; Yang, Na; Kong, Bo; Cao, Bei; Feng, Dong; Yu, Xiaoyi; Ge, Chun; Huang, Jingqiu; Shen, Jianliang; Wang, Pei; Feng, Siqi; Fei, Fei; Guo, Jiahua; He, Jun; Aa, Nan; Chen, Qiang; Pan, Yang; Schumacher, Justin D; Yang, Chung S; Guo, Grace L; Aa, Jiye; Wang, Guangji

    2017-02-01

    Previous studies suggest that the lipid-lowering effect of berberine (BBR) involves actions on the low-density lipoprotein receptor and the AMP-activated protein kinase signaling pathways. However, the implication of these mechanisms is unclear because of the low bioavailability of BBR. Because the main action site of BBR is the gut and intestinal farnesoid X receptor (FXR) plays a pivotal role in the regulation of lipid metabolism, we hypothesized that the effects of BBR on intestinal FXR signaling pathway might account for its pharmacological effectiveness. Using wild type (WT) and intestine-specific FXR knockout (FXR(int-/-)) mice, we found that BBR prevented the development of high-fat-diet-induced obesity and ameliorated triglyceride accumulation in livers of WT, but not FXR(int-/-) mice. BBR increased conjugated bile acids in serum and their excretion in feces. Furthermore, BBR inhibited bile salt hydrolase (BSH) activity in gut microbiota, and significantly increased the levels of tauro-conjugated bile acids, especially tauro-cholic acid(TCA), in the intestine. Both BBR and TCA treatment activated the intestinal FXR pathway and reduced the expression of fatty-acid translocase Cd36 in the liver. These results indicate that BBR may exert its lipid-lowering effect primarily in the gut by modulating the turnover of bile acids and subsequently the ileal FXR signaling pathway. In summary, we provide the first evidence to suggest a new mechanism of BBR action in the intestine that involves, sequentially, inhibiting BSH, elevating TCA, and activating FXR, which lead to the suppression of hepatic expression of Cd36 that results in reduced uptake of long-chain fatty acids in the liver.

  16. Palmitoylation as a key factor to modulate SP-C-lipid interactions in lung surfactant membrane multilayers.

    PubMed

    Roldan, Nuria; Goormaghtigh, Erik; Pérez-Gil, Jesús; Garcia-Alvarez, Begoña

    2015-01-01

    Surfactant protein C (SP-C) has been regarded as the most specific protein linked to development of mammalian lungs, and great efforts have been done to understand its structure-function relationships. Previous evidence has outlined the importance of SP-C palmitoylation to sustain the proper dynamics of lung surfactant, but the mechanism by which this posttranslational modification aids SP-C to stabilize the interfacial surfactant film along the compression-expansion breathing cycles, is still unrevealed. In this work we have compared the structure, orientation and lipid-protein interactions of a native palmitoylated SP-C with those of a non-palmitoylated recombinant SP-C (rSP-C) form in air-exposed multilayer membrane environments, by means of ATR-FTIR spectroscopy. Palmitoylation does not affect the secondary structure of the protein, which exhibits a full α-helical conformation in partly dehydrated phospholipid multilayer films. However, differences between the Amide I band of the IR spectrum of palmitoylated and non-palmitoylated proteins suggest subtle differences affecting the environment of their helical component. These differences are accompanied by differential effects on the IR bands from phospholipid phosphates, indicating that palmitoylation modulates lipid-protein interactions at the headgroup region of phospholipid layers. On the other hand, the relative dichroic absorption of polarized IR has allowed calculating that the palmitoylated protein adopts a more tilted transmembrane orientation than the non-palmitoylated SP-C, likely contributing to more compact, dehydrated and possibly stable multilayer lipid-protein films. As a whole, the behavior of multilayer films containing palmitoylated SP-C may reflect favorable structural properties for surfactant reservoirs at the air-liquid respiratory interface.

  17. Egg Consumption Modulates HDL Lipid Composition and Increases the Cholesterol-Accepting Capacity of Serum in Metabolic Syndrome

    PubMed Central

    Andersen, Catherine J.; Blesso, Christopher N.; Lee, Jiyoung; Barona, Jacqueline; Shah, Dharika; Thomas, Michael J.

    2013-01-01

    We recently demonstrated that daily whole egg consumption during moderate carbohydrate restriction leads to greater increases in plasma HDL-cholesterol (HDL-C) and improvements in HDL profiles in metabolic syndrome (MetS) when compared to intake of a yolk-free egg substitute. We further investigated the effects of this intervention on HDL composition and function, hypothesizing that the phospholipid species present in egg yolk modulate HDL lipid composition to increase the cholesterol-accepting capacity of subject serum. Men and women classified with MetS were randomly assigned to consume either three whole eggs (EGG, n = 20) per day or the equivalent amount of egg substitute (SUB, n = 17) throughout a 12-week moderate carbohydrate-restricted (25–30 % of energy) diet. Relative to other HDL lipids, HDL-cholesteryl ester content increased in all subjects, with greater increases in the SUB group. Further, HDL-triacylglycerol content was reduced in EGG group subjects with normal baseline plasma HDL-C, resulting in increases in HDL-CE/TAG ratios in both groups. Phospholipid analysis by mass spectrometry revealed that HDL became enriched in phosphatidylethanolamine in the EGG group, and that EGG group HDL better reflected sphingomyelin species present in the whole egg product at week 12 compared to baseline. Further, macrophage cholesterol efflux to EGG subject serum increased from baseline to week 12, whereas no changes were observed in the SUB group. Together, these findings suggest that daily egg consumption promotes favorable shifts in HDL lipid composition and function beyond increasing plasma HDL-C in MetS. PMID:23494579

  18. Pretreatment with Fish Oil-Based Lipid Emulsion Modulates Muscle Leukocyte Chemotaxis in Murine Model of Sublethal Lower Limb Ischemia

    PubMed Central

    Shih, Yao-Ming; Shih, Juey-Ming; Yeh, Chiu-Li; Li, Cheng-Che

    2017-01-01

    This study investigated the effects of a fish oil- (FO-) based lipid emulsion on muscle leukocyte chemotaxis and inflammatory responses in a murine model of limb ischemia-reperfusion (IR) injury. Mice were assigned randomly to 1 sham (sham) group, 2 ischemic groups, and 2 IR groups. The sham group did not undergo the ischemic procedure. The mice assigned to the ischemic or IR groups were pretreated intraperitoneally with either saline or FO-based lipid emulsion for 3 consecutive days. The IR procedure was induced by applying a 4.5 oz orthodontic rubber band to the left thigh above the greater trochanter for 120 min and then cutting the band to allow reperfusion. The ischemic groups were sacrificed immediately while the IR groups were sacrificed 24 h after reperfusion. Blood, IR-injured gastrocnemius, and lung tissues were collected for analysis. The results showed that FO pretreatment suppressed the local and systemic expression of several IR-induced proinflammatory mediators. Also, the FO-pretreated group had lower blood Ly6ChiCCR2hi monocyte percentage and muscle M1/M2 ratio than the saline group at 24 h after reperfusion. These findings suggest that FO pretreatment may have a protective role in limb IR injury by modulating the expression of proinflammatory mediators and regulating the polarization of macrophage. PMID:28182087

  19. CFTR in a lipid raft-TNFR1 complex modulates gap junctional intercellular communication and IL-8 secretion

    PubMed Central

    Dudez, Tecla; Borot, Florence; Huang, Song; Kwak, Brenda R.; Bacchetta, Marc; Ollero, Mario; Stanton, Bruce A.; Chanson, Marc

    2013-01-01

    Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) cause a chronic inflammatory response in the lung of patients with Cystic Fibrosis (CF). We have showed that TNF-α signaling through the Src family tyrosine kinases (SFKs) was defective as determined by an inability of TNF-α to regulate gap junctional communication (GJIC) in CF cells. Here, we sought to elucidate the mechanisms linking TNF-α signaling to the functions of CFTR at the molecular level. In a MDCKI epithelial cell model expressing wild-type (WtCFTR) or mutant CFTR lacking its PDZ-interacting motif (CFTR-ΔTRL), TNF-α increased the amount of WtCFTR but not CFTR-ΔTRL in detergent-resistant membrane microdomains (DRMs). This recruitment was modulated by SFK activity and associated with DRM localization of TNFR1 and c-Src. Activation of TNFR1 signaling also decreased GJIC and markedly stimulated IL-8 production in WtCFTR cells. In contrast, the absence of CFTR in DRMs was associated with abnormal TNFR1 signaling as revealed by no recruitment of TNFR1 and c-Src to lipid rafts in CFTR-ΔTRL cells and loss of regulation of GJIC and IL-8 secretion. These results suggest that localization of CFTR in lipid rafts in association with c-Src and TNFR1 provides a responsive signaling complex to regulate GJIC and cytokine signaling. PMID:18255040

  20. The role of exercise in minimizing postprandial oxidative stress in cigarette smokers.

    PubMed

    Bloomer, Richard J; Fisher-Wellman, Kelsey

    2009-01-01

    Cigarette smoking continues to pose a significant health burden on society. Two well-described mechanistic links associating smoking with morbidity and mortality include elevated blood lipids and increased oxidative stress. These variables have traditionally been measured while an individual is fasting, but evidence suggests that postprandial lipemia and oxidative stress provide more important information concerning susceptibility to disease, in particular cardiovascular disease. Cigarette smokers have elevated levels of biomarkers of oxidative stress at rest and experience impaired postprandial lipid and glucose metabolism. We have confirmed these findings while noting an exaggerated oxidative stress response to high-fat feeding. Smoking cessation is without question the best approach to minimizing smoking-induced ill health and disease, but success rates among those who attempt to quit are dismal. Other means to decrease a smoker's susceptibility to oxidative stress-related disease are needed. We propose that exercise may aid in attenuating postprandial oxidative stress, and we do so in 3 distinct ways. First, exercise stimulates an increase in endogenous antioxidant enzyme activity. Second, exercise improves blood triglyceride clearance via a reduced chylomicron-triglyceride half-life and an enhanced lipoprotein lipase activity. Third, exercise improves blood glucose clearance via an enhanced glucose 4 transport protein translocation and protein content, as well as insulin-insulin receptor binding and postreceptor signaling. Improvements in antioxidant status, as well as lipid and glucose processing, may aid greatly in minimizing feeding-induced oxidative stress in smokers. If so, and in accordance with the recent joint initiative of the American College of Sports Medicine and the American Medical Association, exercise may be viewed as a "medicine" for cigarette smokers at increased risk for postprandial oxidative stress. Research into this area may provide

  1. Decoration of intramyocellular lipid droplets with PLIN5 modulates fasting-induced insulin resistance and lipotoxicity in humans.

    PubMed

    Gemmink, Anne; Bosma, Madeleen; Kuijpers, Helma J H; Hoeks, Joris; Schaart, Gert; van Zandvoort, Marc A M J; Schrauwen, Patrick; Hesselink, Matthijs K C

    2016-05-01

    In contrast to insulin-resistant individuals, insulin-sensitive athletes possess high intramyocellular lipid content (IMCL), good mitochondrial function and high perilipin 5 (PLIN5) levels, suggesting a role for PLIN5 in benign IMCL storage. We hypothesised a role for PLIN5 in modulating fasting-mediated insulin resistance. Twelve men were fasted for 60 h, before and after which muscle biopsies were taken and stained for lipid droplets (LDs), PLIN5 and laminin. Confocal microscopy images were analysed for LD size, number, PLIN5 association and subcellular distribution. Fasting elevated IMCL content 2.8-fold and reduced insulin sensitivity (by 55%). Individuals with the most prominent increase in IMCL showed the least reduction in insulin sensitivity (r = 0.657; p = 0.028) and mitochondrial function (r = 0.896; p = 0.006). During fasting, PLIN5 gene expression or PLIN5 protein content in muscle homogenates was unaffected, microscopy analyses revealed that the fraction of PLIN5 associated with LDs (PLIN5+) increased significantly (+26%) upon fasting, suggesting PLIN5 redistribution. The significant increase in LD number (+23%) and size (+23%) upon fasting was entirely accounted for by PLIN5+ LDs, not by LDs devoid of PLIN5. Also the association between IMCL storage capacity and insulin resistance and mitochondrial dysfunction was only apparent for PLIN5+ LDs. Fasting results in subcellular redistribution of PLIN5 and promotes the capacity to store excess fat in larger and more numerous PLIN5-decorated LDs. This associates with blunting of fasting-induced insulin resistance and mitochondrial dysfunction, suggesting a role for PLIN5 in the modulation of fasting-mediated lipotoxicity. trialregister.nl NTR 2042.

  2. VimA-Dependent Modulation of Acetyl Coenzyme A Levels and Lipid A Biosynthesis Can Alter Virulence in Porphyromonas gingivalis

    PubMed Central

    Aruni, A. Wilson; Lee, J.; Osbourne, D.; Dou, Y.; Roy, F.; Muthiah, A.; Boskovic, D. S.

    2012-01-01

    The Porphyromonas gingivalis VimA protein has multifunctional properties that can modulate several of its major virulence factors. To further characterize VimA, P. gingivalis FLL406 carrying an additional vimA gene and a vimA-defective mutant in a different P. gingivalis genetic background were evaluated. The vimA-defective mutant (FLL451) in the P. gingivalis ATCC 33277 genetic background showed a phenotype similar to that of the vimA-defective mutant (FLL92) in the P. gingivalis W83 genetic background. In contrast to the wild type, gingipain activity was increased in P. gingivalis FLL406, a vimA chimeric strain. P. gingivalis FLL451 had a five times higher biofilm-forming capacity than the parent strain. HeLa cells incubated with P. gingivalis FLL92 showed a decrease in invasion, in contrast to P. gingivalis FLL451 and FLL406, which showed increases of 30 and 40%, respectively. VimA mediated coenzyme A (CoA) transfer to isoleucine and reduced branched-chain amino acid metabolism. The lipid A content and associated proteins were altered in the vimA-defective mutants. The VimA chimera interacted with several proteins which were found to have an LXXTG motif, similar to the sorting motif of Gram-positive organisms. All the proteins had an N-terminal signal sequence with a putative sorting signal of L(P/T/S)X(T/N/D)G and two unique signatures of EXGXTX and HISXXGXG, in addition to a polar tail. Taken together, these observations further confirm the multifunctional role of VimA in modulating virulence possibly through its involvement in acetyl-CoA transfer and lipid A synthesis and possibly by protein sorting. PMID:22144476

  3. Availability of self-recorded axillary temperature for assessment of thermic effects of food: relationship between HDL-cholesterol level and postprandial thermoregulation in type 2 diabetic patients.

    PubMed

    Suzuki, S; Nishio, S-i; Ishii, H; Sato, A; Takeda, T; Komatsu, M

    2012-02-01

    The present study was performed to develop a simple procedure for assessment of body temperature and to determine whether postprandial thermoregulation is related to metabolic regulation in diabetic patients. We examined 101 male and female subjects with diabetes. Axillary temperature was measured prior to and after all meals (3 meals per day) and self-recorded for 1 week. The averages were calculated. Positive postprandial thermoregulation (PPT) was defined as a pattern in which each of 3 average postprandial temperatures was higher than the corresponding 3 preprandial temperatures. Negative postprandial thermoregulation (NPT) was defined as the pattern except for PPT. A significant increase in postprandial temperature was observed. With the exception of high-density lipoprotein (HDL)-cholesterol levels, there were no relationships between the categorized postprandial thermoregulation and other factors, including age, sex, body mass index, thyroid function, HbA1c, diabetic complications, lipid metabolism, and calorie intake. Logistic analysis indicated an independent positive relation between HDL-cholesterol and PPT. A simple method for measurement of body temperature indicated that HDL-cholesterol level was predominantly associated with thermic effects of food in diabetic patients, while other metabolic factors showed no such relations. HDL-cholesterol may affect the postprandial regulation of body temperature in diabetic patients. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

  4. Tenoxicam modulates antioxidant redox system and lipid peroxidation in rat brain.

    PubMed

    Naziroğlu, Mustafa; Uğuz, Abdulhadi Cihangir; Gokçimen, Alpaslan; Bülbül, Metin; Karatopuk, Dilek Ulusoy; Türker, Yasin; Cerçi, Celal

    2008-09-01

    We investigated effects of two doses of Tenoxicam, a type 2 cyclooxygenase inhibitor, administration on lipid peroxidation and antioxidant redox system in cortex of the brain in rats. Twenty-two male Wistar rats were randomly divided into three groups. First group was used as control. 10 and 20 mg/kg body weight Tenoxicam were intramuscularly administrated to rats constituting the second and third groups for 10 days, respectively. Both dose of Tenoxicam administration resulted in significant increase in the glutathione peroxidase activity, reduced glutathione and vitamins C and E of cortex of the brain. The lipid peroxidation levels in the cortex of the brain were significantly decreased by the administration. Vitamin A and beta-carotene concentration was not affected by the administration. There was no statistical difference in all values between 10 and 20 mg Tenoxicam administrated groups. In conclusion, treatment of brain with 10 and 20 mg Tenoxicam has protective effects on the oxidative stress by inhibiting free radical and supporting antioxidant redox system.

  5. Modulation of hepatic lipid metabolism by olive oil and its phenols in nonalcoholic fatty liver disease.

    PubMed

    Priore, Paola; Cavallo, Alessandro; Gnoni, Antonio; Damiano, Fabrizio; Gnoni, Gabriele V; Siculella, Luisa

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in western countries, being considered the hepatic manifestation of metabolic syndrome. Cumulative lines of evidence suggest that olive oil, used as primary source of fat by Mediterranean populations, may play a key role in the observed health benefits on NAFLD. In this review, we summarize the state of the art of the knowledge on the protective role of both major and minor components of olive oil on lipid metabolism during NAFLD. In particular, the biochemical mechanisms responsible for the increase or decrease in hepatic lipid content are critically analyzed, taking into account that several studies have often provided different and/or conflicting results in animal models fed on olive oil-enriched diet. In addition, new findings that highlight the hypolipidemic and the antisteatotic actions of olive oil phenols are presented. As mitochondrial dysfunction plays a key role in the pathogenesis of NAFLD, the targeting of these organelles with olive oil phenols as a powerful therapeutic approach is also discussed.

  6. Modulation of Elasticity and Interactions in Charged Lipid Multibilayers: Monovalent Salt Solutions

    PubMed Central

    2016-01-01

    We have studied the electrostatic screening effect of NaCl solutions on the interactions between anionic lipid bilayers in the fluid lamellar phase using a Poisson–Boltzmann-based mean-field approach with constant charge and constant potential limiting charge regulation boundary conditions. The full DLVO potential, including the electrostatic, hydration and van der Waals interactions, was coupled to thermal bending fluctuations of the membranes via a variational Gaussian Ansatz. This allowed us to analyze the coupling between the osmotic pressure and the fluctuation amplitudes and compare them both simultaneously with their measured dependence on the bilayer separation, determined by the small-angle X-ray scattering experiments. High-structural resolution analysis of the scattering data revealed no significant changes of membrane structure as a function of salt concentration. Parsimonious description of our results is consistent with the constant charge limit of the general charge regulation phenomenology, with fully dissociated lipid charge groups, together with a 6-fold reduction of the membranes’ bending rigidity upon increasing NaCl concentration. PMID:27993014

  7. AMPK-dependent modulation of hepatic lipid metabolism by nesfatin-1.

    PubMed

    Yin, Yue; Li, Ziru; Gao, Ling; Li, Yin; Zhao, Jing; Zhang, Weizhen

    2015-12-05

    The aim of this study was to characterize the mechanism by which peripheral nesfatin-1 regulates hepatic lipid metabolism. Continuous peripheral infusion of nesfatin-1 reduced adiposity and plasma levels of triglyceride and cholesterol. In mice fed high fat diet, peripheral nesfatin-1 significantly decreased hepatic steatosis measured by triglyceride content and oil red staining area and diameter. These alterations were associated with a significant reduction in lipogenesis-related transcriptional factors PPARγ and SREBP1, as well as rate-limited enzyme genes such as acaca, fasn, gpam, dgat1 and dgat2. In primary hepatocytes, nesfatin-1 inhibited both basal and oleic acid stimulated triglyceride accumulation, which was accompanied by a decrement in lipogenesis-related genes and an increase in β-oxidation-related genes. In cultured hepatocytes, nesfatin-1 increased levels of AMPK phosphorylation. Inhibition of AMPK by compound C blocked the reduction of triglyceride content elicited by nesfatin-1. Our studies demonstrate that nesfatin-1 attenuates lipid accumulation in hepatocytes by an AMPK-dependent mechanism.

  8. Modulation of lipid rafts by Omega-3 fatty acids in inflammation and cancer: implications for use of lipids during nutrition support.

    PubMed

    Siddiqui, Rafat A; Harvey, Kevin A; Zaloga, Gary P; Stillwell, William

    2007-02-01

    Current understanding of biologic membrane structure and function is largely based on the concept of lipid rafts. Lipid rafts are composed primarily of tightly packed, liquid-ordered sphingolipids/cholesterol/saturated phospholipids that float in a sea of more unsaturated and loosely packed, liquid-disordered lipids. Lipid rafts have important clinical implications because many important membrane-signaling proteins are located within the raft regions of the membrane, and alterations in raft structure can alter activity of these signaling proteins. Because rafts are lipid-based, their composition, structure, and function are susceptible to manipulation by dietary components such as omega-3 polyunsaturated fatty acids and by cholesterol depletion. We review how alteration of raft lipids affects the raft/nonraft localization and hence the function of several proteins involved in cell signaling. We focus our discussion of raft-signaling proteins on inflammation and cancer.

  9. The Modulating Effect of Mechanical Changes in Lipid Bilayers Caused by ApoE-Containing Lipoproteins on Aβ Induced Membrane Disruption

    PubMed Central

    2011-01-01

    A major feature of Alzheimer’s disease (AD), a late-onset neurodegenerative disorder, is the ordered aggregation of the β-amyloid peptide (Aβ) into fibrils that comprise extracellular neuritic plaques found in the disease brain. One of many potential pathways for Aβ toxicity may be modulation of lipid membrane function. Here, we show by in situ atomic force microscopy (AFM) that astrocyte secreted lipoprotein particles (ASLPs) containing different isoforms of apolipoprotein E (apoE), of which the apoE4 allele is a major risk factor for the development of AD, can protect total brain lipid extract bilayers from Aβ1–40 induced disruption. The apoE4 allele was less effective in protecting lipid bilayers from disruption compared with apoE3. Size analysis of apoE-containing ASLPs and mechanical studies of bilayer properties revealed that apoE-containing ASLPs modulate the mechanical properties of bilayers by acquiring some bilayer components (most likely cholesterol and/or oxidatively damaged lipids). Measurement of bilayer mechanical properties was accomplished with scanning probe acceleration microscopy (SPAM). These measurements demonstrated that apoE4 was also less effective in modulating mechanical properties of bilayers in comparison with apoE3. This ability of apoE to alter the mechanical properties of lipid membranes may represent a potential mechanism for the suppression of Aβ1–40 induced bilayer disruption. PMID:22125665

  10. Inflammation-modulating cytokine profile and lipid interaction in HIV-related risk factors for cardiovascular diseases

    PubMed Central

    Gori, Elizabeth; Mduluza, Takafira; Nyagura, Mudavanhu; Stray-Pedersen, Babill; Gomo, Zvenyika Alfred

    2016-01-01

    HIV infection and antiretroviral therapy (ART) are associated with changes in plasma levels of lipoproteins, thus posing the risk of cardiovascular complications in infected individuals. The alteration in plasma lipoprotein levels results from dysregulation of inflammation-modulating cytokines that control lipid metabolism. Little is understood regarding the relationship between the cytokines and serum lipid levels, which have been reported to be altered in adults receiving ART. The objective of this study was to describe the profiles of inflammation-modulating cytokines and their relationship to lipids as cardiovascular disease (CVD) risk factors in HIV infection. This observational cross-sectional study measured plasma levels of interleukin (IL)-10, tumor necrosis factor-alpha (TNF)-α, IL-4, total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-c) in HIV-infected and uninfected adults. A total of 219 HIV-infected participants were enrolled from an HIV treatment center; of them, 187 were receiving ART and 32 were ART naïve, while 65 were HIV-uninfected blood donors. HIV-infected individuals had higher levels of IL-10 (HIV-infected ART-naïve [P=0.0024] and ART-receiving [P=0.033]) than their uninfected counterparts. ART-naïve subjects had significantly higher plasma levels of IL-10 than ART-receiving subjects (P=0.0014). No significant difference was observed in plasma levels of IL-4 and TNF-α across the three groups. Regarding plasma lipoproteins, HDL-c levels were reduced in HIV ART-naïve (P=0.002) and ART-receiving (P=0.015) subjects compared to HIV-uninfected subjects. Similarly, TC levels were lower in the HIV-infected than in the HIV-uninfected group regardless of whether the patients were undergoing ART or not (P<0.001). IL-10 levels correlated with TC levels in the HIV-uninfected group but not in the HIV-infected groups. Levels of HDL-c were reduced, while IL-10 plasma concentrations were elevated in HIV-infected individuals. A

  11. UNCOUPLING PROTEIN-2 MODULATES THE LIPID METABOLIC RESPONSE TO FASTING IN MICE

    PubMed Central

    Sheets, Anthony R.; Fülöp, Péter; Derdák, Zoltán; Kassai, Andrea; Sabo, Edmond; Mark, Nicholas M.; Paragh, György; Wands, Jack R.; Baffy, György

    2008-01-01

    Uncoupling protein-2 (UCP2) regulates insulin secretion by controlling ATP levels in β cells. While UCP2 deficiency improves glycemic control in mice, increased expression of UCP2 interferes with glucose-stimulated insulin secretion. These observations link UCP2 to β cell dysfunction in type 2 diabetes with a perplexing evolutionary role. We found higher residual serum insulin levels and blunted lipid metabolic responses in fasted ucp2−/− mice, supporting the concept that UCP2 evolved to suppress insulin effects and to accommodate the fuel switch to fatty acids during starvation. In the absence of UCP2, fasting initially promotes peripheral lipolysis and hepatic fat accumulation at less than expected rates, but culminates in protracted steatosis indicating diminished hepatic utilization and clearance of fatty acids. We conclude that UCP2-mediated control of insulin secretion is a physiologically relevant mechanism of the metabolic response to fasting. PMID:18292186

  12. Advanced Strategies in Immune Modulation of Cancer Using Lipid-Based Nanoparticles

    PubMed Central

    Mizrahy, Shoshy; Hazan-Halevy, Inbal; Landesman-Milo, Dalit; Ng, Brandon D.; Peer, Dan

    2017-01-01

    Immunotherapy has a great potential in advancing cancer treatment, especially in light of recent discoveries and therapeutic interventions that lead to complete response in specific subgroups of melanoma patients. By using the body’s own immune system, it is possible not only to specifically target and eliminate cancer cells while leaving healthy cells unharmed but also to elicit long-term protective response. Despite the promise, current immunotherapy is limited and fails in addressing all tumor types. This is probably due to the fact that a single treatment strategy is not sufficient in overcoming the complex antitumor immunity. The use of nanoparticle-based system for immunotherapy is a promising strategy that can simultaneously target multiple pathways with the same kinetics to enhance antitumor response. Here, we will highlight the recent advances in the field of cancer immunotherapy that utilize lipid-based nanoparticles as delivery vehicles and address the ongoing challenges and potential opportunities. PMID:28220118

  13. Smoking, inflammatory patterns, and postprandial hypertriglyceridemia

    USDA-ARS?s Scientific Manuscript database

    Background: Smoking is associated with increased postprandial hypertriglyceridemia (PPT). Inflammation and insulin resistance are potential "drivers" for this phenomenon. We tested whether inflammatory patterns and/or insulin resistance explain the effect of smoking on PPT. Methods: Men and women i...

  14. Branched short-chain fatty acids modulate glucose and lipid metabolism in primary adipocytes

    PubMed Central

    Heimann, Emilia; Nyman, Margareta; Pålbrink, Ann-Ki; Lindkvist-Petersson, Karin; Degerman, Eva

    2016-01-01

    ABSTRACT Short-chain fatty acids (SCFAs), e.g. acetic acid, propionic acid and butyric acid, generated through colonic fermentation of dietary fibers, have been shown to reach the systemic circulation at micromolar concentrations. Moreover, SCFAs have been conferred anti-obesity properties in both animal models and human subjects. Branched SCFAs (BSCFAs), e.g., isobutyric and isovaleric acid, are generated by fermentation of branched amino acids, generated from undigested protein reaching colon. However, BSCFAs have been sparsely investigated when referring to effects on energy metabolism. Here we primarily investigate the effects of isobutyric acid and isovaleric acid on glucose and lipid metabolism in primary rat and human adipocytes. BSCFAs inhibited both cAMP-mediated lipolysis and insulin-stimulated de novo lipogenesis at 10 mM, whereas isobutyric acid potentiated insulin-stimulated glucose uptake by all concentrations (1, 3 and 10 mM) in rat adipocytes. For human adipocytes, only SCFAs inhibited lipolysis at 10 mM. In both in vitro models, BSCFAs and SCFAs reduced phosphorylation of hormone sensitive lipase, a rate limiting enzyme in lipolysis. In addition, BSCFAs and SCFAs, in contrast to insulin, inhibited lipolysis in the presence of wortmannin, a phosphatidylinositide 3-kinase inhibitor and OPC3911, a phosphodiesterase 3 inhibitor in rat adipocytes. Furthermore, BSCFAs and SCFAs reduced insulin-mediated phosphorylation of protein kinase B. To conclude, BSCFAs have effects on adipocyte lipid and glucose metabolism that can contribute to improved insulin sensitivity in individuals with disturbed metabolism. PMID:27994949

  15. Plant pentacyclic triterpenic acids as modulators of lipid membrane physical properties.

    PubMed

    Prades, Jesús; Vögler, Oliver; Alemany, Regina; Gomez-Florit, Manuel; Funari, Sérgio S; Ruiz-Gutiérrez, Valentina; Barceló, Francisca

    2011-03-01

    Free triterpenic acids (TTPs) present in plants are bioactive compounds exhibiting multiple nutriceutical activities. The underlying molecular mechanisms have only been examined in part and mainly focused on anti-inflammatory properties, cancer and cardiovascular diseases, in all of which TTPs frequently affect membrane-related proteins. Based on the structural characteristics of TTPs, we assume that their effect on biophysical properties of cell membranes could play a role for their biological activity. In this context, our study is focused on the compounds, oleanolic (3β-hydroxy-12-oleanen-28-oic acid, OLA), maslinic (2α,3β-dihydroxy-12-oleanen-28-oic acid, MSL) and ursolic ((3β)-3-hydroxyurs-12-en-28-oic acid, URL) as the most important TTPs present in orujo olive oil. X-ray diffraction, differential scanning calorimetry, (31)P nuclear magnetic resonance and Laurdan fluorescence data provide experimental evidence that OLA, MSL and URL altered the structural properties of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and DPPC-Cholesterol (Cho) rich membranes, being located into the polar-hydrophobic interphase. Specifically, in DPPC membranes, TTPs altered the structural order of the L(β'), phase without destabilizing the lipid bilayer. The existence of a nonbilayer isotropic phase in coexistence with the liquid crystalline L(α) phase, as observed in DPPC:URL samples, indicated the presence of lipid structures with high curvature (probably inverted micelles). In DPPC:Cho membranes, TTPs affected the membrane phase properties increasing the Laurdan GP values above 40°C. MSL and URL induced segregation of Cho within the bilayer, in contrast to OLA, that reduced the structural organization of the membrane. These results strengthen the relevance of TTP interactions with cell membranes as a molecular mechanism underlying their broad spectrum of biological effects.

  16. Partial Amelioration of Peripheral and Central Symptoms of Huntington's Disease via Modulation of Lipid Metabolism.

    PubMed

    Chen, Jane Y; Tran, Conny; Hwang, Lin; Deng, Gang; Jung, Michael E; Faull, Kym F; Levine, Michael S; Cepeda, Carlos

    2016-01-01

    Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder characterized by uncontrollable dance-like movements, as well as cognitive deficits and mood changes. A feature of HD is a metabolic disturbance that precedes neurological symptoms. In addition, brain cholesterol synthesis is significantly reduced, which could hamper synaptic transmission. Alterations in lipid metabolism as a potential target for therapeutic intervention in the R6/2 mouse model of HD were examined. Electrophysiological recordings in vitro examined the acute effects of cholesterol-modifying drugs. In addition, behavioral testing, effects on synaptic activity, and measurements of circulating and brain tissue concentrations of cholesterol and the ketone β-hydroxybutyrate (BHB), were examined in symptomatic R6/2 mice and littermate controls raised on normal chow or a ketogenic diet (KD). Whole-cell voltage clamp recordings of striatal medium-sized spiny neurons (MSNs) from symptomatic R6/2 mice showed increased frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) compared with littermate controls. Incubation of slices in cholesterol reduced the frequency of large-amplitude sIPSCs. Addition of BHB or the Liver X Receptor (LXR) agonist T0901317 reduced the frequency and amplitude of sIPSCs. Surprisingly, incubation in simvastatin to reduce cholesterol levels also decreased the frequency of sIPSCs. HD mice fed the KD lost weight more gradually, performed better in an open field, had fewer stereotypies and lower brain levels of cholesterol than mice fed a regular diet. Lipid metabolism represents a potential target for therapeutic intervention in HD. Modifying cholesterol or ketone levels acutely in the brain can partially rescue synaptic alterations, and the KD can prevent weight loss and improve some behavioral abnormalities.

  17. Obesity-induced cardiac lipid accumulation in adult mice is modulated by G protein-coupled receptor kinase 2 levels.

    PubMed

    Lucas, Elisa; Vila-Bedmar, Rocio; Arcones, Alba C; Cruces-Sande, Marta; Cachofeiro, Victoria; Mayor, Federico; Murga, Cristina

    2016-11-10

    The leading cause of death among the obese population is heart failure and stroke prompted by structural and functional changes in the heart. The molecular mechanisms that underlie obesity-related cardiac remodeling are complex, and include hemodynamic and metabolic alterations that ultimately affect the functionality of the myocardium. G protein-coupled receptor kinase 2 (GRK2) is an ubiquitous kinase able to desensitize the active form of several G protein-coupled receptors (GPCR) and is known to play an important role in cardiac GPCR modulation. GRK2 has also been recently identified as a negative modulator of insulin signaling and systemic insulin resistance. We investigated the effects elicited by GRK2 downregulation in obesity-related cardiac remodeling. For this aim, we used  9 month-old wild type (WT) and GRK2+/- mice, which display circa 50% lower levels of this kinase, fed with either a standard or a high fat diet (HFD) for 30 weeks. In these mice we studied different parameters related to cardiac growth and lipid accumulation. We find that GRK2+/- mice are protected from obesity-promoted cardiac and cardiomyocyte hypertrophy and fibrosis. Moreover, the marked intracellular lipid accumulation caused by a HFD in the heart is not observed in these mice. Interestingly, HFD significantly increases cardiac GRK2 levels in WT but not in GRK2+/- mice, suggesting that the beneficial phenotype observed in hemizygous animals correlates with the maintenance of GRK2 levels below a pathological threshold. Low GRK2 protein levels are able to keep the PKA/CREB pathway active and to prevent HFD-induced downregulation of key fatty acid metabolism modulators such as Peroxisome proliferator-activated receptor gamma co-activators (PGC1), thus preserving the expression of cardioprotective proteins such as mitochondrial fusion markers mitofusin MFN1 and OPA1. Our data further define the cellular processes and molecular mechanisms by which GRK2 down-regulation is

  18. The interaction of mefloquine hydrochloride with cell membrane models at the air-water interface is modulated by the monolayer lipid composition.

    PubMed

    Goto, Thiago Eichi; Caseli, Luciano

    2014-10-01

    The antiparasitic properties of antiparasitic drugs are believed to be associated with their interactions with the protozoan membrane, encouraging research on the identification of membrane sites capable of drug binding. In this study, we investigated the interaction of mefloquine hydrochloride, known to be effective against malaria, with cell membrane models represented by Langmuir monolayers of selected lipids. It is shown that even small amounts of the drug affect the surface pressure-area isotherms as well as surface vibrational spectra of some lipid monolayers, which points to a significant interaction. The effects on the latter depend on the electrical charge of the monolayer-forming molecules, with the drug activity being particularly distinctive for negatively charged lipids. Therefore, the lipid composition of the monolayer modulates the interaction with the lipophilic drug, which may have important implications in understanding how the drug acts on specific sites of the protozoan membrane.

  19. Effects of chemosignals from sad tears and postprandial plasma on appetite and food intake in humans.

    PubMed

    Oh, Tae Jung; Kim, Min Young; Park, Kyong Soo; Cho, Young Min

    2012-01-01

    Chemosignals from human body fluids may modulate biological functions in humans. The objective of this study was to examine whether chemosignals from human sad tears and postprandial plasma modulate appetite. We obtained fasting and postprandial plasma from male participants and sad tears and saline, which was trickled below the eyelids, from female volunteers. These samples were then randomly distributed to male participants to sniff with a band-aid containing 100 µl of each fluid on four consecutive days in a double-blind fashion. We checked appetite by a visual analogue scale (VAS) and food intake by measuring the consumption of a test meal. In addition, the serum levels of total testosterone and LH were measured. Twenty men (mean age 26.3±4.6 years) were enrolled in this study. They could not discriminate between the smell of fasting and postprandial plasma and the smell of sad tears and trickled saline. Appetite and the amount of food intake were not different between the groups. Although the VAS ratings of appetite correlated with the food intake upon sniffing fasting plasma, postprandial plasma, and trickled saline, there was no such correlation upon sniffing sad tears. In addition, the decrease in serum testosterone levels from the baseline was greater with sad tears than with the trickled saline (-28.6±3.3% vs. -14.0±5.2%; P = 0.019). These data suggest that chemosignals from human sad tears and postprandial plasma do not appear to reduce appetite and food intake. However, further studies are necessary to examine whether sad tears may alter the appetite-eating behavior relation.

  20. Effects of Chemosignals from Sad Tears and Postprandial Plasma on Appetite and Food Intake in Humans

    PubMed Central

    Oh, Tae Jung; Kim, Min Young; Park, Kyong Soo; Cho, Young Min

    2012-01-01

    Chemosignals from human body fluids may modulate biological functions in humans. The objective of this study was to examine whether chemosignals from human sad tears and postprandial plasma modulate appetite. We obtained fasting and postprandial plasma from male participants and sad tears and saline, which was trickled below the eyelids, from female volunteers. These samples were then randomly distributed to male participants to sniff with a band-aid containing 100 µl of each fluid on four consecutive days in a double-blind fashion. We checked appetite by a visual analogue scale (VAS) and food intake by measuring the consumption of a test meal. In addition, the serum levels of total testosterone and LH were measured. Twenty men (mean age 26.3±4.6 years) were enrolled in this study. They could not discriminate between the smell of fasting and postprandial plasma and the smell of sad tears and trickled saline. Appetite and the amount of food intake were not different between the groups. Although the VAS ratings of appetite correlated with the food intake upon sniffing fasting plasma, postprandial plasma, and trickled saline, there was no such correlation upon sniffing sad tears. In addition, the decrease in serum testosterone levels from the baseline was greater with sad tears than with the trickled saline (−28.6±3.3% vs. −14.0±5.2%; P = 0.019). These data suggest that chemosignals from human sad tears and postprandial plasma do not appear to reduce appetite and food intake. However, further studies are necessary to examine whether sad tears may alter the appetite-eating behavior relation. PMID:22870321

  1. Accumulating exercise and postprandial health in adolescents.

    PubMed

    Bond, Bert; Williams, Craig A; Jackman, Sarah R; Woodward, Adam; Armstrong, Neil; Barker, Alan R

    2015-09-01

    To examine the influence of exercise intensity on postprandial health outcomes in adolescents when exercise is accumulated throughout the day. 19 adolescents (9 male, 13.7±0.4 years old) completed three 1-day trials in a randomised order: (1) rest (CON); or four bouts of (2) 2×1 min cycling at 90% peak power with 75 s recovery (high-intensity interval exercise; HIIE); or (3) cycling at 90% of the gas exchange threshold (moderate-intensity exercise; MIE), which was work-matched to HIIE. Each bout was separated by 2 hours. Participants consumed a high fat milkshake for breakfast and lunch. Postprandial triacylglycerol (TAG), glucose, systolic blood pressure (SBP) and fat oxidation were assessed throughout the day. There was no effect of trial on total area under the curve (TAUC) for TAG (P=0.87). TAUC-glucose was lower in HIIE compared to CON (P=0.03, ES=0.42) and MIE (P=0.04, ES=0.41), with no difference between MIE and CON (P=0.89, ES=0.04). Postprandial SBP was lower in HIIE compared to CON (P=0.04, ES=0.50) and MIE (P=0.04, ES=0.40), but not different between MIE and CON (P=0.52, ES=0.11). Resting fat oxidation was increased in HIIE compared to CON (P=0.01, ES=0.74) and MIE (P=0.05, ES=0.51), with no difference between MIE and CON (P=0.37, ES=0.24). Neither exercise trial attenuated postprandial lipaemia. However, accumulating brief bouts of HIIE, but not MIE, reduced postprandial plasma glucose and SBP, and increased resting fat oxidation in adolescent boys and girls. The intensity of accumulated exercise may therefore have important implications for health outcomes in youth. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Platelet function in the postprandial period

    PubMed Central

    2012-01-01

    Background Postprandial hyperlipidemia and hyperglycemia have been related to cardiovascular events. Among different underlying mechanisms platelet activation seems to be responsible too. No comparable data between various tests in normo- vs. hyperlipidemics before and at different time intervals are available after a fat meal. We aimed to compare 9 of them within the same patients at several time points in postprandial hyperlipidemia. Results For some tests baseline values between the groups were significantly different (TXB2, platelet sensitivity, sedimentation and WU-test). However, hyperlipidemia revealed a variable influence on the tests examined. Some of the available tests apparently sensitive to show platelet activation reflect the increase in triglycerides (TG), such as the sedimentation index. ADP-induced platelet aggregatory activity in count adjusted washed isolated platelet samples during postprandial hyperlipidemia indicates mildly enhanced platelet activity, but does not seem to induce significant changes in aggregation. In patients with severe hypertriglyceridemia (> 400 mg/dl fasting) changes in platelet function are more pronounced due to delayed decay and may last up to 16 hours paralleling TG reaching the prevalue. The overwhelming majority of platelet function tests do not significantly respond to postprandial hyperlipidemia. The correlation between the tests applied is poor. For standardization purpose, platelet aggregation tests, aimed to examine proaggregatory capacity in atherosclerosis, should only be performed at the same time of the day after a fasting period > 6 hours. The great variation in preanalytical work-up on comparison of various tests, large number of platelet tests available and their respective potential value are discussed. Conclusions At present, the suspicion that platelet function is significantly activated in the postprandial period cannot be supported by any of the tests used. The information provided is valuable to

  3. Fish oil fatty acids improve postprandial vascular reactivity in healthy men.

    PubMed

    Armah, Christopher K; Jackson, Kim G; Doman, Izzy; James, Lewis; Cheghani, Farah; Minihane, Anne M

    2008-06-01

    Chronic fish oil intervention had been shown to have a positive impact on endothelial function. Although high-fat meals have often been associated with a loss of postprandial vascular reactivity, studies examining the effects of fish oil fatty acids on vascular function in the postprandial phase are limited. The aim of the present study was to examine the impact of the addition of fish oil fatty acids to a standard test meal on postprandial vascular reactivity. A total of 25 men received in a random order either a placebo oil meal (40 g of mixed fat; fatty acid profile representative of the U.K. diet) or a fish oil meal (31 g of mixed fat and 9 g of fish oil) on two occasions. Vascular reactivity was measured at baseline (0 h) and 4 h after the meal by laser Doppler iontophoresis, and blood samples were taken for the measurement of plasma lipids, total nitrite, glucose and insulin. eNOS (endothelial NO synthase) and NADPH oxidase gene expression were determined in endothelial cells after incubation with TRLs (triacylglycerol-rich lipoproteins) isolated from the plasma samples taken at 4 h. Compared with baseline, sodium nitroprusside (an endothelium-independent vasodilator)-induced reactivity (P=0.024) and plasma nitrite levels (P=0.001) were increased after the fish oil meal. In endothelial cells, postprandial TRLs isolated after the fish oil meal increased eNOS and decreased NADPH oxidase gene expression compared with TRLs isolated following the placebo oil meal (Ppostprandial endothelium-independent vasodilation.

  4. The modulation of the permeability and the cellular uptake of liposome by stable anchoring of lipid-conjugated pluronic on liposome.

    PubMed

    Kim, Jong Chul; Chungt, Yong-Il; Kim, Young Ha; Tae, Giyoong

    2014-01-01

    Controlling the permeability of liposome is important to modulate the release behavior of drug from the liposome. Pluronic F127 (PF127) is a biocompatible tri-block copolymer, which can interact with lipid bilayer of liposomes and make leakages that allow the release of hydrophilic substance from liposome interior. However, the interaction between unmodified PF127 and lipid bilayer is not very strong and the incorporated PF127 is easily desorbed from the liposomes in an infinite reservoir condition. In this paper, we conjugated lipid molecule (1,2-distearoyl-sn-glycero-3-phosphoethanolamine [DSPE]) at the both ends of PF127 to increase the interaction between polymer and liposome. This lipid-conjugated PF127 was incorporated into the liposomes and it remained stably without desorption from liposomes in an infinite reservoir condition. The stably bound PF127 increased the release rate of hydrophilic drug from liposomes in a dose-dependent manner. Moreover, the lipid-conjugated PF127 changed the surface property of liposomes and inhibited its cellular uptake when the incorporated amount was above 2.5 wt%. In conclusion, the lipid-conjugated PF127 could function as a stable anchor on the lipid bilayer of liposomes to control the permeability as well as provide the hydrophilic surface of liposomes in an open system like an in vivo situation.

  5. Experimental model of postprandial hypertriglyceridemia in sucrose-fed rats and the effectiveness of atorvastatin in the model.

    PubMed

    Funatsu, Toshiyuki; Kakuta, Hirotoshi; Takasu, Toshiyuki; Noguchi, Masahiro; Suzuki, Masanori; Miyata, Keiji

    2003-05-01

    Although postprandial hypertriglyceridemia has drawn attention as an independent risk factor of cardiovascular disease, there is no established animal model that shows a physiological transitory change in lipoprotein metabolism after ingestion of a fatty meal. We developed an animal model of postprandial hypertriglyceridemia using sucrose-fed rats, and used this model to evaluate the effect of atorvastatin on this condition. Compared with normal rats, sucrose-fed rats orally loaded with olive oil showed a high and prolonged increase in plasma triglyceride (TG) concentration accompanied by both an increase in TG secretion and decrease in TG clearance. Atorvastatin (30 mg/kg orally) for 2 weeks reduced not only fasting plasma TG concentration, but also the postprandial TG concentration. Atorvastatin also suppressed rates of TG secretion in both chylomicron (CM)-rich (d < 0.96 g/mL) and very-low-density lipoprotein (VLDL) (d = 0.96 to 1.006 g/mL) fractions after oral fat loading. Further, atorvastatin improved the elimination time of exogenous TG emulsion only in the nonfasted, namely, high plasma TG condition. These results indicate that this animal model satisfactorily replicates the postprandial hypertriglyceridemia observed in humans and may therefore be useful in evaluation of lipid-lowering agents. Furthermore, atorvastatin not only improves fasting but also postprandial lipoprotein metabolism, presumably by reducing TG secretion from the liver or intestine or both, and by secondarily increasing TG-rich lipoprotein clearance by eliminating saturation.

  6. Electric Field-Induced Changes in Lipids Investigated by Modulated Excitation FTIR Spectroscopy

    PubMed Central

    Schwarzott, Michael; Lasch, Peter; Baurecht, Dieter; Naumann, Dieter; Fringeli, Urs Peter

    2004-01-01

    The effect of electric fields on dry oriented multibilayers of dimyristoylphosphatidylcholine (DMPC) was investigated by transmission Fourier transform infrared electric field modulated excitation (E-ME) spectroscopy. A periodic rectangular electric potential (0–150 V, 1.25 Hz, 28.4°C ± 0.2°C) was applied across the sample. To discriminate electric field-induced effects from possible temperature-induced effects resulting from a current flow (<1 pA) across the sample, corresponding temperature-modulated excitation (T-ME) measurements within the temperature uncertainty limits of ±0.2°C at 28.4°C were performed. T-ME induced reversible gauche defects in the hydrocarbon chains, whereas E-ME resulted in reversible compression of dry DMPC bilayers. Periodic variation of the tilt angle of the hydrocarbon chains is suggested. The degree of absorbance modulation in the CH-stretching region was found to be in the order of 1:700, corresponding to a variation of the bilayer thickness of Δz = 0.0054 nm. Using a series connection of capacitors as equivalent circuit of the cell resulted in E = (1.2 ± 0.7) × 107 V/m for the electric field in DMPC. Young's elasticity modulus of DMPC could be calculated to be E⊥ = 2.2 × 106 Pa ± 1.8 × 106 Pa, which is in good agreement with published data obtained by electric field-dependent capacitance measurements. PMID:14695270

  7. Central nervous system regulation of intestinal lipid and lipoprotein metabolism.

    PubMed

    Farr, Sarah; Taher, Jennifer; Adeli, Khosrow

    2016-02-01

    In response to nutrient availability, the small intestine and brain closely communicate to modulate energy homeostasis and metabolism. The gut-brain axis involves complex nutrient sensing mechanisms and an integration of neuronal and hormonal signaling. This review summarizes recent evidence implicating the gut-brain axis in regulating lipoprotein metabolism, with potential implications for the dyslipidemia of insulin resistant states. The intestine and brain possess distinct mechanisms for sensing lipid availability, which triggers subsequent regulation of feeding, glucose homeostasis, and adipose tissue metabolism. More recently, central receptors, neuropeptides, and gut hormones that communicate with the brain have been shown to modulate hepatic and intestinal lipoprotein metabolism via parasympathetic and sympathetic signaling. Gut-derived glucagon-like peptides appear to be particularly important in modulating the intestinal secretion of chylomicron particles via a novel brain-gut axis. Dysregulation of these pathways may contribute to postprandial diabetic dyslipidemia. Emerging evidence implicates the central and enteric nervous systems in controlling many aspects of lipid and lipoprotein metabolism. Bidirectional communication between the gut and brain involving neuronal pathways and gut peptides is critical for regulating feeding and metabolism, and forms a neuroendocrine circuit to modulate dietary fat absorption and intestinal production of atherogenic chylomicron particles.

  8. Postprandial Dysmetabolism and Oxidative Stress in Type 2 Diabetes: Pathogenetic Mechanisms and Therapeutic Strategies.

    PubMed

    Sottero, Barbara; Gargiulo, Simona; Russo, Isabella; Barale, Cristina; Poli, Giuseppe; Cavalot, Franco

    2015-09-01

    Postprandial dysmetabolism in type 2 diabetes (T2D) is known to impact the progression and evolution of this complex disease process. However, the underlying pathogenetic mechanisms still require full elucidation to provide guidance for disease prevention and treatment. This review focuses on the marked redox changes and inflammatory stimuli provoked by the spike in blood glucose and lipids in T2D individuals after meals. All the causes of exacerbated postprandial oxidative stress in T2D were analyzed, also considering the consequence of enhanced inflammation on vascular damage. Based on this in-depth analysis, current strategies of prevention and pharmacologic management of T2D were critically reexamined with particular emphasis on their potential redox-related rationale.

  9. Modulation of CD14 and TLR4.MD-2 activities by a synthetic lipid A mimetic

    PubMed Central

    Cighetti, Roberto; Ciaramelli, Carlotta; Sestito, Stefania Enza; Zanoni, Ivan; Kubik, Łukasz; Ardá-Freire, Ana; Calabrese, Valentina; Granucci, Francesca; Jerala, Roman; Martín-Santamaría, Sonsoles; Jiménez-Barbero, Jesus

    2014-01-01

    Monosaccharide lipid A mimetics composed by a glucosamine core linked to two fatty acid chains and bearing one or two phosphates have been synthesized. While compounds 1 and 2, with one phosphate group, were practically inactive in inhibiting LPS-induced TLR4 signaling and cytokine production in HEK-blue™ cells and murine macrophages, compound 3 with two phosphates was found to be active in efficiently inhibiting TLR4 signal in both cell types. The direct interaction of molecule 3 with MD-2 co-receptor has been investigated by means of NMR and molecular modeling/docking analysis. This compound also interacts directly with CD14 receptor, stimulating its internalization by endocytosis. Experiments on macrophages show that the effect on CD14 reinforces the activity on MD-2.TLR4, because compound 3 activity is higher when CD14 is important for TLR4 signaling i,e, at low LPS concentration. The dual MD-2 and CD14 targeting, accompanied by good solubility in water and lack of toxicity, suggests the use of monosaccharide 3 as a lead compound to develop drugs directed against TLR4-related syndromes. PMID:24339336

  10. Modulation of lipid metabolism by Centella asiatica in oxidative stress rats.

    PubMed

    Hussin, M; Hamid, A A; Mohamad, S; Saari, N; Bakar, F; Dek, S P

    2009-03-01

    A study was carried out to investigate the effects of Centella asiatica leaf on lipid metabolism of oxidative stress rats. The rats were fed 0.1% hydrogen peroxide (H(2)O(2)) with either 0.3% (w/w) C. asiatica extract, 5%C. asiatica powder (w/w), or 0.3% (w/w) alpha-tocopherol for 25 wk. Results of the study showed that C. asiatica powder significantly (P < 0.05) lowered serum low-density lipoprotein compared to that of control rats (rats fed H(2)O(2) only). At the end of the study C. asiatica-fed rats were also found to have significantly (P < 0.05) higher high-density lipoprotein and lower triglyceride level compared to rats fed only normal diet. However, cholesterol level of rats fed both C. asiatica extract and powder was found to be significantly (P < 0.05) higher compared to that of control rats. It was interesting to note that consumption of C. asiatica significantly decreased body and liver weights of the rats. Histological examinations revealed no obvious changes in all rats studied. Quantitative analysis of C. asiatica leaf revealed high concentration of total phenolic compounds, in particular, catechin, quercetin, and rutin.

  11. WIP modulates dendritic spine actin cytoskeleton by transcriptional control of lipid metabolic enzymes.

    PubMed

    Franco-Villanueva, Ana; Fernández-López, Estefanía; Gabandé-Rodríguez, Enrique; Bañón-Rodríguez, Inmaculada; Esteban, Jose Antonio; Antón, Inés M; Ledesma, María Dolores

    2014-08-15

    We identify Wiskott-Aldrich syndrome protein (WASP)-interacting protein (WIP) as a novel component of neuronal synapses whose absence increases dendritic spine size and filamentous actin levels in an N-WASP/Arp2/3-independent, RhoA/ROCK/profilinIIa-dependent manner. These effects depend on the reduction of membrane sphingomyelin (SM) due to transcriptional upregulation of neutral sphingomyelinase (NSM) through active RhoA; this enhances RhoA binding to the membrane, raft partitioning and activation in steady state but prevents RhoA changes in response to stimulus. Inhibition of NSM or SM addition reverses RhoA, filamentous actin and functional anomalies in synapses lacking WIP. Our findings characterize WIP as a link between membrane lipid composition and actin cytoskeleton at dendritic spines. They also contribute to explain cognitive deficits shared by individuals bearing mutations in the region assigned to the gene encoding for WIP. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Plasma Lipid Profiling in a Rat Model of Hepatocellular Carcinoma: Potential Modulation Through Quinolone Administration

    PubMed Central

    Shariff, Mohamed I.F.; Tognarelli, Joshua M.; Lewis, Matthew R.; Want, Elizabeth J.; Mohamed, Fatma El Zahra; Ladep, Nimzing G.; Crossey, Mary M.E.; Khan, Shahid A.; Jalan, Rajiv; Holmes, Elaine; Taylor-Robinson, Simon D.

    2015-01-01

    Background/Aims The primary aim of this study was to characterise the blood metabolic profile of hepatocellular carcinoma (HCC) in a rat model, and the secondary aim was to evaluate the effect of the quinolone, norfloxacin on metabolic profiles and exploring the role that gut sterilisation may have on HCC development. Methods HCC was induced in 10 Fischer rats by administration of intra-peritoneal diethylnitrosamine (DEN) and oral N-nitrosomorpholine. Plasma was collected upon sacrifice. Five of these rats were concomitantly administered oral norfloxacin. Six Fischer non-treated rats acted as healthy controls. Proton nuclear magnetic resonance (NMR) spectra were acquired using a 600 MHz NMR system. Results Control animals were 120 g heavier than diseased counterparts. Proton NMR spectra from diseased rats displayed significant decreases in lipoproteins, unsaturated fatty acids, acetyl-glycoprotein, acetoacetate, and glucose (P ≤ 0.001). Plasma citrate and formate levels were increased (P = 0.02). Norfloxacin appeared to abrogate this effect slightly. Conclusion The spectral profiles of plasma in rats with HCC display marked changes with relation to lipid metabolism and cellular turnover. Norfloxacin appears to moderate these metabolic alterations to a small degree. PMID:26900269

  13. The HIV matrix protein p17 induces hepatic lipid accumulation via modulation of nuclear receptor transcriptoma

    PubMed Central

    Renga, Barbara; Francisci, Daniela; Carino, Adriana; Marchianò, Silvia; Cipriani, Sabrina; Chiara Monti, Maria; Del Sordo, Rachele; Schiaroli, Elisabetta; Distrutti, Eleonora; Baldelli, Franco; Fiorucci, Stefano

    2015-01-01

    Liver disease is the second most common cause of mortality in HIV-infected persons. Exactly how HIV infection per se affects liver disease progression is unknown. Here we have investigated mRNA expression of 49 nuclear hormone receptors (NRs) and 35 transcriptional coregulators in HepG2 cells upon stimulation with the HIV matrix protein p17. This viral protein regulated mRNA expression of some NRs among which LXRα and its transcriptional co-activator MED1 were highly induced at mRNA level. Dissection of p17 downstream intracellular pathway demonstrated that p17 mediated activation of Jak/STAT signaling is responsible for the promoter dependent activation of LXR. The treatment of both HepG2 as well as primary hepatocytes with HIV p17 results in the transcriptional activation of LXR target genes (SREBP1c and FAS) and lipid accumulation. These effects are lost in HepG2 cells pre-incubated with a serum from HIV positive person who underwent a vaccination with a p17 peptide as well as in HepG2 cells pre-incubated with the natural LXR antagonist gymnestrogenin. These results suggest that HIV p17 affects NRs and their related signal transduction thus contributing to the progression of liver disease in HIV infected patients. PMID:26469385

  14. Modulation Effect of Peroxisome Proliferator-Activated Receptor Agonists on Lipid Droplet Proteins in Liver

    PubMed Central

    Zhu, Yun-Xia; Zhang, Ming-Liang; Zhong, Yuan; Wang, Chen; Jia, Wei-Ping

    2016-01-01

    Peroxisome proliferator-activated receptor (PPAR) agonists are used for treating hyperglycemia and type 2 diabetes. However, the mechanism of action of these agonists is still under investigation. The lipid droplet-associated proteins FSP27/CIDEC and LSDP5, regulated directly by PPARγ and PPARα, are associated with hepatic steatosis and insulin sensitivity. Here, we evaluated the expression levels of FSP27/CIDEC and LSDP5 and the regulation of these proteins by consumption of a high-fat diet (HFD) or administration of PPAR agonists. Mice with diet-induced obesity were treated with the PPARγ or PPARα agonist, pioglitazone or fenofibrate, respectively. Liver tissues from db/db diabetic mice and human were also collected. Interestingly, FSP27/CIEDC was expressed in mouse and human livers and was upregulated in obese C57BL/6J mice. Fenofibrate treatment decreased hepatic triglyceride (TG) content and FSP27/CIDEC protein expression in mice fed an HFD diet. In mice, LSDP5 was not detected, even in the context of insulin resistance or treatment with PPAR agonists. However, LSDP5 was highly expressed in humans, with elevated expression observed in the fatty liver. We concluded that fenofibrate greatly decreased hepatic TG content and FSP27/CIDEC protein expression in mice fed an HFD, suggesting a potential regulatory role for fenofibrate in the amelioration of hepatic steatosis. PMID:26770990

  15. The HIV matrix protein p17 induces hepatic lipid accumulation via modulation of nuclear receptor transcriptoma.

    PubMed

    Renga, Barbara; Francisci, Daniela; Carino, Adriana; Marchianò, Silvia; Cipriani, Sabrina; Chiara Monti, Maria; Del Sordo, Rachele; Schiaroli, Elisabetta; Distrutti, Eleonora; Baldelli, Franco; Fiorucci, Stefano

    2015-10-15

    Liver disease is the second most common cause of mortality in HIV-infected persons. Exactly how HIV infection per se affects liver disease progression is unknown. Here we have investigated mRNA expression of 49 nuclear hormone receptors (NRs) and 35 transcriptional coregulators in HepG2 cells upon stimulation with the HIV matrix protein p17. This viral protein regulated mRNA expression of some NRs among which LXRα and its transcriptional co-activator MED1 were highly induced at mRNA level. Dissection of p17 downstream intracellular pathway demonstrated that p17 mediated activation of Jak/STAT signaling is responsible for the promoter dependent activation of LXR. The treatment of both HepG2 as well as primary hepatocytes with HIV p17 results in the transcriptional activation of LXR target genes (SREBP1c and FAS) and lipid accumulation. These effects are lost in HepG2 cells pre-incubated with a serum from HIV positive person who underwent a vaccination with a p17 peptide as well as in HepG2 cells pre-incubated with the natural LXR antagonist gymnestrogenin. These results suggest that HIV p17 affects NRs and their related signal transduction thus contributing to the progression of liver disease in HIV infected patients.

  16. Caenorhabditis elegans PAQR-2 and IGLR-2 Protect against Glucose Toxicity by Modulating Membrane Lipid Composition

    PubMed Central

    Svensk, Emma; Devkota, Ranjan; Ståhlman, Marcus; Ranji, Parmida; Rauthan, Manish; Magnusson, Fredrik; Hammarsten, Sofia; Johansson, Maja; Borén, Jan; Pilon, Marc

    2016-01-01

    In spite of the worldwide impact of diabetes on human health, the mechanisms behind glucose toxicity remain elusive. Here we show that C. elegans mutants lacking paqr-2, the worm homolog of the adiponectin receptors AdipoR1/2, or its newly identified functional partner iglr-2, are glucose intolerant and die in the presence of as little as 20 mM glucose. Using FRAP (Fluorescence Recovery After Photobleaching) on living worms, we found that cultivation in the presence of glucose causes a decrease in membrane fluidity in paqr-2 and iglr-2 mutants and that genetic suppressors of this sensitivity act to restore membrane fluidity by promoting fatty acid desaturation. The essential roles of paqr-2 and iglr-2 in the presence of glucose are completely independent from daf-2 and daf-16, the C. elegans homologs of the insulin receptor and its downstream target FoxO, respectively. Using bimolecular fluorescence complementation, we also show that PAQR-2 and IGLR-2 interact on plasma membranes and thus may act together as a fluidity sensor that controls membrane lipid composition. PMID:27082444

  17. Activation of peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) suppresses postprandial lipidemia through fatty acid oxidation in enterocytes

    SciTech Connect

    Kimura, Rino; Takahashi, Nobuyuki; Murota, Kaeko; Yamada, Yuko; Niiya, Saori; Kanzaki, Noriyuki; Murakami, Yoko; Moriyama, Tatsuya; Goto, Tsuyoshi; Kawada, Teruo

    2011-06-24

    Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of fatty acid oxidation-related genes in human intestinal epithelial Caco-2 cells. {yields} PPAR{alpha} activation also increased oxygen consumption rate and CO{sub 2} production and decreased secretion of triglyceride and ApoB from Caco-2 cells. {yields} Orally administration of bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and CO{sub 2} production in small intestinal epithelial cells. {yields} Treatment with bezafibrate decreased postprandial serum concentration of triglyceride after oral injection of olive oil in mice. {yields} It suggested that intestinal lipid metabolism regulated by PPAR{alpha} activation suppresses postprandial lipidemia. -- Abstract: Activation of peroxisome proliferator-activated receptor (PPAR)-{alpha} which regulates lipid metabolism in peripheral tissues such as the liver and skeletal muscle, decreases circulating lipid levels, thus improving hyperlipidemia under fasting conditions. Recently, postprandial serum lipid levels have been found to correlate more closely to cardiovascular diseases than fasting levels, although fasting hyperlipidemia is considered an important risk of cardiovascular diseases. However, the effect of PPAR{alpha} activation on postprandial lipidemia has not been clarified. In this study, we examined the effects of PPAR{alpha} activation in enterocytes on lipid secretion and postprandial lipidemia. In Caco-2 enterocytes, bezafibrate, a potent PPAR{alpha} agonist, increased mRNA expression levels of fatty acid oxidation-related genes, such as acyl-CoA oxidase, carnitine palmitoyl transferase, and acyl-CoA synthase, and oxygen consumption rate (OCR) and suppressed secretion levels of both triglycerides and apolipoprotein B into the basolateral side. In vivo experiments revealed that feeding high-fat-diet containing bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and

  18. SNPs in FNDC5 (irisin) are associated with obesity and modulation of glucose and lipid metabolism in Saudi subjects.

    PubMed

    Al-Daghri, Nasser M; Mohammed, Abdul Khader; Al-Attas, Omar S; Amer, Osama E; Clerici, Mario; Alenad, Amal; Alokail, Majed S

    2016-03-11

    Irisin is a recently identified myokine that plays an important role in preventing obesity and insulin resistance. We investigated whether the common FNDC5 (irisin precursor) gene variants influence susceptibility to obesity and type 2 diabetes (T2D) and verified the impact of FNDC5 gene variants on serum irisin levels, glucose and lipid metabolism in a Saudi population. Genomic DNA from 814 (394 T2DM and 414 controls) subjects were genotyped for the five common SNPs (rs3480A/G, rs1746661G/T, rs1298190A/G, rs726344A/G and rs1570569G/T) of the FNDC5 gene using the TaqMan genotyping assay. Biochemical parameters and hematic concentrations of irisin and insulin as well as anthropometric indices were collected. Serum irisin levels were higher in T2DM patients compared to controls (p < 0.0001). Analyses of FNDC5 SNPs showed that: 1) The rs3480 GG associates with decreased risk of obesity (p = 0.005; odds ratio: 0.48) and lower body mass index (BMI) values (p = 0.03). In addition, GGAAG was identified as the protective haplotype against risk of obesity (p = 0.001; odds ratio: 0.23). 2) The rs1746661 G allele associates with higher triglyceride (TG) levels (p = 0.019). 3) The rs157069 TT genotype associates with higher fasting insulin (p = 0.029) and HOMA-IR (p = 0.002) as well as with lower circulating irisin levels (p = 0.016). SNPs in FNDC5 gene correlates with obesity and glucose-lipid metabolism possibly because they modulate the serum levels of irisin.

  19. Glucose Induces Sensitivity to Oxygen Deprivation and Modulates Insulin/IGF-1 Signaling and Lipid Biosynthesis in Caenorhabditis elegans

    PubMed Central

    Garcia, Anastacia M.; Ladage, Mary L.; Dumesnil, Dennis R.; Zaman, Khadiza; Shulaev, Vladimir; Azad, Rajeev K.; Padilla, Pamela A.

    2015-01-01

    Diet is a central environmental factor that contributes to the phenotype and physiology of individuals. At the root of many human health issues is the excess of calorie intake relative to calorie expenditure. For example, the increasing amount of dietary sugars in the human diet is contributing to the rise of obesity and type 2 diabetes. Individuals with obesity and type 2 diabetes have compromised oxygen delivery, and thus it is of interest to investigate the impact a high-sugar diet has on oxygen deprivation responses. By utilizing the Caenorhabditis elegans genetic model system, which is anoxia tolerant, we determined that a glucose-supplemented diet negatively impacts responses to anoxia and that the insulin-like signaling pathway, through fatty acid and ceramide synthesis, modulates anoxia survival. Additionally, a glucose-supplemented diet alters lipid localization and initiates a positive chemotaxis response. Use of RNA-sequencing analysis to compare gene expression responses in animals fed either a standard or glucose-supplemented diet revealed that glucose impacts the expression of genes involved with multiple cellular processes including lipid and carbohydrate metabolism, stress responses, cell division, and extracellular functions. Several of the genes we identified show homology to human genes that are differentially regulated in response to obesity or type 2 diabetes, suggesting that there may be conserved gene expression responses between C. elegans fed a glucose-supplemented diet and a diabetic and/or obesity state observed in humans. These findings support the utility of the C. elegans model for understanding the molecular mechanisms regulating dietary-induced metabolic diseases. PMID:25762526

  20. Endoplasmic Reticulum Stress and Ca2+ Depletion Differentially Modulate the Sterol Regulatory Protein PCSK9 to Control Lipid Metabolism.

    PubMed

    Lebeau, Paul; Al-Hashimi, Ali; Sood, Sudesh; Lhoták, Šárka; Yu, Pei; Gyulay, Gabriel; Paré, Guillaume; Chen, S R Wayne; Trigatti, Bernardo; Prat, Annik; Seidah, Nabil G; Austin, Richard C

    2017-01-27

    Accumulating evidence implicates endoplasmic reticulum (ER) stress as a mediator of impaired lipid metabolism, thereby contributing to fatty liver disease and atherosclerosis. Previous studies demonstrated that ER stress can activate the sterol regulatory element-binding protein-2 (SREBP2), an ER-localized transcription factor that directly up-regulates sterol regulatory genes, including PCSK9 Given that PCSK9 contributes to atherosclerosis by targeting low density lipoprotein (LDL) receptor (LDLR) degradation, this study investigates a novel mechanism by which ER stress plays a role in lipid metabolism by examining its ability to modulate PCSK9 expression. Herein, we demonstrate the existence of two independent effects of ER stress on PCSK9 expression and secretion. In cultured HuH7 and HepG2 cells, agents or conditions that cause ER Ca(2+) depletion, including thapsigargin, induced SREBP2-dependent up-regulation of PCSK9 expression. In contrast, a significant reduction in the secreted form of PCSK9 protein was observed in the media from both thapsigargin- and tunicamycin (TM)-treated HuH7 cells, mouse primary hepatocytes, and in the plasma of TM-treated C57BL/6 mice. Furthermore, TM significantly increased hepatic LDLR expression and reduced plasma LDL concentrations in mice. Based on these findings, we propose a model in which ER Ca(2+) depletion promotes the activation of SREBP2 and subsequent transcription of PCSK9. However, conditions that cause ER stress regardless of their ability to dysregulate ER Ca(2+) inhibit PCSK9 secretion, thereby reducing PCSK9-mediated LDLR degradation and promoting LDLR-dependent hepatic cholesterol uptake. Taken together, our studies provide evidence that the retention of PCSK9 in the ER may serve as a potential strategy for lowering LDL cholesterol levels.

  1. Mango modulates body fat and plasma glucose and lipids in mice fed a high-fat diet.

    PubMed

    Lucas, Edralin A; Li, Wenjia; Peterson, Sandra K; Brown, Angela; Kuvibidila, Solo; Perkins-Veazie, Penny; Clarke, Stephen L; Smith, Brenda J

    2011-11-01

    Consumption of fruits and vegetables has been investigated for their role in the prevention of many chronic conditions. Among the fruits, mango provides numerous bioactive compounds such as carotenoids, vitamin C and phenolic compounds, which have been shown to have antioxidant and anti-inflammatory properties. The present study examined the effects of dietary supplementation of freeze-dried mango pulp, in comparison with the hypolipidaemic drug, fenofibrate, and the hypoglycaemic drug, rosiglitazone, in reducing adiposity and alterations in glucose metabolism and lipid profile in mice fed a high-fat (HF) diet. Male C57BL/6J mice were randomly divided into six treatment groups (eight to nine/group): control (10 % energy from fat); HF (60 % energy from fat); HF+1 or 10 % freeze-dried mango (w/w); HF+fenofibrate (500 mg/kg diet); HF+rosiglitazone (50 mg/kg diet). After 8 weeks of treatment, mice receiving the HF diet had a higher percentage body fat (P = 0·0205) and epididymal fat mass (P = 0·0037) compared with the other treatment groups. Both doses of freeze-dried mango, similar to fenofibrate and rosiglitazone, prevented the increase in epididymal fat mass and the percentage of body fat. Freeze-dried mango supplementation at the 1 % dose improved glucose tolerance as shown by approximately 35 % lower blood glucose area under the curve compared with the HF group. Moreover, freeze-dried mango lowered insulin resistance, as indicated by the homeostasis model assessment of insulin resistance, to a similar extent as rosiglitazone and modulated NEFA. The present findings demonstrate that incorporation of freeze-dried mango in the diet of mice improved glucose tolerance and lipid profile and reduced adiposity associated with a HF diet.

  2. Ellagitannins and Flavan-3-ols from Raspberry Pomace Modulate Caecal Fermentation Processes and Plasma Lipid Parameters in Rats.

    PubMed

    Fotschki, Bartosz; Juśkiewicz, Jerzy; Sójka, Michał; Jurgoński, Adam; Zduńczyk, Zenon

    2015-12-21

    Raspberry pomace is a source of polyphenols, which nutritional and health promoting properties are not sufficiently known. The aim of this 8-weeks study was to scrutinize if raspberry extracts (REs) with different ellagitannins to flavan-3-ols ratios might favorably affect the caecal fermentation processes and blood lipid profile in rats. Forty male Wistar rats were fed with a standard diet or its modification with two types of REs (E1 and E2) characterized by different ratios of ellagitannins to flavan-3-ols (7.7 and 3.1 for E1 and E2, respectively) and added to a diet at two dosages of polyphenolic compounds (0.15 and 0.30% of a diet; L and H treatments, respectively). Irrespective of polyphenols dietary level, both REs reduced the activity of bacterial β-glucuronidase, increased production of butyric acid in the caecum and reduced triacylglycerols in blood plasma. The E1 treatment at both dosages caused more effective reduction in the concentration of ammonia and elevated acetate level in the caecal digesta than E2. On the other hand, only the E2 treatment lowered value of the atherogenic index when compared with control group. When comparing dosages of REs, a higher one was more potent to reduce the activity of bacterial β-glucosidase, β-, α-galactosidase and lowered value of the HDL profile in plasma. To conclude, REs may favorably modulate the activity of the caecal microbiota and blood lipid profile in rats; however, the intensity of these effects may be related to the dosages of dietary polyphenols and to their profile, e.g., ellagitannins to flavan-3-ols ratio.

  3. Genetic Variations at ABCG5/G8 Genes Modulate Plasma Lipids Concentrations in Patients with Familial Hypercholesterolemia

    PubMed Central

    Garcia-Rios, A; Perez-Martinez, P; Fuentes, F; Mata, P; Lopez-Miranda, J; Alonso, R; Rodriguez, F; Garcia-Olid, A; Ruano, J; Ordovas, JM; Perez-Jimenez, F

    2010-01-01

    Objective To investigate the association of four common single nucleotide polymorphisms (SNPs) at ABCG5 (i7892A>G, i18429C>T, Gln604GluC>G, i11836G>A) and five at ABCG8 (5U145T>G, Tyr54CysA>G, Asp19HisG>C, i14222T>C, and Thr400LysG>T) with plasma lipids concentrations and to explore the interaction between those SNPs and smoking in patients with FH. Methods and Results ABCG5/G8 SNPs were genotyped in 500 subjects with genetic diagnosis of FH. Carriers of the minor A allele at the ABCG5_i11836G>A SNP displayed significantly higher HDL-C concentrations (P=0.023) than G/G subjects. In addition, carriers of the minor G allele at the ABCG5_Gln604GluC>G SNP had significantly lower VLDL-C (P=0.011) and lower TG (P=0.017) concentrations than homozygous C/C. Interestingly, a significant gene-smoking interaction was found, in which carriers of the minor alleles at ABCG5 (i7892A>G, i18429C>T, i11836G>A) SNPs displayed significantly lower HDL-C, higher TC and higher TG respectively, only in smokers. On the other hand, non-smokers carriers of the minor alleles at ABCG5 (i18429C>T and Gln604GluC>G) SNPs had significantly lower TG concentrations (P=0.012 and P=0.035) compared with homozygous for the major allele. Conclusions Our data support the notion that ABCG5/G8 genetic variants modulate plasma lipids concentrations in patients with FH and confirm that this effect could be influenced by smoking. Therefore, these results suggest that gene-environmental interactions can affect the clinical phenotype of FH. PMID:20172523

  4. Experimental dog model for assessment of fasting and postprandial fatty acid metabolism: pitfalls and feasibility.

    PubMed

    Bellanger, S; Benrezzak, O; Battista, M C; Naimi, F; Labbé, S M; Frisch, F; Normand-Lauzière, F; Gallo-Payet, N; Carpentier, A C; Baillargeon, J P

    2015-07-01

    The dog is a widely-used model for conducting metabolic studies. This is mainly due to its large size and its physiology which is relatively similar to that of humans. Here, we attempted to optimize a postprandial metabolic study protocol used in dogs. Following acclimatization, female mongrel dogs underwent 9 h profiling for time-course baseline plasma data on triglyceride, adrenocorticotropic hormone (ACTH) and cortisol levels. One week later, carotid and jugular catheters were surgically inserted for sampling and infusions. Initial post-operative care, based on the literature (Protocol 1), consisted of analgesia (buprenorphine every 8-12 h and 2-3 doses/day of acepromazine), restriction by Pavlov harness within cages, and a two- to three-day recovery period. Throughout the experiment, dogs received a lipid tracer diluted in 5% bovine serum albumin (BSA). Compared with baseline, animals vomited (n = 6/6) and exhibited high ACTH + cortisol levels (stress biomarkers), resulting in blunted triglyceride peak levels. To avoid these undesirable effects, post-operative care was modified (Protocol 2) as follows: animals (n = 19) were given a single dose of buprenorphine and no acepromazine, were unrestrained and free to move within cages, the recovery period was extended to seven days, and the lipid tracer was diluted in 0.002% versus 5% BSA. Using this modified protocol, postprandial plasma-triglyceride and ACTH/cortisol patterns were similar to baseline values. Controlling for stressors, as well as for factors which may alter proper digestion, is critical for all postprandial metabolic studies. Our results show that an optimized postprandial metabolic protocol used in dogs reduces experimental variability, while improving animal care and comfort. © The Author(s) 2015.

  5. Epigenome-wide association study of triglyceride postprandial responses to a high-fat dietary challenge.

    PubMed

    Lai, Chao-Qiang; Wojczynski, Mary K; Parnell, Laurence D; Hidalgo, Bertha A; Irvin, Marguerite Ryan; Aslibekyan, Stella; Province, Michael A; Absher, Devin M; Arnett, Donna K; Ordovás, José M

    2016-12-01

    Postprandial lipemia (PPL), the increased plasma TG concentration after consuming a high-fat meal, is an independent risk factor for CVD. Individual responses to a meal high in fat vary greatly, depending on genetic and lifestyle factors. However, only a few loci have been associated with TG-PPL response. Heritable epigenomic changes may be significant contributors to the unexplained inter-individual PPL variability. We conducted an epigenome-wide association study on 979 subjects with DNA methylation measured from CD4(+) T cells, who were challenged with a high-fat meal as a part of the Genetics of Lipid Lowering Drugs and Diet Network study. Eight methylation sites encompassing five genes, LPP, CPT1A, APOA5, SREBF1, and ABCG1, were significantly associated with PPL response at an epigenome-wide level (P < 1.1 × 10(-7)), but no methylation site reached epigenome-wide significance after adjusting for baseline TG levels. Higher methylation at LPP, APOA5, SREBF1, and ABCG1, and lower methylation at CPT1A methylation were correlated with an increased TG-PPL response. These PPL-associated methylation sites, also correlated with fasting TG, account for a substantially greater amount of phenotypic variance (14.9%) in PPL and fasting TG (16.3%) when compared with the genetic contribution of loci identified by our previous genome-wide association study (4.5%). In summary, the epigenome is a large contributor to the variation in PPL, and this has the potential to be used to modulate PPL and reduce CVD.

  6. Drug uptake, lipid rafts, and vesicle trafficking modulate resistance to an anticancer lysophosphatidylcholine analogue in yeast.

    PubMed

    Cuesta-Marbán, Álvaro; Botet, Javier; Czyz, Ola; Cacharro, Luis M; Gajate, Consuelo; Hornillos, Valentín; Delgado, Javier; Zhang, Hui; Amat-Guerri, Francisco; Acuña, A Ulises; McMaster, Christopher R; Revuelta, José Luis; Zaremberg, Vanina; Mollinedo, Faustino

    2013-03-22

    The ether-phospholipid edelfosine, a prototype antitumor lipid (ATL), kills yeast cells and selectively kills several cancer cell types. To gain insight into its mechanism of action, we performed chemogenomic screens in the Saccharomyces cerevisiae gene-deletion strain collection, identifying edelfosine-resistant mutants. LEM3, AGP2, and DOC1 genes were required for drug uptake. Edelfosine displaced the essential proton pump Pma1p from rafts, inducing its internalization into the vacuole. Additional ATLs, including miltefosine and perifosine, also displaced Pma1p from rafts to the vacuole, suggesting that this process is a major hallmark of ATL cytotoxicity in yeast. Radioactive and synthetic fluorescent edelfosine analogues accumulated in yeast plasma membrane rafts and subsequently the endoplasmic reticulum. Although both edelfosine and Pma1p were initially located at membrane rafts, internalization of the drug toward endoplasmic reticulum and Pma1p to the vacuole followed different routes. Drug internalization was not dependent on endocytosis and was not critical for yeast cytotoxicity. However, mutants affecting endocytosis, vesicle sorting, or trafficking to the vacuole, including the retromer and ESCRT complexes, prevented Pma1p internalization and were edelfosine-resistant. Our data suggest that edelfosine-induced cytotoxicity involves raft reorganization and retromer- and ESCRT-mediated vesicular transport and degradation of essential raft proteins leading to cell death. Cytotoxicity of ATLs is mainly dependent on the changes they induce in plasma membrane raft-located proteins that lead to their internalization and subsequent degradation. Edelfosine toxicity can be circumvented by inactivating genes that then result in the recycling of internalized cell-surface proteins back to the plasma membrane.

  7. Ceramide modulates HERG potassium channel gating by translocation into lipid rafts

    PubMed Central

    Ganapathi, Sindura B.; Fox, Todd E.; Elmslie, Keith S.

    2010-01-01

    Human ether-à-go-go-related gene (HERG) potassium channels play an important role in cardiac action potential repolarization, and HERG dysfunction can cause cardiac arrhythmias. However, recent evidence suggests a role for HERG in the proliferation and progression of multiple types of cancers, making it an attractive target for cancer therapy. Ceramide is an important second messenger of the sphingolipid family, which due to its proapoptotic properties has shown promising results in animal models as an anticancer agent. Yet the acute effects of ceramide on HERG potassium channels are not known. In the present study we examined the effects of cell-permeable C6-ceramide on HERG potassium channels stably expressed in HEK-293 cells. C6-ceramide (10 μM) reversibly inhibited HERG channel current (IHERG) by 36 ± 5%. Kinetically, ceramide induced a significant hyperpolarizing shift in the current-voltage relationship (ΔV1/2 = −8 ± 0.5 mV) and increased the deactivation rate (43 ± 3% for τfast and 51 ± 3% for τslow). Mechanistically, ceramide recruited HERG channels within caveolin-enriched lipid rafts. Cholesterol depletion and repletion experiments and mathematical modeling studies confirmed that inhibition and gating effects are mediated by separate mechanisms. The ceramide-induced hyperpolarizing gating shift (raft mediated) could offset the impact of inhibition (raft independent) during cardiac action potential repolarization, so together they may nullify any negative impact on cardiac rhythm. Our results provide new insights into the effects of C6-ceramide on HERG channels and suggest that C6-ceramide can be a promising therapeutic for cancers that overexpress HERG. PMID:20375276

  8. Effect of short term aerobic exercise on fasting and postprandial lipoprotein subfractions in healthy sedentary men.

    PubMed

    Sabaka, Peter; Kruzliak, Peter; Balaz, David; Komornikova, Andrea; Celovska, Denisa; Cammarota, Giovanni; Kusendova, Katarina; Bendzala, Matej; Rodrigo, Luis; Dukat, Andrej; Kwon, Taeg Kyu; Dvorakova, Magdalena Chottova; Gaspar, Ludovit

    2015-11-25

    Our goal was to investigate the effect of short term exercise on fasting and postprandial lipoprotein profile. Healthy sedentary men exercised 20 min for four days. The intensity of exercise was modulated to maintain 75-80 % of a calculated HRmax. Before and after the exercise program, fasting and postprandial (4 h after standard meal) concentrations of lipoprotein subfractions were measured by an electrophoresis in polyacrylamide gel and total concentrations of TAG, LDL and HDL by enzymatic colorimetric method. After 2 days of rest, fasting and postprandial concentrations of lipoprotein fractions and subfractions were measured to determine a persistency of a changes in the lipoprotein profile. 4 days of physical exercise led to statistically significant decrease of concentration of triacylglycerol in fasting (76.29 ± 20.07, 53.92 ± 10.90, p < 0.05) and postprandial state (139.06 ± 23.72, 96.55 ± 25.21, p < 0.05) VLDL in fasting (21.88 ± 3.87, 18.00 ± 3.93, p < 0.05) and postprandial state (23.88 ± 3.52, 19.25 ± 3.62, p < 0.05), total cholesterol in fasting (162.26 ± 23.38, 148.91 ± 17.72, p < 0.05) and postprandial state (163.73 ± 23.02, 150.08 ± 18.11, p < 0.05). Atherogenic medium LDL decreased also in fasting (9.89 ± 3.27, 6.22 ± 2.55, p < 0.001) and postprandial state (8.88 ± 6.51, 6.88 ± 5.57, p < 0.001). However decrease of large IDL (25.38 ± 3.54, 23.88 ± 3.91, p < 0.05) and large LDL particles (42.89 ± 11.40, 38.67 ± 9.30) was observed only in postprandial state. Total HDL concentration remained unchanged but we observed statistically significant decrease of small HDL particles in fasting (6.11 ± 2.89, 4.22, p < 0.05) and postprandial state (6.44 ± 3.21, 4.56 ± 1.33, p < 0.05). Concentration of these particles are associated with progression of atherosclerosis. All changes of fasting and postprandial lipoprotein

  9. Lysophospholipids modulate channel function by altering the mechanical properties of lipid bilayers

    PubMed Central

    1994-01-01

    Lipid metabolites, free fatty acids and lysophospholipids, modify the function of membrane proteins including ion channels. Such alterations can occur through signal transduction pathways, but may also result from "direct" effects of the metabolite on the protein. To investigate possible mechanisms for such direct effects, we examined the alterations of gramicidin channel function by lysophospholipids (LPLs): lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), lysophosphatidylserine (LPS), and lysophosphatidylinositol (LPI). The experiments were done on planar bilayers formed by diphytanoylphosphatidylcholine in n-decane a system where receptor- mediated effects can be excluded. At aqueous concentrations below the critical micelle concentration (CMC), LPLs can increase the dimerization constant for membrane-bound gramicidin up to 500-fold (at 2 microM). The relative potency increases as a function of the size of the polar head group, but does not seem to vary as a function of head group charge. The increased dimerization constant results primarily from an increase in the rate constant for channel formation, which can increase more than 100-fold (in the presence of LPC and LPI), whereas the channel dissociation rate constant decreases only about fivefold. The LPL effect cannot be ascribed to an increased membrane fluidity, which would give rise to an increased channel dissociation rate constant. The ability of LPC to decrease the channel dissociation rate constant varies as a function of channel length (which is always less than the membrane's equilibrium thickness): as the channel length is decreased, the potency of LPC is increased. LPC has no effect on membrane thickness or the surface tension of monolayers at the air/electrolyte interface. The bilayer-forming glycerolmonooleate does not decrease the channel dissociation rate constant. These results show that LPLs alter gramicidin channel function by altering the membrane deformation energy, and

  10. Lysophospholipids modulate channel function by altering the mechanical properties of lipid bilayers.

    PubMed

    Lundbaek, J A; Andersen, O S

    1994-10-01

    Lipid metabolites, free fatty acids and lysophospholipids, modify the function of membrane proteins including ion channels. Such alterations can occur through signal transduction pathways, but may also result from "direct" effects of the metabolite on the protein. To investigate possible mechanisms for such direct effects, we examined the alterations of gramicidin channel function by lysophospholipids (LPLs): lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), lysophosphatidylserine (LPS), and lysophosphatidylinositol (LPI). The experiments were done on planar bilayers formed by diphytanoylphosphatidylcholine in n-decane a system where receptor-mediated effects can be excluded. At aqueous concentrations below the critical micelle concentration (CMC), LPLs can increase the dimerization constant for membrane-bound gramicidin up to 500-fold (at 2 microM). The relative potency increases as a function of the size of the polar head group, but does not seem to vary as a function of head group charge. The increased dimerization constant results primarily from an increase in the rate constant for channel formation, which can increase more than 100-fold (in the presence of LPC and LPI), whereas the channel dissociation rate constant decreases only about fivefold. The LPL effect cannot be ascribed to an increased membrane fluidity, which would give rise to an increased channel dissociation rate constant. The ability of LPC to decrease the channel dissociation rate constant varies as a function of channel length (which is always less than the membrane's equilibrium thickness): as the channel length is decreased, the potency of LPC is increased. LPC has no effect on membrane thickness or the surface tension of monolayers at the air/electrolyte interface. The bilayer-forming glycerolmonooleate does not decrease the channel dissociation rate constant. These results show that LPLs alter gramicidin channel function by altering the membrane deformation energy, and

  11. Ion transport through lipid bilayers by synthetic ionophores: modulation of activity and selectivity.

    PubMed

    De Riccardis, Francesco; Izzo, Irene; Montesarchio, Daniela; Tecilla, Paolo

    2013-12-17

    The ion-coupled processes that occur in the plasma membrane regulate the cell machineries in all the living organisms. The details of the chemical events that allow ion transport in biological systems remain elusive. However, investigations of the structure and function of natural and artificial transporters has led to increasing insights about the conductance mechanisms. Since the publication of the first successful artificial system by Tabushi and co-workers in 1982, synthetic chemists have designed and constructed a variety of chemically diverse and effective low molecular weight ionophores. Despite their relative structural simplicity, ionophores must satisfy several requirements. They must partition in the membrane, interact specifically with ions, shield them from the hydrocarbon core of the phospholipid bilayer, and transport ions from one side of the membrane to the other. All these attributes require amphipathic molecules in which the polar donor set used for ion recognition (usually oxygens for cations and hydrogen bond donors for anions) is arranged on a lipophilic organic scaffold. Playing with these two structural motifs, donor atoms and scaffolds, researchers have constructed a variety of different ionophores, and we describe a subset of interesting examples in this Account. Despite the ample structural diversity, structure/activity relationships studies reveal common features. Even when they include different hydrophilic moieties (oxyethylene chains, free hydroxyl, etc.) and scaffolds (steroid derivatives, neutral or polar macrocycles, etc.), amphipathic molecules, that cannot span the entire phospholipid bilayer, generate defects in the contact zone between the ionophore and the lipids and increase the permeability in the bulk membrane. Therefore, topologically complex structures that span the entire membrane are needed to elicit channel-like and ion selective behaviors. In particular the alternate-calix[4]arene macrocycle proved to be a versatile

  12. Dietary spices as beneficial modulators of lipid profile in conditions of metabolic disorders and diseases.

    PubMed

    Srinivasan, Krishnapura

    2013-04-25

    Spices are valued for their medicinal properties besides their use as food adjuncts to enhance the sensory quality of food. Dietary garlic, onion, fenugreek, red pepper, turmeric, and ginger have been proven to be effective hypocholesterolemics in experimentally induced hypercholesterolemia. The hypolipidemic potential of fenugreek in diabetic subjects and of garlic and onion in humans with induced lipemia has been demonstrated. Capsaicin and curcumin - the bioactive compounds of red pepper and turmeric - are documented to be efficacious at doses comparable to usual human intake. Capsaicin and curcumin have been shown to be hypotriglyceridemic, thus preventing accumulation of fat in the liver under adverse situations by enhancing triglyceride transport out of the liver. Capsaicin, curcumin, fenugreek, ginger, and onion enhance secretion of bile acids into bile. These hypocholesterolemic spices/spice principles reduce blood and liver cholesterol by enhancing cholesterol conversion to bile acids through activation of hepatic cholesterol-7α-hydroxylase. Many human trials have been carried out with garlic, onion, and fenugreek. The mechanism underlying the hypocholesterolemic and hypotriglyceridemic influence of spices is fairly well understood. Health implications of the hypocholesterolemic effect of spices experimentally documented are cardio-protection, protection of the structural integrity of erythrocytes by restoration of membrane cholesterol/phospholipid profile and prevention of cholesterol gallstones by modulation of the cholesterol saturation index in bile.

  13. The Mechanism of L-Arginine Modulates Signal Proteins Involved in Glucose and Lipid Metabolic Imbalance.

    PubMed

    Hu, Shengdi; Han, Meng; Rezaei, Arash; Li, Defa; Guoyao, W; Ma, Xi

    2016-06-26

    Type 2 diabetes has become a global public health problem affecting approximately 380 million people throughout the world. It can cause many complications and lead to greater mortality. At present, there is no available medicine for effectively preventing diabetes. L-arginine, a functional amino acid, the precursor of nitric oxide, plays a crucial role in maintenance, reproduction, growth, anti-aging and immunity in animals. Growing clinical evidence indicates that dietary L-arginine supplementation can reduce obesity, decrease arterial blood pressure, resist oxidation and normalize endothelial dysfunction to cause remission of type 2 diabetes. The potential molecular mechanism may play a role in modulating glucose homeostasis, promoting lipolysis, maintaining hormone level, ameliorating insulin resistance, and fetal programing in early stage. The possible signaling pathway of the beneficial effects of L-arginine likely involves L-arginine-nitric oxide pathway through which cell signal protein can be activated. Accumulating studies have indicated that L-arginine may have potential to prevent and/or relieve type 2 diabetes via restoring insulin sensitivity in vivo.

  14. The P-glycoprotein Inhibitor GF120918 Modulates Ca2+-Dependent Processes and Lipid Metabolism in Toxoplasma Gondii

    PubMed Central

    Bottova, Iveta; Sauder, Ursula; Olivieri, Vesna; Hehl, Adrian B.; Sonda, Sabrina

    2010-01-01

    Up-regulation of the membrane-bound efflux pump P-glycoprotein (P-gp) is associated with the phenomenon of multidrug-resistance in pathogenic organisms, including protozoan parasites. In addition, P-gp plays a role in normal physiological processes, however our understanding of these P-gp functions remains limited. In this study we investigated the effects of the P-gp inhibitor GF120918 in Toxoplasma gondii, a model apicomplexan parasite and an important human pathogen. We found that GF120918 treatment severely inhibited parasite invasion and replication. Further analyses of the molecular mechanisms involved revealed that the P-gp inhibitor modulated parasite motility, microneme secretion and egress from the host cell, all cellular processes known to depend on Ca2+ signaling in the parasite. In support of a potential role of P-gp in Ca2+-mediated processes, immunoelectron and fluorescence microscopy showed that T. gondii P-gp was localized in acidocalcisomes, the major Ca2+ storage in the parasite, at the plasma membrane, and in the intravacuolar tubular network. In addition, metabolic labeling of extracellular parasites revealed that inhibition or down-regulation of T. gondii P-gp resulted in aberrant lipid synthesis. These results suggest a crucial role of T. gondii P-gp in essential processes of the parasite biology and further validate the potential of P-gp activity as a target for drug development. PMID:20386707

  15. Postprandial lipemia in the elderly involves increased incorporation of ingested fat in plasma free fatty acids and small (Sf 20-400) triglyceride-rich lipoproteins.

    PubMed

    Puga, Guilherme M; Meyer, Christian; Everman, Sarah; Mandarino, Lawrence J; Katsanos, Christos S

    2011-08-01

    In the elderly, the rise in postprandial plasma triglyceride (TG) concentrations is increased, contributing to their increased risk of cardiovascular disease. We sought to determine the incorporation of ingested fat (whipping cream enriched with [1,1,1-(13)C]triolein) into plasma lipids during the postprandial period in six healthy elderly (67 ± 1 yr old) and six healthy young (23 ± 2 yr old) subjects. Blood and expired air samples were taken before and at 2-h intervals during the 8-h postprandial period. As expected, the area under the curve of postprandial plasma TG concentrations was larger in the elderly compared with the young subjects (152 ± 38 vs. 66 ± 27 mg·dl(-1)·h, P < 0.05). The incorporation of [(13)C]oleate in plasma free fatty acids (FFAs) and TG of the small (S(f) = 20-400) triglyceride-rich lipoprotein (TRL) fraction was significantly higher in the elderly compared with the young subjects, resulting in increased postprandial contributions of the ingested lipid to plasma FFAs (41 ± 3 vs. 26 ± 6%, P < 0.05) and the small TRL fraction (36 ± 5 vs. 21 ± 3%, P < 0.05) in elderly. Plasma apoB-100 concentration was higher, whereas the rate of oxidation of the ingested lipid was lower (P < 0.05) in the elderly. We conclude that increased postprandial lipemia in the elderly involves increased contribution of ingested lipid to the plasma small TRLs. This appears to be driven at least in part by increased appearance of the ingested fat as plasma FFA and increased availability of apo B-100 lipoproteins in the elderly.

  16. Postprandial lipemia in the elderly involves increased incorporation of ingested fat in plasma free fatty acids and small (Sf 20–400) triglyceride-rich lipoproteins

    PubMed Central

    Puga, Guilherme M.; Meyer, Christian; Everman, Sarah; Mandarino, Lawrence J.

    2011-01-01

    In the elderly, the rise in postprandial plasma triglyceride (TG) concentrations is increased, contributing to their increased risk of cardiovascular disease. We sought to determine the incorporation of ingested fat (whipping cream enriched with [1,1,1-13C]triolein) into plasma lipids during the postprandial period in six healthy elderly (67 ± 1 yr old) and six healthy young (23 ± 2 yr old) subjects. Blood and expired air samples were taken before and at 2-h intervals during the 8-h postprandial period. As expected, the area under the curve of postprandial plasma TG concentrations was larger in the elderly compared with the young subjects (152 ± 38 vs. 66 ± 27 mg·dl−1·h, P < 0.05). The incorporation of [13C]oleate in plasma free fatty acids (FFAs) and TG of the small (Sf = 20–400) triglyceride-rich lipoprotein (TRL) fraction was significantly higher in the elderly compared with the young subjects, resulting in increased postprandial contributions of the ingested lipid to plasma FFAs (41 ± 3 vs. 26 ± 6%, P < 0.05) and the small TRL fraction (36 ± 5 vs. 21 ± 3%, P < 0.05) in elderly. Plasma apoB-100 concentration was higher, whereas the rate of oxidation of the ingested lipid was lower (P < 0.05) in the elderly. We conclude that increased postprandial lipemia in the elderly involves increased contribution of ingested lipid to the plasma small TRLs. This appears to be driven at least in part by increased appearance of the ingested fat as plasma FFA and increased availability of apo B-100 lipoproteins in the elderly. PMID:21558545

  17. Protection by polyphenols of postprandial human plasma and low-density lipoprotein modification: the stomach as a bioreactor.

    PubMed

    Kanner, Joseph; Gorelik, Shlomit; Roman, Sirota; Kohen, Ron

    2012-09-12

    Recent studies dramatically showed that the removal of circulating modified low-density lipoprotein (LDL) results in complete prevention of atherosclerosis. The gastrointestinal tract is constantly exposed to food, some of it containing oxidized compounds. Lipid oxidation in the stomach was demonstrated by ingesting heated red meat in rats. Red wine polyphenols added to the rats' meat diet prevented lipid peroxidation in the stomach and absorption of malondialdehyde (MDA) in rat plasma. In humans, postprandial plasma MDA levels rose by 3-fold after a meal of red meat cutlets. MDA derived from meat consumption caused postprandial plasma LDL modification in human. The levels of plasma MDA showed a 75% reduction by consumption of red wine polyphenols during the meat meal. Locating the main biological site of action of polyphenols in the stomach led to a revision in the understanding of how antioxidants work in vivo and may help to elucidate the mechanism involved in the protective effects of polyphenols in human health.

  18. Wild blueberry (Vaccinium angustifolium)-enriched diet improves dyslipidaemia and modulates the expression of genes related to lipid metabolism in obese Zucker rats.

    PubMed

    Vendrame, Stefano; Daugherty, Allison; Kristo, Aleksandra S; Klimis-Zacas, Dorothy

    2014-01-28

    The present study investigated the potential of a wild blueberry (WB)-enriched diet to improve blood lipid profile and modulate the expression of genes related to lipid homeostasis in obese Zucker rats (OZR), a model of the metabolic syndrome with severe dyslipidaemia. For this purpose, twenty OZR and twenty lean Zucker rats (LZR; controls) were placed either on a control (C) or an 8 % WB diet for 8 weeks. Plasma total cholesterol (TC), HDL-cholesterol and TAG concentrations were determined. The relative expression of six genes involved in lipid metabolism was also determined in both the liver and the abdominal adipose tissue (AAT). Plasma TAG and TC concentrations were significantly lower in the OZR following WB consumption (4228 (sem 471) and 2287 (sem 125) mg/l, respectively) than in those on the C diet (5475 (sem 315) and 2631 (sem 129) mg/l, P< 0·05), while there was no change in HDL-cholesterol concentration. No significant effects were observed for plasma lipids in the LZR. Following WB consumption, the expression of the transcription factors PPARα and PPARγ in the OZR was increased in the AAT, while that of sterol regulatory element-binding protein 1 (SREBP-1) was decreased in the liver and AAT. The expression of fatty acid synthase was significantly decreased in both the liver and AAT and that of ATP-binding cassette transporter 1 was increased in the AAT following WB consumption. In conclusion, WB consumption appears to improve lipid profiles and modulate the expression of key enzymes and transcription factors of lipid metabolism in severely dyslipidaemic rats.

  19. Effects of Aerobic Exercise on Postprandial Carbohydrate and Lipoprotein Metabolism Following Cookie Ingestion in Healthy Young Women.

    PubMed

    Hashimoto, Sayuki; Mizutani, Erika; Suzuki, Maiko; Yoshida, Akihiro; Naito, Michitaka

    2015-01-01

    We examined the acute effects of postprandial aerobic exercise on glucose and lipid metabolism following cookie ingestion. Fifteen healthy young women with a sedentary lifestyle, normal weight and apolipoprotein E3/3 participated. After a 12-h overnight fast, each subject ingested a cookie (1.53 g/kg, Meal Test C) and then performed two trials, one with postprandial exercise (E trial) and one without exercise (C trial), in a randomized crossover design. A single 30-min bout of walking exercise was performed 20 min after the cookie intake. Venous blood samples were drawn before (0 h) and 20 min and 1, 2, 4, and 6 h after cookie ingestion. The Δglucose concentration was not significantly different between the two trials, but the Δinsulin concentration at 1 h and the incremental area under the curve (IAUC) (0-2 h)-insulin in the E trial were significantly lower than in the C trial. The ratio of glucose/insulin at 1 h was significantly higher in the E trial than in the C trial. The ΔTG, ΔRLP-TG, ΔapoB48 and ΔRemL-C concentrations at 1 h in the E trial were significantly higher than in the C trial. The IAUC (0-2 h)-apoB48 in the E trial was significantly larger than in the C trial. Postprandial exercise showed an insulin-sparing effect following the cookie ingestion by increasing insulin sensitivity. However, postprandial exercise transiently stimulated the secretion of exogenous apoB48-containing lipoprotein during the early period, and no further effects were observed. These results suggest that postprandial aerobic exercise is effective for the promotion of postprandial carbohydrate metabolism, but not lipidemia.

  20. Enhanced thermic effect of food, postprandial NEFA suppression and raised adiponectin in obese women who eat slowly.

    PubMed

    Reddy, Narendra L; Peng, Chenjing; Carreira, Marcos C; Halder, Louise; Hattersley, John; Piya, Milan K; Tripathi, Gyanendra; Randeva, Harpal S; Casanueva, Felipe F; McTernan, Philip G; Kumar, Sudhesh; Barber, Thomas M

    2015-06-01

    Meal duration may influence cardiometabolic health. The aim of this study was to explore postprandial effects of meal duration on human metabolism and appetite. Postprandial comparisons following a standard meal eaten slowly over 40 min ('D40') and the same meal eaten quickly over 10 min ('D10') on a different day. Each participant therefore acted as their own control, thereby limiting confounding factors. Obese premenopausal Caucasian women (n = 10) with confirmed normoglycaemia were recruited from an obesity clinic at UHCW, Coventry UK. Subjects underwent whole-body calorimetry (8-h) on two separate days. Following standard lunch (D40 vs D10), 4-h postprandial analysis included thermic effect of food (TEF) and bloods taken at predefined times (including baseline fasting). Analytes included lipid profile, adiponectin, insulin, glucose, ghrelin, leptin, endotoxin, gut and pancreatic hormones. Appetite was measured using visual-analogue scales and ad libitum food intake at subsequent meal. Paired sample t-tests [including area under the curve (AUC)] were used to compare D40 and D10 trials. Postprandial TEF (over 240-min) was significantly greater for D40 than D10 [mean (SEM): 80·9 kcal (3·8) vs 29·9 kcal (3·4); 10·6% vs 3·9%, respectively, P = 0·006; AUC 71·7 kcal.h vs 22·4 kcal.h, respectively, P = 0·02]. Postprandial plasma NEFA was significantly lower, and adiponectin levels were significantly higher for D40 than D10 [AUC (SEM): NEFA 627 μmol.h/l (56) vs 769 μmol.h/l (60), respectively, P = 0·02; adiponectin 33·4 μg.h/ml (3·9) vs 27·3 μg.h/ml (3·8), respectively, P = 0·04]. Other postprandial analytes and appetite measures were equivalent. In obese women, eating slowly associates with enhanced TEF, elevated serum adiponectin and suppressed NEFA. © 2015 John Wiley & Sons Ltd.

  1. An interesterified palm olein test meal decreases early-phase postprandial lipemia compared to palm olein: a randomized controlled trial.

    PubMed

    Hall, Wendy L; Brito, Marcela Fiuza; Huang, Junlan; Wood, Lucy V; Filippou, Androulla; Sanders, Thomas A B; Berry, Sarah E E

    2014-09-01

    Palm oil that has been interesterified to produce a higher proportion of palmitic acid (16:0) in the sn-2 position reduces postprandial lipemia in young, normolipidemic men and women, but effects in older subjects with higher fasting triacylglycerol (TAG) concentrations are unknown. We tested the hypothesis that high-fat meals rich in interesterified palm olein (IPO) decrease lipemia and alter plasma lipoprotein fraction composition compared to native palm olein (NPO) in men aged 40-70 years with fasting TAG concentrations ≥1.2 mmol/L. Postprandial changes in plasma lipids following meals containing 75 g fat (NPO and IPO) were compared using a randomized, double-blind crossover design (n = 11). Although there were no significant differences in plasma TAG concentrations between meals over the total 6-h postprandial measurement period, IPO resulted in a decreased plasma TAG response during the first 4 h of the postprandial period (iAUC 1.65 mmol/L h, 95% CI 1.01-2.29) compared to NPO (iAUC 2.33 mmol/L h, 95% CI 1.58-3.07); meal effect P = 0.024. Chylomicron fraction TAG concentrations at 4-6 h were slightly reduced following IPO compared to NPO [NPO-IPO mean difference 0.29 mmol/L (95% CI -0.01-0.59), P = 0.055]. There were no differences in IDL fraction TAG, cholesterol or apolipoprotein B48 concentrations following IPO compared with NPO. In conclusion, consuming a meal containing palm olein with a higher proportion of 16:0 in the sn-2 position decreases postprandial lipemia compared to native palm olein during the early phase of the postprandial period in men with higher than optimal fasting triacylglycerol concentrations.

  2. An apolipoprotein A-II polymorphism (-265T/C, rs5082), regulates postprandial response to a saturated fat overload in healthy men

    USDA-ARS?s Scientific Manuscript database

    Apolipoprotein (Apo) A-II is an apolipoprotein with an unknown role in lipid metabolism. It has been suggested that the presence of the less frequent allele of a single nucleotide polymorphism (Apo A-II -265T/C, rs5082) reduces the transcription rate of Apo A-II and enhances VLDL postprandial cleara...

  3. Urine Albumin Excretion as a Marker of Acute Glycemic Changes in Isolated Postprandial Hyperglycemia

    PubMed Central

    Shilpasree, Alagilawada S; Patil, Vidya S; Patil, Vijayetha P; Ingleshwar, Deepti G

    2017-01-01

    Introduction: Postprandial hyperglycemia is a major risk factor for the development of cardiovascular diseases (CVDs), and Most of the times it occurs in patients with normal glycemic control diagnosed by fasting blood glucose (FBG) and glycated hemoglobin levels. Urine albumin excretion (UAE) is an independent predictor of CVD risk. Aim: To estimate UAE in isolated postprandial hyperglycemia (IPPHG) patients and to assess the relationship of UAE with FBG and postprandial blood glucose (PPBG) levels. Settings and Design: A cross-sectional study was carried out in 318 patients with Type II diabetes in the age group 30–60 years for 6 months. Materials and Methods: Patients were divided into five groups based on their FBG and PPBG values. UAE and lipid profile were measured in all the groups. Statistical Analysis: UAE and lipid profile in different groups were compared using ANOVA. Regression analysis was used to predict the variation of UAE with FBG, PPBG, and total cholesterol (TC). Results: Patients with IPPHG had significantly higher albumin excretion compared to normoglycemia (NG) group [P < 0.0001]. In impaired glucose tolerance and isolated fasting hyperglycemia groups, it did not differ significantly from NG group [P = 0.206 and P = 0.173]. Lipid profile did not show any significant difference between the groups. On regression analysis, PPBG but not FBG or TC correlated positively with UAE. Conclusion: UAE is easy, less expensive, and Widely available method done on spot urine samples which predicts the acute glycemic changes and increased risk of developing CVDs in patients with IPPHG. PMID:28042215

  4. The influence of weight excess on the postprandial lipemia in adolescents

    PubMed Central

    2013-01-01

    Background Postprandial lipemia (PL) in adults has been extensively studied, but little explored in youth. The aim of this study was to evaluate the influence of weight excess on postprandial lipemia in adolescents. Methods Eighty-three adolescents were classified into Groups 1 (n= 49, overweight) and 2 (n=34, eutrophic). Total cholesterol (TC), triglycerides (TG), HDL and LDL cholesterol were measured before, 2 and 4 hours after a standardized 25 g lipid and 25 g of carbohydrate test meal; glycemia and insulin measured only at baseline. Anthropometric evaluation was performed. Results Basal TG were higher in Group 1 (p= 0.022). The total increase (Δ-TG), corresponding to the difference between the maximum and the basal TG level was similar in both groups (29.8 ± 21.5 mg/dl vs. 28.2 ± 24.5 mg/dl, p= 0.762). TC, HDL and LDL did not change significantly throughout the test. By analyzing all the adolescents together, the waist circumference was positively correlated with TG at fasting (r = 0.223; p= 0.044) and at 4 hours (r = 0.261; p= 0.019). Only overweight adolescents with hypertriglyceridemia, who also had higher HOMA-IR, presented significant elevation of TG levels 2 and 4 hours after the overload. Conclusion The behavior of lipoproteins in the post-prandial state is similar in eutrophic and overweight adolescents. Thus, apparently the weight excess does not induce post prandial lipemic alterations. PMID:23406056

  5. Specific polyunsaturated fatty acids modulate lipid delivery and oocyte development in C. elegans revealed by molecular-selective label-free imaging

    NASA Astrophysics Data System (ADS)

    Chen, Wei-Wen; Yi, Yung-Hsiang; Chien, Cheng-Hao; Hsiung, Kuei-Ching; Ma, Tian-Hsiang; Lin, Yi-Chun; Lo, Szecheng J.; Chang, Ta-Chau

    2016-08-01

    Polyunsaturated fatty acids (PUFAs) exhibit critical functions in biological systems and their importance during animal oocyte maturation has been increasingly recognized. However, the detailed mechanism of lipid transportation for oocyte development remains largely unknown. In this study, the transportation of yolk lipoprotein (lipid carrier) and the rate of lipid delivery into oocytes in live C. elegans were examined for the first time by using coherent anti-Stokes Raman scattering (CARS) microscopy. The accumulation of secreted yolk lipoprotein in the pseudocoelom of live C. elegans can be detected by CARS microscopy at both protein (~1665 cm‑1) and lipid (~2845 cm‑1) Raman bands. In addition, an image analysis protocol was established to quantitatively measure the levels of secreted yolk lipoprotein aberrantly accumulated in PUFA-deficient fat mutants (fat-1, fat-2, fat-3, fat-4) and PUFA-supplemented fat-2 worms (the PUFA add-back experiments). Our results revealed that the omega-6 PUFAs, not omega-3 PUFAs, play a critical role in modulating lipid/yolk level in the oocytes and regulating reproductive efficiency of C. elegans. This work demonstrates the value of using CARS microscopy as a molecular-selective label-free imaging technique for the study of PUFA regulation and oocyte development in C. elegans.

  6. Specific polyunsaturated fatty acids modulate lipid delivery and oocyte development in C. elegans revealed by molecular-selective label-free imaging

    PubMed Central

    Chen, Wei-Wen; Yi, Yung-Hsiang; Chien, Cheng-Hao; Hsiung, Kuei-Ching; Ma, Tian-Hsiang; Lin, Yi-Chun; Lo, Szecheng J.; Chang, Ta-Chau

    2016-01-01

    Polyunsaturated fatty acids (PUFAs) exhibit critical functions in biological systems and their importance during animal oocyte maturation has been increasingly recognized. However, the detailed mechanism of lipid transportation for oocyte development remains largely unknown. In this study, the transportation of yolk lipoprotein (lipid carrier) and the rate of lipid delivery into oocytes in live C. elegans were examined for the first time by using coherent anti-Stokes Raman scattering (CARS) microscopy. The accumulation of secreted yolk lipoprotein in the pseudocoelom of live C. elegans can be detected by CARS microscopy at both protein (~1665 cm−1) and lipid (~2845 cm−1) Raman bands. In addition, an image analysis protocol was established to quantitatively measure the levels of secreted yolk lipoprotein aberrantly accumulated in PUFA-deficient fat mutants (fat-1, fat-2, fat-3, fat-4) and PUFA-supplemented fat-2 worms (the PUFA add-back experiments). Our results revealed that the omega-6 PUFAs, not omega-3 PUFAs, play a critical role in modulating lipid/yolk level in the oocytes and regulating reproductive efficiency of C. elegans. This work demonstrates the value of using CARS microscopy as a molecular-selective label-free imaging technique for the study of PUFA regulation and oocyte development in C. elegans. PMID:27535493

  7. Lipid antigens in immunity

    PubMed Central

    Dowds, C. Marie; Kornell, Sabin-Christin

    2014-01-01

    Lipids are not only a central part of human metabolism but also play diverse and critical roles in the immune system. As such, they can act as ligands of lipid-activated nuclear receptors, control inflammatory signaling through bioactive lipids such as prostaglandins, leukotrienes, lipoxins, resolvins, and protectins, and modulate immunity as intracellular phospholipid- or sphingolipid-derived signaling mediators. In addition, lipids can serve as antigens and regulate immunity through the activation of lipid-reactive T cells, which is the topic of this review. We will provide an overview of the mechanisms of lipid antigen presentation, the biology of lipid-reactive T cells, and their contribution to immunity. PMID:23999493

  8. Comparative study of the modulation of fructose/sucrose-induced hepatic steatosis by mixed lipid formulations varying in unsaturated fatty acid content.

    PubMed

    Siddiqui, Rafat A; Xu, Zhidong; Harvey, Kevin A; Pavlina, Thomas M; Becker, Michael J; Zaloga, Gary P

    2015-01-01

    steatosis, with fructose being more potent. All mixed lipids similarly inhibited steatosis, limiting lipid content to levels found in the control (starch) animals. Lipogenesis and stearoyl-CoA-1 desaturase activity were increased in the sucrose and fructose groups. Levels of these enzymatic processes remained at baseline in all of the lipid groups. This is the first study to compare various complex lipid mixtures, based upon dietary oils with different types of long-chain fatty acids, upon development of sucrose/fructose-induced steatosis. Both carbohydrate source and lipid content appear important for the modulation of steatosis. Moderate intake of complex lipids with high unsaturated to saturated fatty acid ratios inhibited both lipogenesis and steatosis.

  9. In vitro curcumin modulates ferric nitrilotriacetate (Fe-NTA) and hydrogen peroxide (H2O2)-induced peroxidation of microsomal membrane lipids and DNA damage.

    PubMed

    Iqbal, Mohammad; Okazaki, Yasumasa; Okada, Shigeru

    2003-01-01

    A number of investigations have implicated the involvement of free radicals in various pathogenic process including initiation/promotion stages of carcinogenesis and antioxidants have been considered to be a protective agent for this reason. An iron chelate, ferric nitrilotriacetate (Fe-NTA), is a potent nephrotoxic agent and induces acute and subacute renal proximal tubular necrosis by catalyzing the decomposition of hydrogen peroxide-derived production of hydroxyl radicals, which are known to cause lipid peroxidation and DNA damage. The latter is associated with a high incidence of renal adenocarcinoma in rodents. Lipid peroxidation and DNA damage are the principal manifestation of Fe-NTA-induced toxicity, which could be mitigated by antioxidants. In this study, we therefore investigated the effect of curcumin, a polyphenolic compound from Curcuma longa for a possible protection against lipid peroxidation and DNA damage induced by Fe-NTA and hydrogen peroxide in vitro. Incubation of renal microsomal membrane/and or calf thymus DNA with hydrogen peroxide (40 mM) in the presence of Fe-NTA (0.1 mM) induces renal microsomal lipid peroxidation and DNA damage to about 2.2-and 5.6-fold, respectively, as compared to saline treated control (P<0.001). Induction of renal microsomal lipid peroxidation and DNA damage was modulated by curcumin dose dependently. In lipid peroxidation protection studies, curcumin treatment showed a dose-dependent strong inhibition (18-80% inhibition, P<0.05-0.001) of Fe-NTA and hydrogen peroxide-induced lipid peroxidation as measured by MDA formation in renal microsomes. Similarly, in DNA-sugar damage protection studies, curcumin treatment also showed a dose dependent inhibition (22-57% inhibition, P<0.05-0.001) of DNA-sugar damage. From these studies, it was concluded that curcumin modulates Fe-NTA and hydrogen peroxide-induced peroxidation of microsomal membrane lipids and DNA damage. Curcumin might, therefore, be a suitable candidate for the

  10. Epigenetic modulation of the biophysical properties of drug-resistant cell lipids to restore drug transport and endocytic functions.

    PubMed

    Vijayaraghavalu, Sivakumar; Peetla, Chiranjeevi; Lu, Shan; Labhasetwar, Vinod

    2012-09-04

    In our recent studies exploring the biophysical characteristics of resistant cell lipids, and the role they play in drug transport, we demonstrated the difference of drug-resistant breast cancer cells from drug-sensitive cells in lipid composition and biophysical properties, suggesting that cancer cells acquire a drug-resistant phenotype through the alteration of lipid synthesis to inhibit intracellular drug transport to protect from cytotoxic effect. In cancer cells, epigenetic changes (e.g., DNA hypermethylation) are essential to maintain this drug-resistant phenotype. Thus, altered lipid synthesis may be linked to epigenetic mechanisms of drug resistance. We hypothesize that reversing DNA hypermethylation in resistant cells with an epigenetic drug could alter lipid synthesis, changing the cell membrane's biophysical properties to facilitate drug delivery to overcome drug resistance. Herein we show that treating drug-resistant breast cancer cells (MCF-7/ADR) with the epigenetic drug 5-aza-2'-deoxycytidine (decitabine) significantly alters cell lipid composition and biophysical properties, causing the resistant cells to acquire biophysical characteristics similar to those of sensitive cell (MCF-7) lipids. Following decitabine treatment, resistant cells demonstrated increased sphingomyelinase activity, resulting in a decreased sphingomyelin level that influenced lipid domain structures, increased membrane fluidity, and reduced P-glycoprotein expression. Changes in the biophysical characteristics of resistant cell lipids facilitated doxorubicin transport and restored endocytic function for drug delivery with a lipid-encapsulated form of doxorubicin, enhancing the drug efficacy. In conclusion, we have established a new mechanism for efficacy of an epigenetic drug, mediated through changes in lipid composition and biophysical properties, in reversing cancer drug resistance.

  11. Expression profile of malignant and nonmalignant lesions of esophagus and stomach: differential activity of functional modules related to inflammation and lipid metabolism.

    PubMed

    Gomes, Luciana I; Esteves, Gustavo H; Carvalho, Alex F; Cristo, Elier B; Hirata, Roberto; Martins, Waleska K; Marques, Sarah M; Camargo, Luiz P; Brentani, Helena; Pelosof, Adriane; Zitron, Cláudia; Sallum, Rubens A; Montagnini, André; Soares, Fernando A; Neves, E Jordão; Reis, Luiz F L

    2005-08-15

    Adenocarcinomas of stomach and esophagus are frequently associated with preceding inflammatory alterations of the normal mucosa. Whereas intestinal metaplasia of the gastric mucosa is associated with higher risk of malignization, Barrett's disease is a risk factor for adenocarcinoma of the esophagus. Barrett's disease is characterized by the substitution of the squamous mucosa of the esophagus by a columnar tissue classified histopathologically as intestinal metaplasia. Using cDNA microarrays, we determined the expression profile of normal gastric and esophageal mucosa as well as intestinal metaplasia and adenocarcinomas from both organs. Data were explored to define functional alterations related to the transformation from squamous to columnar epithelium and the malignant transformation from intestinal metaplasia to adenocarcinomas. Based on their expression profile, adenocarcinomas of the esophagus showed stronger correlation with intestinal metaplasia of the stomach than with Barrett's mucosa. Second, we identified two functional modules, lipid metabolism and cytokine, as being altered with higher statistical significance. Whereas the lipid metabolism module is active in samples representing intestinal metaplasia and inactive in adenocarcinomas, the cytokine module is inactive in samples representing normal esophagus and esophagitis. Using the concept of relevance networks, we determined the changes in linear correlation of genes pertaining to these two functional modules. Exploitation of the data presented herein will help in the precise molecular characterization of adenocarcinoma from the distal esophagus, avoiding the topographical and descriptive classification that is currently adopted, and help with the proper management of patients with Barrett's disease.

  12. Femoral lipectomy increases postprandial lipemia in women

    PubMed Central

    Hernandez, Teri L.; Bessesen, Daniel H.; Cox-York, Kimberly A.; Erickson, Christopher B.; Law, Christopher K.; Anderson, Molly K.; Wang, Hong; Jackman, Matthew R.

    2015-01-01

    Femoral subcutaneous adipose tissue (SAT) appears to be cardioprotective compared with abdominal SAT, possibly through better triglyceride (TG) sequestration. We hypothesized that removal of femoral SAT would increase postprandial TG through a reduction in dietary fatty acid (FA) storage. Normal-weight (means ± SD; BMI 23.9 ± 2.6 kg/m2) women (n = 29; age 45 ± 6 yr) were randomized to femoral lipectomy (LIPO) or control (CON) and followed for 1 yr. Regional adiposity was measured by DEXA and CT. A liquid meal labeled with [14C]oleic acid was used to trace the appearance of dietary FA in plasma (6-h postprandial TG), breath (24-h oxidation), and SAT (24-h [14C]TG storage). Fasting LPL activity was measured in abdominal and femoral SAT. DEXA leg fat mass was reduced after LIPO vs. CON (Δ−1.4 ± 0.7 vs. 0.1 ± 0.5 kg, P < 0.001) and remained reduced at 1 yr (−1.1 ± 1.4 vs. −0.2 ± 0.5 kg, P < 0.05), as did CT thigh subcutaneous fat area (−39.6 ± 36.6 vs. 4.7 ± 14.6 cm2, P < 0.05); DEXA trunk fat mass and CT visceral fat area were unchanged. Postprandial TG increased (5.9 ± 7.7 vs. −0.6 ± 5.3 × 103 mg/dl, P < 0.05) and femoral SAT LPL activity decreased (−21.9 ± 22.3 vs. 10.5 ± 26.5 nmol·min−1·g−1, P < 0.05) 1 yr following LIPO vs. CON. There were no group differences in 14C-labeled TG appearing in abdominal and femoral SAT or elsewhere. In conclusion, femoral fat remained reduced 1 yr following lipectomy and was accompanied by increased postprandial TG and reduced femoral SAT LPL activity. There were no changes in storage of meal-derived FA or visceral fat. Our data support a protective role for femoral adiposity on circulating TG independent of dietary FA storage and visceral adiposity. PMID:25968576

  13. Protective effects of tocotrienols against lipid-induced nephropathy in experimental type-2 diabetic rats by modulation in TGF-β expression.

    PubMed

    Siddiqui, Shabeena; Ahsan, Haseeb; Khan, Mohammad Rashid; Siddiqui, Waseem A

    2013-12-01

    Dyslipidemia is common in patients with diabetes mellitus (DM) and is considered a risk factor for the progression of diabetic nephropathy (DN). Hyperlipidemia and hyperglycemia act synergistically to induce renal injury. The present study was designed to investigate the protective effects of tocotrienols as tocotrienol-rich fraction (TRF) extracted from palm (PO) and rice bran oils (RBO) against lipid induced nephropathy in type-2 diabetic rats and its probable molecular mechanism. Male Wistar rats (175-200 g) were divided into four groups. The first group served as diabetic control, while the second and third groups received PO-TRF and RBO-TRF, respectively by gavage over a period of sixteen weeks post-induction of diabetes. The fourth group comprised of age-matched rats that served as normal control. The effects of TRF on serum lipid profile, oxidative stress markers, expression of TGF-β, fibronectin and collagen type IV were analyzed in the kidney of diabetic rats. Treatment with PO-TRF and RBO-TRF significantly improved glycemic status, serum lipid profile and renal function in type-2 diabetic rats. In addition, TRF supplementation down-regulated the expression of TGF-β, fibronectin and collagen type IV in the kidney of diabetic rats. Transforming growth factor-β (TGF-β) plays a critical role in progression of DN, but its modulation by tocotrienols in DN remains unexplored. TRF ameliorated lipid induced nephropathy in type-2 diabetes by its hypoglycemic, hypolipidemic and antioxidant activities as well as by modulation of TGF-β to prevent increased expression of collagen type IV and fibrinogen. We finally propose a mechanism for the expression of molecular markers that are significant in the events leading to diabetic nephropathy and its modulation by tocotrienols/TRF.

  14. Modulation of folding and assembly of the membrane protein bacteriorhodopsin by intermolecular forces within the lipid bilayer.

    PubMed

    Curran, A R; Templer, R H; Booth, P J

    1999-07-20

    Three different lipid systems have been developed to investigate the effect of physicochemical forces within the lipid bilayer on the folding of the integral membrane protein bacteriorhodopsin. Each system consists of lipid vesicles containing two lipid species, one with phosphatidylcholine and the other with phosphatidylethanolamine headgroups, but the same hydrocarbon chains: either L-alpha-1, 2-dioleoyl, L-alpha-1,2-dipalmitoleoyl, or L-alpha-1,2-dimyristoyl. Increasing the mole fraction of the phosphatidylethanolamine lipid increases the desire of each monolayer leaflet in the bilayer to curve toward water. This increases the torque tension of such monolayers, when they are constrained to remain flat in the vesicle bilayer. Consequently, the lateral pressure in the hydrocarbon chain region increases, and we have used excimer fluorescence from pyrene-labeled phosphatidylcholine lipids to probe these pressure changes. We show that bacteriorhodopsin regenerates to about 95% yield in vesicles of 100% phosphatidylcholine. The regeneration yield decreases as the mole fraction of the corresponding phosphatidylethanolamine component is increased. The decrease in yield correlates with the increase in lateral pressure which the lipid chains exert on the refolding protein. We suggest that the increase in lipid chain pressure either hinders insertion of the denatured state of bacterioopsin into the bilayer or slows a folding step within the bilayer, to the extent that an intermediate involved in bacteriorhodopsin regeneration is effectively trapped.

  15. The PPARα agonist fenofibrate suppresses B-cell lymphoma in mice by modulating lipid metabolism☆☆☆

    PubMed Central

    Huang, Jianfeng; Das, Suman Kumar; Jha, Pooja; Al Zoughbi, Wael; Schauer, Silvia; Claudel, Thierry; Sexl, Veronika; Vesely, Paul; Birner-Gruenberger, Ruth; Kratky, Dagmar; Trauner, Michael; Hoefler, Gerald

    2013-01-01

    Obesity is associated with an increased risk for malignant lymphoma development. We used Bcr/Abl transformed B cells to determine the impact of aggressive lymphoma formation on systemic lipid mobilization and turnover. In wild-type mice, tumor size significantly correlated with depletion of white adipose tissues (WAT), resulting in increased serum free fatty acid (FFA) concentrations which promote B-cell proliferation in vitro. Moreover, B-cell tumor development induced hepatic lipid accumulation due to enhanced hepatic fatty acid (FA) uptake and impaired FA oxidation. Serum triglyceride, FFA, phospholipid and cholesterol levels were significantly elevated. Consistently, serum VLDL/LDL-cholesterol and apolipoprotein B levels were drastically increased. These findings suggest that B-cell tumors trigger systemic lipid mobilization from WAT to the liver and increase VLDL/LDL release from the liver to promote tumor growth. Further support for this concept stems from experiments where we used the peroxisome proliferator-activated receptor α (PPARα) agonist and lipid-lowering drug fenofibrate that significantly suppressed tumor growth independent of angiogenesis and inflammation. In addition to WAT depletion, fenofibrate further stimulated FFA uptake by the liver and restored hepatic FA oxidation capacity, thereby accelerating the clearance of lipids released from WAT. Furthermore, fenofibrate blocked hepatic lipid release induced by the tumors. In contrast, lipid utilization in the tumor tissue itself was not increased by fenofibrate which correlates with extremely low expression levels of PPARα in B-cells. Our data show that fenofibrate associated effects on hepatic lipid metabolism and deprivation of serum lipids are capable to suppress B-cell lymphoma growth which may direct novel treatment strategies. This article is part of a Special Issue entitled Lipid Metabolism in Cancer. PMID:23628473

  16. Nocardia brasiliensis Cell Wall Lipids Modulate Macrophage and Dendritic Responses That Favor Development of Experimental Actinomycetoma in BALB/c Mice

    PubMed Central

    Trevino-Villarreal, J. Humberto; Vera-Cabrera, Lucio; Valero-Guillén, Pedro L.

    2012-01-01

    Nocardia brasiliensis is a Gram-positive facultative intracellular bacterium frequently isolated from human actinomycetoma. However, the pathogenesis of this infection remains unknown. Here, we used a model of bacterial delipidation with benzine to investigate the role of N. brasiliensis cell wall-associated lipids in experimental actinomycetoma. Delipidation of N. brasiliensis with benzine resulted in complete abolition of actinomycetoma without affecting bacterial viability. Chemical analyses revealed that trehalose dimycolate and an unidentified hydrophobic compound were the principal compounds extracted from N. brasiliensis with benzine. By electron microscopy, the extracted lipids were found to be located in the outermost membrane layer of the N. brasiliensis cell wall. They also appeared to confer acid-fastness. In vitro, the extractable lipids from the N. brasiliensis cell wall induced the production of the proinflammatory cytokines interleukin-1β (IL-1β), IL-6, and CCL-2 in macrophages. The N. brasiliensis cell wall extractable lipids inhibited important macrophage microbicidal effects, such as tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) production, phagocytosis, bacterial killing, and major histocompatibility complex class II (MHC-II) expression in response to gamma interferon (IFN-γ). In dendritic cells (DCs), N. brasiliensis cell wall-associated extractable lipids suppressed MHC-II, CD80, and CD40 expression while inducing tumor growth factor β (TGF-β) production. Immunization with delipidated N. brasiliensis induced partial protection preventing actinomycetoma. These findings suggest that N. brasiliensis cell wall-associated lipids are important for actinomycetoma development by inducing inflammation and modulating the responses of macrophages and DCs to N. brasiliensis. PMID:22851755

  17. Cancer-preventive rexinoid modulates neutral lipid contents of mammary epithelial cells through a peroxisome proliferator-activated receptor γ-dependent mechanism.

    PubMed

    Uray, Iván P; Rodenberg, Jennifer M; Bissonnette, Reid P; Brown, Powel H; Mancini, Michael A

    2012-02-01

    Synthetic rexinoids effectively suppress both estrogen receptor-positive and estrogen receptor-negative mammary tumors in animal models, which makes them prime candidates for a novel class of cancer-preventive agents. When used in combination with chemotherapy for non-small-cell lung cancer, the rexinoid bexarotene was most effective for patients who developed hypertriglyceridemia as a side effect. Although serum triglycerides originate from the liver, the effect of bexarotene on lipogenesis in breast epithelial cells is not known. Gene expression studies with normal mammary epithelial cells indicated that rexinoids modulate lipid metabolism, particularly enzymes involved in triglyceride synthesis. High-content analysis revealed dose-dependent accumulation of neutral lipids within adipocyte differentiation-related protein-associated cytoplasmic lipid droplets after long-term bexarotene treatment. Bexarotene also induced mRNA and protein levels for peroxisome proliferator-activated receptor (PPAR) γ, whereas selective knockdown of PPARγ attenuated the induction of both lipid droplets and adipocyte differentiation-related protein. Pharmacological activation of PPARγ, but not PPARα or retinoic acid receptors, effectively induced lipid accumulation. Furthermore, the combination of the PPARγ agonist rosiglitazone with bexarotene synergistically suppressed the growth of human mammary epithelial cells and revealed a strong, nonlinear, inverse correlation of cell growth with lipid droplet accumulation in the cell population. These findings indicate that rexinoids activate a lipogenic program in mammary epithelial cells through a retinoid X receptor/PPARγ-mediated mechanism. It is noteworthy that combining low doses of bexarotene with the PPARγ agonist rosiglitazone provides effective growth suppression of mammary epithelial cells, potentially dissociating systemic adverse effects associated with standard bexarotene treatment from the antiproliferative effects on

  18. PPP2R5C Couples Hepatic Glucose and Lipid Homeostasis

    PubMed Central

    Cheng, Yong-Sheng; Seibert, Oksana; Klöting, Nora; Dietrich, Arne; Straßburger, Katrin; Fernández-Veledo, Sonia; Vendrell, Joan J.; Zorzano, Antonio; Blüher, Matthias; Herzig, Stephan; Berriel Diaz, Mauricio; Teleman, Aurelio A.

    2015-01-01

    In mammals, the liver plays a central role in maintaining carbohydrate and lipid homeostasis by acting both as a major source and a major sink of glucose and lipids. In particular, when dietary carbohydrates are in excess, the liver converts them to lipids via de novo lipogenesis. The molecular checkpoints regulating the balance between carbohydrate and lipid homeostasis, however, are not fully understood. Here we identify PPP2R5C, a regulatory subunit of PP2A, as a novel modulator of liver metabolism in postprandial physiology. Inactivation of PPP2R5C in isolated hepatocytes leads to increased glucose uptake and increased de novo lipogenesis. These phenotypes are reiterated in vivo, where hepatocyte specific PPP2R5C knockdown yields mice with improved systemic glucose tolerance and insulin sensitivity, but elevated circulating triglyceride levels. We show that modulation of PPP2R5C levels leads to alterations in AMPK and SREBP-1 activity. We find that hepatic levels of PPP2R5C are elevated in human diabetic patients, and correlate with obesity and insulin resistance in these subjects. In sum, our data suggest that hepatic PPP2R5C represents an important factor in the functional wiring of energy metabolism and the maintenance of a metabolically healthy state. PMID:26440364

  19. PPP2R5C Couples Hepatic Glucose and Lipid Homeostasis.

    PubMed

    Cheng, Yong-Sheng; Seibert, Oksana; Klöting, Nora; Dietrich, Arne; Straßburger, Katrin; Fernández-Veledo, Sonia; Vendrell, Joan J; Zorzano, Antonio; Blüher, Matthias; Herzig, Stephan; Berriel Diaz, Mauricio; Teleman, Aurelio A

    2015-10-01

    In mammals, the liver plays a central role in maintaining carbohydrate and lipid homeostasis by acting both as a major source and a major sink of glucose and lipids. In particular, when dietary carbohydrates are in excess, the liver converts them to lipids via de novo lipogenesis. The molecular checkpoints regulating the balance between carbohydrate and lipid homeostasis, however, are not fully understood. Here we identify PPP2R5C, a regulatory subunit of PP2A, as a novel modulator of liver metabolism in postprandial physiology. Inactivation of PPP2R5C in isolated hepatocytes leads to increased glucose uptake and increased de novo lipogenesis. These phenotypes are reiterated in vivo, where hepatocyte specific PPP2R5C knockdown yields mice with improved systemic glucose tolerance and insulin sensitivity, but elevated circulating triglyceride levels. We show that modulation of PPP2R5C levels leads to alterations in AMPK and SREBP-1 activity. We find that hepatic levels of PPP2R5C are elevated in human diabetic patients, and correlate with obesity and insulin resistance in these subjects. In sum, our data suggest that hepatic PPP2R5C represents an important factor in the functional wiring of energy metabolism and the maintenance of a metabolically healthy state.

  20. Profiling the Oxylipin and Endocannabinoid Metabolome by UPLC-ESI-MS/MS in Human Plasma to Monitor Postprandial Inflammation

    PubMed Central

    Gouveia-Figueira, Sandra; Späth, Jana; Zivkovic, Angela M.; Nording, Malin L.

    2015-01-01

    Bioactive lipids, including oxylipins, endocannabinoids, and related compounds may function as specific biochemical markers of certain aspects of inflammation. However, the postprandial responsiveness of these compounds is largely unknown; therefore, changes in the circulating oxylipin and endocannabinoid metabolome in response to a challenge meal were investigated at six occasions in a subject who freely modified her usual diet. The dietary change, and especially the challenge meal itself, represented a modification of precursor fatty acid status, with expectedly subtle effects on bioactive lipid levels. To detect even the slightest alteration, highly sensitive ultra-performance liquid chromatography (UPLC) coupled to electrospray ionization (ESI) tandem mass spectrometry (MS/MS) methods for bioactive lipid profiling was employed. A previously validated UPLC-ESI-MS/MS method for profiling the endocannabinoid metabolome was used, while validation of an UPLC-ESI-MS/MS method for oxylipin analysis was performed with acceptable outcomes for a majority of the parameters according to the US Food and Drug Administration guidelines for linearity (0.9938 < R2 < 0.9996), limit of detection (0.0005–2.1 pg on column), limit of quantification (0.0005–4.2 pg on column), inter- and intraday accuracy (85–115%) and precision (< 5%), recovery (40–109%) and stability (40–105%). Forty-seven of fifty-two bioactive lipids were detected in plasma samples at fasting and in the postprandial state (0.5, 1, and 3 hours after the meal). Multivariate analysis showed a significant shift of bioactive lipid profiles in the postprandial state due to inclusion of dairy products in the diet, which was in line with univariate analysis revealing seven compounds (NAGly, 9-HODE, 13-oxo-ODE, 9(10)-EpOME, 12(13)-EpOME, 20-HETE, and 11,12-DHET) that were significantly different between background diets in the postprandial state (but not at fasting). The only change in baseline levels at fasting

  1. Protective effects of tocotrienols against lipid-induced nephropathy in experimental type-2 diabetic rats by modulation in TGF-β expression

    SciTech Connect

    Siddiqui, Shabeena; Ahsan, Haseeb; Khan, Mohammad Rashid; Siddiqui, Waseem A.

    2013-12-01

    Dyslipidemia is common in patients with diabetes mellitus (DM) and is considered a risk factor for the progression of diabetic nephropathy (DN). Hyperlipidemia and hyperglycemia act synergistically to induce renal injury. The present study was designed to investigate the protective effects of tocotrienols as tocotrienol-rich fraction (TRF) extracted from palm (PO) and rice bran oils (RBO) against lipid induced nephropathy in type-2 diabetic rats and its probable molecular mechanism. Male Wistar rats (175–200 g) were divided into four groups. The first group served as diabetic control, while the second and third groups received PO-TRF and RBO-TRF, respectively by gavage over a period of sixteen weeks post-induction of diabetes. The fourth group comprised of age-matched rats that served as normal control. The effects of TRF on serum lipid profile, oxidative stress markers, expression of TGF-β, fibronectin and collagen type IV were analyzed in the kidney of diabetic rats. Treatment with PO-TRF and RBO-TRF significantly improved glycemic status, serum lipid profile and renal function in type-2 diabetic rats. In addition, TRF supplementation down-regulated the expression of TGF-β, fibronectin and collagen type IV in the kidney of diabetic rats. Transforming growth factor-β (TGF-β) plays a critical role in progression of DN, but its modulation by tocotrienols in DN remains unexplored. TRF ameliorated lipid induced nephropathy in type-2 diabetes by its hypoglycemic, hypolipidemic and antioxidant activities as well as by modulation of TGF-β to prevent increased expression of collagen type IV and fibrinogen. We finally propose a mechanism for the expression of molecular markers that are significant in the events leading to diabetic nephropathy and its modulation by tocotrienols/TRF. - Highlights: • The nephroprotective effect of TRF in type-2 diabetic rats was investigated. • Treatment with TRF improved glycemic status, lipid profile and renal functions in rats

  2. Prostaglandin synthesis inhibition and postprandial intestinal hyperemia.

    PubMed

    Gallavan, R H; Chou, C C

    1982-02-01

    The effect of prostaglandin synthesis inhibition on the postprandial intestinal hyperemia was examined in the jejunum of anesthetized dogs. Both intravenous and intra-arterial infusion of the cyclooxygenase inhibitors indomethacin and mefenamic acid reduced resting jejunal blood flow and markedly enhanced the food-induced jejunal hyperemia. The jejunal vascular response to food did not change after either intravenous or intra-arterial infusion of the carrier solutions or intra-arterial infusion of angiotensin II. The enhancement of the jejunal hyperemia was associated with an increase in the food-induced increase in jejunal oxygen consumption. Infusion of the cyclooxygenase inhibitors increased the mean amplitude of the monophasic intestinal contractions; however, this did not appear to play a role in the enhancement of the food-induced hyperemia. The study indicates that inhibition of prostaglandin synthesis has a marked effect on the postprandial intestinal hyperemia and that this may be due to its enhancement of the jejunal metabolic response to food. The prostaglandins involved and their mechanism of action are unknown.

  3. Sterol carrier protein 2 regulates proximal tubule size in the Xenopus pronephric kidney by modulating lipid rafts.

    PubMed

    Cerqueira, Débora M; Tran, Uyen; Romaker, Daniel; Abreu, José G; Wessely, Oliver

    2014-10-01

    The kidney is a homeostatic organ required for waste excretion and reabsorption of water, salts and other macromolecules. To this end, a complex series of developmental steps ensures the formation of a correctly patterned and properly proportioned organ. While previous studies have mainly focused on the individual signaling pathways, the formation of higher order receptor complexes in lipid rafts is an equally important aspect. These membrane platforms are characterized by differences in local lipid and protein compositions. Indeed, the cells in the Xenopus pronephric kidney were positive for the lipid raft markers ganglioside GM1 and Caveolin-1. To specifically interfere with lipid raft function in vivo, we focused on the Sterol Carrier Protein 2 (scp2), a multifunctional protein that is an important player in remodeling lipid raft composition. In Xenopus, scp2 mRNA was strongly expressed in differentiated epithelial structures of the pronephric kidney. Knockdown of scp2 did not interfere with the patterning of the kidney along its proximo-distal axis, but dramatically decreased the size of the kidney, in particular the proximal tubules. This phenotype was accompanied by a reduction of lipid rafts, but was independent of the peroxisomal or transcriptional activities of scp2. Finally, disrupting lipid micro-domains by inhibiting cholesterol synthesis using Mevinolin phenocopied the defects seen in scp2 morphants. Together these data underscore the importance for localized signaling platforms in the proper formation of the Xenopus kidney.

  4. Scopoletin prevents alcohol-induced hepatic lipid accumulation by modulating the AMPK-SREBP pathway in diet-induced obese mice.

    PubMed

    Lee, Hae-In; Yun, Kyeong Won; Seo, Kown-Il; Kim, Myung-Joo; Lee, Mi-Kyung

    2014-04-01

    This study investigated the effects of scopoletin on alcohol-induced hepatic lipid accumulation in diet-induced obese mice and its mechanism. Alcohol (25% v/v, 5g/kg body weight) was orally administered once a day for 6 weeks to mice fed with a high-fat diet (35%kcal) with or without scopoletin (0.05%, wt/wt). Scopoletin reduced plasma acetaldehyde, fatty acid, total cholesterol, triglyceride and insulin levels, hepatic lipid and droplets and fasting blood glucose levels that were increased by alcohol. Scopoletin significantly activated hepatic AMPK and inhibited ACC and SREBP-1c and the activities of lipogenic enzymes, such as FAS, PAP and G6PD compared to the alcohol control group. Moreover, scopoletin significantly inhibited hepatic CYP2E1 activity and protein levels but elevated the activities of SOD, CAT, GSH-Px and GST and the levels of GSH compared to the alcohol control group. The hepatic lipid peroxide level was significantly lowered by scopoletin supplementation in alcohol-administered obese mice. Taken together, these results suggested that scopoletin can ameliorate alcohol-induced hepatic lipid accumulation by modulating AMPK-SREBP pathway-mediated lipogenesis in mice fed a high-fat diet. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Suitability of 3-point versus 7-point postprandial retinyl palmitate AUC in human bioavailability studies.

    PubMed

    Herrero-Barbudo, Carmen; Granado-Lorencio, Fernando; Olmedilla-Alonso, Begoña

    2008-02-01

    Bioavailability is a critical feature in the assessment of the role of micronutrients in human health. Although postprandial behaviour does not predict long-term responses and acute responses, it is accepted that the study of triglyceride-rich lipoprotein fractions reflects newly absorbed lipids from recent meals. To assess the predictive value of a 3-point versus 7-point post-prandial response (area under the curve) in nutrient bioavailability studies in humans. We used results from a human bioavailability study (n = 19) that consisted of a single-dose pharmacokinetic assay involving three types of commercially available vitamin A and E fortified milk. Correlation coefficients between 3-point AUC (AUCp, predictive) versus 7-point AUC (AUCc, conventional) ranged between r = 0.81 (P < 0.001) for vitamin A-fortified skim milk and r = 0.95 (P < 0.001) for whole milk. Bland-Altman representations showed a good agreement between the two methods with 95% of the differences within the concordance limits. More than 90% of the subjects were correctly classified in the same or adjacent quartiles and he calculated relative absorption of vitamin A from the foods was, on average, <5% lower using the AUCp compared to that estimated using AUCc. The use of the 3-point approach may be a reliable alternative to assess the relative postprandial lipid response in human bioavailability studies. Nevertheless, since this approach has been studied considering one nutrient (i.e. preformed vitamin A) and one type of food (i.e. milk), its applicability to other nutrients and foods should be tested.

  6. Postprandial morphological response of the intestinal epithelium of the Burmese python (Python molurus).

    PubMed

    Lignot, Jean-Hervé; Helmstetter, Cécile; Secor, Stephen M

    2005-07-01

    The postprandial morphological changes of the intestinal epithelium of Burmese pythons were examined using fasting pythons and at eight time points after feeding. In fasting pythons, tightly packed enterocytes possess very short microvilli and are arranged in a pseudostratified fashion. Enterocyte width increases by 23% within 24 h postfeeding, inducing significant increases in villus length and intestinal mass. By 6 days postfeeding, enterocyte volume had peaked, following as much as an 80% increase. Contributing to enterocyte hypertrophy is the cellular accumulation of lipid droplets at the tips and edges of the villi of the proximal and middle small intestine, but which were absent in the distal small intestine. At 3 days postfeeding, conventional and environmental scanning electron microscopy revealed cracks and lipid extrusion along the narrow edges of the villi and at the villus tips. Transmission electron microscopy demonstrated the rapid postprandial lengthening of enterocyte microvilli, increasing 4.8-fold in length within 24 h, and the maintaining of that length through digestion. Beginning at 24 h postfeeding, spherical particles were found embedded apically within enterocytes of the proximal and middle small intestine. These particles possessed an annular-like construction and were stained with the calcium-stain Alizarine red S suggesting that they were bone in origin. Following the completion of digestion, many of the postprandial responses were reversed, as observed by the atrophy of enterocytes, the shortening of villi, and the retraction of the microvilli. Further exploration of the python intestine will reveal the underlying mechanisms of these trophic responses and the origin and fate of the engulfed particles.

  7. Annotated compound data for modulators of detergent-solubilised or lipid-reconstituted respiratory type II NADH dehydrogenase activity obtained by compound library screening

    PubMed Central

    Dunn, Elyse A.; Cook, Gregory M.; Heikal, Adam

    2015-01-01

    The energy-generating membrane protein NADH dehydrogenase (NDH-2), a proposed antibacterial drug target (see “Inhibitors of type II NADH:menaquinone oxidoreductase represent a class of antitubercular drugs” Weinstein et al. 2005 [1]), was screened for modulators of activity in either detergent-solublised or lipid reconstituted (proteolipsome) form. Here we present an annotated list of compounds identified in a small-scale screen against NDH-2. The dataset contains information regarding the libraries screened, the identities of hit compounds and the physicochemical properties governing solubility and permeability. The implications of these data for future antibiotic discovery are discussed in our associated report, “Comparison of lipid and detergent enzyme environments for identifying inhibitors of membrane-bound energy-transducing proteins” [2]. PMID:26862571

  8. Annotated compound data for modulators of detergent-solubilised or lipid-reconstituted respiratory type II NADH dehydrogenase activity obtained by compound library screening.

    PubMed

    Dunn, Elyse A; Cook, Gregory M; Heikal, Adam

    2016-03-01

    The energy-generating membrane protein NADH dehydrogenase (NDH-2), a proposed antibacterial drug target (see "Inhibitors of type II NADH:menaquinone oxidoreductase represent a class of antitubercular drugs" Weinstein et al. 2005 [1]), was screened for modulators of activity in either detergent-solublised or lipid reconstituted (proteolipsome) form. Here we present an annotated list of compounds identified in a small-scale screen against NDH-2. The dataset contains information regarding the libraries screened, the identities of hit compounds and the physicochemical properties governing solubility and permeability. The implications of these data for future antibiotic discovery are discussed in our associated report, "Comparison of lipid and detergent enzyme environments for identifying inhibitors of membrane-bound energy-transducing proteins" [2].

  9. Dual modulation of both lipid oxidation and synthesis by peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -1beta in cultured myotubes.

    PubMed

    Espinoza, Daniel O; Boros, Laszlo G; Crunkhorn, Sarah; Gami, Hiral; Patti, Mary-Elizabeth

    2010-04-01

    The peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family is a key regulator of mitochondrial function, and reduced mRNA expression may contribute to muscle lipid accumulation in obesity and type 2 diabetes. To characterize the effects of PGC-1 on lipid metabolism, we overexpressed PGC-1alpha and PGC-1beta in C2C12 myotubes using adenoviral vectors. Both PGC-1alpha and -1beta increased palmitate oxidation [31% (P<0.01) and 26% (P<0.05), respectively] despite reductions in cellular uptake [by 6% (P<0.05) and 21% (P<0.001)]. Moreover, PGC-1alpha and -1beta increased mRNA expression of genes regulating both lipid oxidation (e.g., CPT1b and ACADL/M) and synthesis (FAS, CS, ACC1/2, and DGAT1). To determine the net effect, we assessed lipid composition in PGC-1-expressing cells. Total lipid content decreased by 42% in palmitate-loaded serum-starved cells overexpressing PGC-1alpha (P<0.05). In contrast, in serum-replete cells, total lipid content was not significantly altered, but fatty acids C14:0, C16:0, C18:0, and C18:1 were increased 2- to 4-fold for PGC-1alpha/beta (P<0.05). Stable isotope-based dynamic metabolic profiling in serum-replete cells labeled with (13)C substrates revealed both increased de novo fatty acid synthesis from glucose and increased fatty acid synthesis by chain elongation with either PGC-1alpha or -1beta expression. These results indicate that PGC-1 can promote both lipid oxidation and synthesis, with net balance determined by the nutrient/hormonal environment.-Espinoza, D. O., Boros, L. G., Crunkhorn, S., Gami, H., Patti, M.-E. Dual Modulation of both lipid oxidation and synthesis by peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -1beta in cultured myotubes.

  10. Membrane lipid physical state and modulation of the Na+,Mg2+-ATPase activity in Acholeplasma laidlawii B.

    PubMed Central

    Silvius, J R; McElhaney, R N

    1980-01-01

    Careful analysis of the Arrhenius plot of the Na+,Mg2+-ATPase (ATP pyrophosphohydrolase, EC 3.6.1.8) activity in Acholeplasma laidlawii B membranes of varying fatty acid composition has been combined with differential thermal analysis of the membrane lipid phase transitions to evaluate the effects of membrane lipid properties on the enzyme activity. Our results indicate that the enzyme is active only in association with liquid-crystalline lipids, exhibiting a significant heat capacity of activation, delta Cp++, for the ATP hydrolytic reaction in this case. Quantitative analyses of Arrhenius plots for the enzyme activity in membranes whose lipids exhibit a gel-to-liquid-crystalline phase transition in the physiological temperature range suggest that the ATPase is inactivated when its boundary lipids undergo a phase transition that is driven by the bulk lipid phase transition but is less cooperative than the latter. Our results suggest that the familiar "biphasic linear" Arrhenius plots obtained for many membrane enzymes may in fact have a more complex shape, analysis of which can furnish useful information regarding the behavior of the enzyme molecule. Images PMID:6445554

  11. Fatty acids from VLDL lipolysis products induce lipid droplet accumulation in human monocytes

    PubMed Central

    den Hartigh, Laura J; Connolly-Rohrbach, Jaime E; Fore, Samantha; Huser, Thomas R; Rutledge, John C

    2010-01-01

    One mechanism by which monocytes become activated postprandially is by exposure to triglyceride (TG)-rich lipoproteins such as very low-density lipoproteins (VLDL). VLDL are hydrolyzed by lipoprotein lipase (LpL) at the blood-endothelial cell interface, releasing free fatty acids. In this study, we examined postprandial monocyte activation in more detail, and found that lipolysis products generated from postprandial VLDL induce the formation of lipid-filled droplets within cultured THP-1 monocytes, characterized by coherent anti-stokes Raman spectroscopy. Organelle-specific stains revealed an association of lipid droplets with the endoplasmic reticulum, confirmed by electron microscopy. Lipid droplet formation was reduced when LpL-released fatty acids were bound by bovine serum albumin, which also reduced cellular inflammation. Furthermore, saturated fatty acids induced more lipid droplet formation in monocytes compared to mono- and polyunsaturated fatty acids. Monocytes treated with postprandial VLDL lipolysis products contained lipid droplets with more intense saturated Raman spectroscopic signals than monocytes treated with fasting VLDL lipolysis products. In addition, we found that human monocytes isolated during the peak postprandial period contain more lipid droplets compared to those from the fasting state, signifying that their development is not limited to cultured cells but also occurs in vivo. In summary, circulating free fatty acids can mediate lipid droplet formation in monocytes and potentially be used as a biomarker to assess an individual’s risk of developing atherosclerotic cardiovascular disease. PMID:20208007

  12. Impact of postprandial glycaemia on health and prevention of disease

    PubMed Central

    Blaak, E E; Antoine, J-M; Benton, D; Björck, I; Bozzetto, L; Brouns, F; Diamant, M; Dye, L; Hulshof, T; Holst, J J; Lamport, D J; Laville, M; Lawton, C L; Meheust, A; Nilson, A; Normand, S; Rivellese, A A; Theis, S; Torekov, S S; Vinoy, S

    2012-01-01

    Postprandial glucose, together with related hyperinsulinemia and lipidaemia, has been implicated in the development of chronic metabolic diseases like obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). In this review, available evidence is discussed on postprandial glucose in relation to body weight control, the development of oxidative stress, T2DM, and CVD and in maintaining optimal exercise and cognitive performance. There is mechanistic evidence linking postprandial glycaemia or glycaemic variability to the development of these conditions or in the impairment in cognitive and exercise performance. Nevertheless, postprandial glycaemia is interrelated with many other (risk) factors as well as to fasting glucose. In many studies, meal-related glycaemic response is not sufficiently characterized, or the methodology with respect to the description of food or meal composition, or the duration of the measurement of postprandial glycaemia is limited. It is evident that more randomized controlled dietary intervention trials using effective low vs. high glucose response diets are necessary in order to draw more definite conclusions on the role of postprandial glycaemia in relation to health and disease. Also of importance is the evaluation of the potential role of the time course of postprandial glycaemia. PMID:22780564

  13. Postprandial Glucose as a Risk Factor for Elevated Intraocular Pressure

    PubMed Central

    Wu, Chen-Jung; Fang, Wen-Hui; Kao, Tung-Wei; Chen, Ying-Jen; Liaw, Fang-Yih; Chang, Yaw-Wen; Wang, Gia-Chi; Peng, Tao-Chun; Chen, Wei-Liang

    2016-01-01

    The aim of this study was to investigate the association between postprandial glucose and intraocular pressure in a relatively healthy population. We examined 1,439 adults getting a health check-up in a health promotion center at Tri-Service General Hospital (TSGH) in Taiwan between 2012 and 2013. All participants underwent examinations to measure metabolic variables and intraocular pressure. Multiple linear regression analyses were performed to assess the relationship between postprandial glucose and intraocular pressure. The levels of postprandial glucose were divided into quartiles with subjects in the lowest quartile being regarded as the reference group to perform quartile-based analysis. Covariate adjustment was designed for three models for further analysis. Subjects with higher quartiles of postprandial glucose level had a higher systolic blood pressure, a greater waist circumference and an elevated fasting glucose level (all p < 0.001). The β coefficient with adjusted covariates showed a significant positive association between postprandial glucose and intraocular pressure. The trends of intraocular pressure across increasing quartiles of postprandial glucose were statistically significant (all p for trend < 0.001). Thus, higher levels of postprandial glucose positively correlated with elevated intraocular pressure. PMID:27977733

  14. Effect of Cinnamon Tea on Postprandial Glucose Concentration

    PubMed Central

    Bernardo, Maria Alexandra; Santos, Elisabeth; Moncada, Margarida Maria; Singh, Jaipaul; de Mesquita, Maria Fernanda

    2015-01-01

    Glycaemic control, in particular at postprandial period, has a key role in prevention of different diseases, including diabetes and cardiovascular events. Previous studies suggest that postprandial high blood glucose levels (BGL) can lead to an oxidative stress status, which is associated with metabolic alterations. Cinnamon powder has demonstrated a beneficial effect on postprandial glucose homeostasis in animals and human models. The purpose of this study is to investigate the effect of cinnamon tea (C. burmannii) on postprandial capillary blood glucose level on nondiabetic adults. Participants were given oral glucose tolerance test either with or without cinnamon tea in a randomized clinical trial. The data revealed that cinnamon tea administration slightly decreased postprandial BGL. Cinnamon tea ingestion also results in a significantly lower postprandial maximum glucose concentration and variation of maximum glucose concentration (p < 0.05). Chemical analysis showed that cinnamon tea has a high antioxidant capacity, which may be due to its polyphenol content. The present study provides evidence that cinnamon tea, obtained from C. burmannii, could be beneficial for controlling glucose metabolism in nondiabetic adults during postprandial period. PMID:26258147

  15. Apigenin, a modulator of PPARγ, attenuates HFD-induced NAFLD by regulating hepatocyte lipid metabolism and oxidative stress via Nrf2 activation.

    PubMed

    Feng, Xiujing; Yu, Wen; Li, Xinda; Zhou, Feifei; Zhang, Wenlong; Shen, Qi; Li, Jianxin; Zhang, Can; Shen, Pingping

    2017-07-15

    Lipid metabolic disorders and oxidative stress in the liver are key steps in the progression of nonalcoholic fatty liver disease (NAFLD), which is a major risk factor for the development of metabolic syndrome. To date, no pharmacological treatment for this condition has been approved. Our previous study has found that the food-derived compound apigenin (Api) significantly attenuates obesity-induced metabolic syndrome by acting as a peroxisome proliferator-activated receptor gamma modulator (PPARM). Herein, a high fat diet (HFD) induced NAFLD model was used to dig out whether Api had the effect on NAFLD. The results showed that Api had obvious effect in restraining NAFLD progression, including attenuating HFD induced lipid accumulation and oxidative stress in vivo. As a PPARM, although Api did significantly inhibit the expression of PPARγ target genes encoding the protein associated with lipid metabolism, it had no obvious activating effect on PPARγ. Interestingly, we found that Api promoted Nrf2 into the nucleus, thereby markedly activating Nrf2 to inhibit the lipid metabolism related genes and increase the oxidative stress related genes. Further Nrf2 knockdown/knockout and overexpression experiments showed that Api regulating PPARγ target genes was dependent on Nrf2 activation and the activation of Nrf2 counteracted the activation effect of PPARγ by Api. Importantly, we also found that Api might bind with Nrf2 via auto dock and ITC assay. Therefore, our results indicate that Api ameliorates NAFLD by a novel regulating mode of Nrf2 and PPARγ in inhibiting lipid metabolism and oxidative stress abnormity. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Lactobacillus gasseri SBT2055 reduces postprandial and fasting serum non-esterified fatty acid levels in Japanese hypertriacylglycerolemic subjects

    PubMed Central

    2014-01-01

    Background Lactobacillus gasseri SBT2055 (LG2055) inhibits dietary fat absorption in rats and exerts preventive effects on abdominal adiposity in rats and humans. The present study aimed to evaluate the effects of LG2055 on postprandial serum lipid responses in Japanese subjects with hypertriacylglycerolemia after the intake of oral fat-loading test (OFLT) meals. Methods We conducted a single-blind, placebo-controlled, within-subject, repeated-measure intervention trial. Twenty subjects initially ingested the fermented milk (FM) without LG2055 for 4 weeks (control FM period), followed by a 4-week washout period, and then consumed FM containing LG2055 for 4 weeks (active FM period). The subjects were asked to consume FM at 200 g/day. At the end of each 4-week period, an 8-h OFLT was conducted. Blood samples were collected at fasting and every hour for 8 h after OFLT meal intake. Thereafter, postprandial serum non-esterified fatty acid (NEFA) and triacylglycerol (TAG) levels and fasting blood parameters were measured. Results The OFLT showed that the postprandial serum NEFA levels from 120 to 480 min and the postprandial serum TAG level at 120 min in the active FM period were significantly (P < 0.05) lower than those in the control FM period. The fasting serum NEFA level in the active FM period significantly (P < 0.001) decreased at week 4 from the initial period compared with the control FM period. Conclusions The consumption of probiotic LG2055 reduced postprandial and fasting serum NEFA levels, suggesting its possible contribution to the reduction of the risk for obesity and type 2 diabetes mellitus. Trial registration UMIN000011605 PMID:24548293

  17. Lactobacillus gasseri SBT2055 reduces postprandial and fasting serum non-esterified fatty acid levels in Japanese hypertriacylglycerolemic subjects.

    PubMed

    Ogawa, Akihiro; Kadooka, Yukio; Kato, Ken; Shirouchi, Bungo; Sato, Masao

    2014-02-19

    Lactobacillus gasseri SBT2055 (LG2055) inhibits dietary fat absorption in rats and exerts preventive effects on abdominal adiposity in rats and humans. The present study aimed to evaluate the effects of LG2055 on postprandial serum lipid responses in Japanese subjects with hypertriacylglycerolemia after the intake of oral fat-loading test (OFLT) meals. We conducted a single-blind, placebo-controlled, within-subject, repeated-measure intervention trial. Twenty subjects initially ingested the fermented milk (FM) without LG2055 for 4 weeks (control FM period), followed by a 4-week washout period, and then consumed FM containing LG2055 for 4 weeks (active FM period). The subjects were asked to consume FM at 200 g/day. At the end of each 4-week period, an 8-h OFLT was conducted. Blood samples were collected at fasting and every hour for 8 h after OFLT meal intake. Thereafter, postprandial serum non-esterified fatty acid (NEFA) and triacylglycerol (TAG) levels and fasting blood parameters were measured. The OFLT showed that the postprandial serum NEFA levels from 120 to 480 min and the postprandial serum TAG level at 120 min in the active FM period were significantly (P < 0.05) lower than those in the control FM period. The fasting serum NEFA level in the active FM period significantly (P < 0.001) decreased at week 4 from the initial period compared with the control FM period. The consumption of probiotic LG2055 reduced postprandial and fasting serum NEFA levels, suggesting its possible contribution to the reduction of the risk for obesity and type 2 diabetes mellitus. UMIN000011605.

  18. Postprandial hyperlipidemia as a potential residual risk factor.

    PubMed

    Nakamura, Kazufumi; Miyoshi, Toru; Yunoki, Kei; Ito, Hiroshi

    2016-04-01

    Statin therapy targeting reduction of low-density lipoprotein cholesterol (LDL-C) decreases the risk of coronary heart disease (CHD) and all-cause mortality. However, a substantial number of cases of CHD are not prevented and residual risk factors remain unsettled. A high triglyceride (TG) level is considered to be an important and residual risk factor. Postprandial hyperlipidemia is a condition in which TG-rich chylomicron remnants are increased during the postprandial period and hypertriglycedemia is protracted. Postprandial hyperlipidemia evokes atherogenesis during the postprandial period. Several prospective studies have revealed that nonfasting serum TG levels predict the incidence of CHD. Values of TG, remnant lipoprotein cholesterol, and remnant lipoprotein TG after fat loading were significantly higher in diabetes patients with insulin resistance than in diabetes patients without insulin resistance. Endothelial dysfunction is an initial process of atherogenesis and it contributes to the pathogenesis of CHD. Postprandial hyperlipidemia (postprandial hypertriglyceridemia) is involved in the production of proinflammatory cytokines, recruitment of neutrophils, and generation of oxidative stress, resulting in endothelial dysfunction in healthy subjects, hypertriglyceridemic patients, or type 2 diabetic patients. Effective treatment has not been established till date. Ezetimibe or omega-3 fatty acids significantly decrease postprandial TG elevation and postprandial endothelial dysfunction. Ezetimibe or omega-3 fatty acids added to statin therapy reduce serum TG levels and result in good outcomes in patients with CHD. In conclusion, postprandial hyperlipidemia is an important and residual risk factor especially in patients with insulin resistance syndrome (metabolic syndrome) and diabetes mellitus. Further studies are needed to establish effective treatment.

  19. Antiobesity efficacy of GLP-1 receptor agonist liraglutide is associated with peripheral tissue-specific modulation of lipid metabolic regulators.

    PubMed

    Decara, Juan; Arrabal, Sergio; Beiroa, Daniel; Rivera, Patricia; Vargas, Antonio; Serrano, Antonia; Pavón, Francisco Javier; Ballesteros, Joan; Dieguez, Carlos; Nogueiras, Rubén; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2016-11-12

    To investigate the role of glucagon-like-peptide-1 receptor (GLP-1R) in peripheral lipid metabolism. Both lean and high-fat diet (HFD)-induced obesity (DIO) rats were used to compare the peripheral effects of the subcutaneous and repeated administration of the GLP-1R agonist liraglutide on the expression of key regulators involved in lipid metabolism, β-oxidation and thermogenesis in liver, abdominal muscle, and epididymal white adipose tissue (eWAT). We observed that liraglutide reduced caloric intake, body weight, and plasma levels of triglycerides and VLDL in a diet-independent manner. However, changes in liver fat content and the expression of lipid metabolism regulators were produced in a diet and tissue-dependent manner. In lean rats, liraglutide increased the gene/protein expression of elements involved in lipogenesis (ChREBP, Acaca/ACC, Fasn/FAS, Scd1/SCD1, PPARα/γ), β-oxidation (CPT1b), and thermogenesis (Cox4i1, Ucp1/UCP1) in eWAT and muscle, which suggest an increase in fatty-acid flux and utilization to activate energy expenditure. Regarding DIO rats, the specific reduction of liver lipid content by liraglutide was associated with a decreased expression of main elements involved in lipogenesis (phospho-ACC), peroxisomal β-oxidation (ACOX1), and lipid flux/storage (Pparγ/PPARγ) in liver, which suggest a recovery of lipid homeostasis. Interestingly, the muscle of DIO rats treated with liraglutide showed a decreased expression of PPARγ and the thermogenic factor UCP1. These results help us to better understand the peripheral mechanisms regulating lipid metabolism that underlay the effectiveness of GLP-1 analogues for the treatment of diabetes and obesity. © 2016 BioFactors, 42(6):600-611, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

  20. Aerobic Capacity and Postprandial Flow Mediated Dilation.

    PubMed

    Ballard, Kevin D; Miller, James J; Robinson, James H; Olive, Jennifer L

    The consumption of a high-fat meal induces transient vascular dysfunction. Aerobic exercise enhances vascular function in healthy individuals. Our purpose was to determine if different levels of aerobic capacity impact vascular function, as measured by flow mediated dilation, following a high-fat meal. Flow mediated dilation of the brachial artery was determined before, two- and four-hours postprandial a high-fat meal in young males classified as highly trained (n = 10; VO2max = 74.6 ± 5.2 ml·kg·min(-1)) or moderately active (n = 10; VO2max = 47.3 ± 7.1 ml·kg·min(-1)). Flow mediated dilation was reduced at two- (p < 0.001) and four-hours (p < 0.001) compared to baseline for both groups but was not different between groups at any time point (p = 0.108). Triglycerides and insulin increased at two- (p < 0.001) and four-hours (p < 0.05) in both groups. LDL-C was reduced at four-hours (p = 0.05) in highly trained subjects, and two- and four-hours (p ≤ 0.01) in moderately active subjects. HDL-C decreased at two- (p = 0.024) and four-hours (p = 0.014) in both groups. Glucose increased at two-hours postprandial for both groups (p = 0.003). Our results indicate that a high-fat meal results in reduced endothelium-dependent vasodilation in highly trained and moderately active individuals with no difference between groups. Thus, high aerobic capacity does not protect against transient reductions in vascular function after the ingestion of a single high-fat meal compared to individuals who are moderately active.

  1. Ventral hippocampal neurons inhibit postprandial energy intake.

    PubMed

    Hannapel, Reilly C; Henderson, Yoko H; Nalloor, Rebecca; Vazdarjanova, Almira; Parent, Marise B

    2017-03-01

    Evidence suggests that the memory of a recently ingested meal limits subsequent intake. Given that ventral hippocampal (vHC) neurons are involved in memory and energy intake, the present experiment tested the hypothesis that vHC neurons contribute to the formation of a memory of a meal and inhibit energy intake during the postprandial period. We tested (1) whether pharmacological inactivation of vHC neurons during the period following a sucrose meal, when the memory of the meal would be undergoing consolidation, accelerates the onset of the next sucrose meal and increases intake and (2) whether sucrose intake increases vHC expression of the synaptic plasticity marker activity-regulated cytoskeletal-associated protein (Arc). Adult male Sprague-Dawley rats were trained to consume a 32% sucrose solution daily at the same time and location. On the experimental day, the rats were given intra-vHC infusions of the GABAA receptor agonist muscimol or vehicle after they finished their first sucrose meal. Compared to vehicle infusions, postmeal intra-vHC muscimol infusions decreased the latency to the next sucrose meal, increased the amount of sucrose consumed during that meal, increased the total number of sucrose meals and the total amount of sucrose ingested. In addition, rats that consumed sucrose had higher levels of Arc expression in both vHC CA1 and CA3 subfields than cage control rats. Collectively, these findings are the first to show that vHC neurons inhibit energy intake during the postprandial period and support the hypothesis that vHC neurons form a memory of a meal and inhibit subsequent intake. © 2016 Wiley Periodicals, Inc.

  2. Prebeta1-HDL is elevated in the fasting state, but markedly reduced postprandially in poorly controlled type 2 diabetic patients.

    PubMed

    Hirayama, Satoshi; Ito, Takako; Miyazaki, Osamu; Kamimura, Takashi; Hanyu, Osamu; Seino, Utako; Ito, Seiki; Aizawa, Yoshifusa; Miida, Takashi

    2009-03-01

    Prebeta1-HDL is a minor HDL subfraction that is an initial acceptor of cellular free cholesterol. Prebeta1-HDL is elevated in hypertriglyceridemia, which is exaggerated with postprandial hyperglycemia. We investigated whether the prebeta1-HDL concentration changes postprandially in type 2 diabetic patients and blood glucose (BG) control reduces this change. We examined 9 healthy controls and 20 diabetic patients with poor BG control. Seven blood samples (30 min before and 2 h after each meal, and at midnight) were obtained daily in the poor (poor-GC: n=20) and improved (imp-GC: n=11) glycemic control phases of diabetic patients after intensive insulin therapy and a low-calorie diet. The prebeta1-HDL concentration did not change postprandially in the controls. However, the fasting prebeta1-HDL concentration in the poor-GC phase was 28.3% higher than in the controls (25.4+/-6.8 vs 19.8+/-6.9 mg/l ApoAI, p<0.05) and decreased markedly after breakfast (20.9+/-7.7 mg/l ApoAI, p<0.01). In the imp-GC phase, the prebeta1-HDL concentration showed no morning surge, as in the controls. Type 2 diabetic patients in the poor-GC phase have high prebeta1-HDL levels in the morning, followed by a gradual reduction until midnight. BG control diminishes this postprandial change. Glucose metabolism may be involved in modulating reverse cholesterol transport in type 2 diabetic patients.

  3. Modulation of pyridinium cationic lipid-DNA complex properties by pyridinium gemini surfactants and its impact on lipoplex transfection properties

    PubMed Central

    Sharma, Vishnu Dutt; Lees, Julia; Hoffman, Nicholas E.; Brailoiu, Eugen; Madesh, Muniswamy; Wunder, Stephanie L.; Ilies, Marc A.

    2014-01-01

    The study presents the effects of blending a cationic gemini surfactant into cationic lipid bilayers and its impact towards plasmid DNA compaction and delivery process. Using nanoDSC, dynamic light scattering, zeta potential and electrophoretic mobility measurements, together with transfection (2D- and 3D-) and viability assays, we identified the main physicochemical parameters of the lipid bilayers, liposomes and lipoplexes that are affected by the gemini surfactant addition. We also correlated the cationic bilayer composition with the dynamics of the DNA compaction process, and with transfection efficiency, cytotoxicity and internalization mechanism of the resultant nucleic acid complexes. We found that blending of gemini surfactant into the cationic bilayers fluidized the supramolecular assemblies, reduced the amount of positive charge required to fully compact the plasmid DNA and, in certain cases, changed the internalization mechanism of the lipoplexes. Transfection efficiency of select ternary lipoplexes derived from cationic gemini surfactants and lipids was several times superior to transfection efficiency of corresponding binary lipoplexes, also surpassing standard transfection systems. The overall impact of gemini surfactants into the formation and dynamic of cationic bilayers was found to depend heavily on the presence of co-lipids, their nature and amount present into lipoplexes. The study confirmed the possibility of combining the specific properties of pyridinium gemini surfactants and cationic lipids synergistically for obtaining efficient synthetic transfection systems with negligible cytotoxicity useful for therapeutic gene delivery. PMID:24377350

  4. Antidepressants Accumulate in Lipid Rafts Independent of Monoamine Transporters to Modulate Redistribution of the G Protein, Gαs.

    PubMed

    Erb, Samuel J; Schappi, Jeffrey M; Rasenick, Mark M

    2016-09-16

    Depression is a significant public health problem for which currently available medications, if effective, require weeks to months of treatment before patients respond. Previous studies have shown that the G protein responsible for increasing cAMP (Gαs) is increasingly localized to lipid rafts in depressed subjects and that chronic antidepressant treatment translocates Gαs from lipid rafts. Translocation of Gαs, which shows delayed onset after chronic antidepressant treatment of rats or of C6 glioma cells, tracks with the delayed onset of therapeutic action of antidepressants. Because antidepressants appear to specifically modify Gαs localized to lipid rafts, we sought to determine whether structurally diverse antidepressants accumulate in lipid rafts. Sustained treatment of C6 glioma cells, which lack 5-hydroxytryptamine transporters, showed marked concentration of several antidepressants in raft fractions, as revealed by increased absorbance and by mass fingerprint. Closely related molecules without antidepressant activity did not concentrate in raft fractions. Thus, at least two classes of antidepressants accumulate in lipid rafts and effect translocation of Gαs to the non-raft membrane fraction, where it activates the cAMP-signaling cascade. Analysis of the structural determinants of raft localization may both help to explain the hysteresis of antidepressant action and lead to design and development of novel substrates for depression therapeutics.

  5. Minor Contribution of Endogenous GLP-1 and GLP-2 to Postprandial Lipemia in Obese Men

    PubMed Central

    Matikainen, Niina; Björnson, Elias; Söderlund, Sanni; Borén, Christofer; Eliasson, Björn; Pietiläinen, Kirsi H.; Bogl, Leonie H.; Hakkarainen, Antti; Lundbom, Nina; Rivellese, Angela; Riccardi, Gabriele; Després, Jean-Pierre; Alméras, Natalie; Holst, Jens Juul; Deacon, Carolyn F.; Borén, Jan; Taskinen, Marja-Riitta

    2016-01-01

    Context Glucose and lipids stimulate the gut-hormones glucagon-like peptide (GLP)-1, GLP-2 and glucose-dependent insulinotropic polypeptide (GIP) but the effect of these on human postprandial lipid metabolism is not fully clarified. Objective To explore the responses of GLP-1, GLP-2 and GIP after a fat-rich meal compared to the same responses after an oral glucose tolerance test (OGTT) and to investigate possible relationships between incretin response and triglyceride-rich lipoprotein (TRL) response to a fat-rich meal. Design Glucose, insulin, GLP-1, GLP-2 and GIP were measured after an OGTT and after a fat-rich meal in 65 healthy obese (BMI 26.5–40.2 kg/m2) male subjects. Triglycerides (TG), apoB48 and apoB100 in TG-rich lipoproteins (chylomicrons, VLDL1 and VLDL2) were measured after the fat-rich meal. Main Outcome Measures Postprandial responses (area under the curve, AUC) for glucose, insulin, GLP-1, GLP-2, GIP in plasma, and TG, apoB48 and apoB100 in plasma and TG-rich lipoproteins. Results The GLP-1, GLP-2 and GIP responses after the fat-rich meal and after the OGTT correlated strongly (r = 0.73, p<0.0001; r = 0.46, p<0.001 and r = 0.69, p<0.001, respectively). Glucose and insulin AUCs were lower, but the AUCs for GLP-1, GLP-2 and GIP were significantly higher after the fat-rich meal than after the OGTT. The peak value for all hormones appeared at 120 minutes after the fat-rich meal, compared to 30 minutes after the OGTT. After the fat-rich meal, the AUCs for GLP-1, GLP-2 and GIP correlated significantly with plasma TG- and apoB48 AUCs but the contribution was very modest. Conclusions In obese males, GLP-1, GLP-2 and GIP responses to a fat-rich meal are greater than following an OGTT. However, the most important explanatory variable for postprandial TG excursion was fasting triglycerides. The contribution of endogenous GLP-1, GLP-2 and GIP to explaining the variance in postprandial TG excursion was minor. PMID:26752550

  6. A whole-grain cereal-based diet lowers postprandial plasma insulin and triglyceride levels in individuals with metabolic syndrome.

    PubMed

    Giacco, R; Costabile, G; Della Pepa, G; Anniballi, G; Griffo, E; Mangione, A; Cipriano, P; Viscovo, D; Clemente, G; Landberg, R; Pacini, G; Rivellese, A A; Riccardi, G

    2014-08-01

    Until recently, very few intervention studies have investigated the effects of whole-grain cereals on postprandial glucose, insulin and lipid metabolism, and the existing studies have provided mixed results. The objective of this study was to evaluate the effects of a 12-week intervention with either a whole-grain-based or a refined cereal-based diet on postprandial glucose, insulin and lipid metabolism in individuals with metabolic syndrome. Sixty-one men and women age range 40-65 years, with the metabolic syndrome were recruited to participate in this study using a parallel group design. After a 4-week run-in period, participants were randomly assigned to a 12-week diet based on whole-grain products (whole-grain group) or refined cereal products (control group). Blood samples were taken at the beginning and end of the intervention, both fasting and 3 h after a lunch, to measure biochemical parameters. Generalized linear model (GLM) was used for between-group comparisons. Overall, 26 participants in the control group and 28 in the whole-grain group completed the dietary intervention. Drop-outs (five in the control and two in the whole-grain group) did not affect randomization. After 12 weeks, postprandial insulin and triglyceride responses (evaluated as average change 2 and 3 h after the meal, respectively) decreased by 29% and 43%, respectively, in the whole-grain group compared to the run-in period. Postprandial insulin and triglyceride responses were significantly lower at the end of the intervention in the whole-grain group compared to the control group (p = 0.04 and p = 0.05; respectively) whereas there was no change in postprandial response of glucose and other parameters evaluated. A twelve week whole-grain cereal-based diet, compared to refined cereals, reduced postprandial insulin and triglycerides responses. This finding may have implications for type 2 diabetes risk and cardiovascular disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Ethanolic Extract of Vitis thunbergii Exhibits Lipid Lowering Properties via Modulation of the AMPK-ACC Pathway in Hypercholesterolemic Rabbits

    PubMed Central

    Pan, Chun-Hsu; Tsai, Chia-Hua; Lin, Wen-Hsin; Chen, Guo-Yan; Wu, Chieh-Hsi

    2012-01-01

    Vitis thunbergii (VT) is a wild grape that has been shown to provide various cardioprotective effects. The present study was designed to examine whether a VT extract could reduce serum lipid levels and prevent atherogenesis in a hypercholesterolemic rabbit model. At the end of an 8-week study, our results showed that a VT extract supplement markedly suppressed the serum levels of cholesterol and low-density lipoprotein, reduced lipid accumulation in liver tissues, and limited aortic fatty streaks. Our findings suggest that the VT extract activated AMPK (5′-adenosine monophosphate-activated protein kinase) with subsequent inhibition of the activation of ACC (acetyl-CoA carboxylase). Our results suggest that this VT extract could be further developed as a potential lipid-lowering agent and as a natural health food to prevent atherogenesis. PMID:22536284

  8. Lipid ingredients in moisturizers can modulate skin responses to UV in barrier-disrupted human skin in vivo.

    PubMed

    Byun, Hee Jin; Cho, Kwang Hyun; Eun, Hee Chul; Lee, Min-Jung; Lee, Youngae; Lee, Serah; Chung, Jin Ho

    2012-02-01

    Chemicals with a molecular weight <500 and adequate lipid solubility can penetrate the intact human skin. As many lipid ingredients in moisturizers have molecular weights <500, the lipid ingredients may penetrate into the skin and affect skin responses to UV; however, little is known about this phenomenon. To evaluate the effects of major lipid ingredients in moisturizers on skin responses to UV in tape-stripped human skin in vivo. We evaluated the effects of three major lipid ingredients in moisturizers (cholesterol, linoleic acid, and a synthetic ceramide, N-oleoyl-phytosphingosine) on skin responses to UV in the tape-stripped skin of healthy volunteers. After 2 days of lipid-application, the areas were irradiated with UV, and skin samples were obtained 24h after irradiation. Histologic features and the expression of the markers of collagen metabolism and inflammatory mediators were evaluated. Compared to vehicle, topical cholesterol significantly decreased the degree of dermal inflammatory infiltrates and exocytosis, and also decreased the expression of MMP-1, IL-6, and IL-1ß mRNA. In contrast, topical linoleic acid increased the induction of apoptotic cells, and the expression of MMP-1 and IL-6 mRNA. N-oleoyl-phytosphingosine increased the expression of MMP-1 and IL-6 mRNA, while decreasing the expression of COX-2 mRNA. Topical cholesterol can protect the barrier-disrupted skin against UV-induced damage, while linoleic acid or N-oleoyl-phytosphingosine alone has the potential to aggravate the damage. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  9. Epigenome-wide association study of triglyceride postprandial responses to a high-fat dietary challenge[S

    PubMed Central

    Lai, Chao-Qiang; Wojczynski, Mary K.; Parnell, Laurence D.; Hidalgo, Bertha A.; Irvin, Marguerite Ryan; Aslibekyan, Stella; Province, Michael A.; Absher, Devin M.; Arnett, Donna K.; Ordovás, José M.

    2016-01-01

    Postprandial lipemia (PPL), the increased plasma TG concentration after consuming a high-fat meal, is an independent risk factor for CVD. Individual responses to a meal high in fat vary greatly, depending on genetic and lifestyle factors. However, only a few loci have been associated with TG-PPL response. Heritable epigenomic changes may be significant contributors to the unexplained inter-individual PPL variability. We conducted an epigenome-wide association study on 979 subjects with DNA methylation measured from CD4+ T cells, who were challenged with a high-fat meal as a part of the Genetics of Lipid Lowering Drugs and Diet Network study. Eight methylation sites encompassing five genes, LPP, CPT1A, APOA5, SREBF1, and ABCG1, were significantly associated with PPL response at an epigenome-wide level (P < 1.1 × 10−7), but no methylation site reached epigenome-wide significance after adjusting for baseline TG levels. Higher methylation at LPP, APOA5, SREBF1, and ABCG1, and lower methylation at CPT1A methylation were correlated with an increased TG-PPL response. These PPL-associated methylation sites, also correlated with fasting TG, account for a substantially greater amount of phenotypic variance (14.9%) in PPL and fasting TG (16.3%) when compared with the genetic contribution of loci identified by our previous genome-wide association study (4.5%). In summary, the epigenome is a large contributor to the variation in PPL, and this has the potential to be used to modulate PPL and reduce CVD. PMID:27777315

  10. The ACAT inhibitor avasimibe increases the fractional clearance rate of postprandial triglyceride-rich lipoproteins in miniature pigs.

    PubMed

    Burnett, John R; Telford, Dawn E; Barrett, P Hugh R; Huff, Murray W

    2005-12-30

    Previously, we have shown, in vivo, that the acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitor avasimibe decreases hepatic apolipoprotein (apo) B secretion into plasma. To test the hypothesis that avasimibe modulates postprandial triglyceride-rich lipoprotein (TRL) metabolism in vivo, an oral fat load (2 g fat/kg) containing retinol was given to 9 control miniature pigs and to 9 animals after 28 days treatment with avasimibe (10 mg/kg/day, n=5; 25 mg/kg/day, n=4). The kinetic parameters for plasma retinyl palmitate (RP) metabolism were determined by multi-compartmental modeling using SAAM II. Avasimibe decreased the 2-h TRL (d<1.006 g/mL; S(f)>20) triglyceride concentrations by 34%. The TRL triglyceride 0-12 h area under the curve (AUC) was decreased by 21%. In contrast, avasimibe had no effect on peak TRL RP concentrations, time to peak, or its rate of appearance into plasma, however, the TRL RP 0-12 h AUC was decreased by 17%. Analysis of the RP kinetic parameters revealed that the TRL fractional clearance rate (FCR) was increased 1.4-fold with avasimibe. The TRL RP FCR was negatively correlated with very low density lipoprotein (VLDL) apoB production rate measured in the fasting state (r=-0.504). No significant changes in total intestinal lipid concentrations were observed. Thus, although avasimibe had no effect on intestinal TRL secretion, plasma TRL clearance was significantly increased; an effect that may relate to a decreased