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Sample records for modulates postprandial lipid

  1. Atrial Natriuretic Peptide Induces Postprandial Lipid Oxidation in Humans

    PubMed Central

    Birkenfeld, Andreas L.; Budziarek, Petra; Boschmann, Michael; Moro, Cedric; Adams, Frauke; Franke, Gabriele; Berlan, Michel; Marques, Marie A.; Sweep, Fred C.G.J.; Luft, Friedrich C.; Lafontan, Max; Jordan, Jens

    2008-01-01

    OBJECTIVE—Atrial natriuretic peptide (ANP) regulates arterial blood pressure. In addition, ANP has recently been shown to promote human adipose tissue lipolysis through cGMP-mediated hormone-sensitive lipase activation. We hypothesized that ANP increases postprandial free fatty acid (FFA) availability and energy expenditure while decreasing arterial blood pressure. RESEARCH DESIGN AND METHODS—We infused human ANP (25 ng · kg−1 · min−1) in 12 men (age 32 ± 0.8 years, BMI 23.3 ± 0.4 kg/m2) before, during, and 2 h after ingestion of a standardized high-fat test meal in a randomized, double-blind, cross-over fashion. Cardiovascular changes were monitored by continuous electrocardiogram and beat-by-beat blood pressure recordings. Metabolism was monitored through venous blood sampling, intramuscular and subcutaneous abdominal adipose tissue microdialysis, and indirect calorimetry. RESULTS—ANP infusion decreased mean arterial blood pressure by 4 mmHg during the postprandial phase (P < 0.01 vs. placebo). At the same time, ANP induced lipolysis systemically (P < 0.05 vs. placebo) and locally in subcutaneous abdominal adipose tissue (P < 0.0001 vs. placebo), leading to a 50% increase in venous glycerol (P < 0.01) and FFA (P < 0.05) concentrations compared with placebo. The increase in FFA availability with ANP was paralleled by a 15% increase in lipid oxidation rates (P < 0.05 vs. placebo), driving a substantial increase in postprandial energy expenditure (P < 0.05 vs. placebo). CONCLUSIONS—Our data identify the ANP system as a novel pathway regulating postprandial lipid oxidation, energy expenditure, and concomitantly arterial blood pressure. The findings could have therapeutic implications. PMID:18835931

  2. 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. PMID:24618586

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  4. 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. PMID:25872426

  5. Effects of angiopoietin-like protein 3 deficiency on postprandial lipid and lipoprotein metabolism.

    PubMed

    Minicocci, Ilenia; Tikka, Anna; Poggiogalle, Eleonora; Metso, Jari; Montali, Anna; Ceci, Fabrizio; Labbadia, Giancarlo; Fontana, Mario; Di Costanzo, Alessia; Maranghi, Marianna; Rosano, Aldo; Ehnholm, Christian; Donini, Lorenzo Maria; Jauhiainen, Matti; Arca, Marcello

    2016-06-01

    The consequences of angiopoietin-like protein 3 (ANGPTL3) deficiency on postprandial lipid and lipoprotein metabolism has not been investigated in humans. We studied 7 homozygous (undetectable circulating ANGPTL3 levels) and 31 heterozygous (50% of circulating ANGPTL3 levels) subjects with familial combined hypolipidemia (FHBL2) due to inactivating ANGPTL3 mutations in comparison with 35 controls. All subjects were evaluated at fasting and during 6 h after a high fat meal. Postprandial lipid and lipoprotein changes were quantified by calculating the areas under the curve (AUCs) using the 6 h concentration data. Plasma changes of β-hydroxybutyric acid (β-HBA) were measured as marker of hepatic oxidation of fatty acids. Compared with controls, homozygotes showed lower incremental AUCs (iAUCs) of total TG (-69%, P < 0.001), TG-rich lipoproteins (-90%, P < 0.001), apoB-48 (-78%, P = 0.032), and larger absolute increase of FFA (128%, P < 00.1). Also, heterozygotes displayed attenuated postprandial lipemia, but the difference was significant only for the iAUC of apoB-48 (-28%; P < 0.05). During the postprandial period, homozygotes, but not heterozygotes, showed a lower increase of β-HBA. Our findings demonstrate that complete ANGPTL3 deficiency associates with highly reduced postprandial lipemia probably due to faster catabolism of intestinally derived lipoproteins, larger expansion of the postprandial FFA pool, and decreased influx of dietary-derived fatty acids into the liver. These results add information on mechanisms underlying hypolipidemia in FHBL2. PMID:27040449

  6. Dietary strategies for improving post-prandial glucose, lipids, inflammation, and cardiovascular health.

    PubMed

    O'Keefe, James H; Gheewala, Neil M; O'Keefe, Joan O

    2008-01-22

    The highly processed, calorie-dense, nutrient-depleted diet favored in the current American culture frequently leads to exaggerated supraphysiological post-prandial spikes in blood glucose and lipids. This state, called post-prandial dysmetabolism, induces immediate oxidant stress, which increases in direct proportion to the increases in glucose and triglycerides after a meal. The transient increase in free radicals acutely triggers atherogenic changes including inflammation, endothelial dysfunction, hypercoagulability, and sympathetic hyperactivity. Post-prandial dysmetabolism is an independent predictor of future cardiovascular events even in nondiabetic individuals. Improvements in diet exert profound and immediate favorable changes in the post-prandial dysmetabolism. Specifically, a diet high in minimally processed, high-fiber, plant-based foods such as vegetables and fruits, whole grains, legumes, and nuts will markedly blunt the post-meal increase in glucose, triglycerides, and inflammation. Additionally, lean protein, vinegar, fish oil, tea, cinnamon, calorie restriction, weight loss, exercise, and low-dose to moderate-dose alcohol each positively impact post-prandial dysmetabolism. Experimental and epidemiological studies indicate that eating patterns, such as the traditional Mediterranean or Okinawan diets, that incorporate these types of foods and beverages reduce inflammation and cardiovascular risk. This anti-inflammatory diet should be considered for the primary and secondary prevention of coronary artery disease and diabetes. PMID:18206731

  7. Postprandial hyperglycemia impairs vascular endothelial function in healthy men by inducing lipid peroxidation and increasing asymmetric dimethylarginine:arginine.

    PubMed

    Mah, Eunice; Noh, Sang K; Ballard, Kevin D; Matos, Manuel E; Volek, Jeff S; Bruno, Richard S

    2011-11-01

    Postprandial hyperglycemia induces vascular endothelial dysfunction (VED) and increases future cardiovascular disease risk. We hypothesized that postprandial hyperglycemia would decrease vascular function in healthy men by inducing oxidative stress and proinflammatory responses and increasing asymmetric dimethylarginine:arginine (ADMA:arginine), a biomarker that is predictive of reduced NO biosynthesis. In a randomized, cross-over design, healthy men (n = 16; 21.6 ± 0.8 y) ingested glucose or fructose (75 g) after an overnight fast. Brachial artery flow-mediated dilation (FMD), plasma glucose and insulin, antioxidants, malondialdehyde (MDA), inflammatory proteins, arginine, and ADMA were measured at regular intervals during the 3-h postprandial period. Baseline FMD did not differ between trials (P > 0.05). Postprandial FMD was reduced following the ingestion of glucose only. Postprandial MDA concentrations increased to a greater extent following the ingestion of glucose compared to fructose. Plasma arginine decreased and the ratio of ADMA:arginine increased to a greater extent following the ingestion of glucose. Inflammatory cytokines and cellular adhesion molecules were unaffected by the ingestion of either sugar. Postprandial AUC(0-3 h) for FMD and MDA were inversely related (r = -0.80; P < 0.05), suggesting that hyperglycemia-induced lipid peroxidation suppresses postprandial vascular function. Collectively, these findings suggest that postprandial hyperglycemia in healthy men reduces endothelium-dependent vasodilation by increasing lipid peroxidation independent of inflammation. Postprandial alterations in arginine and ADMA:arginine also suggest that acute hyperglycemia may induce VED by decreasing NO bioavailability through an oxidative stress-dependent mechanism. Additional work is warranted to define whether inhibiting lipid peroxidation and restoring arginine metabolism would mitigate hyperglycemia-mediated decreases in vascular function. PMID:21940510

  8. Influence of genetic factors in the modulation of postprandial lipemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Postprandial lipemia is traditionally defined by the extent and duration of the increase in plasma triglycerides in response to a fat-enriched meal. The relationship between alimentary lipemia and coronary disease is of great interest in view of the epidemiological and experimental evidence that und...

  9. 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

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

    PubMed

    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

  11. Postprandial Responses to Lipid and Carbohydrate Ingestion in Repeated Subcutaneous Adipose Tissue Biopsies in Healthy Adults

    PubMed Central

    Dordevic, Aimee L.; Pendergast, Felicity J.; Morgan, Han; Villas-Boas, Silas; Caldow, Marissa K.; Larsen, Amy E.; Sinclair, Andrew J.; Cameron-Smith, David

    2015-01-01

    Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 ± 3.3 year (mean ± standard deviation (SD)); body mass index (BMI) 24.1 ± 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water), carbohydrate (maltodextrin) or lipid (dairy-cream). Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h), as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) increased in all three groups, without an increase in circulating TNF-α. Serum leptin (0.6-fold, p = 0.03) and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001) decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed. PMID:26140541

  12. Postprandial Responses to Lipid and Carbohydrate Ingestion in Repeated Subcutaneous Adipose Tissue Biopsies in Healthy Adults.

    PubMed

    Dordevic, Aimee L; Pendergast, Felicity J; Morgan, Han; Villas-Boas, Silas; Caldow, Marissa K; Larsen, Amy E; Sinclair, Andrew J; Cameron-Smith, David

    2015-07-01

    Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 ± 3.3 year (mean ± standard deviation (SD)); body mass index (BMI) 24.1 ± 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water), carbohydrate (maltodextrin) or lipid (dairy-cream). Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h), as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) increased in all three groups, without an increase in circulating TNF-α. Serum leptin (0.6-fold, p = 0.03) and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001) decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed. PMID:26140541

  13. 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. PMID:25651043

  14. 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. PMID:25831145

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. 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. PMID:25308668

  17. Concomitant Intake of Quercetin with a Grain-Based Diet Acutely Lowers Postprandial Plasma Glucose and Lipid Concentrations in Pigs

    PubMed Central

    Wein, Silvia; Wolffram, Siegfried

    2014-01-01

    Treatment goals of diabetes mellitus type 2 (DMT2) include glycemic control and reduction of nonglycemic risk factors, for example, dyslipidemia. Quercetin, a plant-derived polyphenol, often discussed for possible antidiabetic effects, was investigated for acute postprandial glucose- and lipid-lowering effects in healthy growing pigs. Male pigs (n = 16, body weight = BW 25–30 kg) were fed flavonoid-poor grain-based meals without (GBM) or with quercetin (GBMQ). In a first experiment, postprandial plasma concentrations of glucose, nonesterified fatty acids (NEFA), and triacylglycerols were analyzed in 8 pigs receiving 500 g of either GBM or GBMQ (10 mg/kg BW) in a cross-over design. Blood samples were collected before, and up to 5 h every 30 min, as well as 6 and 8 h after the feeding. In the second experiment, 2 h after ingestions of 1000 g of either GBM or GBMQ (50 mg/kg BW) animals were sacrificed; gastric content was collected and analyzed for dry matter content. Quercetin ingestion reduced postprandial glucose, NEFA, and TG concentration, but two hours after ingestion of the meal no effect on gastric emptying was observed. Our results point to inhibitory effects of quercetin on nutrient absorption, which appear not to be attributable to delayed gastric emptying. PMID:24847478

  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. PMID:25595097

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The effects of docosahexaenoic acid (DHA) on the concentrations of different subclasses of VLDL, LDL and HDL particles, and their mean diameters in fasting and postprandial plasma has not been studied. Objective: To determine the effects of DHA supplementation on the concentrations of a...

  20. Postprandial lipid responses to an alpha-linolenic acid-rich oil, olive oil and butter in women: A randomized crossover trial

    PubMed Central

    2011-01-01

    Background Postprandial lipaemia varies with gender and the composition of dietary fat due to the partitioning of fatty acids between beta-oxidation and incorporation into triacylglycerols (TAGs). Increasing evidence highlights the importance of postprandial measurements to evaluate atherogenic risk. Postprandial effects of alpha-linolenic acid (ALA) in women are poorly characterized. We therefore studied the postprandial lipid response of women to an ALA-rich oil in comparison with olive oil and butter, and characterized the fatty acid composition of total lipids, TAGs, and non-esterified fatty acids (NEFAs) in plasma. Methods A randomized crossover design (n = 19) was used to compare the postprandial effects of 3 meals containing 35 g fat. Blood samples were collected at regular intervals for 7 h. Statistical analysis was carried out with ANOVA (significant difference = P < 0.05). Results No significant difference was seen in incremental area under the curve (iAUC) plasma-TAG between the meals. ALA and oleic acid levels were significantly increased in plasma after ALA-rich oil and olive oil meals, respectively. Palmitic acid was significantly increased in plasma-TAG after the butter meal. The ratios of 18:2 n-6 to18:3 n-3 in plasma-TAGs, three and seven hours after the ALA-rich oil meal, were 1.5 and 2.4, respectively. The corresponding values after the olive oil meal were: 13.8 and 16.9; and after the butter meal: 9.0 and 11.6. Conclusions The postprandial p-TAG and NEFA response in healthy pre-menopausal women was not significantly different after the intake of an ALA-rich oil, olive oil and butter. The ALA-rich oil significantly affected different plasma lipid fractions and improved the ratio of n-6 to n-3 fatty acids several hours postprandially. PMID:21711508

  1. Ext1 heterozygosity causes a modest effect on postprandial lipid clearance in humans[S

    PubMed Central

    Mooij, Hans L.; Bernelot Moens, Sophie J.; Gordts, Philip L. S. M.; Stanford, Kristin I.; Foley, Erin M.; van den Boogert, Marjolein A. W.; Witjes, Julia J.; Hassing, H. Carlijne; Tanck, Michael W.; van de Sande, Michiel A. J.; Levels, J. Han; Kastelein, John J. P.; Stroes, Erik S. G.; Dallinga-Thie, Geesje M.; Esko, Jeff D.; Nieuwdorp, Max

    2015-01-01

    Elevated nonfasting TG-rich lipoprotein levels are a risk factor for CVD. To further evaluate the relevance of LDL-receptor (LDLr) pathway and heparan sulfate proteoglycans (HSPGs) in TG homeostasis, we analyzed fasting and postprandial TG levels in mice bearing combined heterozygous mutations in both Exostosin (Ext) 1 and Ldlr, in subjects with hereditary multiple exostosis (HME) due to a heterozygous loss-of-function mutation in EXT1 or EXT2 (N = 13), and in patients with heterozygous mutations in LDLR [familial hypercholesterolemia (FH)] and SNPs in major HSPG-related genes (n = 22). Mice bearing a homozygous mutation in hepatic Ext1 exhibited elevated plasma TGs similar to mice lacking other key enzymes involved in HSPG assembly. Compound heterozygous mice lacking Ldlr and Ext1 showed synergy on plasma TG accumulation and postprandial clearance. In human subjects, a trend was observed in HME patients toward reduced postprandial TG clearance with a concomitant reduction in chylomicron clearance [area under the curve (AUC)-retinyl ester (RE) HME, 844 ± 127 vs. controls, 646 ± 119 nM/h, P = 0.09]. Moreover, in FH subjects with a high HSPG gene score, retinyl palmitate excursions were higher (AUC-RE, 2,377 ± 293 vs. 1,565 ± 181 nM/h, P < 0.05). Incremental AUC-apoB48 was similar between the groups. In conclusion, the data are supportive for a minor yet additive role of HSPG in human postprandial TG clearance, and further studies are warranted. PMID:25568062

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  3. Postprandial lipid response following a high fat meal in rats adapted to dietary fiber.

    PubMed

    Redard, C L; Davis, P A; Middleton, S J; Schneeman, B O

    1992-02-01

    Rats were adapted to diets containing 5 g/100 g cellulose (CL), 5 g/100 g oat bran fiber (OB) or 5 g/100 g psyllium husk (Psy) for 4 wk. Following a 12-h fast, animals were either killed at 0 h (baseline) or fed 4.5 g of a test meal that provided 50% energy from fat, then killed at 1, 4 or 6 h postprandially. Fasting plasma and HDL cholesterol concentrations were lower in Psy-fed animals than in rats fed either CL or OB. Plasma triglycerides increased significantly from baseline (0 h) in all groups but did not differ among diet treatments. Increases in triglyceride content of the treatments. Increases in triglyceride content of the chylomicron/VLDL fraction occurred in the CL- and OB-fed groups and in the HDL fraction of the Psy-fed group during the postprandial period. In unfed animals the hepatic and intestinal levels of apolipoprotein A-IV mRNA were higher in the CL-fed group than in the groups fed OB and Psy. Apolipoprotein B mRNA was higher in the intestine of the OB-fed group than in the groups fed CL and Psy and had a significant gradient along the small intestine, increasing in the distal third. The results suggest that chronic consumption of fiber is less likely to modify the acute plams triglyceride response to a fat-containing test meal than if a fiber supplement is incorporated into the meal. PMID:1310107

  4. Short-Term Effect of Pitavastatin Treatment on Glucose and Lipid Metabolism and Oxidative Stress in Fasting and Postprandial State Using a Test Meal in Japanese Men

    PubMed Central

    Kakuda, Hirokazu; Nakato, Mio; Takekoshi, Noboru

    2013-01-01

    Introduction. The objective of this study was to clarify how pitavastatin affects glucose and lipid metabolism, renal function, and oxidative stress. Methods. Ten Japanese men (average age of 33.9 years) were orally administered 2 mg of pitavastatin for 4 weeks. Postprandial glucose, lipoprotein metabolism, and oxidative stress markers were evaluated at 0 and 4 weeks of pitavastatin treatment (2 mg once daily) with a test meal consisting of total calories: 460 kcal, carbohydrates: 56.5 g (226 kcal), protein: 18 g (72 kcal), lipids: 18 g (162 kcal), and NaCl: 1.6 g. Metabolic parameters were measured at 0, 60, and 120 minutes after test meal ingestion. Results. After administration of pitavastatin, serum total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, arachidonic acid, insulin, and adjusted urinary excretion of uric acid decreased, whereas creatinine clearance (CCr) and uric acid clearance (CUA) increased. And postprandial versus fasting urine 8-hydroxydeoxyguanosine remained unchanged, while postprandial versus fasting isoprostane decreased after pitavastatin treatment. Next, we compared postprandial glucose and lipid metabolism after test meal ingestion before and after pitavastatin administration. Incremental areas under the curve significantly decreased for triglycerides (P < 0.05) and remnant-like particle cholesterol (P < 0.01), while those for apolipoprotein E (apoE), glucose, insulin, and high-sensitivity C-reactive protein remained unchanged. Conclusion. Pitavastatin improves postprandial oxidative stress along with hyperlipidemia. PMID:24386561

  5. The Postprandial Effects of a Moderately High-Fat Meal on Lipid Profiles and Vascular Inflammation in Alzheimer’s Disease Patients: A Pilot Study

    PubMed Central

    Altman, Robin; Keenan, Alison H.; Newman, John W.; Rutledge, John C.

    2015-01-01

    Objective Alzheimer’s disease (AD) is a neurodegenerative disease of aging with unknown causative factors. Accumulating evidence suggests that inflammation and neurovascular dysfunction play important roles in AD. The postprandial period following a moderately high-fat meal is associated with vascular inflammation in young, healthy individuals; however, this relationship has not been investigated in Alzheimer’s patients despite their exaggerated inflammatory state. Methods Patients with AD and age-matched control subjects were recruited through the UC Davis Alzheimer’s Disease Center. All subjects consumed a moderately high-fat breakfast meal. Fasting and postprandial blood samples were collected for lipid, lipoprotein, and oxylipin analyses, as well as assays for cytokine levels and monocyte activation. Results The plasma lipid analyses revealed similar levels of triglycerides and esterified oxylipins between groups, but there was an interaction between postprandial non-esterified fatty acid (NEFA) levels and body mass index in the AD group compared to the control subjects. The AD group also had increased behenic acid and decreased linoleic and oleic acids in the postprandial period; however, these were not significantly different. Inflammatory assays revealed elevated fasting levels of interleukin (IL)-10 and IL-12 p70, but no change in monocyte activation in the AD group. Conclusion The postprandial period following a moderately high-fat meal is not associated with an exaggerated inflammatory state in Alzheimer’s patients, and basal esterified oxylipin profiles do not indicate elevated oxidative stress. However, the baseline inflammatory state during fasting in AD patients includes elevated levels of plasma IL-10 and IL-12 p70, which may indicate a balance between immune responses mediated by these interleukins. PMID:26029731

  6. D-Fagomine lowers postprandial blood glucose and modulates bacterial adhesion.

    PubMed

    Gómez, Livia; Molinar-Toribio, Eunice; Calvo-Torras, María Ángeles; Adelantado, Carles; Juan, M Emília; Planas, Joana M; Cañas, Xavier; Lozano, Carles; Pumarola, Sergio; Clapés, Pere; Torres, Josep Lluís

    2012-06-01

    D-Fagomine is an iminosugar originally isolated from seeds of buckwheat (Fagopyrum sculentum Moench), present in the human diet and now available as a pure crystalline product. We tested D-fagomine for activities connected to a reduction in the risk of developing insulin resistance, becoming overweight and suffering from an excess of potentially pathogenic bacteria. The activities were: intestinal sucrase inhibition in vitro (rat mucosa and everted intestine sleeves), modulation of postprandial blood glucose in rats, bacterial agglutination and bacterial adhesion to pig intestinal mucosa. When ingested together with sucrose or starch, D-fagomine lowered blood glucose in a dose-dependent manner without stimulating insulin secretion. D-Fagomine reduced the area under the curve (0-120 min) by 20 % (P < 0·01) and shifted the time to maximum blood glucose concentration (Tmax) by 15 min at doses of 1-2 mg/kg body weight when administered together with 1 g sucrose/kg body weight. Moreover, D-fagomine (0·14 mm) agglutinated 60 % of Enterobacteriaceae (Escherichia coli, Salmonella enterica serovar Typhimurium) populations (P < 0·01), while it did not show this effect on Bifidobacterium spp. or Lactobacillus spp. At the same concentration, d-fagomine significantly (P < 0·001) inhibited the adhesion of Enterobacteriaceae (95-99 % cells in the supernatant) and promoted the adhesion of Lactobacillus acidophilus (56 % cells in the supernatant) to intestinal mucosa. D-Fagomine did not show any effect on bacterial cell viability. Based on all this evidence, D-fagomine may be used as a dietary ingredient or functional food component to reduce the health risks associated with an excessive intake of fast-digestible carbohydrates, or an excess of potentially pathogenic bacteria. PMID:22017795

  7. Postprandial changes in the proteome are modulated by dietary fat in patients with metabolic syndrome.

    PubMed

    Camargo, Antonio; Rangel-Zúñiga, Oriol Alberto; Peña-Orihuela, Patricia; Marín, Carmen; Pérez-Martínez, Pablo; Delgado-Lista, Javier; Gutierrez-Mariscal, Francisco Miguel; Malagón, María M; Roche, Helen M; Tinahones, Francisco José; Perez-Jimenez, Francisco; Lopez-Miranda, José

    2013-01-01

    Metabolic syndrome is a multicomponent disorder whose etiology is the result of a complex interaction between genetic, metabolic and environmental factors including dietary habits. Our aim was to identify proteome-diet interactions during the postprandial state after the acute intake of four meals with different qualities of fat in the proteome of peripheral blood mononuclear cells. A randomized controlled trial conducted within the LIPGENE study assigned 39 metabolic syndrome patients to one of four meals: a high-saturated-fatty-acid (HSFA) meal, a high-monounsaturated-fatty-acid (HMUFA) meal and two high-polyunsaturated-fatty-acid (from walnut) (HPUFA) meals supplemented with n-3 PUFA or placebo. We analyzed the postprandial changes in the whole proteome of both nuclear and cytoplasmic fractions of peripheral blood mononuclear cells by two-dimensional proteomics. Twenty-three proteins were differentially expressed. HSFA intake caused the postprandial increase of proteins responding to oxidative stress (HSPA1A, PDIA3 and PSME1) and DNA damage (SMC6), whereas HMUFA intake led to the up-regulation of HSPA1A and PDIA3. HPUFA meal supplementation with n-3 PUFA produced peroxisomal beta-oxidation inhibition by down-regulation of ECH1, a process related to insulin signaling improvement. In conclusion, HSFA meal intake causes deleterious postprandial changes in the proteome in terms of DNA damage and procoagulant state, which reflect a higher postprandial oxidative stress after HSFA meal intake as compared to intake of HMUFA and HPUFA meals. Moreover, the addition of long-chain n-3 PUFA to an HPUFA meal may improve insulin signaling and exerts an anti-inflammatory effect when compared to an HPUFA meal. PMID:22959058

  8. Body Position Modulates Gastric Emptying and Affects the Post-Prandial Rise in Plasma Amino Acid Concentrations Following Protein Ingestion in Humans

    PubMed Central

    Holwerda, Andrew M.; Lenaerts, Kaatje; Bierau, Jörgen; van Loon, Luc J. C.

    2016-01-01

    Dietary protein digestion and amino acid absorption kinetics determine the post-prandial muscle protein synthetic response. Body position may affect gastrointestinal function and modulate the post-prandial rise in plasma amino acid availability. We aimed to assess the impact of body position on gastric emptying rate and the post-prandial rise in plasma amino acid concentrations following ingestion of a single, meal-like amount of protein. In a randomized, cross-over design, eight healthy males (25 ± 2 years, 23.9 ± 0.8 kg·m−2) ingested 22 g protein and 1.5 g paracetamol (acetaminophen) in an upright seated position (control) and in a −20° head-down tilted position (inversion). Blood samples were collected during a 240-min post-prandial period and analyzed for paracetamol and plasma amino acid concentrations to assess gastric emptying rate and post-prandial amino acid availability, respectively. Peak plasma leucine concentrations were lower in the inversion compared with the control treatment (177 ± 15 vs. 236 ± 15 mmol·L−1, p < 0.05), which was accompanied by a lower plasma essential amino acid (EAA) response over 240 min (31,956 ± 6441 vs. 50,351 ± 4015 AU; p < 0.05). Peak plasma paracetamol concentrations were lower in the inversion vs. control treatment (5.8 ± 1.1 vs. 10.0 ± 0.6 mg·L−1, p < 0.05). Gastric emptying rate and post-prandial plasma amino acid availability are significantly decreased after protein ingestion in a head-down tilted position. Therefore, upright body positioning should be considered when aiming to augment post-prandial muscle protein accretion in both health and disease. PMID:27089362

  9. 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

  10. 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

  11. 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. PMID:23964645

  12. Small GTPase Rab40c associates with lipid droplets and modulates the biogenesis of lipid droplets.

    PubMed

    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

  13. 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. PMID:25366236

  14. Prevention of postprandial metabolic stress in humans: role of fruit-derived products.

    PubMed

    Morabito, Giuseppa; Kucan, Petra; Serafini, Mauro

    2015-01-01

    The consumption of unbalanced meals, consisting of foods rich in lipids and/or carbohydrates and calories, has been associated to a postprandial metabolic stress that involves the increase of the production of free radicals and proinflammatory markers. Growing evidence suggest that dietary polyphenols contained in fruit-derived products, such as fruit juices, are involved in the role played by plant foods in disease prevention. Their association to a calorie-dense meal may help to attenuate the onset of postprandial metabolic and inflammatory stress. The available evidence in the literature investigating the effects of polyphenols rich fruit juices on the modulation of postprandial-induced metabolic stress in humans will be presented and discussed. PMID:25335991

  15. Bioactive lipids as modulators of immunity, inflammation and emotions.

    PubMed

    Chiurchiù, Valerio; Maccarrone, Mauro

    2016-08-01

    Lipids are not only constituents of cellular membranes but also key signaling mediators, thus acting as 'bioactive lipids'. Among the prominent roles exerted by bioactive lipids are immune regulation, inflammation and maintenance of homeostasis. Accumulated evidence indicates the existence of a bidirectional relationship between immune and nervous systems, whereby inflammatory mediators can directly modulate emotions that, in turn, can strongly influence immune responses, thus affecting health. This review summarizes current knowledge on the ability of several families of bioactive lipids to regulate immunity and inflammation (through pro-inflammatory or anti-inflammatory effects), as well as to control emotions and mood-related manifestations, advocating these substances as an attractive interface between 'mind' and 'body', and as a potential target to treat inflammatory/immune-mediated mood disorders. PMID:27372887

  16. Research: Treatment A randomized crossover study to assess the effect of an oat-rich diet on glycaemic control, plasma lipids and postprandial glycaemia, inflammation and oxidative stress in Type 2 diabetes

    PubMed Central

    McGeoch, S C; Johnstone, A M; Lobley, G E; Adamson, J; Hickson, K; Holtrop, G; Fyfe, C; Clark, L F; Pearson, D W M; Abraham, P; Megson, I L; MacRury, S M

    2013-01-01

    Aims In the UK, lifestyle intervention is first-line management in Type 2 diabetes. It is unclear what type of diet is most efficacious for improving glycaemic control. This study investigated the effects of an oat-enriched diet on glycaemic control, postprandial glycaemia, inflammation and oxidative stress compared with standard dietary advice. Methods In a randomized crossover design, 27 volunteers with Type 2 diabetes, managed on diet and lifestyle only, were observed for two consecutive 8-week periods following either the oat-enriched diet or re-enforced standard dietary advice. Volunteers attended at baseline (habitual intake) and 8 and 16 weeks. Measurements included basic clinical measurements and fasted and postprandial (3-h) glucose and insulin in response to a healthy test meal. Markers of inflammation and oxidative stress, including high-sensitivity C-reactive protein, interleukin 6, interleukin 18, tumour necrosis factor-alpha, adiponectin, thiobarbituric acid reactive substances, oxygen radical antioxidant capacity, oxidized LDL and urinary isoprostanes, were also measured at fasting and in the postprandial period. Results There were no diet-related effects on glycaemic control or glycaemic or insulinaemic responses to the test meal. Total cholesterol (5.1 ± 1.0 vs. 4.9 ± 0.8 mmol/l, P = 0.019) concentrations declined following the oat-enriched diet compared with standard dietary advice. There was a postprandial decline in adiponectin concentration (P = 0.009), but no effect of dietary intervention. None of the measures of oxidative stress or inflammation were altered by the oat-enriched diet compared with standard dietary advice. Conclusion The oat-enriched diet had a modest impact on lipid lowering, but did not impact on oxidative stress or inflammation in these volunteers with Type 2 diabetes. PMID:23668675

  17. Reduced alpha(2)-adrenergic sensitivity of subcutaneous abdominal adipocytes as a modulator of fasting and postprandial triglyceride levels in men.

    PubMed

    Imbeault, P; Couillard, C; Tremblay, A; Després, J P; Mauriège, P

    2000-09-01

    This study examined the postprandial lipemia of two groups of men displaying similar age, body weight, and regional fat distribution, but characterized by either low (n = 11) or high (n = 15) alpha(2)-adrenergic sensitivity of subcutaneous abdominal adipocytes. In addition to fat cell lipolysis, adipose tissue lipoprotein lipase (AT-LPL) as well as postheparin plasma LPL activities were measured in the fasting state. Fasting AT-LPL and PH-LPL activities were similar in both groups. Maximal adipose cell lipolysis induced by isoproterenol (beta-adrenergic agonist) as well as the beta-adrenergic sensitivity did not differ between both groups of men. The selective alpha(2)-adrenergic agonist UK-14304 promoted a similar antilipolytic response in subcutaneous abdominal adipocytes from both groups. However, the alpha(2)-adrenergic sensitivity, defined as the dose of UK-14304 that produced half-maximal inhibition of lipolysis (IC(50)), was significantly different between groups (P < 0.0001). Men with low versus high subcutaneous abdominal fat cell alpha(2)-adrenergic sensitivity showed higher fasting TG levels. In the whole group, a positive relationship was observed between log-transformed IC(50) UK-14304 values of subcutaneous adipocytes and fasting TG levels (r = 0.39, P < 0.05), suggesting that a low abdominal adipose cell alpha(2)-adrenergic sensitivity is associated with high TG levels. After the consumption of a high-fat meal, subjects with low subcutaneous abdominal adipose cell alpha(2)-adrenergic sensitivity showed higher TG levels in total, medium, and small triglyceride-rich lipoprotein (TRL) fractions at 0- to 6-h time points than men with high adipocyte alpha(2)-adrenergic sensitivity (P values ranging from 0.01 to 0.05). Stepwise regression analysis showed that the fasting TG concentration was the only variable retained as a significant predictor of the area under the curve of TG levels in total TRL fractions (73% of variance) among independent variables

  18. Modulation of Endotoxicity of Shigella Generalized Modules for Membrane Antigens (GMMA) by Genetic Lipid A Modifications

    PubMed Central

    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

    2014-01-01

    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. PMID:25023285

  19. Schistosoma mansoni: modulation of schistosomular lipid composition by serum.

    PubMed

    Rumjanek, F D; McLaren, D J

    1981-08-01

    Human serum and foetal calf serum have been compared in terms of their ability to modify the biochemical and immunological properties of the schistosomular surface. Artificially transformed schistosomula were incubated in the presence of serum for 24 h and then radioiodinated using the chloramine T method. With this method only lipids are labelled. Foetal calf serum produces a net loss of lipids from the schistosomula, particularly of mono- and diglycerides. Human serum however, promotes not only a loss of mono- and diglycerides, but also a substantial uptake of cholesterol and triglycerides. Schistosomula recovered from the lungs of mice could also be labelled and contained besides triglycerides, an increased amount of cholesterol esters. The modulation of surface lipids in worms cultured with human serum correlates with the observation that such schistosomula develop significantly greater protection against eosinophil-mediated cytotoxicity in vitro than do individuals incubated with foetal calf serum. On the other hand, schistosomula cultured in the presence of either human serum or foetal calf serum develop the same degree of protection against complement-dependent lethal antibody; this result indicates that resistance against complement-mediated damage may be independent of the uptake of cholesterol and/or triglycerides, and might involve only limited alterations in the surface configuration of the schistosomulum. PMID:7278882

  20. 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. PMID:26951856

  1. Alogliptin ameliorates postprandial lipemia and postprandial endothelial dysfunction in non- diabetic subjects: a preliminary report

    PubMed Central

    2013-01-01

    Background Postprandial hyperlipidemia impairs endothelial function and participates in the development of atherosclerosis. We investigated the postprandial effects of a dipeptidyl peptidase IV inhibitor, alogliptin, on endothelial dysfunction and the lipid profile. Methods A randomized cross-over trial design in 10 healthy volunteers (8 males and 2 females, 35 ± 10 years) was performed. The postprandial effects before and after a 1-week treatment of 25 mg/day alogliptin on endothelial function were assessed with brachial artery flow-mediated dilation (FMD) and changing levels of lipids, apolipoprotein B48 (apoB-48), glucose, glucagon, insulin, and glucagon-like peptide-1 (GLP-1) during fasting and at 2, 4, 6, and 8 h after a standard meal loading test. Results Alogliptin treatment significantly suppressed the postprandial elevation in serum triglyceride (incremental area under the curve [AUC]; 279 ± 31 vs. 182 ± 32 mg h/dl, p = 0.01), apoB-48 (incremental AUC; 15.4 ± 1.7 vs. 11.7 ± 1.1 μg h/ml, p = 0.04), and remnant lipoprotein cholesterol (RLP-C) (incremental AUC: 29.3 ± 3.2 vs. 17.6 ± 3.3 mg h/dl, p = 0.01). GLP-1 secretion was significantly increased after alogliptin treatment. Postprandial endothelial dysfunction (maximum decrease in%FMD, from −4.2 ± 0.5% to −2.6 ± 0.4%, p = 0.03) was significantly associated with the maximum change in apoB-48 (r = −0.46, p = 0.03) and RLP-C (r = −0.45, p = 0.04). Conclusion Alogliptin significantly improved postprandial endothelial dysfunction and postprandial lipemia, suggesting that alogliptin may be a promising anti-atherogenic agent. PMID:23298374

  2. 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. PMID:26849821

  3. 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

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

    PubMed

    Therrien, Alexandre; Lafleur, Michel

    2016-01-19

    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

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

    PubMed

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

    2015-11-01

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

  6. 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

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

    PubMed

    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 needed

  8. Phenotypic modulation of macrophages in response to plaque lipids

    PubMed Central

    Adamson, Samantha; Leitinger, Norbert

    2014-01-01

    Purpose of review The accumulation of macrophages in the vascular wall is a hallmark of atherosclerosis. The biological properties of atherosclerotic plaque macrophages determine lesion size, composition and stability. In atherosclerotic plaques, macrophages encounter a microenvironment that is comprised of a variety of lipid oxidation products, each of which has diverse biological effects. In this review, we summarize recent advances in our understanding of the effects of plaque lipids on macrophage phenotypic polarization. Recent findings Atherosclerotic lesions in mice and in humans contain various macrophage phenotypes, which play different roles in mediating inflammation, the clearance of dead cells, and possibly resolution. Macrophages alter their phenotype and biological function in response to plaque lipids through the upregulation of specific sets of genes. Interaction of oxidized lipids with pattern recognition receptors and activation of the inflammasome by cholesterol crystals drive macrophages towards an inflammatory M1 phenotype. A new phenotype, Mox, develops when oxidized phospholipids activate stress response genes via Nrf2. Other lipid mediators such as nitrosylated-fatty acids and omega-3 fatty acid-derived products polarize plaque macrophages towards anti-inflammatory and proresolving phenotypes. Summary A deeper understanding of how lipids that accumulate in atherosclerotic plaques affect macrophage phenotype and function and thus atherosclerotic lesion development and stability will help to devise novel strategies for intervention. PMID:21841486

  9. 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

  10. 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.

  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. 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

  13. The rs340874 PROX1 type 2 diabetes mellitus risk variant is associated with visceral fat accumulation and alterations in postprandial glucose and lipid metabolism.

    PubMed

    Kretowski, Adam; Adamska, Edyta; Maliszewska, Katarzyna; Wawrusiewicz-Kurylonek, Natalia; Citko, Anna; Goscik, Joanna; Bauer, Witold; Wilk, Juliusz; Golonko, Anna; Waszczeniuk, Magdalena; Lipinska, Danuta; Hryniewicka, Justyna; Niemira, Magdalena; Paczkowska, Magdalena; Ciborowski, Michal; Gorska, Maria

    2015-03-01

    Large-scale meta-analyses of genome-wide association studies have recently confirmed that the rs340874 single-nucleotide polymorphism in PROX1 gene is associated with fasting glycemia and type 2 diabetes mellitus; however, the mechanism of this link was not well established. The aim of our study was to evaluate the functional/phenotypic differences related to rs340874 PROX1 variants. The study group comprised 945 subjects of Polish origin (including 634 with BMI > 25) without previously known dysglycemia. We analyzed behavioral patterns (diet, physical activity), body fat distribution and glucose/fat metabolism after standardized meals and during the oral glucose tolerance test. We found that the carriers of the rs340874 PROX1 CC genotype had higher nonesterified fatty acids levels after high-fat meal (p = 0.035) and lower glucose oxidation (p = 0.014) after high-carbohydrate meal in comparison with subjects with other PROX1 genotypes. Moreover, in subjects with CC variant, we found higher accumulation of visceral fat (p < 0.02), but surprisingly lower daily food consumption (p < 0.001). We hypothesize that lipid metabolism alterations in subjects with the PROX1 CC genotype may be a primary cause of higher glucose levels after glucose load, since the fatty acids can inhibit insulin-stimulated glucose uptake by decreasing carbohydrate oxidation. Our observations suggest that the PROX1 variants have pleiotropic effect on disease pathways and it seem to be a very interesting goal of research on prevention of obesity and type 2 diabetes mellitus. The study may help to understand the mechanisms of visceral obesity and type 2 diabetes mellitus risk development. PMID:25601634

  14. 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

  15. The protein level of isoenergetic formulae does not modulate postprandial insulin secretion in piglets and has no consequences on later glucose tolerance.

    PubMed

    Blat, Sophie; Morise, Anne; Sauret, Anne; Louveau, Isabelle; Macé, Katherine; Le Huërou-Luron, Isabelle; Sève, Bernard

    2012-07-14

    Early postnatal nutrition is involved in metabolic programming, an excess of protein being suspected to enhance early growth and the propensity to later develop insulin resistance and type 2 diabetes mellitus. The aim of the present study was to test the hypothesis that excessive protein intake during the suckling period would overstimulate the endocrine pancreas in the short term and alter durably its maturation, contributing to the later disruption of glucose homeostasis. Normal-birth-weight and low-birth-weight piglets were fed isoenergetic formulae providing an adequate-protein (AP, equivalent to sow milk) or a high-protein (HP, +48 %) supply between 7 and 28 d of age and were fed a standard diet until 70 d of age. During the formula-feeding period, the HP formula did not modify postprandial insulin secretion but transiently increased fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR, P < 0·05). Fasting insulin and HOMA-IR were restored to AP piglets' values 1 month after weaning. The structure of the endocrine pancreas was not affected by the protein content of the formula. The weight at birth had no major effect on the studied parameters. We concluded that a high-protein supply during the suckling period does not interfere with insulin secretion and endocrine pancreas maturation in the short term. It has no consequences either on glucose tolerance 1 month after weaning. The present study demonstrated that up-regulation of postprandial insulin secretion is not involved in higher growth observed in piglets fed a HP formula. PMID:22018265

  16. Lipid metabolizing enzyme activities modulated by phospholipid substrate lateral distribution.

    PubMed

    Salinas, Dino G; Reyes, Juan G; De la Fuente, Milton

    2011-09-01

    Biological membranes contain many domains enriched in phospholipid lipids and there is not yet clear explanation about how these domains can control the activity of phospholipid metabolizing enzymes. Here we used the surface dilution kinetic theory to derive general equations describing how complex substrate distributions affect the activity of enzymes following either the phospholipid binding kinetic model (which assumes that the enzyme molecules directly bind the phospholipid substrate molecules), or the surface-binding kinetic model (which assumes that the enzyme molecules bind to the membrane before binding the phospholipid substrate). Our results strongly suggest that, if the enzyme follows the phospholipid binding kinetic model, any substrate redistribution would increase the enzyme activity over than observed for a homogeneous distribution of substrate. Besides, enzymes following the surface-binding model would be independent of the substrate distribution. Given that the distribution of substrate in a population of micelles (each of them a lipid domain) should follow a Poisson law, we demonstrate that the general equations give an excellent fit to experimental data of lipases acting on micelles, providing reasonable values for kinetic parameters--without invoking special effects such as cooperative phenomena. Our theory will allow a better understanding of the cellular-metabolism control in membranes, as well as a more simple analysis of the mechanisms of membrane acting enzymes. PMID:21108012

  17. Anionic Lipids Modulate the Activity of the Aquaglyceroporin GlpF

    PubMed Central

    Klein, Noreen; Hellmann, Nadja; Schneider, Dirk

    2015-01-01

    The structure and composition of a biological membrane can severely influence the activity of membrane-embedded proteins. Here, we show that the E. coli aquaglyceroporin GlpF has only little activity in lipid bilayers formed from native E. coli lipids. Thus, at first glance, GlpF appears to not be optimized for its natural membrane environment. In fact, we found that GlpF activity was severely affected by negatively charged lipids regardless of the exact chemical nature of the lipid headgroup, whereas GlpF was not sensitive to changes in the lateral membrane pressure. These observations illustrate a potential mechanism by which the activity of an α-helical membrane protein is modulated by the negative charge density around the protein. PMID:26287624

  18. Modulation of Innate Immune Signalling by Lipid-Mediated MAVS Transmembrane Domain Oligomerization

    PubMed Central

    Ron, David; Volmer, Romain

    2015-01-01

    RIG-I-like receptors detect viral RNA in infected cells and promote oligomerization of the outer mitochondrial membrane protein MAVS to induce innate immunity to viral infection through type I interferon production. Mitochondrial reactive oxygen species (mROS) have been shown to enhance anti-viral MAVS signalling, but the mechanisms have remained obscure. Using a biochemical oligomerization-reporter fused to the transmembrane domain of MAVS, we found that mROS inducers promoted lipid-dependent MAVS transmembrane domain oligomerization in the plane of the outer mitochondrial membrane. These events were mirrored by Sendai virus infection, which similarly induced lipid peroxidation and promoted lipid-dependent MAVS transmembrane domain oligomerization. Our observations point to a role for mROS-induced changes in lipid bilayer properties in modulating antiviral innate signalling by favouring the oligomerization of MAVS transmembrane domain in the outer-mitochondrial membrane. PMID:26317833

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  20. 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. PMID:25967672

  1. Lipoprotein lipase is an important modulator of lipid uptake and storage in hypothalamic neurons.

    PubMed

    Libby, Andrew E; Wang, Hong; Mittal, Richa; Sungelo, Mitchell; Potma, Eric; Eckel, Robert H

    2015-09-18

    LPL is the rate-limiting enzyme for uptake of TG-derived FFA in peripheral tissues, and the enzyme is expressed in the brain and CNS. We previously created a mouse which lacks neuronal LPL. This animal becomes obese on a standard chow, and we observed reduced lipid uptake in the hypothalamus at 3 months preceding obesity. In our present study, we replicated the animal phenotype in an immortalized mouse hypothalamic cell line (N41) to examine how LPL affects expression of AgRP as well as entry and storage of lipids into neurons. We show that LPL is able to modulate levels of the orexigenic peptide AgRP. LPL also exerts effects on lipid uptake into culture neurons, and that uptake of neutral lipid can be enhanced even by mutant LPL lacking catalytic activity. N41 cells also accumulate neutral lipid in droplets, and this is at least in part regulated by LPL. These data in addition to those published in mice with neuron-specific deletion of LPL suggest that neuronal LPL is an important regulator of lipid homeostasis in neurons and that alterations in LPL levels may have important effects on systemic metabolism and neuronal lipid biology. PMID:26265042

  2. Uric acid as a modulator of glucose and lipid metabolism.

    PubMed

    Lima, William Gustavo; Martins-Santos, Maria Emília Soares; Chaves, Valéria Ernestânia

    2015-09-01

    In humans, uric acid is the final oxidation product of purine catabolism. The serum uric acid level is based on the balance between the absorption, production and excretion of purine. Uric acid is similarly produced in the liver, adipose tissue and muscle and is primarily excreted through the urinary tract. Several factors, including a high-fructose diet and the use of xenobiotics and alcohol, contribute to hyperuricaemia. Hyperuricaemia belongs to a cluster of metabolic and haemodynamic abnormalities, called metabolic syndrome, characterised by abdominal obesity, glucose intolerance, insulin resistance, dyslipidaemia and hypertension. Hyperuricaemia reduction in the Pound mouse or fructose-fed rats, as well as hyperuricaemia induction by uricase inhibition in rodents and studies using cell culture have suggested that uric acid plays an important role in the development of metabolic syndrome. These studies have shown that high uric acid levels regulate the oxidative stress, inflammation and enzymes associated with glucose and lipid metabolism, suggesting a mechanism for the impairment of metabolic homeostasis. Humans lacking uricase, the enzyme responsible for uric acid degradation, are susceptible to these effects. In this review, we summarise the current knowledge of the effects of uric acid on the regulation of metabolism, primarily focusing on liver, adipose tissue and skeletal muscle. PMID:26133655

  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. 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

  5. Postprandial metabolism of meal triglyceride in humans*,**

    PubMed Central

    Lambert, Jennifer E.; Parks, Elizabeth J.

    2012-01-01

    The intake of dietary fat above energy needs has contributed to the growing rates of obesity worldwide. The concept of disease development occurring in the fed state now has much support and dysregulation of substrate flux may occur due to poor handling of dietary fat in the immediate postprandial period. The present paper will review recent observations implicating cephalic phase events in the control of enterocyte lipid transport, the impact of varying the composition of meals on subsequent fat metabolism, and the means by which dietary lipid carried in chylomicrons can lead to elevated postprandial non-esterified fatty acid concentrations. This discussion is followed by an evaluation of the data on quantitative meal fat oxidation at the whole body level and an examination of dietary fat clearance to peripheral tissues — with particular attention paid to skeletal muscle and liver given the role of ectopic lipid deposition in insulin resistance. Estimates derived from data of dietary-TG clearance show good agreement with clearance to the liver equaling 8–12% of meal fat in lean subjects and this number appears higher (10–16%) in subjects with diabetes and fatty liver disease. Finally, we discuss new methods with which to study dietary fatty acid partitioning in vivo. Future research is needed to include a more comprehensive understanding of 1) the potential for differential oxidation of saturated versus unsaturated fatty acids which might lead to meaningful energy deficit and whether this parameter varies based on insulin sensitivity, 2) whether compartmentalization exists for diet-derived fatty acids within tissues vs. intracellular pools, and 3) the role of reduced peripheral fatty acid clearance in the development of fatty liver disease. Further advancements in the quantitation of dietary fat absorption and disposal will be central to the development of therapies designed to treat diet-induced obesity. This article is part of a Special Issue entitled

  6. Modulating lipid dynamics and membrane fluidity to drive rapid folding of a transmembrane barrel

    PubMed Central

    Maurya, Svetlana Rajkumar; Chaturvedi, Deepti; Mahalakshmi, Radhakrishnan

    2013-01-01

    Lipid-protein interactions, critical for the folding, stability and function of membrane proteins, can be both of mechanical and chemical nature. Mechanical properties of lipid systems can be suitably influenced by physical factors so as to facilitate membrane protein folding. We demonstrate here that by modulating lipid dynamics transiently using heat, rapid folding of two 8-stranded transmembrane β-barrel proteins OmpX and OmpA1–171, in micelles and vesicles, can be achieved within seconds. Folding kinetics using this ‘heat shock’ method shows a dramatic ten to several hundred folds increase in refolding rate along with ~100% folding efficiency. We establish that OmpX thus folded is highly thermostable even in detergent micelles, and retains structural characteristics comparable to the protein in bilayers. PMID:23771099

  7. Immunobiology of lipid-modulated UV-carcinogenesis.

    PubMed

    Black, H S; Okotie-Eboh, G; Gerguis, J

    1998-07-10

    Previous studies have demonstrated that high levels of dietary fat exacerbate UV-carcinogenic expression and suppress immunoresponsiveness. The latter may account for the former response. We have explored this possibility through T-lymphocyte transfer studies. Groups of HRA.HRII-c/+/Skh hairless mice were fed isocaloric diets containing high (12%, wt./wt.) or low (0.75%) levels of corn oil and irradiated 5 days/week (1.0 J cm-2/day) for 11 weeks with filtered FS-40 sunlamps. At weeks nine and 12, enriched T-cells from high-fat donors that had received 11 weeks of UV were transferred intravenously to low-fat recipients. Median tumor times for high-fat, low-fat recipient, and low-fat groups were 15.8, 18.5, and 21.6 weeks, respectively. The significantly (P < 0.03) shortened primary tumor latent period in low-fat-fed animals resulting from transfer of relatively low levels of T-cells derived from chronically irradiated high-fat donors demonstrates that the influence of dietary fat upon UV-carcinogenic expression is, at least partially, mediated via immunologic mechanisms. Further studies suggest that fat-modulated carcinogenesis can, itself, be regulated immunologically. A soluble T-14 (mouse squamous carcinoma cell line) cell-free fraction was injected subcutaneously at axillae and inguen of animals fed the high-fat diet during the first three weeks of UV or immediately post-UV. At week four post-UV, animals were challenged with T-14 cells injected subcutaneously at both flanks. 21 days post-challenge the tumor volumes of low-fat and high-fat immunized animals were zero versus 593 mm3 for the high-fat group (P < 0.007). Such treatment significantly (P < 0.03) increases the latent period of UV-induced primary tumors as well, when compared to non-treated high-fat-fed animals. PMID:9757594

  8. 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.

  9. Modulation of a Small Two-Domain Lipid Vesicle by Linactants

    PubMed Central

    2015-01-01

    Linactants, molecules that preferentially localize at the boundary of lipid membrane domains, are attracting considerable attention in recent years due to the recognition that they might regulate lipid-phase separation and thereby modulate membrane morphology. Recent studies have also shown that clustering of some line active agents enhances their ability to modulate membrane curvature. However, the molecular origin of this phenomenon, and the degree to which it impacts biological membranes, remains poorly understood. In this work, we have investigated how linactants induce shape change in multidomain small unilamallar vesicles (SUVs) using extensive dissipative particle dynamics simulations. The linactant was modeled as a two-tailed hybrid lipid with the two tails differing in preference for different lipid domains. We found that addition of a small amount of linactants (∼1%) to a two-domain vesicle leads to substantial reduction in the line tension and neck curvature at the domain boundary. Using cross-linking as a surrogate for clustering, we further show that linactant clusters substantially enhance the boundary preference and therefore the reduction in neck curvature. Moreover, on the basis of analyses of the corresponding changes in the membrane energetics, we highlight how linactants might stabilize nanoscale domains. These results have important implications for the potential existence and physical explanations of nanosized domains in biological membranes. PMID:25003709

  10. Impact of Lipid Raft Integrity on 5-HT3 Receptor Function and its Modulation by Antidepressants

    PubMed Central

    Nothdurfter, Caroline; Tanasic, Sascha; Di Benedetto, Barbara; Rammes, Gerhard; Wagner, Eva-Maria; Kirmeier, Thomas; Ganal, Vanessa; Kessler, Julia S; Rein, Theo; Holsboer, Florian; Rupprecht, Rainer

    2010-01-01

    Because of the biochemical colocalization of the 5-HT3 receptor and antidepressants within raft-like domains and their antagonistic effects at this ligand-gated ion channel, we investigated the impact of lipid raft integrity for 5-HT3 receptor function and its modulation by antidepressants. Treatment with methyl-β-cyclodextrine (MβCD) markedly reduced membrane cholesterol levels and caused a more diffuse membrane distribution of the lipid raft marker protein flotillin-1 indicating lipid raft impairment. Both amplitude and charge of serotonin evoked cation currents were diminished following cholesterol depletion by either MβCD or simvastatin (Sim), whereas the functional antagonistic properties of the antidepressants desipramine (DMI) and fluoxetine (Fluox) at the 5-HT3 receptor were retained. Although both the 5-HT3 receptor and flotillin-1 were predominantly found in raft-like domains in western blots following sucrose density gradient centrifugation, immunocytochemistry revealed only a coincidental degree of colocalization of these two proteins. These findings and the persistence of the antagonistic effects of DMI and Fluox against 5-HT3 receptors after lipid raft impairment indicate that their modulatory effects are likely mediated through non-raft 5-HT3 receptors, which are not sufficiently detected by means of sucrose density gradient centrifugation. In conclusion, lipid raft integrity appears to be important for 5-HT3 receptor function in general, whereas it is not a prerequisite for the antagonistic properties of antidepressants such as DMI and Fluox at this ligand-gated ion channel. PMID:20200506

  11. 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. PMID:25818259

  12. Modulation of lipid metabolic defects rescues cleft palate in Tgfbr2 mutant mice.

    PubMed

    Iwata, Junichi; Suzuki, Akiko; Pelikan, Richard C; Ho, Thach-Vu; Sanchez-Lara, Pedro A; Chai, Yang

    2014-01-01

    Mutations in transforming growth factor beta (TGFβ) receptor type II (TGFBR2) cause Loeys-Dietz syndrome, characterized by craniofacial and cardiovascular abnormalities. Mice with a deletion of Tgfbr2 in cranial neural crest cells (Tgfbr2(fl/fl);Wnt1-Cre mice) develop cleft palate as the result of abnormal TGFβ signaling activation. However, little is known about metabolic processes downstream of TGFβ signaling during palatogenesis. Here, we show that Tgfbr2 mutant palatal mesenchymal cells spontaneously accumulate lipid droplets, resulting from reduced lipolysis activity. Tgfbr2 mutant palatal mesenchymal cells failed to respond to the cell proliferation stimulator sonic hedgehog, derived from the palatal epithelium. Treatment with p38 mitogen-activated protein kinase (MAPK) inhibitor or telmisartan, a modulator of p38 MAPK activation and lipid metabolism, blocked abnormal TGFβ-mediated p38 MAPK activation, restoring lipid metabolism and cell proliferation activity both in vitro and in vivo. Our results highlight the influence of alternative TGFβ signaling on lipid metabolic activities, as well as how lipid metabolic defects can affect cell proliferation and adversely impact palatogenesis. This discovery has broader implications for the understanding of metabolic defects and potential prevention of congenital birth defects. PMID:23975680

  13. Modulation of the interaction between neurotensin receptor NTS1 and Gq protein by lipid

    PubMed Central

    Inagaki, Sayaka; Ghirlando, Rodolfo; White, Jim F.; Gvozdenovic-Jeremic, Jelena; Northup, John K.; Grisshammer, Reinhard

    2012-01-01

    Membrane lipids have been implicated to influence the activity of G protein-coupled receptors (GPCRs). Almost all of our knowledge on the role of lipids on GPCR and G protein function comes from work on the visual pigment rhodopsin and its G protein transducin, which reside in a highly specialized membrane environment. Thus insight gained from rhodopsin signaling may not be simply translated to other non-visual GPCRs. Here, we investigated the effect of lipid head group charges on the signal transduction properties of the class A GPCR neurotensin receptor 1 (NTS1) under defined experimental conditions, using self-assembled phospholipid nanodiscs prepared with the zwitter-ionic lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), the negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (POPG), or a POPC/POPG mixture. A combination of dynamic light scattering and sedimentation velocity showed that NTS1 was monomeric in POPC-, POPC/POPG- and POPG-nanodiscs. Binding of the agonist neurotensin to NTS1 occurred with similar affinities and was essentially unaffected by the phospholipid composition. In contrast, Gq protein coupling to NTS1 in various lipid nanodiscs was significantly different and the apparent affinity of Gαq and Gβ1γ1 to activated NTS1 increased with increasing POPG content. NTS1-catalyzed GDP/GTPγS nucleotide exchange at Gαq in the presence of Gβ1γ1 and neurotensin was crucially affected by the lipid type, with exchange rates higher by one or two orders of magnitude in POPC/POPG- and POPG-nanodiscs, respectively, compared to POPC-nanodiscs. Our data demonstrate that negatively charged lipids in the immediate vicinity of a non-visual GPCR modulate the G protein-coupling step. PMID:22306739

  14. Age-related changes in retinoic, docosahexaenoic and arachidonic acid modulation in nuclear lipid metabolism.

    PubMed

    Gaveglio, Virginia L; Pascual, Ana C; Giusto, Norma M; Pasquaré, Susana J

    2016-08-15

    The aim of this work was to study how age-related changes could modify several enzymatic activities that regulate lipid mediator levels in nuclei from rat cerebellum and how these changes are modulated by all-trans retinoic acid (RA), docosahexaenoic acid (DHA) and arachidonic acid (AA). The higher phosphatidate phosphohydrolase activity and lower diacylglycerol lipase (DAGL) activity observed in aged animals compared with adults could augment diacylglycerol (DAG) availability in the former. Additionally, monoacylglycerol (MAG) availability could be high due to an increase in lysophosphatidate phosphohydrolase (LPAPase) activity and a decrease in monocylglycerol lipase activity. Interestingly, RA, DHA and AA were observed to modulate these enzymatic activities and this modulation was found to change in aged rats. In adult nuclei, whereas RA led to high DAG and MAG production through inhibition of their hydrolytic enzymes, DHA and AA promoted high MAG production by LPAPase and DAGL stimulation. In contrast, in aged nuclei RA caused high MAG generation whereas DHA and AA diminished it through LPAPase activity modulation. These results demonstrate that aging promotes a different nuclear lipid metabolism as well as a different type of non-genomic regulation by RA, DHA and AA, which could be involved in nuclear signaling events. PMID:27355428

  15. 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

  16. 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

  17. 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. PMID:26374445

  18. 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. PMID:26173584

  19. Neuroactive steroid treatment modulates myelin lipid profile in diabetic peripheral neuropathy.

    PubMed

    Mitro, Nico; Cermenati, Gaia; Brioschi, Elisabetta; Abbiati, Federico; Audano, Matteo; Giatti, Silvia; Crestani, Maurizio; De Fabiani, Emma; Azcoitia, Inigo; Garcia-Segura, Luis Miguel; Caruso, Donatella; Melcangi, Roberto Cosimo

    2014-09-01

    Diabetic peripheral neuropathy causes a decrease in the levels of dihydroprogesterone and 5α-androstane-3α,17β-diol (3α-diol) in the peripheral nerves. These two neuroactive steroids exert protective effects, by mechanisms that still remain elusive. We have previously shown that the activation of Liver X Receptors improves the peripheral neuropathic phenotype in diabetic rats. This protective effect is accompanied by the restoration to control values of the levels of dihydroprogesterone and 3α-diol in peripheral nerves. In addition, activation of these receptors decreases peripheral myelin abnormalities by improving the lipid desaturation capacity, which is strongly blunted by diabetes, and ultimately restores the myelin lipid profile to non-diabetic values. On this basis, we here investigate whether dihydroprogesterone or 3α-diol may exert their protective effects by modulating the myelin lipid profile. We report that both neuroactive steroids act on the lipogenic gene expression profile in the sciatic nerve of diabetic rats, reducing the accumulation of myelin saturated fatty acids and promoting desaturation. These changes were associated with a reduction in myelin structural alterations. These findings provide evidence that dihydroprogesterone and 3α-diol are protective agents against diabetic peripheral neuropathy by regulating the de novo lipogenesis pathway, which positively influences myelin lipid profile. PMID:24607810

  20. Specific ions modulate diffusion dynamics of hydration water on lipid membrane surfaces.

    PubMed

    Song, Jinsuk; Franck, John; Pincus, Philip; Kim, Mahn Won; Han, Songi

    2014-02-12

    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

  1. 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

  2. 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

  3. Lipid-mediated Protein-protein Interactions Modulate Respiration-driven ATP Synthesis

    PubMed Central

    Nilsson, Tobias; Lundin, Camilla Rydström; Nordlund, Gustav; Ädelroth, Pia; von Ballmoos, Christoph; Brzezinski, Peter

    2016-01-01

    Energy conversion in biological systems is underpinned by membrane-bound proton transporters that generate and maintain a proton electrochemical gradient across the membrane which used, e.g. for generation of ATP by the ATP synthase. Here, we have co-reconstituted the proton pump cytochrome bo3 (ubiquinol oxidase) together with ATP synthase in liposomes and studied the effect of changing the lipid composition on the ATP synthesis activity driven by proton pumping. We found that for 100 nm liposomes, containing 5 of each proteins, the ATP synthesis rates decreased significantly with increasing fractions of DOPA, DOPE, DOPG or cardiolipin added to liposomes made of DOPC; with e.g. 5% DOPG, we observed an almost 50% decrease in the ATP synthesis rate. However, upon increasing the average distance between the proton pumps and ATP synthases, the ATP synthesis rate dropped and the lipid dependence of this activity vanished. The data indicate that protons are transferred along the membrane, between cytochrome bo3 and the ATP synthase, but only at sufficiently high protein densities. We also argue that the local protein density may be modulated by lipid-dependent changes in interactions between the two proteins complexes, which points to a mechanism by which the cell may regulate the overall activity of the respiratory chain. PMID:27063297

  4. 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

  5. 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

  6. 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

  7. A role for direct interactions in the modulation of rhodopsin by -3 polyunsaturated lipids

    NASA Astrophysics Data System (ADS)

    Grossfield, Alan; Feller, Scott E.; Pitman, Michael C.

    2006-03-01

    Rhodopsin, the G protein-coupled receptor primarily responsible for sensing light, is found in an environment rich in polyunsaturated lipid chains and cholesterol. Biophysical experiments have shown that lipid unsaturation and cholesterol both have significant effects on rhodopsin's stability and function; -3 polyunsaturated chains, such as docosahexaenoic acid (DHA), destabilize rhodopsin and enhance the kinetics of the photocycle, whereas cholesterol has the opposite effect. Here, we use molecular dynamics simulations to investigate the possibility that polyunsaturated chains modulate rhodopsin stability and kinetics via specific direct interactions. By analyzing the results of 26 independent 100-ns simulations of dark-adapted rhodopsin, we found that DHA routinely forms tight associations with the protein in a small number of specific locations qualitatively different from the nonspecific interactions made by saturated chains and cholesterol. Furthermore, the presence of tightly packed DHA molecules tends to weaken the interhelical packing. These results are consistent with recent NMR work, which proposes that rhodopsin binds DHA, and they suggest a molecular rationale for DHA's effects on rhodopsin stability and kinetics. cholesterol | molecular dynamics | fatty acid | protein-lipid interactions

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

    PubMed

    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 the

  9. 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

  10. 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

  11. 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 (β1-, β2-, β3-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 β2-AR knockout (KO) and wildtype (WT) control mice to define further the role of β2-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 β2-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 β2-ARs in the regulation of lipid and glucose metabolism during aging. The effect of β2-AR ablation on caloric intake during aging is currently not known and requires investigation. Future studies are also warranted to delineate the β2-AR-mediated mechanisms involved in the control of lipid and glucose homeostasis, especially in the context of a growing aging population. PMID:26952573

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

    PubMed

    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

  13. 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

  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. The role of the M4 lipid-sensor in the folding, trafficking, and allosteric modulation of nicotinic acetylcholine receptors.

    PubMed

    Hénault, Camille M; Sun, Jiayin; Therien, J P Daniel; daCosta, Corrie J B; Carswell, Casey L; Labriola, Jonathan M; Juranka, Peter F; Baenziger, John E

    2015-09-01

    With the availability of high resolution structural data, increasing attention has focused on the mechanisms by which drugs and endogenous compounds allosterically modulate nicotinic acetylcholine receptor (nAChR) function. Lipids are potent modulators of the nAChR from Torpedo. Membrane lipids influence nAChR function by both conformational selection and kinetic mechanisms, stabilizing varying proportions of pre-existing resting, open, desensitized, and uncoupled conformations, as well as influencing the transitions between these conformational states. Structural and functional data highlight a role for the lipid-exposed M4 transmembrane α-helix of each subunit in lipid sensing, and suggest that lipids influence gating by altering the binding of M4 to the adjacent transmembrane α-helices, M1 and M3. M4 has also been implicated in both the folding and trafficking of nAChRs to the cell surface, as well as in the potentiation of nAChR gating by neurosteroids. Here, we discuss the roles of M4 in the folding, trafficking, and allosteric modulation of nAChRs. We also consider the hypothesis that variable chemistry at the M4-M1/M3 transmembrane α-helical interface in different nAChR subunits governs the capacity for potentiation by activating lipids. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. PMID:25433148

  16. Effect of selenium deficiency and glutathione-modulating agents on diquat toxicity and lipid peroxidation in rats.

    PubMed

    Awad, J A; Burk, R F; Roberts, L J

    1994-09-01

    The dipyridyl herbicide diquat undergoes redox cycling in vivo resulting in superoxide generation. Diquat administration causes hepatic and renal toxicity in rodents. Selenium deficiency worsens this injury and lipid peroxidation is a prominent feature of the toxicity. However, there is limited data regarding the role of lipid peroxidation in diquat-induced toxicity in selenium-adequate animals. In addition, little is known about the effect of glutathione-modulating agents on diquat-induced toxicity and lipid peroxidation in vivo. F2-isoprostanes are novel prostanoids which, both free in plasma and esterified to phospholipids in tissues, are markers of lipid peroxidation in vivo. By using F2-isoprostane quantitation, we examined the effects of selenium deficiency and modulation of glutathione status with 1,3-bis (2-chloroethyl)-1-nitrosourea, phorone or buthionine sulfoximine on diquat-induced toxicity and lipid peroxidation. F2-isoprostanes increased 2- to 9-fold in plasma, liver, kidney and lung in selenium-adequate Fischer 344 rats with liver injury after receiving 100 mumol of diquat per kg. Selenium deficiency or modulation of glutathione status increased diquat toxicity. This was accompanied by 10- to 100-fold increases in plasma and kidney F2-isoprostane levels. Liver F2-isoprostanes were increased 2- to 5-fold. These studies suggest that glutathione, in addition to selenium, is an important defense against diquat-induced toxicity and lipid peroxidation. PMID:7932197

  17. Fao cell. A tissue culture model for lipoprotein synthesis and secretion. II. Modulation by lipid depletion and supplementation

    SciTech Connect

    Scarino, M.L.; Howell, K.E.

    1987-05-01

    We have shown that the Fao cell, a differentiated rat hepatoma line, is an excellent model for the study of the synthesis of lipoproteins. Here we demonstrate that variation of the lipid composition of the growth medium significantly modulates the composition and quantity of particles formed. Three growth conditions were compared: normal, lipid-depleted, and lipid-supplemented. The synthesis of both the protein and lipid moieties of the lipoproteins was quantitated using the radioactive metabolic precursors (/sup 35/S)methionine and (/sup 14/C)acetate. The total secretion of the cells was collected and fractionated into four density classes equivalent to plasma lipoproteins and a bottom fraction equivalent to plasma proteins. Each density class was evaluated for the apoprotein distribution after separation by SDS-PAGE and for lipid distribution and composition after lipid extraction. ApoE accounts for approx. 15% of the total protein synthesized and is the major apoprotein. The amount synthesized remains relatively constant under all growth conditions. In contrast, the amount of apoB synthesis varies over 600-fold. In lipid-depleted conditions, only 0.01 times the normal amount was synthesized, while in lipid-supplemented conditions 6.2 times the normal amount was synthesized. ApoB was associated with the lighter fraction; therefore the modulation increased the quantity of low-density particles formed. A similar but far less pronounced variation of the heavier particles and the apoA-I concentration was obtained. Under lipid-depleted conditions, 0.75 times the normal amount was synthesized, while under lipid-supplemented conditions 2.6 times the normal quantity was synthesized.

  18. Postprandial Hyperglycemia and Glycemic Variability

    PubMed Central

    Standl, Eberhard; Schnell, Oliver; Ceriello, Antonio

    2011-01-01

    The aim of this article is to evaluate the pros and cons of a specific impact of postprandial hyperglycemia and glycemic variability on the—mainly cardiovascular (CV)—complications of diabetes, above and beyond the average blood glucose (BG) as measured by HbA1c or fasting plasma glucose (FPG). The strongest arguments in favor of this hypothesis come from impressive pathophysiological studies, also in the human situation. Measures of oxidative stress and endothelial dysfunction seem to be especially closely related to glucose peaks and even more so to fluctuating high and low glucose concentrations and can be restored to normal by preventing those glucose peaks or wide glucose excursions. The epidemiological evidence, which is more or less confined to postprandial hyperglycemia and postglucose load glycemia, is also rather compelling in favor of the hypothesis, although certainly not fully conclusive as there are also a number of conflicting results. The strongest cons are seen in the missing evidence as derived from randomized prospective intervention studies targeting postprandial hyperglycemia longer term, i.e., over several years, and seeking to reduce hard CV end points. In fact, several such intervention studies in men have recently failed to produce the intended beneficial outcome results. As this evidence by intervention is, however, key for the ultimate approval of a treatment concept in patients with diabetes, the current net balance of attained evidence is not in favor of the hypothesis here under debate, i.e., that we should care about postprandial hyperglycemia and glycemic variability. The absence of a uniformly accepted standard of how to estimate these parameters adds a further challenge to this whole debate. PMID:21525442

  19. Peroxisome proliferator-activated receptor alpha polymorphisms and postprandial lipemia in healthy men

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peroxisome proliferator-activated receptor alpha (PPARA) is a ligand-dependent transcription factor that plays a key role in lipid and glucose homeostasis. This study evaluated whether variants of PPARA are associated with postprandial lipemia. Subjects were given a single fat load comprised of 60% ...

  20. 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. PMID:27157327

  1. A role for direct interactions in the modulation of rhodopsin by ω-3 polyunsaturated lipids

    PubMed Central

    Grossfield, Alan; Feller, Scott E.; Pitman, Michael C.

    2006-01-01

    Rhodopsin, the G protein-coupled receptor primarily responsible for sensing light, is found in an environment rich in polyunsaturated lipid chains and cholesterol. Biophysical experiments have shown that lipid unsaturation and cholesterol both have significant effects on rhodopsin’s stability and function; ω-3 polyunsaturated chains, such as docosahexaenoic acid (DHA), destabilize rhodopsin and enhance the kinetics of the photocycle, whereas cholesterol has the opposite effect. Here, we use molecular dynamics simulations to investigate the possibility that polyunsaturated chains modulate rhodopsin stability and kinetics via specific direct interactions. By analyzing the results of 26 independent 100-ns simulations of dark-adapted rhodopsin, we found that DHA routinely forms tight associations with the protein in a small number of specific locations qualitatively different from the nonspecific interactions made by saturated chains and cholesterol. Furthermore, the presence of tightly packed DHA molecules tends to weaken the interhelical packing. These results are consistent with recent NMR work, which proposes that rhodopsin binds DHA, and they suggest a molecular rationale for DHA’s effects on rhodopsin stability and kinetics. PMID:16547139

  2. Type 2 diabetes mellitus is characterized by reduced postprandial adiponectin response: a possible link with diabetic postprandial dyslipidemia.

    PubMed

    Annuzzi, Giovanni; Bozzetto, Lutgarda; Patti, Lidia; Santangelo, Carmela; Giacco, Rosalba; Di Marino, Lucrezia; De Natale, Claudia; Masella, Roberta; Riccardi, Gabriele; Rivellese, Angela A

    2010-04-01

    We investigated postprandial plasma and adipose tissue (AT) adiponectin changes in relation to obesity and type 2 diabetes mellitus. Fasting and 6 hours after a standard fat-rich meal blood samples (adiponectin, glucose, insulin, lipids) and needle biopsies of abdominal subcutaneous AT (adiponectin messenger RNA, lipoprotein lipase activity) were taken in 10 obese diabetic (OD), 11 obese nondiabetic (OND), and 11 normal-weight control (C) men. The OD and OND subjects had similar adiposity (body mass index, waist circumference) and insulin resistance (hyperinsulinemic euglycemic clamp). Fasting plasma adiponectin and AT gene expression were not significantly different between groups. After meal, plasma adiponectin decreased in OD but significantly increased in OND and C, the changes being significantly different between groups (analysis of variance, P = .01); adiponectin messenger RNA decreased in OD (-0.27 +/- 0.25 AU, P = .01) but was unchanged in OND (P = .59) and C (P = .45). After meal, plasma adiponectin correlated inversely with triglyceride and cholesterol concentrations in chylomicrons and large very low-density lipoprotein, and directly with AT lipoprotein lipase activity (P < .05 for all). Type 2 diabetes mellitus is associated with lower postprandial plasma levels and AT gene expression of adiponectin independently of degree of adiposity and whole-body insulin sensitivity. In patients with diabetes, this may exacerbate postprandial abnormalities of lipoprotein metabolism. PMID:19922965

  3. 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

    2016-08-01

    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. PMID:26441050

  4. Pharmacological modulation of dietary lipid-induced cerebral capillary dysfunction: Considerations for reducing risk for Alzheimer's disease.

    PubMed

    Pallebage-Gamarallage, Menuka; Takechi, Ryusuke; Lam, Virginie; Elahy, Mina; Mamo, John

    2016-06-01

    An increasing body of evidence suggests that cerebrovascular dysfunction and microvessel disease precede the evolution of hallmark pathological features that characterise Alzheimer's disease (AD), consistent with a causal association for onset or progression. Recent studies, principally in genetically unmanipulated animal models, suggest that chronic ingestion of diets enriched in saturated fats and cholesterol may compromise blood-brain barrier (BBB) integrity resulting in inappropriate blood-to-brain extravasation of plasma proteins, including lipid macromolecules that may be enriched in amyloid-β (Aβ). Brain parenchymal retention of blood proteins and lipoprotein bound Aβ is associated with heightened neurovascular inflammation, altered redox homeostasis and nitric oxide (NO) metabolism. Therefore, it is a reasonable proposition that lipid-lowering agents may positively modulate BBB integrity and by extension attenuate risk or progression of AD. In addition to their robust lipid lowering properties, reported beneficial effects of lipid-lowering agents were attributed to their pleiotropic properties via modulation of inflammation, oxidative stress, NO and Aβ metabolism. The review is a contemporary consideration of a complex body of literature intended to synthesise focussed consideration of mechanisms central to regulation of BBB function and integrity. Emphasis is given to dietary fat driven significant epidemiological evidence consistent with heightened risk amongst populations consuming greater amounts of saturated fats and cholesterol. In addition, potential neurovascular benefits associated with the use of hypolipidemic statins, probucol and fenofibrate are also presented in the context of lipid-lowering and pleiotropic properties. PMID:26678521

  5. A lipid-mediated conformational switch modulates the thermosensing activity of DesK.

    PubMed

    Inda, María Eugenia; Vandenbranden, Michel; Fernández, Ariel; de Mendoza, Diego; Ruysschaert, Jean-Marie; Cybulski, Larisa Estefanía

    2014-03-01

    The thermosensor DesK is a multipass transmembrane histidine-kinase that allows the bacterium Bacillus subtilis to adjust the levels of unsaturated fatty acids required to optimize membrane lipid fluidity. The cytoplasmic catalytic domain of DesK behaves like a kinase at low temperature and like a phosphatase at high temperature. Temperature sensing involves a built-in instability caused by a group of hydrophilic residues located near the N terminus of the first transmembrane (TM) segment. These residues are buried in the lipid phase at low temperature and partially "buoy" to the aqueous phase at higher temperature with the thinning of the membrane, promoting the required conformational change. Nevertheless, the core question remains poorly understood: How is the information sensed by the transmembrane region converted into a rearrangement in the cytoplasmic catalytic domain to control DesK activity? Here, we identify a "linker region" (KSRKERERLEEK) that connects the TM sensor domain with the cytoplasmic catalytic domain involved in signal transmission. The linker adopts two conformational states in response to temperature-dependent membrane thickness changes: (i) random coiled and bound to the phospholipid head groups at the water-membrane interface, promoting the phosphatase state or (ii) unbound and forming a continuous helix spanning a region from the membrane to the cytoplasm, promoting the kinase state. Our results uphold the view that the linker is endowed with a helix/random coil conformational duality that enables it to behave like a transmission switch, with helix disruption decreasing the kinase/phosphatase activity ratio, as required to modulate the DesK output response. PMID:24522108

  6. Silibinin modulates lipid homeostasis and inhibits nuclear factor kappa B activation in experimental nonalcoholic steatohepatitis.

    PubMed

    Salamone, Federico; Galvano, Fabio; Cappello, Francesco; Mangiameli, Andrea; Barbagallo, Ignazio; Li Volti, Giovanni

    2012-06-01

    Nonalcoholic steatohepatitis (NASH) is associated with increased liver-related mortality. Disturbances in hepatic lipid homeostasis trigger oxidative stress and inflammation (ie, lipotoxicity), leading to the progression of NASH. This study aimed at identifying whether silibinin may influence the molecular events of lipotoxicity in a mouse model of NASH. Eight-week-old db/db mice were fed a methionine-choline deficient (MCD) diet for 4 weeks and treated daily with silibinin (20 mg/kg intraperitoneally) or vehicle. Liver expression and enzyme activity of stearoyl-CoA desaturase-1 and acyl-CoA oxidase, and expression of liver fatty acid-binding protein were assessed. Hepatic levels of reactive oxygen species, thiobarbituric acid-reactive substances (TBARS), 3-nitrotyrosine (3-NT), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NFkB) activities were also determined. Silibinin administration decreased serum alanine aminotransferase and improved liver steatosis, hepatocyte ballooning, and lobular inflammation in db/db mice fed an MCD diet. Gene expression and activity of stearoyl-CoA desaturase-1 were reduced in db/db mice fed an MCD diet compared with lean controls and were increased by silibinin; moreover, silibinin treatment induced the expression and activity of acyl-CoA oxidase and the expression of liver fatty acid-binding protein. Vehicle-treated animals displayed increased hepatic levels of reactive oxygen species and TBARS, 3-NT staining, and iNOS expression; silibinin treatment markedly decreased reactive oxygen species and TBARS and restored 3-NT and iNOS to the levels of control mice. db/db mice fed an MCD diet consistently had increased NFkB p65 and p50 binding activity; silibinin administration significantly decreased the activity of both subunits. Silibinin treatment counteracts the progression of liver injury by modulating lipid homeostasis and suppressing oxidative stress-mediated lipotoxicity and NFkB activation in experimental

  7. Almonds decrease postprandial glycemia, insulinemia, and oxidative damage in healthy individuals.

    PubMed

    Jenkins, David J A; Kendall, Cyril W C; Josse, Andrea R; Salvatore, Sara; Brighenti, Furio; Augustin, Livia S A; Ellis, Peter R; Vidgen, Edward; Rao, A Venket

    2006-12-01

    Strategies that decrease postprandial glucose excursions, including digestive enzyme inhibition, and low glycemic index diets result in lower diabetes incidence and coronary heart disease (CHD) risk, possibly through lower postprandial oxidative damage to lipids and proteins. We therefore assessed the effect of decreasing postprandial glucose excursions on measures of oxidative damage. Fifteen healthy subjects ate 2 bread control meals and 3 test meals: almonds and bread; parboiled rice; and instant mashed potatoes, balanced in carbohydrate, fat, and protein, using butter and cheese. We obtained blood samples at baseline and for 4 h postprandially. Glycemic indices for the rice (38 +/- 6) and almond meals (55 +/- 7) were less than for the potato meal (94 +/- 11) (P < 0.003), as were the postprandial areas under the insulin concentration time curve (P < 0.001). No postmeal treatment differences were seen in total antioxidant capacity. However, the serum protein thiol concentration increased following the almond meal (15 +/- 14 mmol/L), indicating less oxidative protein damage, and decreased after the control bread, rice, and potato meals (-10 +/- 8 mmol/L), when data from these 3 meals were pooled (P = 0.021). The change in protein thiols was also negatively related to the postprandial incremental peak glucose (r = -0.29, n = 60 observations, P = 0.026) and peak insulin responses (r = -0.26, n = 60 observations, P = 0.046). Therefore, lowering postprandial glucose excursions may decrease the risk of oxidative damage to proteins. Almonds are likely to lower this risk by decreasing the glycemic excursion and by providing antioxidants. These actions may relate to mechanisms by which nuts are associated with a decreased risk of CHD. PMID:17116708

  8. Adipocyte-derived lipids increase angiotensin-converting enzyme (ACE) expression and modulate macrophage phenotype.

    PubMed

    Kohlstedt, Karin; Trouvain, Caroline; Namgaladze, Dmitry; Fleming, Ingrid

    2011-03-01

    Human monocytes/macrophages express the angiotensin-converting enzyme (ACE) but nothing is known about its role under physiological conditions. As adipose tissue contains resident macrophages that have been implicated in the generation of insulin resistance in expanding fat mass, we determined whether adipocytes release factors that affect ACE expression and function in monocytes. Incubation of human monocyte-derived macrophages with conditioned medium from freshly isolated human adipocytes (BMI = 25.4 ± 0.96) resulted in a 4-fold increase in ACE expression. The effect was insensitive to denaturation and different proteases but abolished after lipid extraction. mRNA levels of the major histocompatibility complex class II protein increased in parallel with ACE, whereas the expression of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, and cyclooxygenase-2 decreased. As a consequence of the reduction in MCP-1, monocyte recruitment was also attenuated. Moreover, adipocyte-conditioned medium prevented the interferon (IFN)-γ induced formation of TNF-α, IL-6, and MCP-1, all markers of classically-activated (M1 type) macrophages. The decrease in cytokine expression in adipocyte-conditioned medium-treated macrophages was sensitive to ACE silencing by small interfering RNA (siRNA). Accordingly, ACE overexpression in THP-1 cells mimicked the effect of adipocyte-conditioned medium. In both cell types, ACE inhibition failed to affect the changes induced by adipocyte conditioned-medium treatment and ACE overexpression. Thus, the modulation of macrophage polarization by ACE appears to be mediated independently of enzyme activity, probably via intracellular signaling. Interestingly, human macrophage ACE expression was also upregulated by IL-4 and IL-13, which promote the "alternative" activation of macrophages and decreased by LPS and IFN-γ. Mechanistically, adipocyte-conditioned medium stimulated the phosphorylation of

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

    PubMed

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

    2013-09-01

    Carotene-15,15'-monooxygenase (CMO-I) cleaves β-carotene to form vitamin A, whereas carotene-9',10'-monooxygenase (CMO-II) preferentially cleaves non-provitamin A carotenoids. Recent reports indicate that β-carotene metabolites regulate dietary lipid uptake, whereas lycopene regulates peroxisome proliferator-activated receptor 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 insulin-like growth factor 1 levels and cholesterol levels, but elevated liver lipids and cholesterol compared with wild-type mice. The diets did not modulate these genotypic perturbations, but lycopene and tomato powder significantly decreased serum insulin-like growth factor 1. Tomato powder also increased hepatic peroxisome proliferator-activated receptor 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

  10. 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

  11. Epstein-Barr virus LMP1 modulates lipid raft microdomains and the vimentin cytoskeleton for signal transduction and transformation.

    PubMed

    Meckes, David G; Menaker, Nathan F; Raab-Traub, Nancy

    2013-02-01

    The Epstein-Barr virus (EBV) is an important human pathogen that is associated with multiple cancers. The major oncoprotein of the virus, latent membrane protein 1 (LMP1), is essential for EBV B-cell immortalization and is sufficient to transform rodent fibroblasts. This viral transmembrane protein activates multiple cellular signaling pathways by engaging critical effector molecules and thus acts as a ligand-independent growth factor receptor. LMP1 is thought to signal from internal lipid raft containing membranes; however, the mechanisms through which these events occur remain largely unknown. Lipid rafts are microdomains within membranes that are rich in cholesterol and sphingolipids. Lipid rafts act as organization centers for biological processes, including signal transduction, protein trafficking, and pathogen entry and egress. In this study, the recruitment of key signaling components to lipid raft microdomains by LMP1 was analyzed. LMP1 increased the localization of phosphatidylinositol 3-kinase (PI3K) and its activated downstream target, Akt, to lipid rafts. In addition, mass spectrometry analyses identified elevated vimentin in rafts isolated from LMP1 expressing NPC cells. Disruption of lipid rafts through cholesterol depletion inhibited PI3K localization to membranes and decreased both Akt and ERK activation. Reduction of vimentin levels or disruption of its organization also decreased LMP1-mediated Akt and ERK activation and inhibited transformation of rodent fibroblasts. These findings indicate that LMP1 reorganizes membrane and cytoskeleton microdomains to modulate signal transduction. PMID:23152522

  12. 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

  13. 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

  14. 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. PMID:26707880

  15. 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

  16. 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

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

    PubMed Central

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

    2015-01-01

    Progestins induce lipid accumulation in progesterone receptor (PR)-positive breast cancer cells. We speculated that progestin-induced alterations in lipid biology confer resistance to chemotherapy. To examine the biology of lipid loaded breast cancer cells, we used a model of progestin-induced lipid synthesis. T47D (PR-positive) and MDA-MB-231(PR-negative) cell lines were used to study progestin response. Oil red O staining of T47D cells treated with progestin showed lipid droplet formation was PR dependent, glucose dependent and reduced sensitivity to docetaxel. This protection was not observed in PR-negative MDA-MB-231 cells. Progestin treatment induced stearoyl CoA desaturase-1 (SCD-1) enzyme expression and chemical inhibition of SCD-1 diminished lipid droplets and cell viability, suggesting the importance of lipid stores in cancer cell survival. Gas chromatography/mass spectroscopy analysis of phospholipids from progestin-treated T47D cells revealed an increase in unsaturated fatty acids, with oleic acid as most abundant. Cells surviving docetaxel treatment also contained more oleic acid in phospholipids, suggesting altered membrane fluidity as a potential mechanism of chemoresistance mediated in part by SCD-1. Lastly, intact docetaxel molecules were present within progestin induced lipid droplets, suggesting a protective quenching effect of intracellular lipid droplets. Our studies suggest the metabolic adaptations produced by progestin provide novel metabolic targets for future combinatorial therapies for progestin-responsive breast cancers. PMID:22922095

  18. 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

  19. Potential scorpionate antibiotics: targeted hydrolysis of lipid II containing model membranes by vancomycin-TACzyme conjugates and modulation of their antibacterial activity by Zn-ions.

    PubMed

    Bauke Albada, H; Arnusch, Christopher J; Branderhorst, Hilbert M; Verel, Anne-Marie; Janssen, Wouter T M; Breukink, Eefjan; de Kruijff, Ben; Pieters, Roland J; Liskamp, Rob M J

    2009-07-15

    The antibiotic vancomycin-that binds lipid II in the bacterial cell membrane-was conjugated to a mono- and tetravalent mimic of the tris-histidine catalytic triad of metalloenzymes. Targeted hydrolysis by the conjugate was observed using model membranes containing lipid II, and in vitro MIC-values of the targeted mimic constructs could be modulated by Zn-ions. PMID:19524434

  20. 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. PMID:25194937

  1. 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. PMID:23176795

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

    PubMed Central

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

    2014-01-01

    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. PMID:24423726

  3. Vitamin D3 mediated effects on postprandial leukocyte activation and arterial stiffness in men and women.

    PubMed

    Klop, B; van de Geijn, G-J M; Birnie, E; Njo, T L; Janssen, H W; Jansen, H G; Jukema, J W; Elte, J W F; Castro Cabezas, M

    2014-05-01

    Postprandial inflammation is considered to be pro-atherogenic. Vitamin D can reduce inflammation and arterial stiffness. We hypothesized that vitamin D3 improves postprandial arterial elasticity by the modulation of leukocyte activation. Healthy volunteers underwent two oral fat-loading tests (OFLTs). The augmentation index (AIx) and flow cytometric quantification of leukocyte activation markers were measured. After the first OFLT, 100 000 IU of vitamin D3 was administered and a second OFLT was carried out 7 days later. Six men and six women were included. A favorable reduction in AIx was found after vitamin D3 supplementation (P=0.042) in both genders. After vitamin D3, exclusively in women a reduction in the area under the postprandial curve for monocytes CD11b and CD35 by 10.5% (P=0.016) and 12.5% (P=0.04) and neutrophil CD11b by 17.0% (P=0.014) was observed. In conclusion, vitamin D3 probably increased postprandial arterial elasticity in men and women, but reduced postprandial leukocyte activation exclusively in women. PMID:24619107

  4. Mitochondrial membrane lipids in life and death and their molecular modulation by diet: tuning the furnace.

    PubMed

    Monteiro, João P; Morais, Catarina M; Oliveira, Paulo J; Jurado, Amália S

    2014-01-01

    The traditional view of mitochondria as cell powerhouses is a matter of common knowledge, but the overall view of these extraordinary organelles has been revolutionized in the last years. In fact, a large number of important and diverse processes take place at the mitochondrial level, which clearly surpass the energy production scope, intruding the critical fragile balance between cell life and death. The entangled biochemistry of mitochondrial membranes has been found to be dependent on specific lipid requirements, with cardiolipin holding a great part of the raised functional interest. Mitochondria contain a complex membrane system, based on a variety of lipids and exquisite asymmetries. Mitochondria lipid membrane composition depends on a tight interplay with the endoplasmic reticulum, from which some of the lipids present in the mitochondrial membranes have to be imported, at least in the form of precursors. Here, we review some external interventions resulting in alterations of mitochondrial lipid content, namely dietary interventions and genetic manipulation. Such manipulations of mitochondrial membrane lipid composition should result in physiological impact, given the importance of lipid-protein interactions within the mitochondrial membrane boundaries. We provide arguments for future experiments using the most modern chemical and biophysical approaches as well as computer simulation studies applied to appropriate biological membrane model systems, in order to identify the effects exerted by diet-induced lipid changes on membrane physical properties. PMID:24953065

  5. Modulation of endomembranes morphodynamics in the secretory/retrograde pathways depends on lipid diversity.

    PubMed

    Boutté, Yohann; Moreau, Patrick

    2014-12-01

    Membrane lipids are crucial bricks for cell and organelle compartmentalization and their physical properties and interactions with other membrane partners (lipids or proteins) reveal lipids as key actors of the regulation of membrane morphodynamics in many cellular functions and especially in the secretory/retrograde pathways. Studies on membrane models have indicated diverse mechanisms by which membranes bend. Moreover, in vivo studies also indicate that membrane curvature can play crucial roles in the regulation of endomembrane morphodynamics, organelle morphology and transport vesicle formation. A role for enzymes of lipid metabolism and lipid-protein interactions will be discussed as crucial mechanisms in the regulation of membrane morphodynamics in the secretory/retrograde pathways. PMID:25233477

  6. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  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. PMID:26856891

  9. Saturated fat-rich diet increases fetal lipids and modulates LPL and leptin receptor expression in rat placentas.

    PubMed

    Mazzucco, M B; Higa, R; Capobianco, E; Kurtz, M; Jawerbaum, A; White, V

    2013-06-01

    Metabolic alterations in obese and overweight mothers impact the placenta and the fetus, leading to anomalies in fetal growth and lipid accretion. The primary aim of the study was to examine the effect of a saturated fat-rich diet (FD) on growth, lipid accretion, and lipases, leptin and leptin receptor (ObR) expression in the placenta and fetal liver. We also aimed to find a role for fetal leptin in the modulation of placental and fetal liver lipase and ObR expression. Six-week-old rats were fed with a standard rat chow (control) or a 25% FD for 7 weeks until mating and during pregnancy. Also, in a group of control rats, fetuses were injected with leptin on days 19, 20, and 21 of pregnancy. On day 21, we assessed lipidemia, insulinemia, and leptinemia in mothers and fetuses. In the placenta and fetal liver, lipid concentration was assessed by thin layer chromatography (TLC) and the gene expression of lipoprotein lipase (LPL), endothelial lipase, insulin receptor (Insr), leptin, and ObR by RT-PCR. The FD induced hypertriglyceridemia and hyperleptinemia (P<0.01) in mothers and fetuses, an increase in maternal (P<0.05) and fetal weight (P<0.01), overaccumulation of lipids in fetal liver (P<0.01), and enhanced leptin expression in the placenta and fetal liver (P<0.05). Placental expression of IR and LPL was increased (P<0.05), and ObR decreased (P<0.05) in the FD group. Fetal administration of leptin induced the placental and fetal liver downregulation of ObR (P<0.05) and upregulation of LPL expression (P<0.05). The FD led to increased fetal lipid levels, which may result from high maternal lipid availability and fetal leptin effects. PMID:23482704

  10. Human Immunodeficiency Virus Type 1 Nef protein modulates the lipid composition of virions and host cell membrane microdomains

    PubMed Central

    Brügger, Britta; Krautkrämer, Ellen; Tibroni, Nadine; Munte, Claudia E; Rauch, Susanne; Leibrecht, Iris; Glass, Bärbel; Breuer, Sebastian; Geyer, Matthias; Kräusslich, Hans-Georg; Kalbitzer, Hans Robert; Wieland, Felix T; Fackler, Oliver T

    2007-01-01

    Background The Nef protein of Human Immunodeficiency Viruses optimizes viral spread in the infected host by manipulating cellular transport and signal transduction machineries. Nef also boosts the infectivity of HIV particles by an unknown mechanism. Recent studies suggested a correlation between the association of Nef with lipid raft microdomains and its positive effects on virion infectivity. Furthermore, the lipidome analysis of HIV-1 particles revealed a marked enrichment of classical raft lipids and thus identified HIV-1 virions as an example for naturally occurring membrane microdomains. Since Nef modulates the protein composition and function of membrane microdomains we tested here if Nef also has the propensity to alter microdomain lipid composition. Results Quantitative mass spectrometric lipidome analysis of highly purified HIV-1 particles revealed that the presence of Nef during virus production from T lymphocytes enforced their raft character via a significant reduction of polyunsaturated phosphatidylcholine species and a specific enrichment of sphingomyelin. In contrast, Nef did not significantly affect virion levels of phosphoglycerolipids or cholesterol. The observed alterations in virion lipid composition were insufficient to mediate Nef's effect on particle infectivity and Nef augmented virion infectivity independently of whether virus entry was targeted to or excluded from membrane microdomains. However, altered lipid compositions similar to those observed in virions were also detected in detergent-resistant membrane preparations of virus producing cells. Conclusion Nef alters not only the proteome but also the lipid composition of host cell microdomains. This novel activity represents a previously unrecognized mechanism by which Nef could manipulate HIV-1 target cells to facilitate virus propagation in vivo. PMID:17908312

  11. Modulation of ileal bile acid transporter (ASBT) activity by depletion of plasma membrane cholesterol: association with lipid rafts

    PubMed Central

    Annaba, Fadi; Sarwar, Zaheer; Kumar, Pradeep; Saksena, Seema; Turner, Jerrold R.; Dudeja, Pradeep K.; Gill, Ravinder K.; Alrefai, Waddah A.

    2016-01-01

    Apical sodium-dependent bile acid transporter (ASBT) represents a highly efficient conservation mechanism of bile acids via mediation of their active transport across the luminal membrane of terminal ileum. To gain insight into the cellular regulation of ASBT, we investigated the association of ASBT with cholesterol and sphingolipid-enriched specialized plasma membrane microdomains known as lipid rafts and examined the role of membrane cholesterol in maintaining ASBT function. Human embryonic kidney (HEK)-293 cells stably transfected with human ASBT, human ileal brush-border membrane vesicles, and human intestinal epithelial Caco-2 cells were utilized for these studies. Floatation experiments on Optiprep density gradients demonstrated the association of ASBT protein with lipid rafts. Disruption of lipid rafts by depletion of membrane cholesterol with methyl-β-cyclodextrin (MβCD) significantly reduced the association of ASBT with lipid rafts, which was paralleled by a decrease in ASBT activity in Caco-2 and HEK-293 cells treated with MβCD. The inhibition in ASBT activity by MβCD was blocked in the cells treated with MβCD-cholesterol complexes. Kinetic analysis revealed that MβCD treatment decreased the Vmax of the transporter, which was not associated with alteration in the plasma membrane expression of ASBT. Our study illustrates that cholesterol content of lipid rafts is essential for the optimal activity of ASBT and support the association of ASBT with lipid rafts. These findings suggest a novel mechanism by which ASBT activity may be rapidly modulated by alterations in cholesterol content of plasma membrane and thus have important implications in processes related to maintenance of bile acid and cholesterol homeostasis. PMID:18063707

  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

    2016-03-01

    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 (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. PMID:26961949

  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. Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are critical in modulating T cell responses.

    PubMed

    Chiurchiù, Valerio; Leuti, Alessandro; Dalli, Jesmond; Jacobsson, Anders; Battistini, Luca; Maccarrone, Mauro; Serhan, Charles N

    2016-08-24

    Resolution of inflammation is a finely regulated process mediated by specialized proresolving lipid mediators (SPMs), including docosahexaenoic acid (DHA)-derived resolvins and maresins. The immunomodulatory role of SPMs in adaptive immune cells is of interest. We report that D-series resolvins (resolvin D1 and resolvin D2) and maresin 1 modulate adaptive immune responses in human peripheral blood lymphocytes. These lipid mediators reduce cytokine production by activated CD8(+) T cells and CD4(+) T helper 1 (TH1) and TH17 cells but do not modulate T cell inhibitory receptors or abrogate their capacity to proliferate. Moreover, these SPMs prevented naïve CD4(+) T cell differentiation into TH1 and TH17 by down-regulating their signature transcription factors, T-bet and Rorc, in a mechanism mediated by the GPR32 and ALX/FPR2 receptors; they concomitantly enhanced de novo generation and function of Foxp3(+) regulatory T (Treg) cells via the GPR32 receptor. These results were also supported in vivo in a mouse deficient for DHA synthesis (Elovl2(-/-)) that showed an increase in TH1/TH17 cells and a decrease in Treg cells compared to wild-type mice. Additionally, either DHA supplementation in Elovl2(-/-) mice or in vivo administration of resolvin D1 significantly reduced cytokine production upon specific stimulation of T cells. These findings demonstrate actions of specific SPMs on adaptive immunity and provide a new avenue for SPM-based approaches to modulate chronic inflammation. PMID:27559094

  15. 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

  16. From fatty-acid sensing to chylomicron synthesis: role of intestinal lipid-binding proteins.

    PubMed

    Buttet, Marjorie; Traynard, Véronique; Tran, Thi Thu Trang; Besnard, Philippe; Poirier, Hélène; Niot, Isabelle

    2014-01-01

    Today, it is well established that the development of obesity and associated diseases results, in part, from excessive lipid intake associated with a qualitative imbalance. Among the organs involved in lipid homeostasis, the small intestine is the least studied even though it determines lipid bioavailability and largely contributes to the regulation of postprandial hyperlipemia (triacylglycerols (TG) and free fatty acids (FFA)). Several Lipid-Binding Proteins (LBP) are expressed in the small intestine. Their supposed intestinal functions were initially based on what was reported in other tissues, and took no account of the physiological specificity of the small intestine. Progressively, the identification of regulating factors of intestinal LBP and the description of the phenotype of their deletion have provided new insights into cellular and molecular mechanisms involved in fat absorption. This review will discuss the physiological contribution of each LBP in the main steps of intestinal absorption of long-chain fatty acids (LCFA): uptake, trafficking and reassembly into chylomicrons (CM). Moreover, current data indicate that the small intestine is able to adapt its lipid absorption capacity to the fat content of the diet, especially through the coordinated induction of LBP. This adaptation requires the existence of a mechanism of intestinal lipid sensing. Emerging data suggest that the membrane LBP CD36 may operate as a lipid receptor that triggers an intracellular signal leading to the modulation of the expression of LBP involved in CM formation. This event could be the starting point for the optimized synthesis of large CM, which are efficiently degraded in blood. Better understanding of this intestinal lipid sensing might provide new approaches to decrease the prevalence of postprandial hypertriglyceridemia, which is associated with cardiovascular diseases, insulin resistance and obesity. PMID:23958439

  17. Relevance of postprandial lipemia in metabolic syndrome.

    PubMed

    Garcia-Rios, Antonio; Delgado-Lista, Javier; Perez-Martinez, Pablo; Delgado-Casado, Nieves; Perez-Jimenez, Francisco; Lopez-Miranda, Jose

    2013-11-01

    Metabolic Syndrome (MetS) is a complex disorder defined by the aggregation of interconnected cardiometabolic risk factors which increase the risk of diabetes mellitus type 2 and cardiovascular disease (CVD). MetS is currently a matter of concern and it will continue to be in the future, since there is likely to be a dramatic increase in its prevalence, and subjects with MetS will have an increased risk of mortality, mainly through CVD. Moreover, the implications on the global health burden and the worldwide epidemic of this complex disorder will impact greatly on socioeconomic cost. MetS is therefore a matter of serious concern and we need to understand its etiology in order to improve strategies of treatment and prevention. In this regard, postprandial lipemia has increased in importance over the last few years as it has been demonstrated to influence the development of atherosclerosis. In addition, in modern times, fasting is not the typical physiological state of humans; in fact, they spend most of the time in the postprandial state. However, although it is obvious that postprandial lipemia is present in conditions of obesity, little is known about the relevance of postprandial lipemia in MetS. In the current review, we will explore some aspects of postprandial lipemia which could be of interest for understanding the pathogenesis of this complex disorder and which may help us advance towards more personalized nutrition. PMID:24168444

  18. STED Nanoscopy Reveals Molecular Details of Cholesterol- and Cytoskeleton-Modulated Lipid Interactions in Living Cells

    PubMed Central

    Mueller, V.; Ringemann, C.; Honigmann, A.; Schwarzmann, G.; Medda, R.; Leutenegger, M.; Polyakova, S.; Belov, V.N.; Hell, S.W.; Eggeling, C.

    2011-01-01

    Details about molecular membrane dynamics in living cells, such as lipid-protein interactions, are often hidden from the observer because of the limited spatial resolution of conventional far-field optical microscopy. The superior spatial resolution of stimulated emission depletion (STED) nanoscopy can provide new insights into this process. The application of fluorescence correlation spectroscopy (FCS) in focal spots continuously tuned down to 30 nm in diameter distinguishes between free and anomalous molecular diffusion due to, for example, transient binding of lipids to other membrane constituents, such as lipids and proteins. We compared STED-FCS data recorded on various fluorescent lipid analogs in the plasma membrane of living mammalian cells. Our results demonstrate details about the observed transient formation of molecular complexes. The diffusion characteristics of phosphoglycerolipids without hydroxyl-containing headgroups revealed weak interactions. The strongest interactions were observed with sphingolipid analogs, which showed cholesterol-assisted and cytoskeleton-dependent binding. The hydroxyl-containing headgroup of gangliosides, galactosylceramide, and phosphoinositol assisted binding, but in a much less cholesterol- and cytoskeleton-dependent manner. The observed anomalous diffusion indicates lipid-specific transient hydrogen bonding to other membrane molecules, such as proteins, and points to a distinct connectivity of the various lipids to other membrane constituents. This strong interaction is different from that responsible for forming cholesterol-dependent, liquid-ordered domains in model membranes. PMID:21961591

  19. Light Remodels Lipid Biosynthesis in Nannochloropsis gaditana by Modulating Carbon Partitioning between Organelles.

    PubMed

    Alboresi, Alessandro; Perin, Giorgio; Vitulo, Nicola; Diretto, Gianfranco; Block, Maryse; Jouhet, Juliette; Meneghesso, Andrea; Valle, Giorgio; Giuliano, Giovanni; Maréchal, Eric; Morosinotto, Tomas

    2016-08-01

    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

  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. How Alcohol Chain-Length and Concentration Modulate Hydrogen Bond Formation in a Lipid Bilayer

    PubMed Central

    Dickey, Allison N.; Faller, Roland

    2007-01-01

    Molecular dynamics simulations are used to measure the change in properties of a hydrated dipalmitoylphosphatidylcholine bilayer when solvated with ethanol, propanol, and butanol solutions. There are eight oxygen atoms in dipalmitoylphosphatidylcholine that serve as hydrogen bond acceptors, and two of the oxygen atoms participate in hydrogen bonds that exist for significantly longer time spans than the hydrogen bonds at the other six oxygen atoms for the ethanol and propanol simulations. We conclude that this is caused by the lipid head group conformation, where the two favored hydrogen-bonding sites are partially protected between the head group choline and the sn-2 carbonyl oxygen. We find that the concentration of the alcohol in the ethanol and propanol simulations does not have a significant influence on the locations of the alcohol/lipid hydrogen bonds, whereas the concentration does impact the locations of the butanol/lipid hydrogen bonds. The concentration is important for all three alcohol types when the lipid chain order is examined, where, with the exception of the high-concentration butanol simulation, the alcohol molecules having the longest hydrogen-bonding relaxation times at the favored carbonyl oxygen acceptor sites also have the largest order in the upper chain region. The lipid behavior in the high-concentration butanol simulation differs significantly from that of the other alcohol concentrations in the order parameter, head group rotational relaxation time, and alcohol/lipid hydrogen-bonding location and relaxation time. This appears to be the result of the system being very near to a phase transition, and one occurrence of lipid flip-flop is seen at this concentration. PMID:17218462

  2. Modulation of host lipid metabolism by hepatitis C virus: Role of new therapies

    PubMed Central

    Del Campo, José A; Romero-Gómez, Manuel

    2015-01-01

    It is well established that hepatitis C virus (HCV) infection and replication relies on host lipid metabolism. HCV proteins interact and associate with lipid droplets to facilitate virion assembly and production. Besides, circulating infective particles are associated with very low-density lipoprotein. On the other hand, higher serum lipid levels have been associated with sustained viral response to pegylated interferon and ribavirin therapy in chronic HCV infection, suggesting a relevant role in viral clearance for host proteins. Host and viral genetic factors play an essential role in chronic infection. Lipid metabolism is hijacked by viral infection and could determine the success of viral replication. Recently development of direct acting antiviral agents has shown a very high efficacy (> 90%) in sustained viral response rates even for cirrhotic patients and most of the viral genotypes. HCV RNA clearance induced by Sofosbuvir has been associated with an increased concentration and size of the low-density lipoprotein particles. In this review, host genetic factors, viral factors and the interaction between them will be depicted to clarify the major issues involved in viral infection and lipid metabolism. PMID:26478669

  3. Modulation of lipid phase behavior by kosmotropic and chaotropic solutes : Experiment and thermodynamic theory.

    PubMed

    Koynova, R; Brankov, J; Tenchov, B

    1997-01-01

    By means of differential scanning calorimetry and from a review of published data we demonstrate in this work that low-molecular weight kosmotropic substances (water-structure makers) of different chemical structure such as disaccharides, proline, and glycerol have identical effects on the phase behavior of several kinds of phospholipids and glycolipids. These substances favor formation of the high-temperature inverted hexagonal phase (H(II)) and the low-temperature lamellar crystalline (L(c)) and gel (L( β )) phases at the expense of the intermediate lamellar liquid-crystalline phase (L( α )). The latter phase may completely disappear from the phase diagram at high enough solute concentration. By contrast, chaotropic substances (water-structure breakers) such as sodium thiocyanate and guanidine hydrochloride expand the existence range of L( α ) at the expense of the adjacent L( β ) and H(II) phases. Moreover, chaotropes are able to induce the appearance of missing intermediate liquid-crystalline phases in lipids displaying direct L( β )→H(II) transitions in pure water. In previous publications we have considered the influence of chaotropic and kosmotropic substances on the lipid phase behavior as a manifestation of their indirect (Hofmeister) interactions with the lipid aggregates. For a quantitative characterization of this effect, here we derive a general thermodynamic equation between lipid phase transition temperature and solute concentration, analogous to the Clapeyron-Clausius equation between transition temperature and pressure. It provides a clear description in physical quantities of the disparate effects of kosmotropic and chaotropic substances on the relative stability of the lipid-water phases. According to this equation, the magnitude of the solute effect is proportional to the hydration difference of the adjacent lipid phases and inversely proportional to the transition latent heat. The sign and magnitude of the transition shifts depend also

  4. Ameliorative potential of gingerol: Promising modulation of inflammatory factors and lipid marker enzymes expressions in HFD induced obesity in rats.

    PubMed

    Brahma Naidu, Parim; Uddandrao, V V Sathibabu; Ravindar Naik, Ramavat; Suresh, Pothani; Meriga, Balaji; Begum, Mustapha Shabana; Pandiyan, Rajesh; Saravanan, Ganapathy

    2016-01-01

    Obesity, generally linked to hyperlipidemia, has been occurring of late with distressing alarm and has now become a global phenomenon casting a huge economic burden on the health care system of countries around the world. The present study investigated the effects of gingerol over 30 days on the changes in HFD-induced obese rats in marker enzymes of lipid metabolism such as fatty-acid synthase (FAS), Acetyl CoA Carboxylase (ACC), Carnitine Palmitoyl Transferase-1(CPT-1), HMG co-A Reductase (HMGR), Lecithin Choline Acyl Transferase (LCAT) and Lipoprotein Lipase (LPL) and inflammatory markers (TNF-α and IL-6). The rats were treated orally with gingerol (75 mg kg(-1)) once daily for 30 days with a lorcaserin-treated group (10 mg kg(-1)) included for comparison. Changes in body weight, glucose, insulin resistance and expressions of lipid marker enzymes and inflammatory markers in tissues were observed in experimental rats. The administration of gingerol resulted in a significant reduction in body weight gain, glucose and insulin levels, and insulin resistance, which altered the activity, expressions of lipid marker enzymes and inflammatory markers. It showed that gingerol had significantly altered these parameters when compared with HFD control rats. This study confirms that gingerol prevents HFD-induced hyperlipidemia by modulating the expression of enzymes important to cholesterol metabolism. PMID:26493465

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

    PubMed Central

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

    2016-01-01

    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. PMID:27013782

  6. Second-Hand Cigarette Smoke Impairs Bacterial Phagocytosis in Macrophages by Modulating CFTR Dependent Lipid-Rafts

    PubMed Central

    Ni, Inzer; Ji, Changhoon; Vij, Neeraj

    2015-01-01

    Introduction First/Second-hand cigarette-smoke (FHS/SHS) exposure weakens immune defenses inducing chronic obstructive pulmonary disease (COPD) but the underlying mechanisms are not fully understood. Hence, we evaluated if SHS induced changes in membrane/lipid-raft (m-/r)-CFTR (cystic fibrosis transmembrane conductance regulator) expression/activity is a potential mechanism for impaired bacterial phagocytosis in COPD. Methods RAW264.7 murine macrophages were exposed to freshly prepared CS-extract (CSE) containing culture media and/or Pseudomonas-aeruginosa-PA01-GFP for phagocytosis (fluorescence-microscopy), bacterial survival (colony-forming-units-CFU), and immunoblotting assays. The CFTR-expression/activity and lipid-rafts were modulated by transient-transfection or inhibitors/inducers. Next, mice were exposed to acute/sub-chronic-SHS or room-air (5-days/3-weeks) and infected with PA01-GFP, followed by quantification of bacterial survival by CFU-assay. Results We investigated the effect of CSE treatment on RAW264.7 cells infected by PA01-GFP and observed that CSE treatment significantly (p<0.01) inhibits PA01-GFP phagocytosis as compared to the controls. We also verified this in murine model, exposed to acute/sub-chronic-SHS and found significant (p<0.05, p<0.02) increase in bacterial survival in the SHS-exposed lungs as compared to the room-air controls. Next, we examined the effect of impaired CFTR ion-channel-activity on PA01-GFP infection of RAW264.7 cells using CFTR172-inhibitor and found no significant change in phagocytosis. We also similarly evaluated the effect of a CFTR corrector-potentiator compound, VRT-532, and observed no significant rescue of CSE impaired PA01-GFP phagocytosis although it significantly (p<0.05) decreases CSE induced bacterial survival. Moreover, induction of CFTR expression in macrophages significantly (p<0.03) improves CSE impaired PA01-GFP phagocytosis as compared to the control. Next, we verified the link between m

  7. 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. PMID:23180608

  8. DIETARY LIPID AS A FACTOR MODULATING XENOBIOTIC METABOLISM IN CHANNEL CATFISH (ICTALURUS PUNCTATUS)

    EPA Science Inventory

    Adult channel catfish (Ictaiurus punctatus) were fed diets containing menhaden oil (MHO), soybean oil (SBO), or beef tallow (BFT) as lipid sources for 116 d. The effects of these diets on two important hepatic xenobiotic-metabolizing enzyme systems, cytochrome p-45O-dependent mon...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  10. Mycobacterium tuberculosis WhiB3 maintains redox homeostasis by regulating virulence lipid anabolism to modulate macrophage response.

    PubMed

    Singh, Amit; Crossman, David K; Mai, Deborah; Guidry, Loni; Voskuil, Martin I; Renfrow, Matthew B; Steyn, Adrie J C

    2009-08-01

    The metabolic events associated with maintaining redox homeostasis in Mycobacterium tuberculosis (Mtb) during infection are poorly understood. Here, we discovered a novel redox switching mechanism by which Mtb WhiB3 under defined oxidizing and reducing conditions differentially modulates the assimilation of propionate into the complex virulence polyketides polyacyltrehaloses (PAT), sulfolipids (SL-1), phthiocerol dimycocerosates (PDIM), and the storage lipid triacylglycerol (TAG) that is under control of the DosR/S/T dormancy system. We developed an in vivo radio-labeling technique and demonstrated for the first time the lipid profile changes of Mtb residing in macrophages, and identified WhiB3 as a physiological regulator of virulence lipid anabolism. Importantly, MtbDeltawhiB3 shows enhanced growth on medium containing toxic levels of propionate, thereby implicating WhiB3 in detoxifying excess propionate. Strikingly, the accumulation of reducing equivalents in MtbDeltawhiB3 isolated from macrophages suggests that WhiB3 maintains intracellular redox homeostasis upon infection, and that intrabacterial lipid anabolism functions as a reductant sink. MtbDeltawhiB3 infected macrophages produce higher levels of pro- and anti-inflammatory cytokines, indicating that WhiB3-mediated regulation of lipids is required for controlling the innate immune response. Lastly, WhiB3 binds to pks2 and pks3 promoter DNA independent of the presence or redox state of its [4Fe-4S] cluster. Interestingly, reduction of the apo-WhiB3 Cys thiols abolished DNA binding, whereas oxidation stimulated DNA binding. These results confirmed that WhiB3 DNA binding is reversibly regulated by a thiol-disulfide redox switch. These results introduce a new paradigmatic mechanism that describes how WhiB3 facilitates metabolic switching to fatty acids by regulating Mtb lipid anabolism in response to oxido-reductive stress associated with infection, for maintaining redox balance. The link between the WhiB3

  11. 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

  12. Smoking, inflammatory patterns, and postprandial hypertriglyceridemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  13. Postprandial plasma adiponectin response is reduced in prepubertal premature pubarche girls.

    PubMed

    Larqué, Elvira; Gil-Campos, Mercedes; Villada, Isabel; Ramírez-Tortosa, M Carmen; Cañete, Ramón; Gil, Angel

    2010-09-01

    The association between premature pubarche (PP) and metabolic syndrome is controversial and not supported by some authors. The aim of this study was to determine insulin resistance syndrome, plasma adiponectin, and fatty acid profile in PP girls to discern potential confounder variables and markers of metabolic disturbances. We studied 22 prepubertal girls with a diagnosis of PP and 20 healthy controls who differed in body mass index (BMI) (19.33 +/- 0.71 vs 17.30 +/- 0.60). We evaluated insulin resistance syndrome components and postprandial response of adiponectin, nonesterified fatty acids, and fatty acid profile after consumption of a standardized breakfast. No lipid disturbances were detected in the PP group. High-density lipoprotein to low-density lipoprotein cholesterol ratio tended to be lower in PP girls (P = .052), but this effect disappeared when data were adjusted for both BMI and age (P = .480). Insulin levels tended to be higher at 2 hours in PP girls, who showed significantly higher C-peptide area under the curve. In contrast, adiponectin at 3 hours after the meal and postprandial adiponectin area under the curve were significantly lower. The PP girls showed significantly higher percentages of eicosapentaenoic acid in total plasma and plasma phospholipids. No differences were found in the postprandial fatty acid clearance rate. In conclusion, PP girls and controls differed in postprandial plasma adiponectin response and in postprandial plasma C-peptide response after both BMI and age adjustment. Cholesterol plasma disturbances were mainly attributable to their higher BMI, although n-3 polyunsaturated fatty acids were higher because of the PP. PMID:20096425

  14. Uptake of postprandial lipoproteins into bone in vivo: impact on osteoblast function.

    PubMed

    Niemeier, Andreas; Niedzielska, Dagmara; Secer, Rukiye; Schilling, Arndt; Merkel, Martin; Enrich, Carlos; Rensen, Patrick C N; Heeren, Joerg

    2008-08-01

    Dietary lipids and lipophilic vitamins are transported by postprandial lipoproteins and are required for bone metabolism. Despite that, it remains unknown whether bone cells are involved in the uptake of circulating postprandial lipoproteins in vivo. The current study was performed to investigate a putative participation of bone in the systemic postprandial lipoprotein metabolism in mice, to identify potentially involved cell type populations and to analyze whether lipoprotein uptake affects bone function in vivo. As a model for the postprandial state, chylomicron remnants (CR) were injected intravenously into mice. Next to the liver and compared to other organs, bone appeared to be the second most important organ for the clearance of radiolabeled CR particles from the circulation in vivo. In addition, uptake of radiolabeled CR by primary murine osteoblasts and hepatocytes was quantified to be in a similar range in vitro. A complementary approach with fluorescently labeled CR and immunohistochemical staining for apoE proved that intact CR particles were taken up into bone and liver. Electron microscopy localization studies of bone sections revealed CR uptake into sinusoidal endothelial cells, macrophages and osteoblasts. The relative amount of radiolabeled CR uptake into femoral cortical bone, representing predominantly osteoblasts, and bone marrow, representing predominantly non-osteoblast cells, was within the same range. Most importantly, the injection of vitamin K1-enriched CR resulted in an increase of the degree of osteocalcin carboxylation in vivo while total osteocalcin concentrations remained unaffected, giving functional proof that osteoblasts process CR in vivo. In conclusion, here we demonstrate that bone is involved in the postprandial lipoprotein metabolism in mice. Osteoblasts participate in CR clearance from the circulation, which has a direct impact on the secretory function of osteoblasts. PMID:18538644

  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. PMID:27094351

  16. 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. PMID:24997404

  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. 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

  19. 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. PMID:22951888

  20. 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, Pinteraction = 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; Pinteraction = 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, Pinteraction = 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; Pinteraction = 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

  1. 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

  2. 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. PMID:25649276

  3. Modulation of Symbiont Lipid A Signaling by Host Alkaline Phosphatases in the Squid-Vibrio Symbiosis

    PubMed Central

    Rader, Bethany A.; Kremer, Natacha; Apicella, Michael A.; Goldman, William E.; McFall-Ngai, Margaret J.

    2012-01-01

    ABSTRACT The synergistic activity of Vibrio fischeri lipid A and the peptidoglycan monomer (tracheal cytotoxin [TCT]) induces apoptosis in the superficial cells of the juvenile Euprymna scolopes light organ during the onset of the squid-vibrio symbiosis. Once the association is established in the epithelium-lined crypts of the light organ, the host degrades the symbiont’s constitutively produced TCT by the amidase activity of a peptidoglycan recognition protein (E. scolopes peptidoglycan recognition protein 2 [EsPGRP2]). In the present study, we explored the role of alkaline phosphatases in transforming the lipid A of the symbiont into a form that changes its signaling properties to host tissues. We obtained full-length open reading frames for two E. scolopes alkaline phosphatase (EsAP) mRNAs (esap1 and esap2); transcript levels suggested that the dominant light organ isoform is EsAP1. Levels of total EsAP activity increased with symbiosis, but only after the lipid A-dependent morphogenetic induction at 12 h, and were regulated over the day-night cycle. Inhibition of total EsAP activity impaired normal colonization and persistence by the symbiont. EsAP activity localized to the internal regions of the symbiotic juvenile light organ, including the lumina of the crypt spaces where the symbiont resides. These data provide evidence that EsAPs work in concert with EsPGRPs to change the signaling properties of bacterial products and thereby promote persistent colonization by the mutualistic symbiont. PMID:22550038

  4. Various Terpenoids Derived from Herbal and Dietary Plants Function as PPAR Modulators and Regulate Carbohydrate and Lipid Metabolism

    PubMed Central

    Goto, Tsuyoshi; Takahashi, Nobuyuki; Hirai, Shizuka; Kawada, Teruo

    2010-01-01

    Several herbal plants improve medical conditions. Such plants contain many bioactive phytochemicals. Terpenoids (also called “isoprenoids”) constitute one of the largest families of natural products accounting for more than 40,000 individual compounds of both primary and secondary metabolisms. In particular, terpenoids are contained in many herbal plants, and several terpenoids have been shown to be available for pharmaceutical applications, for example, artemisinin and taxol as malaria and cancer medicines, respectively. Various terpenoids are contained in many plants for not only herbal use but also dietary use. In this paper, we describe several bioactive terpenoids contained in herbal or dietary plants, which can modulate the activities of ligand-dependent transcription factors, namely, peroxisome proliferator-activated receptors (PPARs). Because PPARs are dietary lipid sensors that control energy homeostasis, daily eating of these terpenoids might be useful for the management for obesity-induced metabolic disorders, such as type 2 diabetes, hyperlipidemia, insulin resistance, and cardiovascular diseases. PMID:20613991

  5. Crystal Structure of a Voltage-gated K+ Channel Pore Module in a Closed State in Lipid Membranes*

    PubMed Central

    Santos, Jose S.; Asmar-Rovira, Guillermo A.; Han, Gye Won; Liu, Wei; Syeda, Ruhma; Cherezov, Vadim; Baker, Kent A.; Stevens, Raymond C.; Montal, Mauricio

    2012-01-01

    Voltage-gated K+ channels underlie the electrical excitability of cells. Each subunit of the functional tetramer consists of the tandem fusion of two modules, an N-terminal voltage-sensor and a C-terminal pore. To investigate how sensor coupling to the pore generates voltage-dependent channel opening, we solved the crystal structure and characterized the function of a voltage-gated K+ channel pore in a lipid membrane. The structure of a functional channel in a membrane environment at 3.1 Å resolution establishes an unprecedented connection between channel structure and function. The structure is unique in delineating an ion-occupied ready to conduct selectivity filter, a confined aqueous cavity, and a closed activation gate, embodying a dynamic entity trapped in an unstable closed state. PMID:23095758

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

    PubMed Central

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

    2014-01-01

    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

  7. 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

  8. The modulating effect of mechanical changes in lipid bilayers caused by apoE-containing lipoproteins on Aβ induced membrane disruption.

    PubMed

    Legleiter, Justin; Fryer, John D; Holtzman, David M; Kowalewski, Andtomasz

    2011-10-19

    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 Aβ(1-40) 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 Aβ(1-40) induced bilayer disruption. PMID:22125665

  9. AMPK-dependent modulation of hepatic lipid metabolism by nesfatin-1.

    PubMed

    Yin, Yue; Li, Ziru; Gao, Ling; Li, Yin; Zhao, Jing; Zhang, Weizhen

    2015-12-01

    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. PMID:26363221

  10. A glucagon-like endocrine pathway in Drosophila modulates both lipid and carbohydrate homeostasis

    PubMed Central

    Bharucha, K. N.; Tarr, P.; Zipursky, S. L.

    2009-01-01

    SUMMARY The regulation of energy homeostasis is fundamental to all organisms. The Drosophila fat body serves as a repository for both triglycerides and glycogen, combining the energy storage functions of mammalian adipose and hepatic tissues, respectively. Here we show that mutation of the Drosophila adipokinetic hormone receptor (AKHR), a functional analog of the mammalian glucagon receptor, leads to abnormal accumulation of both lipid and carbohydrate. As a consequence of their obese phenotypes, AKHR mutants are markedly starvation resistant. We show that AKHR is expressed in the fat body, and, intriguingly, in a subset of gustatory neurons that mediate sweet taste. Genetic rescue experiments establish that the metabolic phenotypes arise exclusively from the fat body AKHR expression. Behavioral experiments demonstrate that AKHR mutants are neither sedentary nor hyperphagic, suggesting the metabolic abnormalities derive from a genetic propensity to retain energy stores. Taken together, our results indicate that a single endocrine pathway contributes to both lipid and carbohydrate catabolism in the Drosophila fat body. PMID:18805809

  11. High-fat meal induced postprandial inflammation.

    PubMed

    Herieka, Mohammed; Erridge, Clett

    2014-01-01

    Raised levels of circulating inflammatory markers are associated with coronary artery disease, obesity and type II diabetes. It has been proposed that the ingestion of high-fat meals may serve as a stimulus to raise systemic inflammatory tone, although interventional studies have yielded conflicting results. We here review 57 studies of high-fat meal induced acute postprandial inflammation to identify the most frequently reported markers of postprandial inflammation and to compare these results with the highly consistent low-grade endotoxaemia model in man. Most plasma borne markers of inflammation, such as cytokines and soluble adhesion molecules, were not consistently raised after a high-fat meal. However, pro-inflammatory leukocyte surface markers, mRNA and proteins were elevated in almost all studies in which they were measured. These markers followed kinetics similar to those observed following intravenous injection of low doses of endotoxin in man, were positively associated with likelihood of contamination of test meals with pro-inflammatory bacterial molecules and were reduced in several studies examining parallel meals supplemented with foodstuffs containing anti-inflammatory phytochemicals. Future studies of postprandial inflammation may yield more consistent evidence by focusing on leukocyte, rather than plasma-borne, markers of inflammation and by considering the test meal content of pro- and anti-inflammatory dietary constituents. PMID:23847095

  12. 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. PMID:21167812

  13. Production of biomass and lipids by the oleaginous microalgae Monoraphidium sp. QLY-1 through heterotrophic cultivation and photo-chemical modulator induction.

    PubMed

    Zhao, Yongteng; Li, Dafei; Ding, Ke; Che, Raoqiong; Xu, Jun-Wei; Zhao, Peng; Li, Tao; Ma, Huixian; Yu, Xuya

    2016-07-01

    A two-step strategy comprising heterotrophic cultivation and photo-chemical modulator induction was developed to enhance biomass and lipid accumulation in the oleaginous Monoraphidium sp. QLY-1, which was isolated from Qilu Lake in Yunnan Plateau. The algae were first cultivated heterotrophically to achieve high biomass concentration (5.54gL(-1)) with a lipid content of 22.47%. The cultivated algae were diluted, transferred to light environment, and treated with different chemical elicitors. Results showed that the lipid content increased to 36.68% after 3-day of photoinduction. The lipid content was further enhanced by 1.21, 1.32, and 1.29 folds in algal cells treated with nitrogen deficiency, 20gL(-1) NaCl, and 5mM glycine betaine, respectively. The maximum lipid content (48.54%) and lipid productivity (121.27mgL(-1)d(-1)) were obtained in treatments with 20gL(-1) NaCl and 5mM GB, respectively. This study proposes a strategy to efficiently produce lipids by using microalgae. PMID:27058402

  14. An apolipoprotein A-II polymorphism (-265T/C, rs5082), regulates postprandial response to a saturated fat overload in healthy men

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  15. Obesity and Insulin Resistance Are the Main Determinants of Postprandial Lipoprotein Dysmetabolism in Polycystic Ovary Syndrome

    PubMed Central

    Phelan, Niamh; Boran, Gerard; O'Connor, Anna-Louise; Gibney, James

    2016-01-01

    Postprandial dyslipidaemia may be a plausible mechanism by which polycystic ovary syndrome (PCOS) increases cardiovascular risk. We sought to investigate whether the postprandial glucose and insulin and lipid and lipoprotein responses, including that of apolipoprotein B-48 (apoB-48) containing chylomicrons, to a mixed meal are different in obese PCOS women when compared to obese control subjects and whether differences, if any, are related to obesity, insulin resistance (IR), hyperandrogenaemia, or PCOS status. 26 women with PCOS (age 30.4 ± 1.2 years (mean ± SEM), body mass index (BMI) 36.8 ± 1.5 kg/m2) and 26 non-PCOS subjects (age 34.1 ± 0.9 years, BMI 31.5 ± 1.0 kg/m2) were studied before and up to 8 hours following a standard mixed meal. AUC-triglyceride (AUC-TG) was higher and AUC-high-density lipoprotein (AUC-HDL) lower in PCOS women. These differences were not apparent when BMI was accounted for. Insulin sensitivity (SI), AUC-apoB-48, and AUC-apolipoprotein B (AUC-apoB) were found to be independent predictors of AUC-TG, accounting for 55% of the variance. Only AUC-insulin remained significantly elevated following adjustment for BMI. Obesity related IR explains postprandial hypertriglyceridaemia and hyperinsulinaemic responses. Management of obesity in premenopausal women with PCOS is likely to reduce their cardiovascular risk burden. PMID:26989412

  16. 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

  17. Viral infection controlled by a calcium-dependent lipid-binding module in ALIX.

    PubMed

    Bissig, Christin; Lenoir, Marc; Velluz, Marie-Claire; Kufareva, Irina; Abagyan, Ruben; Overduin, Michael; Gruenberg, Jean

    2013-05-28

    ALIX plays a role in nucleocapsid release during viral infection, as does lysobisphosphatidic acid (LBPA). However, the mechanism remains unclear. Here we report that LBPA is recognized within an exposed site in ALIX Bro1 domain predicted by MODA, an algorithm for discovering membrane-docking areas in proteins. LBPA interactions revealed a strict requirement for a structural calcium tightly bound near the lipid interaction site. Unlike other calcium- and phospholipid-binding proteins, the all-helical triangle-shaped fold of the Bro1 domain confers selectivity for LBPA via a pair of hydrophobic residues in a flexible loop, which undergoes a conformational change upon membrane association. Both LBPA and calcium binding are necessary for endosome association and virus infection, as are ALIX ESCRT binding and dimerization capacity. We conclude that LBPA recruits ALIX onto late endosomes via the calcium-bound Bro1 domain, triggering a conformational change in ALIX to mediate the delivery of viral nucleocapsids to the cytosol during infection. PMID:23664863

  18. Trans-unsaturated lipid dynamics: modulation of dielaidoylphosphatidylcholine acyl chain motion by ethanol.

    PubMed Central

    Dalton, L A; Miller, K W

    1993-01-01

    Acyl chain dynamics of the trans-unsaturated lipid, dielaidoylphosphatidylcholine (DEPC), were studied by conventional and saturation transfer electron paramagnetic resonance spectroscopy of aqueous dispersions of DEPC spin labeled with lecithins having doxyl groups at positions 5, 10, and 14 on the sn-2 chain. The gel to liquid crystalline transition is concerted with simultaneous increases in rotational motion about the long axis of the acyl chain (libration) and in gauche-trans conformational interconversions (wobble). Relative to saturated lecithins at similar reduced temperatures the double bond (a) slowed libration by an order of magnitude in both phases, while wobble motions were several times slower, and (b)-produced a pronounced stiffness of the acyl chain near the double bond. Ethanol (0-1.6 M), in addition to its well-known colligative effect on the phase transition, was found to decrease the bilayer order in a concentration-dependent manner. This effect was smaller in the gel than in the liquid crystalline phase, most pronounced next to the double bond, and weakest deep in the bilayer. Ethanol affected slow motions little in the gel phase but wobble and libration correlation times were markedly decreased in the liquid crystalline phase. PMID:8274650

  19. Hepatic FoxOs Regulate Lipid Metabolism via Modulation of Expression of the Nicotinamide Phosphoribosyltransferase Gene*

    PubMed Central

    Tao, Rongya; Wei, Dan; Gao, Hanlin; Liu, Yunlong; DePinho, Ronald A.; Dong, X. Charlie

    2011-01-01

    FoxO transcription factors have been implicated in lipid metabolism; however, the underlying mechanisms are not well understood. Here, in an effort to elucidate such mechanisms, we examined the phenotypic consequences of liver-specific deletion of three members of the FoxO family: FoxO1, FoxO3, and FoxO4. These liver-specific triply null mice, designated LTKO, exhibited elevated triglycerides in the liver on regular chow diet. More remarkably, LTKO mice developed severe hepatic steatosis following placement on a high fat diet. Further analyses revealed that hepatic NAD+ levels and Sirt1 activity were decreased in the liver of the LTKO mice relative to controls. At the mechanistic level, expression profile analyses showed that LTKO livers had significantly down-regulated expression of the nicotinamide phosphoribosyltransferase (Nampt) gene encoding the rate-limiting enzyme in the salvage pathway of NAD+ biosynthesis. Luciferase reporter assays and chromatin immunoprecipitation analyses demonstrated that Nampt is a transcriptional target gene of FoxOs. Significantly, overexpression of Nampt gene reduced, whereas knockdown increased, hepatic triglyceride levels in vitro and in vivo. Thus, FoxOs control the Nampt gene expression and the NAD+ signaling in the regulation of hepatic triglyceride homeostasis. PMID:21388966

  20. Modulation Effect of Peroxisome Proliferator-Activated Receptor Agonists on Lipid Droplet Proteins in Liver.

    PubMed

    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

  1. Caenorhabditis elegans PAQR-2 and IGLR-2 Protect against Glucose Toxicity by Modulating Membrane Lipid Composition.

    PubMed

    Svensk, Emma; Devkota, Ranjan; Ståhlman, Marcus; Ranji, Parmida; Rauthan, Manish; Magnusson, Fredrik; Hammarsten, Sofia; Johansson, Maja; Borén, Jan; Pilon, Marc

    2016-04-01

    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

  2. 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

  3. Pulmonary lung surfactant synthetic peptide concentration-dependent modulation of DPPC and POPG acyl chain order in a DPPC:POPG:palmitic acid lipid mixture.

    PubMed

    Krill, S L; Gupta, S L; Smith, T

    1994-05-01

    Lung surfactant-associated protein interaction with lipid matrices and the effects on lipid thermotropic phase behavior are areas of active research. Many studies limit the lipids to a single or two-component system. The current investigation utilizes a three-lipid component matrix (DPPC:POPG:palmitic acid) to investigate the impact of a synthetic surfactant protein B fragment (SP-B 53-78 DiACM) on the dynamic surface activity of the lipid admixture as measured by a Wilhelmy surface balance. Also, the modulation of the individual lipid acyl chain order by the peptide within the lipid matrix is studied through the use of thermal perturbation FTIR spectroscopy. The data clearly demonstrate a concentration-dependent effect of the peptide on the surface activity with an improvement in the dynamic surface tension diagram characteristics (decreased surface tension and increased collapse plateau) especially at low, 0.36 M%, peptide concentrations. These effects are diminished upon further addition of the peptide. FTIR spectral data demonstrate that the peptide addition results in a significant increase in the acyl chain order of the DPPC and POPG components as measured by the position of the methylene stretching vibrational bands. DPPC is most sensitive to the peptide presence, while the palmitic acid is least affected. The transition temperatures of the individual lipids are also increased with the addition of the peptide. The presence of POPG in the matrix achieves the surface activity similarly seen with natural lung surfactant relative to a DPPC/palmitic acid lipid matrix alone. Its presence increases the sensitivity of the DPPC acyl chains to the presence of the peptide. These effects on the chain order are most probably related to the increased acyl chain fluidity which POPG imparts to the lipid matrix because of the presence of the cis double bond. The phosphatidylglycerol headgroup also adds a negative charge to the lipid matrix which enhances the peptide-lipid

  4. 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

  5. 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

    2015-01-01

    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. PMID:26703543

  6. Glucose induces sensitivity to oxygen deprivation and modulates insulin/IGF-1 signaling and lipid biosynthesis in Caenorhabditis elegans.

    PubMed

    Garcia, Anastacia M; Ladage, Mary L; Dumesnil, Dennis R; Zaman, Khadiza; Shulaev, Vladimir; Azad, Rajeev K; Padilla, Pamela A

    2015-05-01

    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

  7. 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

  8. Several lipid-related gene polymorphisms interact with overweight/obesity to modulate blood pressure levels.

    PubMed

    Yin, Rui-Xing; Wu, Dong-Feng; Aung, Lynn Htet Htet; Yan, Ting-Ting; Cao, Xiao-Li; Long, Xing-Jiang; Miao, Lin; Liu, Wan-Ying; Zhang, Lin; Li, Meng

    2012-01-01

    Little is known about the interactions of single nucleotide polymorphisms (SNPs) and overweight/obesity on blood pressure levels. The present study was undertaken to detect 10 lipid-related gene SNPs and their interactions with overweight/obesity on blood pressure levels. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaII hepatic lipase gene (LIPC) -250G > A, endothelial lipase gene (LIPG) 584C > T, methylenetetrahydrofolate reductase (MTHFR) 677C > T, the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP) rs3757354, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T > C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed in 978 normal weight and 751 overweight/obese subjects. The interactions were detected by factorial regression analysis. The genotypes of ACAT-1 AC, LIPC GA and AA, and SCARB1 TT; LDL-R A-A- and LIPC GA; and SCARB1 TT were interacted with overweight/obesity to increase systolic, diastolic blood pressure (SBP, DBP) and pulse pressure (PP) levels; respectively. The genotypes of ACAT-1 CC; ACAT-1 AA and CC were interacted with overweight/obesity to decrease SBP, PP levels (p < 0.01-0.001); respectively. The differences in blood pressure levels between normal weight and overweight/obese subjects might partly result from different interactions of several SNPs and overweight/obesity. PMID:23109900

  9. Lipid flippase modulates olfactory receptor expression and odorant sensitivity in Drosophila

    PubMed Central

    Ha, Tal Soo; Xia, Ruohan; Zhang, Haiying; Smith, Dean P.

    2014-01-01

    In Drosophila melanogaster, the male-specific pheromone cVA (11-cis-vaccenyl acetate) functions as a sex-specific social cue. However, our understanding of the molecular mechanisms underlying cVA pheromone transduction and its regulation are incomplete. Using a genetic screen combined with an electrophysiological assay to monitor pheromone-evoked activity in the cVA-sensing Or67d neurons, we identified an olfactory sensitivity factor encoded by the dATP8B gene, the Drosophila homolog of mammalian ATP8B. dATP8B is expressed in all olfactory neurons that express Orco, the odorant receptor coreceptor, and the odorant responses in most Orco-expressing neurons are reduced. Or67d neurons are severely affected, with strongly impaired cVA-induced responses and lacking spontaneous spiking in the mutants. The dATP8B locus encodes a member of the P4-type ATPase family thought to flip aminophospholipids such as phosphatidylserine and phosphatidylethanolamine from one membrane leaflet to the other. dATP8B protein is concentrated in the cilia of olfactory neuron dendrites, the site of odorant transduction. Focusing on Or67d neuron function, we show that Or67d receptors are mislocalized in dATP8B mutants and that cVA responses can be restored to dATP8B mutants by misexpressing a wild-type dATP8B rescuing transgene, by expressing a vertebrate P4-type ATPase member in the pheromone-sensing neurons or by overexpressing Or67d receptor subunits. These findings reveal an unexpected role for lipid translocation in olfactory receptor expression and sensitivity to volatile odorants. PMID:24821794

  10. Several Lipid-Related Gene Polymorphisms Interact with Overweight/Obesity to Modulate Blood Pressure Levels

    PubMed Central

    Yin, Rui-Xing; Wu, Dong-Feng; Aung, Lynn Htet Htet; Yan, Ting-Ting; Cao, Xiao-Li; Long, Xing-Jiang; Miao, Lin; Liu, Wan-Ying; Zhang, Lin; Li, Meng

    2012-01-01

    Little is known about the interactions of single nucleotide polymorphisms (SNPs) and overweight/obesity on blood pressure levels. The present study was undertaken to detect 10 lipid-related gene SNPs and their interactions with overweight/obesity on blood pressure levels. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaII hepatic lipase gene (LIPC) −250G > A, endothelial lipase gene (LIPG) 584C > T, methylenetetrahydrofolate reductase (MTHFR) 677C > T, the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP) rs3757354, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T > C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed in 978 normal weight and 751 overweight/obese subjects. The interactions were detected by factorial regression analysis. The genotypes of ACAT-1 AC, LIPC GA and AA, and SCARB1 TT; LDL-R A-A- and LIPC GA; and SCARB1 TT were interacted with overweight/obesity to increase systolic, diastolic blood pressure (SBP, DBP) and pulse pressure (PP) levels; respectively. The genotypes of ACAT-1 CC; ACAT-1 AA and CC were interacted with overweight/obesity to decrease SBP, PP levels (p < 0.01–0.001); respectively. The differences in blood pressure levels between normal weight and overweight/obese subjects might partly result from different interactions of several SNPs and overweight/obesity. PMID:23109900

  11. Femoral lipectomy increases postprandial lipemia in women.

    PubMed

    Hernandez, Teri L; Bessesen, Daniel H; Cox-York, Kimberly A; Erickson, Christopher B; Law, Christopher K; Anderson, Molly K; Wang, Hong; Jackman, Matthew R; Van Pelt, Rachael E

    2015-07-01

    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/m(2)) 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 [(14)C]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 [(14)C]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 cm(2), 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 × 10(3) 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 (14)C-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

  12. The acute respiratory distress syndrome: role of nutritional modulation of inflammation through dietary lipids.

    PubMed

    Mizock, Barry A; DeMichele, Stephen J

    2004-12-01

    The acute respiratory distress syndrome (ARDS) is the most serious form of acute hypoxic respiratory failure. ARDS represents the expression of an acute, diffuse, inflammatory process in the lungs consequent to a variety of infectious and noninfectious conditions. It is characterized pathologically by damage to pulmonary epithelial and endothelial cells, with subsequent alveolar-capillary leak and exudative pulmonary edema. The main clinical features of ARDS include rapid onset of dyspnea, severe defects in gas exchange, and imaging studies demonstrating diffuse pulmonary infiltrates. The role of nutrition in the management of ARDS has traditionally been supportive. Recent research has demonstrated the potential of certain dietary oils (eg, fish oil, borage oil) to modulate pulmonary inflammation, thereby improving lung compliance and oxygenation, and reducing time on mechanical ventilation. This article reviews the alterations in the immune response that underlie ARDS, discusses the physiology of dietary oils as immunonutrients, summarizes animal and human studies that explore the therapeutic effects of dietary oils, and provides clinical recommendations for their use. PMID:16215155

  13. Myelin-Derived Lipids Modulate Macrophage Activity by Liver X Receptor Activation

    PubMed Central

    Huynh-Thu, Vân Anh; Irrthum, Alexandre; Smeets, Hubert J. M.; Gustafsson, Jan-Åke; Steffensen, Knut R.; Mulder, Monique; Stinissen, Piet; Hellings, Niels; Hendriks, Jerome J. A.

    2012-01-01

    Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system in which macrophages and microglia play a central role. Foamy macrophages and microglia, containing degenerated myelin, are abundantly found in active multiple sclerosis lesions. Recent studies have described an altered macrophage phenotype after myelin internalization. However, it is unclear by which mechanisms myelin affects the phenotype of macrophages and how this phenotype can influence lesion progression. Here we demonstrate, by using genome wide gene expression analysis, that myelin-phagocytosing macrophages have an enhanced expression of genes involved in migration, phagocytosis and inflammation. Interestingly, myelin internalization also induced the expression of genes involved in liver-X-receptor signaling and cholesterol efflux. In vitro validation shows that myelin-phagocytosing macrophages indeed have an increased capacity to dispose intracellular cholesterol. In addition, myelin suppresses the secretion of the pro-inflammatory mediator IL-6 by macrophages, which was mediated by activation of liver-X-receptor β. Our data show that myelin modulates the phenotype of macrophages by nuclear receptor activation, which may subsequently affect lesion progression in demyelinating diseases such as multiple sclerosis. PMID:22984598

  14. Myelin-derived lipids modulate macrophage activity by liver X receptor activation.

    PubMed

    Bogie, Jeroen F J; Timmermans, Silke; Huynh-Thu, Vân Anh; Irrthum, Alexandre; Smeets, Hubert J M; Gustafsson, Jan-Åke; Steffensen, Knut R; Mulder, Monique; Stinissen, Piet; Hellings, Niels; Hendriks, Jerome J A

    2012-01-01

    Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system in which macrophages and microglia play a central role. Foamy macrophages and microglia, containing degenerated myelin, are abundantly found in active multiple sclerosis lesions. Recent studies have described an altered macrophage phenotype after myelin internalization. However, it is unclear by which mechanisms myelin affects the phenotype of macrophages and how this phenotype can influence lesion progression. Here we demonstrate, by using genome wide gene expression analysis, that myelin-phagocytosing macrophages have an enhanced expression of genes involved in migration, phagocytosis and inflammation. Interestingly, myelin internalization also induced the expression of genes involved in liver-X-receptor signaling and cholesterol efflux. In vitro validation shows that myelin-phagocytosing macrophages indeed have an increased capacity to dispose intracellular cholesterol. In addition, myelin suppresses the secretion of the pro-inflammatory mediator IL-6 by macrophages, which was mediated by activation of liver-X-receptor β. Our data show that myelin modulates the phenotype of macrophages by nuclear receptor activation, which may subsequently affect lesion progression in demyelinating diseases such as multiple sclerosis. PMID:22984598

  15. 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

  16. The P-glycoprotein inhibitor GF120918 modulates Ca2+-dependent processes and lipid metabolism in Toxoplasma gondii.

    PubMed

    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

  17. 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

  18. 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

  19. 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

  20. 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

  1. Specific polyunsaturated fatty acids modulate lipid delivery and oocyte development in C. elegans revealed by molecular-selective label-free imaging.

    PubMed

    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

  2. Berries and anthocyanins: promising functional food ingredients with postprandial glycaemia-lowering effects.

    PubMed

    Castro-Acosta, Monica L; Lenihan-Geels, Georgia N; Corpe, Christopher P; Hall, Wendy L

    2016-08-01

    The prevalence of type 2 diabetes (T2D) is predicted to reach unprecedented levels in the next few decades. In addition to excess body weight, there may be other overlapping dietary drivers of impaired glucose homeostasis that are associated with an obesogenic diet, such as regular exposure to postprandial spikes in blood glucose arising from diets dominated by highly refined starches and added sugars. Strategies to reduce postprandial hyperglycaemia by optimising the functionality of foods would strengthen efforts to reduce the risk of T2D. Berry bioactives, including anthocyanins, are recognised for their inhibitory effects on carbohydrate digestion and glucose absorption. Regular consumption of berries has been associated with a reduction in the risk of T2D. This review aims to examine the evidence from in vitro, animal and human studies, showing that berries and berry anthocyanins may act in the gut to modulate postprandial glycaemia. Specifically, berry extracts and anthocyanins inhibit the activities of pancreatic α-amylase and α-glucosidase in the gut lumen, and interact with intestinal sugar transporters, sodium-dependent glucose transporter 1 and GLUT2, to reduce the rate of glucose uptake into the circulation. Growing evidence from randomised controlled trials suggests that berry extracts, purées and nectars acutely inhibit postprandial glycaemia and insulinaemia following oral carbohydrate loads. Evidence to date presents a sound basis for exploring the potential for using berries/berry extracts as an additional stratagem to weight loss, adherence to dietary guidelines and increasing physical exercise, for the prevention of T2D. PMID:27170557

  3. 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

  4. Liver-specific overexpression of LPCAT3 reduces postprandial hyperglycemia and improves lipoprotein metabolic profile in mice

    PubMed Central

    Cash, J G; Hui, D Y

    2016-01-01

    Previous studies have shown that group 1B phospholipase A2-mediated absorption of lysophospholipids inhibits hepatic fatty acid β-oxidation and contributes directly to postprandial hyperglycemia and hyperlipidemia, leading to increased risk of cardiometabolic disease. The current study tested the possibility that increased expression of lysophosphatidylcholine acyltransferase-3 (LPCAT3), an enzyme that converts lysophosphatidylcholine to phosphatidylcholine in the liver, may alleviate the adverse effects of lysophospholipids absorbed after a lipid-glucose mixed meal. The injection of an adenovirus vector harboring the human LPCAT3 gene into C57BL/6 mice increased hepatic LPCAT3 expression fivefold compared with mice injected with a control LacZ adenovirus. Postprandial glucose tolerance tests after feeding these animals with a bolus lipid-glucose mixed meal revealed that LPCAT3 overexpression improved postprandial hyperglycemia and glucose tolerance compared with control mice with LacZ adenovirus injection. Mice with LPCAT3 overexpression also showed reduced very low density lipoprotein production and displayed elevated levels of the metabolic- and cardiovascular-protective large apoE-rich high density lipoproteins in plasma. The mechanism underlying the metabolic benefits of LPCAT3 overexpression was shown to be due to the alleviation of lysophospholipid inhibition of fatty acid β-oxidation in hepatocytes. Taken together, these results suggest that specific LPCAT3 induction in the liver may be a viable strategy for cardiometabolic disease intervention. PMID:27110687

  5. The cholestyramine-induced decrease of PYY postprandial response is negatively correlated with fat mass in obese women.

    PubMed

    Rigamonti, A E; Resnik, M; Compri, E; Agosti, F; De Col, A; Monteleone, P; Marazzi, N; Bonomo, S M; Müller, E E; Sartorio, A

    2011-07-01

    Obese patients have decreased fasting and postprandial levels of peptide YY (PYY), an anorexigenic peptide produced by the L cells of the gastrointestinal mucosa. Fatty nutrients are the most powerful stimulus for PYY release. Cholestyramine, an anion exchanger which adsorbs bile salts, reduces digestion of lipids. The aim of the present study was to investigate the effects of cholestyramine or placebo on PYY secretion in obese women administered a high-fat meal [n=8; age: 30.9±2.7 years; BMI: 47.3±3.3 kg/m2]. Postprandial PYY levels in obese women given placebo significantly increased in plasma at 30, 60, 90, and 120 min after meal ingestion. Cholestyramine administration significantly reduced postprandial PYY response at 15, 30, and 60 min. Percent fat mass (FM%) was negatively correlated with the percent increment of plasma PYY concentrations induced by meal administration at 30 min; conversely, there was a positive correlation between FM% and the percent decrement of plasma PYY concentrations induced by cholestyramine at the same time interval. These correlations failed to reach statistical significance when related to BMI. This study implies that in the obese state the altered PYY response to food consumption is a consequence of a dysfunction of L cells, which become less sensitive to the positive feedback effect of lipids. PMID:21769759

  6. Minor components of olive oil facilitate the triglyceride clearance from postprandial lipoproteins in a polarity-dependent manner in healthy men.

    PubMed

    Cabello-Moruno, Rosana; Martinez-Force, Enrique; Montero, Emilio; Perona, Javier S

    2014-01-01

    Postprandial triglyceride-rich lipoproteins (TRLs) are recognized as atherogenic particles whose lipid composition and function can be modified by the composition of dietary oils. This study was designed to test the hypothesis that minor components of pomace olive oil (POMACE) can not only change the composition of postprandial TRL but also affect the clearance of triglyceride (TG) molecular species of postprandial TRL. Meals enriched in either POMACE or refined olive oil (OLIVE) were administered to 10 healthy young men. TRL were isolated from serum at 2, 4, and 6 hours postprandially, and their fatty acid and TG molecular species compositions were analyzed by gas chromatography. The apolipoprotein B concentration was determined by immunoturbidimetry. POMACE and OLIVE, differing mainly in their unsaponifiable fraction, led to similar fatty acid and TG molecular species profiles in postprandial TRL. However, POMACE-TRL presented a higher particle size, estimated as TG to apolipoprotein B ratio, which was also found for the main TG molecular species (trioleoyl-glycerol, palmitoyl-dioleoyl-glycerol, palmitoyl-oeloyl-linoleoyl-glycerol, and dioleoyl-linoleoyl-glycerol). TG from POMACE-TRL also showed higher clearance rates. In this regard, apolar TG (with a higher equivalent carbon number) disappeared more rapidly from TRL particles obtained after the ingestion of either POMACE or OLIVE. In conclusion, minor components of POMACE facilitated TG clearance from TRL by modifying their particle size and the hydrolysis of the most apolar species. PMID:24418245

  7. Effect of Cinnamon Tea on Postprandial Glucose Concentration

    PubMed Central

    Bernardo, Maria Alexandra; Silva, Maria Leonor; Santos, Elisabeth; Moncada, Margarida Maria; Brito, José; Proença, Luis; 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

  8. 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

  9. Lipid raft regulates the initial spreading of melanoma A375 cells by modulating β1 integrin clustering.

    PubMed

    Wang, Ruifei; Bi, Jiajia; Ampah, Khamal Kwesi; Zhang, Chunmei; Li, Ziyi; Jiao, Yang; Wang, Xiaoru; Ba, Xueqing; Zeng, Xianlu

    2013-08-01

    Cell adhesion and spreading require integrins-mediated cell-extracellular matrix interaction. Integrins function through binding to extracellular matrix and subsequent clustering to initiate focal adhesion formation and actin cytoskeleton rearrangement. Lipid raft, a liquid ordered plasma membrane microdomain, has been reported to play major roles in membrane motility by regulating cell surface receptor function. Here, we identified that lipid raft integrity was required for β1 integrin-mediated initial spreading of melanoma A375 cells on fibronectin. We found that lipid raft disruption with methyl-β-cyclodextrin led to the inability of focal adhesion formation and actin cytoskeleton rearrangement by preventing β1 integrin clustering. Furthermore, we explored the possible mechanism by which lipid raft regulates β1 integrin clustering and demonstrated that intact lipid raft could recruit and modify some adaptor proteins, such as talin, α-actinin, vinculin, paxillin and FAK. Lipid raft could regulate the location of these proteins in lipid raft fractions and facilitate their binding to β1 integrin, which may be crucial for β1 integrin clustering. We also showed that lipid raft disruption impaired A375 cell migration in both transwell and wound healing models. Together, these findings provide a new insight for the relationship between lipid raft and the regulation of integrins. PMID:23665237

  10. 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. PMID:26744235

  11. Determination of the rate of rapid lipid transfer induced by poly(ethylene glycol) using the SLM Fourier transform phase and modulation spectrofluorometer.

    PubMed

    Burgess, S W; Wu, J R; Swift, K; Lentz, B R

    1991-06-01

    Rate constants were determined for the transfer of the fluorescent lipid probe 1-palmitoyl-2-[[2-[4-(6-phenyl-trans-1,3,5-hexatrienyl)phenyl]ethyl] oxy]carbonyl]-3-sn-phosphatidylcholine (DPHpPC) between large, unilamellar extrusion vesicles composed either of dipalmitoyl phosphatidylcholine (DPPC) or of DPPC mixed with a small amount (0.5 mol%) of lyso phosphatidylcholine (Lyso PC). Transfer of the lipid probe in the presence of varying concentrations of poly(ethylene glycol) (PEG) was monitored using the SLM 48000-MHF Multi-Harmonic Fourier Transform phase and modulation spectrofluorometer to collect multifrequency phase and modulation fluorescence data sets on a subsecond time scale. The unique ability of this instrument to yield accurate fluorescence lifetime data on this time scale allowed transfer to be detected in terms of a time-dependent change in the fluorescent lifetime distribution associated with the lipid-like DPHpPC probe. This probe demonstrates two short fluoresence decay times (ca. 1.1-1.4 and 4.3-4.8 ns) in a probe-rich environment but a single long lifetime (ca. 7 ns) in a probe-poor environment. A simple two-state model for initial lipid transfer was used to analyze the multifrequency data sets collected over a 4-s time frame to obtain the time rate of change of the concentrations of donor and acceptor probe populations following rapid mixing of vesicles with PEG. The ability to measure fluorescence lifetimes on this time scale has allowed us to show that the of rate of lipid transfer increased dramatically at 35% PEG in both fusing and nonfusing vesicle systems. These results are interpreted in terms of a distinct interbilayer structure associated with intimate bilayer contact induced by high and potentially fusogenic concentrations of PEG. PMID:24242960

  12. 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. PMID:24041758

  13. 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

  14. Nocardia brasiliensis cell wall lipids modulate macrophage and dendritic responses that favor development of experimental actinomycetoma in BALB/c mice.

    PubMed

    Trevino-Villarreal, J Humberto; Vera-Cabrera, Lucio; Valero-Guillén, Pedro L; Salinas-Carmona, Mario C

    2012-10-01

    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

  15. 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

  16. 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

  17. New oral fat tolerance tests feature tailoring of the polyunsaturated/saturated fatty acid ratio to elicit a specific postprandial response.

    PubMed

    Dekker, Mark J; Wright, Amanda J; Mazurak, Vera C; Graham, Terry E; Marangoni, Alejandro G; Robinson, Lindsay E

    2007-12-01

    The impact of dietary fat on postprandial metabolic biomarkers for obesity-related chronic diseases, such as type-2 diabetes and cardiovascular disease, has received significant recent attention. However, there is no standard method to evaluate the postprandial response to dietary fat alone. Our goals were to develop a novel oral fat tolerance test (OFTT) consisting solely of emulsified lipids tailored for specific fatty acid compositions and to evaluate the functionality of specific ratios of polyunsaturated/saturated fatty acid (P/S) loading on postprandial triacylglyceride (TAG) concentrations. Two OFTTs of emulsified lipids were prepared with specific P/S ratios of 0.2 and 2.0. Physical characteristics of the fat blends, including TAG composition, melting point, and emulsion droplet size were quantified. Healthy, older (age>45 y) men (n=8) underwent an 8 h postprandial study wherein they received the OFTT treatment (either the P/S ratio of 0.2 or 2.0), with a total lipid load of 1 g/kg subject body mass. All subjects received both treatments separated by at least 1 week. Both the P/S 0.2 and 2.0 OFTT significantly elevated (p<0.05) blood TAG and free fatty acid concentrations for 8 h without increasing blood glucose or serum insulin concentrations. The predominant fatty acids contained in the P/S 0.2 (palmitic acid, 16:0) and 2.0 (linoleic acid, 18:2(n-6)) OFTT blends were significantly elevated in the blood (p<0.05) during their respective postprandial periods. We concluded that blood TAGs are elevated in a specific pattern through the administration of novel OFTTs with specific P/S blends without eliciting an insulin or glucose response. PMID:18059580

  18. 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

  19. The Compound of Mangiferin-Berberine Salt Has Potent Activities in Modulating Lipid and Glucose Metabolisms in HepG2 Cells

    PubMed Central

    Wang, Can; Jiang, Jian-Dong; Wu, Wei; Kong, Wei-Jia

    2016-01-01

    The mangiferin-berberine (MB) salt was synthesized by ionic bonding of mangiferin (M) and berberine (B) at an equal molecular ratio. This study aimed to investigate the activities of MB salt in modulating lipid and glucose metabolisms in HepG2 cells. After 24 h treatment of the studying compounds, cellular AMP-activated protein kinase α (AMPKα)/acetyl-CoA carboxylase (ACC) protein levels and carnitine palmitoyltransferase (CPT) 1 activities, intracellular lipid contents, mRNA expression levels of target genes, glucose consumption, and glucose production amounts were determined. Compound C (CC) was used in the blocking experiments. Our results showed that MB salt increased p-AMPKα (Thr172)/p-ACC (Ser79) levels and CPT1 activity and suppressed oleic acid- (OA-) induced lipid accumulation and upregulation of lipogenic genes potently in HepG2 cells. The above activities of MB salt were AMPK dependent and were superior to those of M or B when administered at an equal molar concentration. MB salt enhanced basal and insulin-stimulated glucose consumption and suppressed gluconeogenesis more potently than M or B alone. The inhibiting activity of MB salt on cellular gluconeogenesis was AMPK dependent. Our results may support MB salt as a new kind of agent for the development of novel lipid or glucose-lowering drugs in the future. PMID:27123455

  20. Hyperosmolarity in the small intestine contributes to postprandial ghrelin suppression

    PubMed Central

    Overduin, Joost; Tylee, Tracy S.; Frayo, R. Scott

    2014-01-01

    Plasma levels of the orexigenic hormone ghrelin are suppressed by meals with an efficacy dependent on their macronutrient composition. We hypothesized that heterogeneity in osmolarity among macronutrient classes contributes to these differences. In three studies, the impact of small intestinal hyperosmolarity was examined in Sprague-Dawley rats. In study 1, isotonic, 2.5×, and 5× hypertonic solutions of several agents with diverse absorption and metabolism properties were infused duodenally at a physiological rate (3 ml/10 min). Jugular vein blood was sampled before and at 30, 60, 90, 120, 180, 240, and 300 min after infusion. Plasma ghrelin was suppressed dose dependently and most strongly by glucose. Hyperosmolar infusions of lactulose, which transits the small intestine unabsorbed, and 3-O-methylglucose (3-O-MG), which is absorbed like glucose but remains unmetabolized, also suppressed ghrelin. Glucose, but not lactulose or 3-O-MG, infusions increased plasma insulin. In study 2, intestinal infusions of hyperosmolar NaCl suppressed ghrelin, a response that was not attenuated by coinfusion with the neural blocker lidocaine. In study 3, we reconfirmed that the low-osmolar lipid emulsion Intralipid suppresses ghrelin more weakly than isocaloric (but hypertonic) glucose. Importantly, raising Intralipid's osmolarity to that of the glucose solution by nonabsorbable lactulose supplementation enhanced ghrelin suppression to that seen after glucose. Hyperosmolar ghrelin occurred particularly during the initial 3 postinfusion hours. We conclude that small intestinal hyperosmolarity 1) is sufficient to suppress ghrelin, 2) may combine with other postprandial mechanisms to suppress ghrelin, 3) might contribute to altered ghrelin regulation after gastric bypass surgery, and 4) may inform dietary modifications for metabolic health. PMID:24789208

  1. Extended-Release Niacin Acutely Suppresses Postprandial Triglyceridemia

    PubMed Central

    Usman, M. Haris U.; Qamar, Arman; Gadi, Ramprasad; Lilly, Scott; Goel, Harsh; Hampson, Jaison; Mucksavage, Megan L.; Nathanson, Grace A.; Rader, Daniel J.; Dunbar, Richard L.

    2012-01-01

    Background Postprandial triglyceridemia predicts cardiovascular events. Niacin might lower postprandial triglycerides (TG) by restricting free fatty acid (FFA). Immediate-release niacin reduced postprandial TGs, but extended-release niacin failed to do so when dosed the night before a fat challenge. Aims 1) Determine whether extended-release niacin dosed before a fat challenge suppresses postprandial TG. 2) Determine whether postprandial TG is related to FFA restriction. Methods Double-blinded, placebo-controlled, random-order crossover experiment, where healthy volunteers took 2 g extended-release niacin or placebo 1 hour before heavy cream. We sampled blood over 12 hours, and report TG and FFA as means±SD for incremental area under the curve (iAUC) and nadir. Results Combining 43 fat challenges from 22 subjects, postprandial TG iAUC was +312±200 on placebo vs +199±200 mg/dL*h on extended-release niacin (33% drop, p= 0.02). The incremental nadir for FFA was −0.07±0.15 on placebo vs −0.27±0.13 mmol/L on extended-release niacin (p<0.0001), and FFA iAUC fell from +2.9±1.5 to +1.5±1.5 mmol/L*h on extended-release niacin (20% drop, p=0.0015). The TG iAUC was strongly related to the post-dose drop in FFA (r=+0.58, p=0.0007). Conclusions Given right before a fat meal, even a single dose of extended-release niacin suppresses postprandial triglyceridemia. This establishes that postprandial TG suppression is an acute pharmacodynamic effect of extended-release niacin, probably the result of marked FFA restriction. Further study is warranted to determine whether mealtime dosing would augment the clinical efficacy of extended-release niacin therapy. PMID:22840917

  2. Dual modulation of both lipid oxidation and synthesis by peroxisome proliferator-activated receptor-γ coactivator-1α and -1β in cultured myotubes

    PubMed Central

    Espinoza, Daniel O.; Boros, Laszlo G.; Crunkhorn, Sarah; Gami, Hiral; Patti, Mary-Elizabeth

    2010-01-01

    The peroxisome proliferator-activated receptor γ 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-1α and PGC-1β in C2C12 myotubes using adenoviral vectors. Both PGC-1α and -1β 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-1α and -1β 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-1α (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-1α/β (P<0.05). Stable isotope-based dynamic metabolic profiling in serum-replete cells labeled with 13C substrates revealed both increased de novo fatty acid synthesis from glucose and increased fatty acid synthesis by chain elongation with either PGC-1α or -1β 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-γ coactivator-1α and -1β in cultured myotubes. PMID:19906680

  3. 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

  4. Postprandial regulation of hepatic microRNAs predicted to target the insulin pathway in rainbow trout.

    PubMed

    Mennigen, Jan A; Panserat, Stéphane; Larquier, Mélanie; Plagnes-Juan, Elisabeth; Medale, Françoise; Seiliez, Iban; Skiba-Cassy, Sandrine

    2012-01-01

    Rainbow trout are carnivorous fish and poor metabolizers of carbohydrates, which established this species as a model organism to study the comparative physiology of insulin. Following the recent characterisation of key roles of several miRNAs in the insulin action on hepatic intermediary metabolism in mammalian models, we investigated the hypothesis that hepatic miRNA expression is postprandially regulated in the rainbow trout and temporally coordinated in the context of insulin-mediated regulation of metabolic gene expression in the liver. To address this hypothesis, we used a time-course experiment in which rainbow trout were fed a commercial diet after short-term fasting. We investigated hepatic miRNA expression, activation of the insulin pathway, and insulin regulated metabolic target genes at several time points. Several miRNAs which negatively regulate hepatic insulin signaling in mammalian model organisms were transiently increased 4 h after the meal, consistent with a potential role in acute postprandial negative feed-back regulation of the insulin pathway and attenuation of gluconeogenic gene expression. We equally observed a transient increase in omy- miRNA-33 and omy-miRNA-122b 4 h after feeding, whose homologues have potent lipogenic roles in the liver of mammalian model systems. A concurrent increase in the activity of the hepatic insulin signaling pathway and the expression of lipogenic genes (srebp1c, fas, acly) was equally observed, while lipolytic gene expression (cpt1a and cpt1b) decreased significantly 4 h after the meal. This suggests lipogenic roles of omy-miRNA-33 and omy-miRNA-122b may be conserved between rainbow trout and mammals and that these miRNAs may furthermore contribute to acute postprandial regulation of de novo hepatic lipid synthesis in rainbow trout. These findings provide a framework for future research of miRNA regulation of hepatic metabolism in trout and will help to further elucidate the metabolic phenotype of rainbow trout

  5. 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

  6. Hepatic Carboxylesterase 1 Is Induced by Glucose and Regulates Postprandial Glucose Levels

    PubMed Central

    Xu, Jiesi; Yin, Liya; Xu, Yang; Li, Yuanyuan; Zalzala, Munaf; Cheng, Gang; Zhang, Yanqiao

    2014-01-01

    Metabolic syndrome, characterized by obesity, hyperglycemia, dyslipidemia and hypertension, increases the risks for cardiovascular disease, diabetes and stroke. Carboxylesterase 1 (CES1) is an enzyme that hydrolyzes triglycerides and cholesterol esters, and is important for lipid metabolism. Our previous data show that over-expression of mouse hepatic CES1 lowers plasma glucose levels and improves insulin sensitivity in diabetic ob/ob mice. In the present study, we determined the physiological role of hepatic CES1 in glucose homeostasis. Hepatic CES1 expression was reduced by fasting but increased in diabetic mice. Treatment of mice with glucose induced hepatic CES1 expression. Consistent with the in vivo study, glucose stimulated CES1 promoter activity and increased acetylation of histone 3 and histone 4 in the CES1 chromatin. Knockdown of ATP-citrate lyase (ACL), an enzyme that regulates histone acetylation, abolished glucose-mediated histone acetylation in the CES1 chromatin and glucose-induced hepatic CES1 expression. Finally, knockdown of hepatic CES1 significantly increased postprandial blood glucose levels. In conclusion, the present study uncovers a novel glucose-CES1-glucose pathway which may play an important role in regulating postprandial blood glucose levels. PMID:25285996

  7. Review: Management of postprandial diarrhea syndrome.

    PubMed

    Money, Mary E; Camilleri, Michael

    2012-06-01

    Unexpected, urgent, sometimes painful bowel movements after eating are common complaints among adults. Without a clear etiology, if pain is present and resolves with the movements, this is usually labeled "irritable bowel syndrome-diarrhea" based solely on symptoms. If this symptom-based approach is applied exclusively, it may lead physicians not to consider treatable conditions: celiac disease, or maldigestion due to bile acid malabsorption, pancreatic exocrine insufficiency, or an a-glucosidase (sucrase, glucoamylase, maltase, or isomaltase) deficiency. These conditions can be misdiagnosed as irritable bowel syndrome-diarrhea (or functional diarrhea, if pain is not present). Limited testing is currently available to confirm these conditions (antibody screens for celiac disease; fecal fat as a surrogate marker for pancreatic function). Therefore, empirical treatment with alpha amylase, pancreatic enzymes, or a bile acid-binding agent may simultaneously treat these patients and serve as a surrogate diagnostic test. This review will summarize the current evidence for bile acid malabsorption, and deficiencies of pancreatic enzymes or a-glucosidases as potential causes for postprandial diarrhea, and provide an algorithm for treatment options. PMID:22624684

  8. 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

  9. A single Mediterranean meal does not impair postprandial flow-mediated dilatation in healthy men with subclinical metabolic dysregulations.

    PubMed

    Lacroix, Sébastien; Des Rosiers, Christine; Gayda, Mathieu; Nozza, Anna; Thorin, Éric; Tardif, Jean-Claude; Nigam, Anil

    2016-08-01

    Cardiovascular risk factors are known to exacerbate high-saturated fatty acid meal (HSFAM)-induced endothelial dysfunction, but the influence of subclinical metabolic dysregulations and the acute impact of a single mixed Mediterranean-type meal (MMM) remains unknown. Thus, this study has the objective to evaluate the metabolic and vascular effect of such meals in healthy subjects with or without subclinical fasting metabolic dysregulations. Twenty-eight healthy males without overt cardiovascular risk factors randomly ingested 1 of 2 isocaloric meals on separate days. Plasma metabolic markers, fatty acid (FA) profile, and endothelial function (flow-mediated dilatation; FMD) were assessed at baseline and 2 and 4 h after meal ingestion. Unsupervised hierarchical clustering identified 2 subgroups of participants (n = 11 and 17) differing by their baseline metabolic profiles. The MMM did not significantly alter postprandial endothelial function in all subjects, irrespective of baseline metabolic parameters. In contrast, the HSFAM induced postprandial endothelial dysfunction (Δ%FMDabsolute = -5.28 ± 2.54, p < 0.01 vs. MMM) in a subgroup of individuals with significantly greater body mass index, fasting insulinemia, and lipid parameters (n = 11). Finally, the postprandial plasma FA profiles were differentially enriched by the HSFAM and MMM, notably with saturated FAs and omega-3 polyunsaturated FAs, respectively. Collectively, our results highlight the detrimental impact of a single HSFAM on endothelial function in healthy individuals displaying subclinical fasting metabolic dysregulations. Such individuals could benefit from MMM, demonstrated herein to be without any acute detriment to endothelial function. PMID:27454855

  10. Differential effects of EPA versus DHA on postprandial vascular function and the plasma oxylipin profile in men[S

    PubMed Central

    McManus, Seán; Tejera, Noemi; Awwad, Khader; Rigby, Neil; Fleming, Ingrid; Cassidy, Aedin; Minihane, Anne Marie

    2016-01-01

    Our objective was to investigate the impact of EPA versus DHA on arterial stiffness and reactivity and underlying mechanisms (with a focus on plasma oxylipins) in the postprandial state. In a three-arm crossover acute test meal trial, men (n = 26, 35–55 years) at increased CVD risk received a high-fat (42.4 g) test meal providing 4.16 g of EPA or DHA or control oil in random order. At 0 h and 4 h, blood samples were collected to quantify plasma fatty acids, long chain n-3 PUFA-derived oxylipins, nitrite and hydrogen sulfide, and serum lipids and glucose. Vascular function was assessed using blood pressure, reactive hyperemia index, pulse wave velocity, and augmentation index (AIx). The DHA-rich oil significantly reduced AIx by 13% (P = 0.047) with the decrease following EPA-rich oil intervention not reaching statistical significance. Both interventions increased EPA- and DHA-derived oxylipins in the acute postprandial state, with an (1.3-fold) increase in 19,20-dihydroxydocosapentaenoic acid evident after DHA intervention (P < 0.001). In conclusion, a single dose of DHA significantly improved postprandial arterial stiffness as assessed by AIx, which if sustained would be associated with a significant decrease in CVD risk. The observed increases in oxylipins provide a mechanistic insight into the AIx effect. PMID:27170732

  11. Differential effects of EPA versus DHA on postprandial vascular function and the plasma oxylipin profile in men.

    PubMed

    McManus, Seán; Tejera, Noemi; Awwad, Khader; Vauzour, David; Rigby, Neil; Fleming, Ingrid; Cassidy, Aedin; Minihane, Anne Marie

    2016-09-01

    Our objective was to investigate the impact of EPA versus DHA on arterial stiffness and reactivity and underlying mechanisms (with a focus on plasma oxylipins) in the postprandial state. In a three-arm crossover acute test meal trial, men (n = 26, 35-55 years) at increased CVD risk received a high-fat (42.4 g) test meal providing 4.16 g of EPA or DHA or control oil in random order. At 0 h and 4 h, blood samples were collected to quantify plasma fatty acids, long chain n-3 PUFA-derived oxylipins, nitrite and hydrogen sulfide, and serum lipids and glucose. Vascular function was assessed using blood pressure, reactive hyperemia index, pulse wave velocity, and augmentation index (AIx). The DHA-rich oil significantly reduced AIx by 13% (P = 0.047) with the decrease following EPA-rich oil intervention not reaching statistical significance. Both interventions increased EPA- and DHA-derived oxylipins in the acute postprandial state, with an (1.3-fold) increase in 19,20-dihydroxydocosapentaenoic acid evident after DHA intervention (P < 0.001). In conclusion, a single dose of DHA significantly improved postprandial arterial stiffness as assessed by AIx, which if sustained would be associated with a significant decrease in CVD risk. The observed increases in oxylipins provide a mechanistic insight into the AIx effect. PMID:27170732

  12. Black-white differences in postprandial triglyceride response and postheparin lipoprotein lipase and hepatic triglyceride lipase among young men.

    PubMed

    Friday, K E; Srinivasan, S R; Elkasabany, A; Dong, C; Wattigney, W A; Dalferes, E; Berenson, G S

    1999-06-01

    Black-white differences in serum triglycerides and high-density lipoprotein (HDL) cholesterol concentrations are known. However, the metabolic basis for these differences is not clear. This study determined the magnitude of postprandial triglyceride concentrations, lipoprotein lipase and hepatic triglyceride lipase activities in postheparin plasma, and serum lipid and lipoprotein cholesterol concentrations in healthy young adult black men (n = 22) and white men (n = 28). Postprandial triglyceride concentrations were measured at 2, 3, 4, 5, 6, and 8 hours after a standardized test meal. Serum lipid and lipoprotein cholesterol concentrations were similar between the races in this study sample. However, incremental (above basal) increases in triglycerides were significantly greater in white men versus black men at 2 hours (P = .01) and tended to be greater at 3 hours (P = .12) and 4 hours (P = .06) after the fat load. In a multivariate analysis that included age, race, apolipoprotein E (apoE) genotype, fasting triglycerides, obesity measures, alcohol intake, and cigarette use, fasting triglycerides (P = .04) and, to a lesser extent, race (P = .07) were associated independently with the 2-hour incremental increase in triglycerides. The incremental triglyceride response correlated inversely with HDL cholesterol in both whites (r = -.38, P = .04) and blacks (r = -.59, P = .004). Lipoprotein lipase activity was higher (P = .049) and hepatic triglyceride lipase activity lower (P = .0001) in black men compared with white men; racial differences persisted after adjusting for the covariates. While lipoprotein lipase activity tended to associate inversely with the postprandial triglyceride concentration in both races, hepatic triglyceride lipase activity tended to correlate positively in whites and inversely in blacks. These results suggest that compared with whites, blacks may have an efficient lipid-clearing mechanism that could explain the black-white differences in

  13. Postprandial dyslipidemia in men with visceral obesity: an effect of reduced LDL receptor expression?

    PubMed

    Mamo, J C; Watts, G F; Barrett, P H; Smith, D; James, A P; Pal, S

    2001-09-01

    Postprandial lipemia after an oral fat challenge was studied in middle-aged men with visceral obesity. The two groups had similar plasma cholesterol levels, but obese subjects had higher levels of plasma triglyceride and reduced amounts of high-density cholesterol. Fasting plasma insulin was fourfold greater in obese subjects because of concomitant insulin resistance, with a calculated HOMA score of 3.1 +/- 0.6 vs. 0.8 +/- 0.2, respectively. Plasma apolipoprotein B(48) (apoB(48)) and retinyl palmitate (RP) after an oral fat challenge were used to monitor chylomicron metabolism. Compared with lean subjects, the fasting concentration of apoB(48) was more than twofold greater in obese individuals, suggestive of an accumulation of posthydrolyzed particles. After the oral lipid load, the incremental areas under the apoB(48) and RP curves (IAUC) were both significantly greater in obese subjects (apoB(48): 97 +/- 17 vs. 44 +/- 12 microg.ml(-1). h; RP: 3,120 +/- 511 vs. 1,308 +/- 177 U. ml(-1). h, respectively). A delay in the conversion of chylomicrons to remnants probably contributed to postprandial dyslipidemia in viscerally obese subjects. The triglyceride IAUC was 68% greater in obese subjects (4.7 +/- 0.6 vs. 2.8 +/- 0.8 mM. h, P < 0.06). Moreover, peak postprandial triglyceride was delayed by approximately 2 h in obese subjects. The reduction in triglyceride lipolysis in vivo did not appear to reflect changes in hydrolytic enzyme activities. Postheparin plasma lipase rates were found to be similar for lean and obese subjects. In this study, low-density lipoprotein (LDL) receptor expression on monunuclear cells was used as a surrogate marker of hepatic activity. We found that, in obese subjects, the binding of LDL was reduced by one-half compared with lean controls (70.9 +/- 15.07 vs. 38.9 +/- 4.6 ng LDL bound/microg cell protein, P = 0.02). Because the LDL receptor is involved in the removal of proatherogenic chylomicron remnants, we suggest that the hepatic

  14. Raman Spectroscopic Analysis of Biochemical Changes in Individual Triglyceride-Rich Lipoproteins in the Pre- and Postprandial State

    SciTech Connect

    Chan, J; Motton, D; Rutledge, J; Keim, N; Huser, T

    2004-09-13

    Individual triglyceride-rich lipoprotein (TGRL) particles derived from human volunteers are non-destructively analyzed by laser tweezers Raman microspectroscopy and information on their composition and distribution is obtained. The Raman signature of single optically trapped very low-density lipoproteins (VLDL), a subclass of TGRL, which play an important role in cardiovascular disease, exhibits distinct peaks associated with molecular vibrations of fatty acids, proteins, lipids, and structural rearrangements of lipids. Our analysis of pre- and postprandial VLDL exhibits the signature of biochemical changes in individual lipoprotein particles following the consumption of meals. Interaction of VLDL with endothelium leads to the breakdown of complex triacylglycerols and the formation of a highly ordered core of free saturated fatty acids in the particle. A particle distribution analysis reveals trends in the degree to which this process has occurred in particles at different times during the postprandial period. Differences in particle distributions based on the different ratios of polyunsaturated to saturated fats in the consumed meals are also easily discerned. Individual lipoprotein particles hydrolyzed in-vitro through addition of lipoprotein lipase (LpL) exhibit strikingly similar changes in their Raman spectra. These results demonstrate the feasibility of monitoring the dynamics of lipid metabolism of individual TGRL particles as they interact with LpL in the endothelial cell wall using Raman spectroscopy.

  15. Effect of surface-potential modulators on the opening of lipid pores in liposomal and mitochondrial inner membranes induced by palmitate and calcium ions.

    PubMed

    Belosludtsev, Konstantin N; Belosludtseva, Natalia V; Agafonov, Alexey V; Penkov, Nikita V; Samartsev, Victor N; Lemasters, John J; Mironova, Galina D

    2015-10-01

    The effect of surface-potential modulators on palmitate/Ca2+-induced formation of lipid pores was studied in liposomal and inner mitochondrial membranes. Pore formation was monitored by sulforhodamine B release from liposomes and swelling of mitochondria. ζ-potential in liposomes was determined from electrophoretic mobility. Replacement of sucrose as the osmotic agent with KCl decreased negative ζ-potential in liposomes and increased resistance of both mitochondria and liposomes to the pore inducers, palmitic acid, and Ca2+. Micromolar Mg2+ also inhibited palmitate/Ca2+-induced permeabilization of liposomes. The rate of palmitate/Ca2+-induced, cyclosporin A-insensitive swelling of mitochondria increased 22% upon increasing pH from 7.0 to 7.8. At below the critical micelle concentration, the cationic detergent cetyltrimethylammonium bromide (10 μM) and the anionic surfactant sodium dodecylsulfate (10-50 μM) made the ζ-potential less and more negative, respectively, and inhibited and stimulated opening of mitochondrial palmitate/Ca2+-induced lipid pores. Taken together, the findings indicate that surface potential regulates palmitate/Ca2+-induced lipid pore opening. PMID:26014488

  16. Effect of surface-potential modulators on the opening of lipid pores in liposomal and mitochondrial inner membranes induced by palmitate and calcium ions

    PubMed Central

    Belosludtsev, Konstantin N.; Belosludtseva, Natalia V.; Agafonov, Alexey V.; Penkov, Nikita V.; Samartsev, Victor N.; Lemasters, John J.; Mironova, Galina D.

    2016-01-01

    The effect of surface-potential modulators on palmitate/Ca2+-induced formation of lipid pores was studied in liposomal and inner mitochondrial membranes. Pore formation was monitored by sulforhodamine B release from liposomes and swelling of mitochondria. ζ-potential in liposomes was determined from electrophoretic mobility. Replacement of sucrose as the osmotic agent with KCl decreased negative ζ-potential in liposomes and increased resistance of both mitochondria and liposomes to the pore inducers, palmitic acid, and Ca2+. Micromolar Mg2+ also inhibited palmitate/Ca2+-induced permeabilization of liposomes. The rate of palmitate/Ca2+-induced, cyclosporin A-insensitive swelling of mitochondria increased 22% upon increasing pH from 7.0 to 7.8. At below the critical micelle concentration, the cationic detergent cetyltrimethylammonium bromide (10 μM) and the anionic surfactant sodium dodecylsulfate (10–50 μM) made the ζ-potential less and more negative, respectively, and inhibited and stimulated opening of mitochondrial palmitate/Ca2+-induced lipid pores. Taken together, the findings indicate that surface potential regulates palmitate/Ca2+-induced lipid pore opening. PMID:26014488

  17. Investigation into the acute effects of total and partial energy restriction on postprandial metabolism among overweight/obese participants.

    PubMed

    Antoni, Rona; Johnston, Kelly L; Collins, Adam L; Robertson, M Denise

    2016-03-28

    The intermittent energy restriction (IER) approach to weight loss involves short periods of substantial (75-100 %) energy restriction (ER) interspersed with normal eating. This study aimed to characterise the early metabolic response to these varying degrees of ER, which occurs acutely and prior to weight loss. Ten (three female) healthy, overweight/obese participants (36 (SEM 5) years; 29·0 (sem 1·1) kg/m2) took part in this acute three-way cross-over study. Participants completed three 1-d dietary interventions in a randomised order with a 1-week washout period: isoenergetic intake, partial 75 % ER and total 100 % ER. Fasting and postprandial (6-h) metabolic responses to a liquid test meal were assessed the following morning via serial blood sampling and indirect calorimetry. Food intake was also recorded for two subsequent days of ad libitum intake. Relative to the isoenergetic control, postprandial glucose responses were increased following total ER (+142 %; P=0·015) and to a lesser extent after partial ER (+76 %; P=0·051). There was also a delay in the glucose time to peak after total ER only (P=0·024). Both total and partial ER interventions produced comparable reductions in postprandial TAG responses (-75 and -59 %, respectively; both P<0·05) and 3-d energy intake deficits of approximately 30 % (both P=0·015). Resting and meal-induced thermogenesis were not significantly affected by either ER intervention. In conclusion, our data demonstrate the ability of substantial ER to acutely alter postprandial glucose-lipid metabolism (with partial ER producing the more favourable overall response), as well as incomplete energy-intake compensation amongst overweight/obese participants. Further investigations are required to establish how metabolism adapts over time to the repeated perturbations experienced during IER, as well as the implications for long-term health. PMID:26819200

  18. Postprandial cholesteryl ester transfer and high density lipoprotein composition in normotriglyceridemic non-insulin-dependent diabetic patients.

    PubMed

    Durlach, V; Attia, N; Zahouani, A; Leutenegger, M; Girard-Globa, A

    1996-02-01

    Altered postprandial HDL metabolism is a possible cause of defective reverse cholesterol transport and increased cardiovascular risk in diabetic patients with a normal fasting lipoprotein profile. Ten normolipidemic, normoponderal non-insulin dependent diabetes mellitus (NIDDM) patients and seven controls received a 980 kcal meal containing 78 g lipids with 100 000 IU vitamin A. Chylomicron clearance was not different, but area under the curve (AUC) for retinyl palmitate in chylimicron-free serum (remnant clearance) was greater in patients (P < 0.02). LCAT activity increased postprandially to the same extent in both groups. In control subjects, cholesteryl ester transfer protein (CETP) activity (CETA) also increased by 20% (P < 0.01 at 6 h) in parallel with a 20% decrease in HDL2-CE (r = -0.55, P = 0.009). In NIDDM patients, on the contrary, CETA which was 35% higher in the fasting state (P < 0.005), decreased postprandially yet HDL2-CE remained unchanged. Postprandial HDL3 of controls were enriched with phospholipid (PL) (30.3 +/- 2.6% at 6 h) with respect to fasting (25.6 +/- 2.5%, P < 0.01) and to NIDDM-HDL3 (25.8 +/- 1.7% at 6 h, P < 0.01). These results show that variation in plasma CETA has little impact on HDL2-CE in NIDDH subjects. They support the concept that, in controls, the combined enrichment of HDL3 with PL, increased LCAT and CETA create the conditions for stimulation of cell cholesterol efflux and CE transfer to apo B lipoproteins. In NIDDM, because of the lesser HDL3 enrichment with PL and of the inverse trend of CETA, these conditions fail to occur, depriving the patients of a potentially efficient mechanism of unesterified cholesterol (UC) clearance, despite their strictly normal preprandial profile. PMID:8645357

  19. Effect of prior exercise on postprandial triglycerides in overweight young women after ingesting a high-carbohydrate meal.

    PubMed

    Mitchell, Joel B; Rowe, James R; Shah, Meena; Barbee, James J; Watkins, Austen M; Stephens, Chad; Simmons, Steve

    2008-02-01

    To examine the effect of prior exercise on the postprandial lipid response to a high-carbohydrate meal in normal-weight (NW=BMI <25) and overweight (OW=BMI >or= 25) women (age 18-25), 10 NW and 10 OW participants completed 2 conditions separated by 1 month. In the morning, the day after control (CT=no exercise) or exercise conditions (EX=60 min cycling at 60% VO(2peak)), participants consumed a high-carbohydrate meal (80% CHO, 15% protein, 5% fat; 75 kJ/kg BM) followed by 6 hr of hourly blood sampling. Blood was analyzed for triglycerides (TG), blood glucose (BG), and insulin (IN). TG levels over the 6-hr period were lower in NW than OW (p= .021) and lower in EX than in CT (p= .006). Area under the curve (AUC) for TG was lower in NW than OW (p= .016) and EX than CT (p= .003). There were nonsignificant tendencies for reduced BG over time (p= .053) and AUC (p= .083), and IN AUC was lower in EX than in CT (p= .040) for both groups and lower in NW than in OW (p= .039). Prior exercise improved TG levels after a high-carbohydrate meal in both groups, and OW women demonstrated a greater postprandial lipemic response than NW regardless of condition. There were tendencies for improved glucose removal with prior exercise in NW vs. OW. Acute exercise can improve postprandial TG responses and might also improve postprandial BG and IN after a large meal in NW and OW young women. PMID:18272933

  20. Triacontanol and jasmonic acid differentially modulate the lipid organization as evidenced by the fluorescent probe behavior and 31P nuclear magnetic resonance shifts in model membranes.

    PubMed

    Sivakumar Swamy, G; Swamy, Sivakumar G; Ramanarayan, K; Inamdar, Laxmi S; Inamdar, Sanjeev R

    2009-04-01

    Fluorescence resonance energy transfer (FRET), time-resolved fluorescence and anisotropy decays were determined in large unilamellar vesicles (LUVs) of egg phosphatidylcholine with the FRET pair N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2-dipalmitoyl-sn-glycero-3-phospho-ethanolamine as donor and lissamine rhodamine B 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine as acceptor, using 2-ps pulses from a Ti:sapphire laser on LUVs with incorporated plant growth regulators: triacontanol (TRIA) and jasmonic acid (JA). FRET efficiency, energy transfer rate, rotation correlation time, microviscosity, and diffusion coefficient of lateral diffusion of lipids were calculated from these results. It was observed that TRIA and JA differentially modulated all parameters studied. The effect of JA in such modulations was always partially reversed by TRIA. Also, the generalized polarization of laurdan fluorescence indicated that JA enhances the degree of hydration in lipid bilayers to a larger extent than does TRIA. Solid-state (31)P magic-angle spinning nuclear magnetic resonance spectra of LUVs showed two chemical shifts, at 0.009 and -11.988 ppm, at low temperatures (20 degrees C), while at increasing temperatures (20-60 degrees C) only one (at -11.988 ppm) was prominent and the other (0.009 ppm) gradually became obscure. However, LUVs with TRIA exhibited only one of the shifts at 0.353 ppm even at lower temperatures and JA did not affect the chemical shifts. PMID:19418089

  1. Probiotic Strain Bifidobacterium animalis subsp. lactis CECT 8145 Reduces Fat Content and Modulates Lipid Metabolism and Antioxidant Response in Caenorhabditis elegans.

    PubMed

    Martorell, Patricia; Llopis, Silvia; González, Nuria; Chenoll, Empar; López-Carreras, Noemi; Aleixandre, Amaya; Chen, Yang; Karoly, Edwuard D; Ramón, Daniel; Genovés, Salvador

    2016-05-01

    Recently, microbial changes in the human gut have been proposed as a possible cause of obesity. Therefore, modulation of microbiota through probiotic supplements is of great interest to support obesity therapeutics. The present study examines the functional effect and metabolic targets of a bacterial strain, Bifidobacterium animalis subsp. lactis CECT 8145, selected from a screening in Caenorhabditis elegans. This strain significantly reduced total lipids (40.5% ± 2.4) and triglycerides (27.6% ± 0.5), exerting antioxidant effects in the nematode (30% ± 2.8 increase in survival vs control); activities were also preserved in a final food matrix (milk). Furthermore, transcriptomic and metabolomic analyses in nematodes fed with strain CECT 8145 revealed modulation of the energy and lipid metabolism, as well as the tryptophan metabolism (satiety), as the main metabolic targets of the probiotic. In conclusion, our study describes for the first time a new B. animalis subsp. lactis strain, CECT 8145, as a promising probiotic for obesity disorders. Furthermore, the data support future studies in obesity murine models. PMID:27054371

  2. Modulation of pyridinium cationic lipid-DNA complex properties by pyridinium gemini surfactants and its impact on lipoplex transfection properties.

    PubMed

    Sharma, Vishnu Dutt; Lees, Julia; Hoffman, Nicholas E; Brailoiu, Eugen; Madesh, Muniswamy; Wunder, Stephanie L; Ilies, Marc A

    2014-02-01

    The study presents the effects of blending a cationic gemini surfactant into cationic lipid bilayers and its impact on the 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 the internalization mechanism of the resultant nucleic acid complexes. We found that the 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. The transfection efficiency of select ternary lipoplexes derived from cationic gemini surfactants and lipids was several times superior to the 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 colipids, their nature, and amount present in lipoplexes. The study confirmed the possibility of combining the specific properties of pyridinium gemini surfactants and cationic lipids synergistically to obtain efficient synthetic transfection systems with negligible cytotoxicity useful for therapeutic gene delivery. PMID:24377350

  3. Toll-Like Receptor Activation by Generalized Modules for Membrane Antigens from Lipid A Mutants of Salmonella enterica Serovars Typhimurium and Enteritidis

    PubMed Central

    Rossi, Omar; Caboni, Mariaelena; Negrea, Aurel; Necchi, Francesca; Alfini, Renzo; Micoli, Francesca; Saul, Allan; MacLennan, Calman A.

    2016-01-01

    Invasive nontyphoidal Salmonella (iNTS) disease is a neglected disease with high mortality in children and HIV-positive individuals in sub-Saharan Africa, caused primarily by Africa-specific strains of Salmonella enterica serovars Typhimurium and Enteritidis. A vaccine using GMMA (generalized modules for membrane antigens) from S. Typhimurium and S. Enteritidis containing lipid A modifications to reduce potential in vivo reactogenicity is under development. GMMA with penta-acylated lipid A showed the greatest reduction in the level of cytokine release from human peripheral blood monocytes from that for GMMA with wild-type lipid A. Deletion of the lipid A modification genes msbB and pagP was required to achieve pure penta-acylation. Interestingly, ΔmsbB ΔpagP GMMA from S. Enteritidis had a slightly higher stimulatory potential than those from S. Typhimurium, a finding consistent with the higher lipopolysaccharide (LPS) content and Toll-like receptor 2 (TLR2) stimulatory potential of the former. Also, TLR5 ligand flagellin was found in Salmonella GMMA. No relevant contribution to the stimulatory potential of GMMA was detected even when the flagellin protein FliC from S. Typhimurium was added at a concentration as high as 10% of total protein, suggesting that flagellin impurities are not a major factor for GMMA-mediated immune stimulation. Overall, the stimulatory potential of S. Typhimurium and S. Enteritidis ΔmsbB ΔpagP GMMA was close to that of Shigella sonnei GMMA, which are currently in phase I clinical trials. PMID:26865597

  4. Interactions of the C-terminus of lung surfactant protein B with lipid bilayers are modulated by acyl chain saturation.

    PubMed

    Antharam, Vijay C; Farver, R Suzanne; Kuznetsova, Anna; Sippel, Katherine H; Mills, Frank D; Elliott, Douglas W; Sternin, Edward; Long, Joanna R

    2008-11-01

    Lung surfactant protein B (SP-B) is critical to minimizing surface tension in the alveoli. The C-terminus of SP-B, residues 59-80, has much of the surface activity of the full protein and serves as a template for the development of synthetic surfactant replacements. The molecular mechanisms responsible for its ability to restore lung compliance were investigated with circular dichroism, differential scanning calorimetry, and (31)P and (2)H solid-state NMR spectroscopy. SP-B(59-80) forms an amphipathic helix which alters lipid organization and acyl chain dynamics in fluid lamellar phase 4:1 DPPC:POPG and 3:1 POPC:POPG MLVs. At higher levels of SP-B(59-80) in the POPC:POPG lipid system a transition to a nonlamellar phase is observed while DPPC:POPG mixtures remain in a lamellar phase. Deuterium NMR shows an increase in acyl chain order in DPPC:POPG MLVs on addition of SP-B(59-80); in POPC:POPG MLVs, acyl chain order parameters decrease. Our results indicate SP-B(59-80) penetrates deeply into DPPC:POPG bilayers and binds more peripherally to POPC:POPG bilayers. Similar behavior has been observed for KL(4), a peptide mimetic of SP-B which was originally designed using SP-B(59-80) as a template and has been clinically demonstrated to be successful in treating respiratory distress syndrome. The ability of these helical peptides to differentially partition into lipid lamellae based on their degree of monounsaturation and subsequent changes in lipid dynamics suggest a mechanism for lipid organization and trafficking within the dynamic lung environment. PMID:18694722

  5. Interactions of the C-terminus of pulmonary surfactant B with lipid bilayers are modulated by acyl chain saturation

    PubMed Central

    Antharam, Vijay C.; Farver, R. Suzanne; Kuznetsova, Anna; Sippel, Katherine H.; Mills, Frank D.; Elliott, Douglas W.; Sternin, Edward; Long, Joanna R.

    2009-01-01

    Summary Lung surfactant protein B (SP-B) is critical to minimizing surface tension in the alveoli. The C-terminus of SP-B, residues 59-80, has much of the surface activity of the full protein and serves as a template for the development of synthetic surfactant replacements. The molecular mechanisms responsible for its ability to restore lung compliance were investigated with circular dichroism, differential scanning calorimetry, and 31P and 2H solid-state NMR spectroscopy. SP-B59-80 forms an amphipathic helix which alters lipid organization and acyl chain dynamics in fluid lamellar phase 4:1 DPPC:POPG and 3:1 POPC:POPG MLVs. At higher levels of SP-B59-80 in the POPC:POPG lipid system a transition to a nonlamellar phase is observed while DPPC:POPG mixtures remain in a lamellar phase. Deuterium NMR shows an increase in acyl chain order in DPPC:POPG MLVs on addition of SP-B59-80; in POPC:POPG MLVs, acyl chain order parameters decrease. Our results indicate SP-B59-80 penetrates deeply into DPPC:POPG bilayers and binds more peripherally to POPC:POPG bilayers. Similar behavior has been observed for KL4, a peptide mimetic of SP-B which was originally designed using SP-B59-80 as a template and has been clinically demonstrated to be successful in treating respiratory distress syndrome. The ability of these helical peptides to differentially partition into lipid lamellae containing varying levels of monounsaturation and subsequent changes in lipid dynamics suggest a mechanism for lipid organization and trafficking within the dynamic lung environment. PMID:18694722

  6. Effects of an acute bout of moderate-intensity exercise on postprandial lipemia and airway inflammation.

    PubMed

    Johnson, Ariel M; Kurti, Stephanie P; Smith, Joshua R; Rosenkranz, Sara K; Harms, Craig A

    2016-03-01

    A high-fat meal (HFM) induces an increase in blood lipids (postprandial lipemia; PPL), systemic inflammation, and acute airway inflammation. While acute exercise has been shown to have anti-inflammatory and lipid-lowering effects, it is unknown whether exercise prior to an HFM will translate to reduced airway inflammation post-HFM. Our purpose was to determine the effects of an acute bout of exercise on airway inflammation post-HFM and to identify whether any protective effect of exercise on airway inflammation was associated with a reduction in PPL or systemic inflammation. In a randomized cross-over study, 12 healthy, 18- to 29-year-old men (age, 23.0 ± 3.2 years; height, 178.9 ± 5.5 cm; weight, 78.5 ± 11.7 kg) consumed an HFM (1 g fat/1 kg body weight) 12 h following exercise (EX; 60 min at 60% maximal oxygen uptake) or without exercise (CON). Fractional exhaled nitric oxide (FENO; measure of airway inflammation), triglycerides (TG), and inflammatory markers (high-sensitivity C-reactive protein, tumor-necrosis factor-alpha, and interleukin-6) were measured while fasted at 2 h and 4 h post-HFM. FENO increased over time (2 h: CON, p = 0.001; EX, p = 0.002, but not by condition (p = 0.991). TG significantly increased 2 and 4 h post-HFM (p < 0.001), but was not significant between conditions (p = 0.256). Inflammatory markers did not significantly increase by time or condition (p > 0.05). There were no relationships between FENO and TG or systemic inflammatory markers for any time point or condition (p > 0.05). In summary, an acute bout of moderate-intensity exercise performed 12 h prior to an HFM did not change postprandial airway inflammation or lipemia in healthy, 18- to 29-year-old men. PMID:26872295

  7. Dynamics of fat absorption and impact of sham feeding on postprandial lipema

    PubMed Central

    Jauregui, Rosa Chavez; Mattes, Richard D.; Parks, Elizabeth J.

    2010-01-01

    Background and Aims Given the importance of postprandial hyperlipidemia to increase risk for atherosclerosis, in the present study, stable isotope-labeled meals were fed to healthy subjects (7 males and 3 females) to investigate the kinetics chylomicron synthesis and the impact of sensory exposure to lipid on metabolism. Methods Subjects performed 2, 24-hr inpatient studies which entailed consumption of a liquid formula evening meal containing 30g of oil (+13C2 triolein) on day 1. Breakfast (day 2) consisted of TAG fed as capsules (30g oil + 13C7 triolein) to avoid activation of mouth taste receptors. Next, modified sham feeding of cream cheese occurred over 2 hrs. In the 2 trials, the stimulus was higher-fat (HF) and lower-fat (LF) cream cheese. A liquid meal was consumed at lunch. Blood sampling occurred intermittently and chylomicron particles Sf >400-TAG, were analyzed by GC/MS. Results 13C2-Label was found in fasting-state lipoproteins and individuals with higher body fat percentages demonstrated greater dilution of meal-TAG from endogenous sources. For both trials, 13 ± 4% of lipoprotein-TAG oleic acid was derived from the previous evening meal. Incremental AUC for TAG during HF was ~2½ times higher than after LF exposure (46 ±15 vs 17 ± 5 μmol/l × hr, P=0.04). The greater HF morning lipemia occurred with elevated glucose, insulin and NEFA peaks following lunch. Conclusions These data support a connection between enteral lipid metabolism and oral fat exposure, resulting in elevated postprandial lipemia. The results suggest that the intestine may participate in a mechanism coordinating oral fat signaling with control of subsequent macronutrient disposal in the body. PMID:20493191

  8. Meal anticipation potentiates postprandial ghrelin suppression in humans.

    PubMed

    Ott, Volker; Friedrich, Monique; Zemlin, Janna; Lehnert, Hendrik; Schultes, Bernd; Born, Jan; Hallschmid, Manfred

    2012-07-01

    Circulating concentrations of the orexigenic hormone ghrelin show a postprandial decrease in dependence on meal size and composition. Cognitive determinants of postprandial ghrelin suppression in humans are largely unexplored. We assessed the effects of cued meal anticipation on pre- and postprandial concentrations of total plasma ghrelin, pancreatic polypeptide and leptin as well as on markers of glucose metabolism in healthy men. In a between-subject comparison, meal anticipation was induced in 14 fasted men at 08:00 h by the announcement and subsequent presentation of a breakfast buffet. Fifteen fasted control subjects were informed that they would remain fasted until noon. At 10:00 h, both groups were served a rich free-choice breakfast. At 12:00 h, all subjects underwent a snack test assessing casual cookie intake. Circulating concentrations of ghrelin, pancreatic polypeptide, glucose, insulin and leptin were frequently assessed. Preprandial endocrine parameters as well as breakfast intake (all p>0.23) and subsequent snack consumption (p>0.83) were comparable between groups. The postprandial suppression of ghrelin levels observed in both groups was markedly stronger in subjects who had anticipated breakfast intake (p<0.03) while pancreatic polypeptide concentrations did not differ between groups (p>0.56). Results indicate that meal anticipation is a critical determinant of postprandial ghrelin suppression that, as suggested by unaltered pancreatic polypeptide levels, appears to be mediated independent of vagal activation. Our findings highlight the role of subtle cognitive factors in the postprandial regulation of ghrelin secretion, suggesting that neurobehavioral approaches to improved food intake control should take into account meal anticipatory mechanisms. PMID:22094111

  9. Utility of home blood pressure monitoring to evaluate postprandial blood pressure in treated hypertensive patients.

    PubMed

    Alfie, José

    2015-08-01

    Postprandial hypotension, defined as a fall in systolic blood pressure (SBP) of 20 mmHg or greater within 2 hours after a meal, is a risk factor for stroke, coronary events and mortality. The clinical suspicion is typically raised by episodes of postprandial syncope or falls, whereas asymptomatic postprandial hypotension is mostly neglected. The magnitude of the postprandial fall in SBP, as detected by 24-hour recording in apparently healthy middle-aged to elderly subjects, was proportional to the severity of the silent cerebrovascular damage. Postprandial hypotension can also be detected by self-measured blood pressure before and within 2 hours after meals using automatic devices. The review highlights the value of home blood pressure monitoring (HBPM) as a screening test for asymptomatic postprandial hypotension in hypertensive patients. Using a HBPM protocol that included duplicated blood pressure measurements before and after three consecutive lunches, we detected unsuspected postprandial hypotension in 27.4% of the 230 hypertensive patients screened. The prevalence of postprandial hypotension was 13.2% in controlled and 42.2% in uncontrolled hypertensive patients (p < 0.001), raising the dilemma of further lowering blood pressure in the setting of postprandial hypotension. The inclusion of preprandial and postprandial measurements in the protocol of HBPM is useful to identify hypertensive patients with postprandial hypotension and may guide adjustments in antihypertensive treatment according to postprandial blood pressure. PMID:26187907

  10. Postprandial biochemistry changes in penguins (Spheniscus demersus) including hyperuricemia.

    PubMed

    Cray, Carolyn; Stremme, Donald W; Arheart, Kristopher L

    2010-06-01

    In a clinical setting, it is important to differentiate abnormal values that may be a normal change resulting from feeding and those that may be disease related. Such postprandial changes have been identified in mammalian and avian species. In the current study, pre- and postvalues for several routine biochemical analytes from penguins (Spheniscus demersus) were examined. Significant increases were found in uric acid, triglycerides, and bile acids (P < 0.001). Uric acid levels increased more than threefold. These data indicate that postprandial changes should be considered when interpreting abnormal biochemistry values in penguins. PMID:20597226

  11. Lipidomic analyses of female mice lacking hepatic lipase and endothelial lipase indicate selective modulation of plasma lipid species.

    PubMed

    Yang, Yanbo; Kuwano, Takashi; Lagor, William R; Albert, Carolyn J; Brenton, Siobhan; Rader, Daniel J; Ford, David A; Brown, Robert J

    2014-06-01

    Hepatic lipase (HL) and endothelial lipase (EL) share overlapping and complementary roles in lipoprotein metabolism. The deletion of HL and EL alleles in mice raises plasma total cholesterol and phospholipid concentrations. However, the influence of HL and EL in vivo on individual molecular species from each class of lipid is not known. We hypothesized that the loss of HL, EL, or both in vivo may affect select molecular species from each class of lipids. To test this hypothesis, we performed lipidomic analyses on plasma and livers from fasted female wild-type, HL-knockout, EL-knockout, and HL/EL-double knockout mice. Overall, the loss of HL, EL, or both resulted in minimal changes to hepatic lipids; however, select species of CE were surprisingly reduced in the livers of mice only lacking EL. The loss of HL, EL, or both reduced the plasma concentrations for select molecular species of triacylglycerol, diacylglycerol, and free fatty acid. On the other hand, the loss of HL, EL, or both raised the plasma concentrations for select molecular species of phosphatidylcholine, cholesteryl ester, diacylglycerol, sphingomyelin, ceramide, plasmanylcholine, and plasmenylcholine. The increased plasma concentration of select ether phospholipids was evident in the absence of EL, thus suggesting that EL might exhibit a phospholipase A2 activity. Using recombinant EL, we showed that it could hydrolyse the artificial phospholipase A2 substrate 4-nitro-3-(octanoyloxy)benzoic acid. In summary, our study shows for the first time the influence of HL and EL on individual molecular species of several classes of lipids in vivo using lipidomic methods. PMID:24777581

  12. Toxoplasma gondii-skeletal muscle cells interaction increases lipid droplet biogenesis and positively modulates the production of IL-12, IFN-g and PGE2

    PubMed Central

    2014-01-01

    Background The interest in the mechanisms involved in Toxoplasma gondii lipid acquisition has steadily increased during the past few decades, but it remains not completely understood. Here, we investigated the biogenesis and the fate of lipid droplets (LD) of skeletal muscle cells (SkMC) during their interaction with T. gondii by confocal and electron microscopy. We also evaluated whether infected SkMC modulates the production of prostaglandin E2 (PGE2), cytokines interleukin-12 (IL-12) and interferon-gamma (INF-g), and also the cyclooxygenase-2 (COX-2) gene induction. Methods Primary culture of skeletal muscle cells were infected with tachyzoites of T. gondii and analysed by confocal microscopy for observation of LD. Ultrastructural cytochemistry was also used for lipid and sarcoplasmatic reticulum (SR) detection. Dosage of cytokines (IL-12 and INF-g) by ELISA technique and enzyme-linked immunoassay (EIA) for PGE2 measurement were employed. The COX-2 gene expression analysis was performed by real time reverse transcriptase polymerase chain reaction (qRT-PCR). Results We demonstrated that T. gondii infection of SkMC leads to increase in LD number and area in a time course dependent manner. Moreover, the ultrastructural analysis demonstrated that SR and LD are in direct contact with parasitophorous vacuole membrane (PVM), within the vacuolar matrix, around it and interacting directly with the membrane of parasite, indicating that LD are recruited and deliver their content inside the parasitophorous vacuole (PV) in T. gondii-infected SkMC. We also observed a positive modulation of the production of IL-12 and IFN-g, increase of COX-2 mRNA levels in the first hour of T. gondii-SkMC interaction and an increase of prostaglandin E2 (PGE2) synthesis from 6 h up to 48 h of infection. Conclusions Taken together, the close association between SR and LD with PV could represent a source of lipids as well as other nutrients for the parasite survival, and together with the

  13. Cranberries (Oxycoccus quadripetalus) inhibit lipid metabolism and modulate leptin and adiponectin secretion in 3T3-L1 adipocytes.

    PubMed

    Kowalska, Katarzyna; Olejnik, Anna; Rychlik, Joanna; Grajek, Włodzimierz

    2015-10-15

    It has previously been shown that lyophilized cranberries (LCB) decreased lipid accumulation in 3T3-L1 cells and inhibited preadipocyte differentiation by down-regulation of the expression of key transcription factors (PPARγ, C/EBPα, SREBP1) of the adipogenesis pathway. To elucidate the molecular basis of anti-lipogenic activity of LCB, the expression of several genes involved in lipid metabolism, such as adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL), fatty acid synthase (FAS), hormone sensitive lipase (HSL) and perilipin 1 (PLIN1), was examined in the present study. Additionally, the effects of LCB on adiponectin and leptin expression and protein secretion were also investigated. LCB reduced lipid accumulation during preadipocyte differentiation by down-regulation of the mRNA level of aP2, FAS, LPL, HSL and PLIN1. Moreover, LCB decreased leptin gene expression and increased adiponectin gene expression and protein secretion in a dose-dependent manner. Therefore cranberries could be considered as bioactive factors, which are effective in the inhibition of adipose tissue mass production. PMID:25952883

  14. Topological regulation of lipid balance in cells.

    PubMed

    Drin, Guillaume

    2014-01-01

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

  15. 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. PMID:22530973

  16. Excess iodine and high-fat diet combination modulates lipid profile, thyroid hormone, and hepatic LDLr expression values in mice.

    PubMed

    Han, Hao; Xin, Peng; Zhao, Lina; Xu, Jian; Xia, Yun; Yang, Xuefeng; Sun, Xiufa; Hao, Liping

    2012-06-01

    The aim of this study was to illustrate the combined effect of excess iodine and high-fat diet on lipid metabolism and its potential molecular mechanism. Sixty Balb/c mice were randomly allocated to three control groups or three excess iodine groups and fed with a high-fat diet in the absence or presence of 1,200 μg/L iodine for 1, 3, or 6 months, respectively. Serum lipid parameters and serum thyroid hormones were measured. Expressions of scavenger receptor class B type-I (SR-BI) and low density lipoproteins receptor (LDLr) mRNA and protein in liver were detected. Thyroid histology and liver type 1 iodothyronine deiodinase activity were analyzed. At the end of 3 and 6 months, compared with control, serum TC, TG, and LDL-C in excess iodine group were significantly lower (p < 0.05). LDLr expression in liver was increased significantly (p < 0.05) and parallel to the change of serum TC and TG. TT3 and TT4 levels in serum were elevated and TSH decreased significantly (p < 0.05). Liver type I iodothyronine deiodinase activity was significantly higher (p < 0.05) than control at the end of 6 months. Moreover, a time course damage effect of excess iodine combined with high-fat diet on thyroid glands was observed. The present findings demonstrated that excess iodine combined with high-fat diet could cause damage to thyroid glands and lead to thyroid hormone disorder. Those in turn caused the upregulation of hepatic LDLr gene, which resulted in the disorder in serum lipids. PMID:22222482

  17. Experimental Evidence of ω-3 Polyunsaturated Fatty Acid Modulation of Inflammatory Cytokines and Bioactive Lipid Mediators: Their Potential Role in Inflammatory, Neurodegenerative, and Neoplastic Diseases

    PubMed Central

    Calviello, Gabriella; Su, Hui-Min; Weylandt, Karsten H.; Fasano, Elena; Serini, Simona; Cittadini, Achille

    2013-01-01

    A large body of evidence has emerged over the past years to show the critical role played by inflammation in the pathogenesis of several diseases including some cardiovascular, neoplastic, and neurodegenerative diseases, previously not considered inflammation-related. The anti-inflammatory action of ω-3 polyunsaturated fatty acids (PUFAs), as well as their potential healthy effects against the development and progression of the same diseases, has been widely studied by our and others' laboratories. As a result, a rethinking is taking place on the possible mechanisms underlying the beneficial effects of ω-3 PUFAs against these disorders, and, in particular, on the influence that they may exert on the molecular pathways involved in inflammatory process, including the production of inflammatory cytokines and lipid mediators active in the resolving phase of inflammation. In the present review we will summarize and discuss the current knowledge regarding the modulating effects of ω-3 PUFAs on the production of inflammatory cytokines and proresolving or protective lipid mediators in the context of inflammatory, metabolic, neurodegenerative, and neoplastic diseases. PMID:23691510

  18. An epigenomic signature of postprandial hyperglycemia in peripheral blood leukocytes.

    PubMed

    Shim, Sung-Mi; Cho, Yoon-Kyung; Hong, Eun-Jung; Han, Bok-Ghee; Jeon, Jae-Pil

    2016-03-01

    Postprandial hyperglycemia is known to be one of the earliest signs of abnormal glucose homeostasis associated with type 2 diabetes. This study aimed to assess clinical significance of a 1-h postprandial glucose level for the development of diabetes, and identify epigenetic biomarkers of postprandial hyperglycemia. We analyzed clinical data from the oral glucose tolerance tests for healthy subjects (n=4502). The ratio (Glu60/Glu0) of 1-h glucose levels to fasting glucose levels was significantly associated with an insulin sensitive index (QUICKI, quantitative insulin sensitivity check index) (β=0.055, P=1.25E-04) as well as a risk of future pre-diabetic and diabetic conversion. Next, DNA methylation profile analyses of 24 matched pairs of the high and low Glu60/Glu0 ratio subjects showed that specific DNA methylation levels in the promoter region of an olfactory receptor gene (olfactory receptor gene family10 member A4, OR10A4) were associated with the Glu60/Glu0 ratios (β=0.337, P=0.03). Moreover, acute oral glucose challenges decreased the DNA methylation levels of OR10A4 but not the global DNA methylation in peripheral leukocytes of healthy subjects (n=7), indicating that OR10A4 is a specific epigenomic target of postprandial hyperglycemia. This work suggests possible relevance of olfactory receptor genes to an earlier molecular biomarker of peripheral hyperglycemia and diabetic conversion. PMID:26632885

  19. High-Intensity Interval Training for Improving Postprandial Hyperglycemia

    ERIC Educational Resources Information Center

    Little, Jonathan P.; Francois, Monique E.

    2014-01-01

    High-intensity interval training (HIIT) has garnered attention in recent years as a time-efficient exercise option for improving cardiovascular and metabolic health. New research demonstrates that HIIT may be particularly effective for improving postprandial hyperglycemia in individuals with, or at risk for, type 2 diabetes (T2D). These findings…

  20. Local regulation of postprandial motor responses in ileal pouches

    PubMed Central

    Mularczyk, A; Contessini-Avesan..., E; Cesana, B; Bianchi, P; Basilisco, G

    1999-01-01

    BACKGROUND—Local mechanisms are involved in the postprandial regulation of ileal tone in healthy subjects, but whether these mechanisms affect the postprandial tonic response of ileal pouches has not yet been investigated.
AIMS—To study the effect of a meal on pouch tone and phasic motor activity in patients with gut continuity or ileostomy and, in the latter group, the effect of a pouch perfusion with chyme or saline.
PATIENTS—Twenty patients with ileal pouches: 10 with gut continuity and 10 with ileostomy.
METHODS—Pouch tone and the frequency of phasic volume events were recorded with a barostat under fasting and postprandial conditions and after perfusion of the isolated pouch with chyme or saline.
RESULTS—The meal increased pouch tone and the frequency of phasic volume events in the patients with gut continuity, but not in those with ileostomy. Pouch perfusion with chyme induced a greater increase in pouch tone than saline.
CONCLUSIONS—The meal stimulated pouch tone and phasic motor activity. These effects were at least partially related to local pouch stimulation by intraluminal contents.


Keywords: ileal pouches; postprandial motor responses; ileal tone; ileostomy; motor activity; barostat PMID:10486368

  1. A Hamster Model of Diet-Induced Obesity for Preclinical Evaluation of Anti-Obesity, Anti-Diabetic and Lipid Modulating Agents

    PubMed Central

    Hansen, Gitte; Fabricius, Katrine; Hansen, Henrik B.; Jelsing, Jacob; Vrang, Niels

    2015-01-01

    Aim Unlike rats and mice, hamsters develop hypercholesterolemia, and hypertriglyceridemia when fed a cholesterol-rich diet. Because hyperlipidemia is a hallmark of human obesity, we aimed to develop and characterize a novel diet-induced obesity (DIO) and hypercholesterolemia Golden Syrian hamster model. Methods and Results Hamsters fed a highly palatable fat- and sugar-rich diet (HPFS) for 12 weeks showed significant body weight gain, body fat accumulation and impaired glucose tolerance. Cholesterol supplementation to the diet evoked additional hypercholesterolemia. Chronic treatment with the GLP-1 analogue, liraglutide (0.2 mg/kg, SC, BID, 27 days), normalized body weight and glucose tolerance, and lowered blood lipids in the DIO-hamster. The dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin (3.0 mg/kg, PO, QD) also improved glucose tolerance. Treatment with peptide YY3-36 (PYY3-36, 1.0 mg/kg/day) or neuromedin U (NMU, 1.5 mg/kg/day), continuously infused via a subcutaneous osmotic minipump for 14 days, reduced body weight and energy intake and changed food preference from HPFS diet towards chow. Co-treatment with liraglutide and PYY3-36 evoked a pronounced synergistic decrease in body weight and food intake with no lower plateau established. Treatment with the cholesterol uptake inhibitor ezetimibe (10 mg/kg, PO, QD) for 14 days lowered plasma total cholesterol with a more marked reduction of LDL levels, as compared to HDL, indicating additional sensitivity to cholesterol modulating drugs in the hyperlipidemic DIO-hamster. In conclusion, the features of combined obesity, impaired glucose tolerance and hypercholesterolemia in the DIO-hamster make this animal model useful for preclinical evaluation of novel anti-obesity, anti-diabetic and lipid modulating agents. PMID:26266945

  2. Nucleolin-mediated cellular trafficking of DNA nanoparticle is lipid raft and microtubule dependent and can be modulated by glucocorticoid.

    PubMed

    Chen, Xuguang; Shank, Samuel; Davis, Pamela B; Ziady, Assem G

    2011-01-01

    DNA nanoparticles (DNPs) are nonviral gene transfer vectors with excellent in vivo potential. Previously, we reported that cell surface nucleolin directly binds DNPs, and functions as an important receptor for DNPs. However, the fate of the nucleolin-DNP complex following cellular uptake remains elusive. In this study, we examined the role of lipid rafts in the uptake of DNPs, and found that both nucleolin and DNPs are recovered from the low-density raft fractions of the sucrose gradient. Furthermore, nucleolin colocalizes with, and coimmunoprecipitates with a raft protein, flotillin. Disruption of lipid rafts by depleting membrane cholesterol significantly inhibited DNP transfection, while inhibition of other endocytic pathways had little effect. Following the uptake, the nuclear import of the DNPs required microtubules but not F-actin. By coimmunoprecipitation in conjunction with tandem mass spectrometry, we identified glucocorticoid receptor (GCR) as a nucleolin-associated protein, and confirmed this result by western blot. Cortisone or dexamethasone increased nucleolin's association with GCR, and transfection by DNPs. Finally, we detected the expression of nucleolin on the surface of airway epithelia in vivo. Taken together, our findings shed light on important determinants of DNP trafficking in cells and support the notion that nucleolin is a good target for nonviral gene delivery. PMID:20959809

  3. Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis.

    PubMed

    Sallam, Tamer; Jones, Marius C; Gilliland, Thomas; Zhang, Li; Wu, Xiaohui; Eskin, Ascia; Sandhu, Jaspreet; Casero, David; Vallim, Thomas Q de Aguiar; Hong, Cynthia; Katz, Melanie; Lee, Richard; Whitelegge, Julian; Tontonoz, Peter

    2016-06-01

    Liver X receptors (LXRs) are transcriptional regulators of cellular and systemic cholesterol homeostasis. Under conditions of excess cholesterol, LXR activation induces the expression of several genes involved in cholesterol efflux, facilitates cholesterol esterification by promoting fatty acid synthesis, and inhibits cholesterol uptake by the low-density lipoprotein receptor. The fact that sterol content is maintained in a narrow range in most cell types and in the organism as a whole suggests that extensive crosstalk between regulatory pathways must exist. However, the molecular mechanisms that integrate LXRs with other lipid metabolic pathways are incompletely understood. Here we show that ligand activation of LXRs in mouse liver not only promotes cholesterol efflux, but also simultaneously inhibits cholesterol biosynthesis. We further identify the long non-coding RNA LeXis as a mediator of this effect. Hepatic LeXis expression is robustly induced in response to a Western diet (high in fat and cholesterol) or to pharmacological LXR activation. Raising or lowering LeXis levels in the liver affects the expression of genes involved in cholesterol biosynthesis and alters the cholesterol levels in the liver and plasma. LeXis interacts with and affects the DNA interactions of RALY, a heterogeneous ribonucleoprotein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the mouse liver. These findings outline a regulatory role for a non-coding RNA in lipid metabolism and advance our understanding of the mechanisms that coordinate sterol homeostasis. PMID:27251289

  4. Hepatic miR-378 targets p110α and controls glucose and lipid homeostasis by modulating hepatic insulin signalling.

    PubMed

    Liu, Wei; Cao, Hongchao; Ye, Cheng; Chang, Cunjie; Lu, Minghua; Jing, Yanyan; Zhang, Duo; Yao, Xuan; Duan, Zhengjun; Xia, Hongfeng; Wang, Yu-Cheng; Jiang, Jingjing; Liu, Mo-Fang; Yan, Jun; Ying, Hao

    2014-01-01

    Understanding the regulation of insulin signalling in tissues provides insights into carbohydrate and lipid metabolism in physiology and disease. Here we show that hepatic miR-378/378* expression changes in response to fasting and refeeding in mice. Mice overexpressing hepatic miR-378/378* exhibit pure hepatic insulin resistance. miR-378 inhibits hepatic insulin signalling through targeting p110α, a subunit of PI3K and hence a critical component of insulin signalling. Knockdown of hepatic p110α mimics the effect of miR-378, while restoration of p110α expression abolishes the action of miR-378 on insulin signalling as well as its systemic effects on glucose and lipid homeostasis. miR-378/378* knockout mice display hypoglycemia and increased hepatic triglyceride level with enhanced insulin sensitivity. Inhibition of hepatic p110α in miR-378/378* knockout mice corrects the abnormal glucose tolerance. Finally, we show that overexpression of hepatic miR-378/378* ameliorates hepatic steatosis in ob/ob mice without exacerbating hyperglycemia. Our findings establish fasting-responsive miR-378 as a critical regulator of hepatic insulin signalling. PMID:25471065

  5. Upper-body obese women are resistant to postprandial stimulation of protein synthesis

    PubMed Central

    Liebau, Felix; Jensen, Michael D.; Nair, K. Sreekumaran; Rooyackers, Olav

    2014-01-01

    Background and Aims Upper-body, i.e. visceral, obesity is associated with insulin resistance and impaired protein synthesis. It is unclear whether postprandial stimulation of protein synthesis is affected by body fat distribution. We investigated the postprandial protein anabolic response in a cohort of obese women. Methods Participants were studied after an overnight fast and after a mixed meal, grouped as upper-body obese (UBO, waist-to-hip ratio, WHR, >0.85, n=6) vs. lower-body obese (LBO, WHR<0.80, n=7). Lipid and carbohydrate metabolism were assessed by measurements of plasma free fatty acids (FFA), insulin and glucose concentrations, and calculation of the Quicki index from fasting glucose and insulin values. Different labels of stable isotopes of phenylalanine were administered intravenously and orally, and leg and whole-body protein breakdown and synthesis were calculated from phenylalanine/tyrosine isotopic enrichments in femoral arterial and venous blood, using equations for steady-state kinetics. Data are denoted as mean±SD. Results Age (38 vs. 40, p=0.549) and body-mass index (33.7±1.9 vs. 35.0±1.8, p=0.241) were similar in both groups. UBO subjects had more visceral fat (p=0.002) and higher fat-free body mass (FFM) (p=0.015). Plasma insulin concentrations were greater in UBO than LBO women (p=0.013), and UBO were less insulin sensitive (Quicki=0.32±0.01 vs. 0.36±0.02, p=0.005). Protein kinetics across the leg were not different between groups. Fasting whole body protein balance was similarly negative in both groups (UBO −6.5±2.4 vs. LBO −7.6±0.9 μmol/kgFFM/h, p=1.0). Postprandially, whole body protein balance became less positive in UBO than in LBO (14.8±3.7 vs. 20.2±3.7 μmol/kgFFM/h, p=0.017). Conclusions Whole-body protein balance following a meal is less positive in upper-body obese, insulin-resistant, women than in lower-body obese women. PMID:24269078

  6. Garlic essential oil protects against obesity-triggered nonalcoholic fatty liver disease through modulation of lipid metabolism and oxidative stress.

    PubMed

    Lai, Yi-Syuan; Chen, Wei-Cheng; Ho, Chi-Tang; Lu, Kuan-Hung; Lin, Shih-Hang; Tseng, Hui-Chun; Lin, Shuw-Yuan; Sheen, Lee-Yan

    2014-06-25

    This study investigated the protective properties of garlic essential oil (GEO) and its major organosulfur component (diallyl disulfide, DADS) against the development of nonalcoholic fatty liver disease (NAFLD). C57BL/6J mice were fed a normal or high-fat diet (HFD) with/without GEO (25, 50, and 100 mg/kg) or DADS (10 and 20 mg/kg) for 12 weeks. GEO and DADS dose-dependently exerted antiobesity and antihyperlipidemic effects by reducing HFD-induced body weight gain, adipose tissue weight, and serum biochemical parameters. Administration of 50 and 100 mg/kg GEO and 20 mg/kg DADS significantly decreased the release of pro-inflammatory cytokines in liver, accompanied by elevated antioxidant capacity via inhibition of cytochrome P450 2E1 expression during NAFLD development. The anti-NAFLD effects of GEO and DADS were mediated through down-regulation of sterol regulatory element binding protein-1c, acetyl-CoA carboxylase, fatty acid synthase, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase, as well as stimulation of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1. These results demonstrate that GEO and DADS dose-dependently protected obese mice with long-term HFD-induced NAFLD from lipid accumulation, inflammation, and oxidative damage by ameliorating lipid metabolic disorders and oxidative stress. The dose of 20 mg/kg DADS was equally as effective in preventing NAFLD as 50 mg/kg GEO containing the same amount of DADS, which demonstrates that DADS may be the main bioactive component in GEO. PMID:24857364

  7. Partial Amelioration of Peripheral and Central Symptoms of Huntington’s Disease via Modulation of Lipid Metabolism

    PubMed Central

    Chen, Jane Y.; Tran, Conny; Hwang, Lin; Deng, Gang; Jung, Michael E.; Faull, Kym F.; Levine, Michael S.; Cepeda, Carlos

    2016-01-01

    Background 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. Objective Alterations in lipid metabolism as a potential target for therapeutic intervention in the R6/2 mouse model of HD were examined. Methods 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). Results 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. Conclusions 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. PMID:27031732

  8. Birth Cohort, Age, and Sex Strongly Modulate Effects of Lipid Risk Alleles Identified in Genome-Wide Association Studies

    PubMed Central

    Kulminski, Alexander M.; Culminskaya, Irina; Arbeev, Konstantin G.; Arbeeva, Liubov; Ukraintseva, Svetlana V.; Stallard, Eric; Wu, Deqing; Yashin, Anatoliy I.

    2015-01-01

    Insights into genetic origin of diseases and related traits could substantially impact strategies for improving human health. The results of genome-wide association studies (GWAS) are often positioned as discoveries of unconditional risk alleles of complex health traits. We re-analyzed the associations of single nucleotide polymorphisms (SNPs) associated with total cholesterol (TC) in a large-scale GWAS meta-analysis. We focused on three generations of genotyped participants of the Framingham Heart Study (FHS). We show that the effects of all ten directly-genotyped SNPs were clustered in different FHS generations and/or birth cohorts in a sex-specific or sex-unspecific manner. The sample size and procedure-therapeutic issues play, at most, a minor role in this clustering. An important result was clustering of significant associations with the strongest effects in the youngest, or 3rd Generation, cohort. These results imply that an assumption of unconditional connections of these SNPs with TC is generally implausible and that a demographic perspective can substantially improve GWAS efficiency. The analyses of genetic effects in age-matched samples suggest a role of environmental and age-related mechanisms in the associations of different SNPs with TC. Analysis of the literature supports systemic roles for genes for these SNPs beyond those related to lipid metabolism. Our analyses reveal strong antagonistic effects of rs2479409 (the PCSK9 gene) that cautions strategies aimed at targeting this gene in the next generation of lipid drugs. Our results suggest that standard GWAS strategies need to be advanced in order to appropriately address the problem of genetic susceptibility to complex traits that is imperative for translation to health care. PMID:26295473

  9. Dietary anthocyanin-rich Haskap phytochemicals inhibit postprandial hyperlipidemia and hyperglycemia in rats.

    PubMed

    Takahashi, Azusa; Okazaki, Yukako; Nakamoto, Aika; Watanabe, Sanae; Sakaguchi, Hirohide; Tagashira, Yukari; Kagii, Atsuko; Nakagawara, Shunji; Higuchi, Ohki; Suzuki, Takashi; Chiji, Hideyuki

    2014-01-01

    Haskap (Lonicera caerulea L.) fruit contains some bioactive phenolic phytochemicals, mainly cyanidin-3-glucoside (cy3-glc) and chlorogenic acid. The purpose of this study was to investigate the effects of anthocyanin-rich phenolic phytochemical (containing 13.2% anthocyanin) purified from a Haskap fruit (named Haskap phytochemical) on postprandial serum triglyceride and blood glucose levels. The Haskap phytochemical (containing cy 3-glc at 300 mg/kg of body weight) was administered orally to rats fasted for 24 h and 30 min later, a corn oil emulsion was administered to these rats. After the administration, serum triglyceride concentration was measured. An increase in serum triglyceride concentration and the AUC significantly lowered in the Haskap phytochemical-administered group than in the saline-administered group. To evaluate the effect of serum glucose levels, the Haskap phytochemical was orally administered to rats fasted for 24 h and sucrose solution (2 g/kg of body weight) was administered to these rats after 30 min. After the administration, blood glucose level was measured. The Haskap phytochemical significantly reduced the increase in blood glucose levels and AUC in the Haskap phytochemical-administered group than in the saline-administered group. Furthermore, to investigate the long-term effects of Haskap phytochemical intake, high-fat diet (HF diet) with 1.5% or 3.0% Haskap phytochemical was administered to rats for four weeks. The investigation of chronological changes in the serum components of the rats fed HF diets in addition to the administration of Haskap phytochemical showed that the increase in serum triglyceride concentrations, total cholesterol concentrations and blood glucose were significantly suppressed compared to the HF diet-fed control (HF-control). These results suggest that the decrease in postprandial blood lipids and blood glucose by short or long-term Haskap phytochemical ingestion is due to anthocyanin and other polyphenols

  10. Postprandial Changes in High Density Lipoproteins in Rats Subjected to Gavage Administration of Virgin Olive Oil

    PubMed Central

    Martínez-Beamonte, Roberto; Navarro, María A.; Acin, Sergio; Guillén, Natalia; Barranquero, Cristina; Arnal, Carmen; Surra, Joaquín; Osada, Jesus

    2013-01-01

    Background and Aims The present study was designed to verify the influence of acute fat loading on high density lipoprotein (HDL) composition, and the involvement of liver and different segments of small intestine in the changes observed. Methods and Results To address these issues, rats were administered a bolus of 5-ml of extra-virgin olive oil and sacrificed 4 and 8 hours after feeding. In these animals, lipoproteins were analyzed and gene expressions of apolipoprotein and HDL enzymes were assessed in duodenum, jejunum, ileum and liver. Using this experimental design, total plasma and HDL phospholipids increased at the 8-hour-time-point due to increased sphingomyelin content. An increase in apolipoprotein A4 was also observed mainly in lipid-poor HDL. Increased expression of intestinal Apoa1, Apoa4 and Sgms1 mRNA was accompanied by hepatic decreases in the first two genes in liver. Hepatic expression of Abcg1, Apoa1bp, Apoa2, Apoe, Ptlp, Pon1 and Scarb1 decreased significantly following fat gavage, while no changes were observed for Abca1, Lcat or Pla2g7. Significant associations were also noted for hepatic expression of apolipoproteins and Pon1. Manipulation of postprandial triglycerides using an inhibitor of microsomal transfer protein -CP-346086- or of lipoprotein lipase –tyloxapol- did not influence hepatic expression of Apoa1 or Apoa4 mRNA. Conclusion All these data indicate that dietary fat modifies the phospholipid composition of rat HDL, suggesting a mechanism of down-regulation of hepatic HDL when intestine is the main source of those particles and a coordinated regulation of hepatic components of these lipoproteins at the mRNA level, independently of plasma postprandial triglycerides. PMID:23383120

  11. Lipoprotein-Associated Oxidative Stress: A New Twist to the Postprandial Hypothesis

    PubMed Central

    Le, Ngoc-Anh

    2014-01-01

    Oxidative stress is recognized as one of the primary processes underlying the initiation and progression of atherosclerotic vascular disease. Under physiological conditions, the balance between reactive oxygen species (ROS) generation and ROS scavenging is tightly controlled. As part of normal cellular metabolism, regulated oxidative stress is responsible for a variety of cellular responses. Excess generation of ROS that could not be compensated by antioxidant system has been suggested to be responsible for a number of pathological conditions. Due to their short biological half-lives, direct measurement of ROS is not available and surrogate measures are commonly used. Plasma lipoproteins, by virtue of their close interactions with endothelial cells in the vasculature and the susceptibility of their surface lipids to oxidative modification, are perfect biological sensors of oxidative stress in the arterial wall. In particular, with each consumed meal, triglyceride-rich lipoproteins, secreted by the intestine into the circulation, are responsible for the delivery of 20–40 grams of fat to the peripheral tissues. This flux of dietary lipids is accompanied by concomitant increases in glucose, insulin and other meal-associated metabolites. The contribution of postprandial lipemia to the pathogenesis of atherosclerosis has been previously suggested by several lines of investigation. We have extended this hypothesis by demonstrating the acute generation of oxidative epitopes on plasma lipoproteins as well as transient changes in the oxidative susceptibility of plasma lipoproteins. PMID:25548897

  12. A diurnal serum lipid integrates hepatic lipogenesis and peripheral fatty acid utilization

    PubMed Central

    Liu, Sihao; Brown, Jonathan D.; Stanya, Kristopher J.; Homan, Edwin; Leidl, Mathias; Inouye, Karen; Bhargava, Prerna; Gangl, Matthew R.; Dai, Lingling; Hatano, Ben; Hotamisligil, Gökhan S.; Saghatelian, Alan; Plutzky, Jorge; Lee, Chih-Hao

    2014-01-01

    Food intake increases the activity of hepatic de novo lipogenesis, which mediates the conversion of glucose to fats for storage or utilization. In mice, this program follows a circadian rhythm that peaks with nocturnal feeding1,2 and is repressed by Rev-erbα/β and an HDAC3-containing complex3–5 during the day. The transcriptional activators controlling rhythmic lipid synthesis in the dark cycle remain poorly defined. Disturbances in hepatic lipogenesis are also associated with systemic metabolic phenotypes6–8, suggesting that lipogenesis in the liver communicates with peripheral tissues to control energy substrate homeostasis. Here we identify a PPARδ-dependent de novo lipogenic pathway in the liver that modulates fat utilization by muscle via a circulating lipid. The nuclear receptor PPARδ controls diurnal expression of lipogenic genes in the dark/feeding cycle. Liver-specific PPARδ activation increases, while hepatocyte-Ppard deletion reduces, muscle fatty acid (FA) uptake. Unbiased metabolite profiling identifies PC(18:0/18:1), or 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC), as a serum lipid regulated by diurnal hepatic PPARδ activity. PC(18:0/18:1) reduces postprandial lipid levels and increases FA utilization through muscle PPARα. High fat feeding diminishes rhythmic production of PC(18:0/18:1), whereas PC(18:0/18:1) administration in db/db mice improves metabolic homeostasis. These findings reveal an integrated regulatory circuit coupling lipid synthesis in the liver to energy utilization in muscle by coordinating the activity of two closely related nuclear receptors. These data implicate alterations in diurnal hepatic PPARδ-PC(18:0/18:1) signaling in metabolic disorders including obesity. PMID:24153306

  13. African Nutmeg (Monodora Myristica) Lowers Cholesterol and Modulates Lipid Peroxidation in Experimentally Induced Hypercholesterolemic Male Wistar Rats

    PubMed Central

    Onyenibe, Nwozo Sarah; Fowokemi, Kasumu Titilayo; Emmanuel, Oyinloye Babatunji

    2015-01-01

    To evaluate the cholesterol lowering potential and protective ability of aqueous extract of Monodora myristica experimental hypercholesterolemic rats, a short-term study was conducted. Hypercholesterolemia was induced by administering cholesterol orally at a dose of 40 mg/kg/0.3 ml. Plant extracts 100 or 200 mg/kg body weight and Questran 0.26 g/kg were administered five times a week for eight weeks for amelioration. Hypolipidemic effects were evaluated by measuring total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) in the serum, while the protective ability was measured by the extent of lipid peroxidation (LPO) as well as enzymatic and non-enzymatic antioxidants levels in post mitochondrial fractions (PMF) of the hepatic and cardiac homogenates. Serum aminotransferases activities were also monitored. Results obtained shows that treatment with M. myristica elicited a significant reduction in serum TC, TG and LDL-C levels while there was concomitant increase in HDL-C of hypercholesterolemic rats. Elevations in serum aminotransferases activities and LPO level were reversed and a significant amelioration was noticed in enzymatic and non-enzymatic antioxidants status in the liver and heart of hypercholesterolemic rats. This study suggests that M. myristica possess cholesterol lowering potentials and protective ability in experimental hypercholesterolemia rat model. PMID:26199582

  14. African Nutmeg (Monodora Myristica) Lowers Cholesterol and Modulates Lipid Peroxidation in Experimentally Induced Hypercholesterolemic Male Wistar Rats.

    PubMed

    Onyenibe, Nwozo Sarah; Fowokemi, Kasumu Titilayo; Emmanuel, Oyinloye Babatunji

    2015-06-01

    To evaluate the cholesterol lowering potential and protective ability of aqueous extract of Monodora myristica experimental hypercholesterolemic rats, a short-term study was conducted. Hypercholesterolemia was induced by administering cholesterol orally at a dose of 40 mg/kg/0.3 ml. Plant extracts 100 or 200 mg/kg body weight and Questran 0.26 g/kg were administered five times a week for eight weeks for amelioration. Hypolipidemic effects were evaluated by measuring total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) in the serum, while the protective ability was measured by the extent of lipid peroxidation (LPO) as well as enzymatic and non-enzymatic antioxidants levels in post mitochondrial fractions (PMF) of the hepatic and cardiac homogenates. Serum aminotransferases activities were also monitored. Results obtained shows that treatment with M. myristica elicited a significant reduction in serum TC, TG and LDL-C levels while there was concomitant increase in HDL-C of hypercholesterolemic rats. Elevations in serum aminotransferases activities and LPO level were reversed and a significant amelioration was noticed in enzymatic and non-enzymatic antioxidants status in the liver and heart of hypercholesterolemic rats. This study suggests that M. myristica possess cholesterol lowering potentials and protective ability in experimental hypercholesterolemia rat model. PMID:26199582

  15. Modulation of rat testes lipid composition by hormones: Effect of PRL (prolactin) and hCG (human chorionic gonadotropin)

    SciTech Connect

    Sebokova, E.; Wierzbicki, A.; Clandinin, M.T. )

    1988-10-01

    The effect of prolactin (PRL) and human chorionic gonadotropin (hCG) administration for 7 days on the composition and function of rat testicular plasma membrane was investigated. Refractory state in Leydig cells desensitized by hCG decreased the binding capacity for {sup 125}I-labeled hCG and also luteinizing hormone (LH)-induced adenosine 3{prime},5{prime}-cyclic monophosphate (cAMP) and testosterone production. In testicular membranes of hCG-treated animals, a depletion of cholesterol and an increase in total phospholipid content was observed after gonadotropin injection, thereby decreasing the cholesterol-to-phospholipid ratio. Injection of high doses of PRL had no effect on the binding capacity or affinity of the LH-hCG receptor but decreased the response of Leydig cells to LH in terms of cAMP and testosterone synthesis. PRL also increased total and esterified cholesterol and decreased free cholesterol and membrane phospholipid content. The fatty acid composition of testicular lipids was significantly and selectively influenced by both hormonal treatments. These observations suggest that metabolism of cholesterol and long-chain polyunsaturated fatty acids in testicular tissue is affected by chorionic gonadotropin and PRL and may provide the mechanism for regulating steroidogenic functions.

  16. Dietary lipids modulate the expression of miR-107, a miRNA that regulates the circadian system

    PubMed Central

    Daimiel-Ruiz, Lidia; Klett, Mercedes; Konstantinidou, Valentini; Micó, Victor; Aranda, Juan F; García, Belén; Martínez-Botas, Javier; Dávalos, Alberto; Fernández-Hernando, Carlos; Ordovás, Jose M

    2015-01-01

    Scope The increased prevalence of cardiovascular diseases has been hypothesized to be the result of an increased exposure to a host of atherogenic environmental factors, paramount among them being unhealthy dietary habits. Long-chain n-3 polyunsaturated fatty acids (PUFAs) have been shown to have cardio protective effects, partially due to their ability to regulate gene expression. In this regard, increasing attention has been devoted to the role of miRNAs as regulators of multiple metabolic pathways whose deregulation has been associated with CVD risk. In this work we investigated whether miRNA expression was regulated by docosahexanoic acid (DHA), conjugated linoleic acid (CLA) and cholesterol in Caco-2 cells. Results Among the modulated miRNAs, miR-107 was differentially expressed by all treatments and this modulation was independent of its hosting gene, PANK1, possibly through its own promoter, which contains binding sites for metabolically relevant transcription factors. Among the putative target genes of miR-107, we found some genes with key roles in circadian rhythm. Specifically, we demonstrated that binding of miR-107 to the CLOCK gene results in the deregulation of the circadian rhythm of the cells. Conclusions Since chronodisruption has been linked to metabolic disorders such as Type 2 Diabetes (T2D), atherosclerosis, obesity and Cardiovascular Disease (CVD), our findings suggests that miR-107 could represent a new approach for pharmacological treatment of these diseases. PMID:25522185

  17. Salacia oblonga root improves cardiac lipid metabolism in Zucker diabetic fatty rats: Modulation of cardiac PPAR-{alpha}-mediated transcription of fatty acid metabolic genes

    SciTech Connect

    Huang, Tom H.-W.; Yang Qinglin; Harada, Masaki; Uberai, Jasna; Radford, Jane; Li, George Q.; Yamahara, Johji; Roufogalis, Basil D.; Li Yuhao . E-mail: yuhao@pharm.usyd.edu.au

    2006-01-15

    Excess cardiac triglyceride accumulation in diabetes and obesity induces lipotoxicity, which predisposes the myocytes to death. On the other hand, increased cardiac fatty acid (FA) oxidation plays a role in the development of myocardial dysfunction in diabetes. PPAR-{alpha} plays an important role in maintaining homeostasis of lipid metabolism. We have previously demonstrated that the extract from Salacia oblonga root (SOE), an Ayurvedic anti-diabetic and anti-obesity medicine, improves hyperlipidemia in Zucker diabetic fatty (ZDF) rats (a genetic model of type 2 diabetes and obesity) and possesses PPAR-{alpha} activating properties. Here we demonstrate that chronic oral administration of SOE reduces cardiac triglyceride and FA contents and decreases the Oil red O-stained area in the myocardium of ZDF rats, which parallels the effects on plasma triglyceride and FA levels. Furthermore, the treatment suppressed cardiac overexpression of both FA transporter protein-1 mRNA and protein in ZDF rats, suggesting inhibition of increased cardiac FA uptake as the basis for decreased cardiac FA levels. Additionally, the treatment also inhibited overexpression in ZDF rat heart of PPAR-{alpha} mRNA and protein and carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase mRNAs and restored the downregulated acetyl-CoA carboxylase mRNA. These results suggest that SOE inhibits cardiac FA oxidation in ZDF rats. Thus, our findings suggest that improvement by SOE of excess cardiac lipid accumulation and increased cardiac FA oxidation in diabetes and obesity occurs by reduction of cardiac FA uptake, thereby modulating cardiac PPAR-{alpha}-mediated FA metabolic gene transcription.

  18. Modulation of Glucagon-like Peptide-1 (GLP-1) Potency by Endocannabinoid-like Lipids Represents a Novel Mode of Regulating GLP-1 Receptor Signaling*

    PubMed Central

    Cheng, Yu-Hong; Ho, Mei-Shang; Huang, Wei-Ting; Chou, Ying-Ting; King, Klim

    2015-01-01

    Glucagon-like peptide-1 (GLP-1) analogs are approved for treatment of type 2 diabetes and are in clinical trials for disorders including neurodegenerative diseases. GLP-1 receptor (GLP-1R) is expressed in many peripheral and neuronal tissues and is activated by circulating GLP-1. Other than food intake, little is known about factors regulating GLP-1 secretion. Given a normally basal circulating level of GLP-1, knowledge of mechanisms regulating GLP-1R signaling, which has diverse functions in extrapancreatic tissues, remains elusive. In this study, we found that the potency of GLP-1, not exendin 4, is specifically enhanced by the endocannabinoid-like lipids oleoylethanolamide (OEA) and 2-oleoylglycerol but not by stearoylethanolamide (SEA) or palmitoylethanolamide. 9.2 μm OEA enhances the potency of GLP-1 in stimulating cAMP production by 10-fold but does not affect its receptor binding affinity. OEA and 2-oleoylglycerol, but not SEA, bind to GLP-1 in a dose-dependent and saturable manner. OEA but not SEA promoted GLP-1(7–36) amide to trypsin inactivation in a dose-dependent and saturable manner. Susceptibility of GLP-1(7–36) amide to trypsin inactivation is increased 40-fold upon binding to OEA but not to SEA. Our findings indicate that OEA binds to GLP-1(7–36) amide and enhances the potency that may result from a conformational change of the peptide. In conclusion, modulating potency of GLP-1 by physiologically regulated endocannabinoid-like lipids allows GLP-1R signaling to be regulated spatiotemporally at a constant basal GLP-1 level. PMID:25903129

  19. Modulation of Glucagon-like Peptide-1 (GLP-1) Potency by Endocannabinoid-like Lipids Represents a Novel Mode of Regulating GLP-1 Receptor Signaling.

    PubMed

    Cheng, Yu-Hong; Ho, Mei-Shang; Huang, Wei-Ting; Chou, Ying-Ting; King, Klim

    2015-06-01

    Glucagon-like peptide-1 (GLP-1) analogs are approved for treatment of type 2 diabetes and are in clinical trials for disorders including neurodegenerative diseases. GLP-1 receptor (GLP-1R) is expressed in many peripheral and neuronal tissues and is activated by circulating GLP-1. Other than food intake, little is known about factors regulating GLP-1 secretion. Given a normally basal circulating level of GLP-1, knowledge of mechanisms regulating GLP-1R signaling, which has diverse functions in extrapancreatic tissues, remains elusive. In this study, we found that the potency of GLP-1, not exendin 4, is specifically enhanced by the endocannabinoid-like lipids oleoylethanolamide (OEA) and 2-oleoylglycerol but not by stearoylethanolamide (SEA) or palmitoylethanolamide. 9.2 μM OEA enhances the potency of GLP-1 in stimulating cAMP production by 10-fold but does not affect its receptor binding affinity. OEA and 2-oleoylglycerol, but not SEA, bind to GLP-1 in a dose-dependent and saturable manner. OEA but not SEA promoted GLP-1(7-36) amide to trypsin inactivation in a dose-dependent and saturable manner. Susceptibility of GLP-1(7-36) amide to trypsin inactivation is increased 40-fold upon binding to OEA but not to SEA. Our findings indicate that OEA binds to GLP-1(7-36) amide and enhances the potency that may result from a conformational change of the peptide. In conclusion, modulating potency of GLP-1 by physiologically regulated endocannabinoid-like lipids allows GLP-1R signaling to be regulated spatiotemporally at a constant basal GLP-1 level. PMID:25903129

  20. Beneficial effect of tagatose consumption on postprandial hyperglycemia in Koreans: a double-blind crossover designed study.

    PubMed

    Kwak, Jung Hyun; Kim, Min Sun; Lee, Jin Hee; Yang, Yoon Jung; Lee, Ki Ho; Kim, Oh Yoen; Lee, Jong Ho

    2013-08-01

    The present study determined the effect of tagatose supplementation on postprandial hyperglycemia in normal (n = 54) and hyperglycemic subjects [n = 40, impaired fasting glucose (IFG) and newly diagnosed type 2 diabetes]. In a double-blind crossover designed study, study subjects were randomly assigned to consume a sucralose-erythritol drink (the placebo) or a tagatose-containing drink (the test) with a seven-day interval. Finally, 85 subjects completed the study (normal, n = 52; hyperglycemic, n = 33). Blood samples were collected at 0, 30, 60 and 120 min after ingestion and analyzed for fasting and postprandial levels of glucose, insulin and C-peptide. Basic anthropometric parameters and lipid files were also measured. Hyperglycemic subjects were basically older and heavier, and showed higher levels of triglyceride, total- and LDL-cholesterols and apolipoprotein AI and B compared with normal subjects. After consuming the tagatose (5 g)-containing drink, hyperglycemic subjects had a significant reduction in serum levels of glucose at 120 min (p = 0.019) and glucose area under the curve (AUC) (p = 0.017), however these were not observed in normal subjects. When ages were matched between the two groups, the glucose response patterns were shown to be similar. Additionally, normal subjects who received a high-dose of tagatose-containing drinks (10 g) showed significantly lower levels of insulin at 30 min (p = 0.004) and 60 min (p = 0.011), insulin AUC (p = 0.009), and C-peptide at 30 min (p = 0.004), 60 min (p = 0.011) and C-peptide AUC (p = 0.023). In conclusion, a single dietary supplement in the form of a tagatose-containing drink may be beneficial for controlling postprandial glycemic response in Koreans. PMID:23760573

  1. Metabolomics reveals differences in postprandial responses to breads and fasting metabolic characteristics associated with postprandial insulin demand in postmenopausal women.

    PubMed

    Moazzami, Ali A; Shrestha, Aahana; Morrison, David A; Poutanen, Kaisa; Mykkänen, Hannu

    2014-06-01

    Changes in serum metabolic profile after the intake of different food products (e.g., bread) can provide insight into their interaction with human metabolism. Postprandial metabolic responses were compared after the intake of refined wheat (RWB), whole-meal rye (WRB), and refined rye (RRB) breads. In addition, associations between the metabolic profile in fasting serum and the postprandial concentration of insulin in response to different breads were investigated. Nineteen postmenopausal women with normal fasting glucose and normal glucose tolerance participated in a randomized, controlled, crossover meal study. The test breads, RWB (control), RRB, and WRB, providing 50 g of available carbohydrate, were each served as a single meal. The postprandial metabolic profile was measured using nuclear magnetic resonance and targeted LC-mass spectrometry and was compared between different breads using ANOVA and multivariate models. Eight amino acids had a significant treatment effect (P < 0.01) and a significant treatment × time effect (P < 0.05). RWB produced higher postprandial concentrations of leucine (geometric mean: 224; 95% CI: 196, 257) and isoleucine (mean ± SD: 111 ± 31.5) compared with RRB (geometric mean: 165; 95% CI: 147, 186; mean ± SD: 84.2 ± 22.9) and WRB (geometric mean: 190; 95% CI: 174, 207; mean ± SD: 95.8 ± 17.3) at 60 min respectively (P < 0.001). In addition, 2 metabolic subgroups were identified using multivariate models based on the association between fasting metabolic profile and the postprandial concentration of insulin. Women with higher fasting concentrations of leucine and isoleucine and lower fasting concentrations of sphingomyelins and phosphatidylcholines had higher insulin responses despite similar glucose concentration after all kinds of bread (cross-validated ANOVA, P = 0.048). High blood concentration of branched-chain amino acids, i.e., leucine and isoleucine, has been associated with the increased risk of diabetes, which

  2. Hemodynamic and autonomic nervous system responses to mixed meal ingestion in healthy young and old subjects and dysautonomic patients with postprandial hypotension

    NASA Technical Reports Server (NTRS)

    Lipsitz, L. A.; Ryan, S. M.; Parker, J. A.; Freeman, R.; Wei, J. Y.; Goldberger, A. L.

    1993-01-01

    maintained. 2) Dysautonomic patients with postprandial hypotension fail to maintain systemic vascular resistance after a meal. This impairment in vascular response to meal ingestion may underlie the development of postprandial hypotension. 3) The measurement of mean HR or plasma NE does not adequately characterize autonomic cardiac control. Power spectral analysis suggests an impairment in the postprandial autonomic modulation of HR in healthy elderly and dysautonomic subjects, possibly predisposing to hypotension when vascular compensation is inadequate.

  3. Clostridium Butyricum CGMCC0313.1 Modulates Lipid Profile, Insulin Resistance and Colon Homeostasis in Obese Mice.

    PubMed

    Shang, Haixiao; Sun, Jia; Chen, Yong Q

    2016-01-01

    Obesity is associated with a cluster of metabolic disorders and systemic low-grade inflammation involving multiple organs. Recent findings have suggested that intestine is a key organ altered in response to high fat diet (HFD) feeding. Probiotics mainly lactobacillus strains have earlier been implicated in alleviating metabolic disorders. Here we aimed to examine the effects of a naturally occurring butyrate-producing probiotic clostridium butyricum CGMCC0313.1 (CB0313.1) in limiting the development of HFD-induced obesity. Mice treated with CB0313.1 exhibited reduced lipid accumulation in liver and serum, lower circulating insulin levels and improved glucose tolerance and insulin sensitivity. Furthermore, CB0313.1 administration reversed the HFD-induced colonic inflammation as evidenced by reduced tumor necrosis factor (TNF)-α level and increases the interleukin (IL)-10 and IL-22 levels in colon tissue. Additionally to colonic inflammation, CB0313.1 also reduced the colon permeability by upregulating the tight junction (TJ) proteins (claudin-1 and occludin) and contributed to a decreased circulating endotoxin level. In colon content, CB0313.1 administration restored the reduced production of butyrate and other short chain fatty acids (SCFAs) caused by HFD feeding. In adipose tissue, lower transcriptional levels of pro-inflammatory TNF-α, IL-6, IL-1β and monocyte chemotactic protein (MCP)-1 in adipose tissue were observed in CB0313.1-treated mice. Collectively, our data demonstrated that CB0313.1, targeting colon inflammation and permeability, ameliorated HFD-induced obesity, insulin resistance as well as adipose inflammation. PMID:27123997

  4. Clostridium Butyricum CGMCC0313.1 Modulates Lipid Profile, Insulin Resistance and Colon Homeostasis in Obese Mice

    PubMed Central

    Shang, Haixiao

    2016-01-01

    Obesity is associated with a cluster of metabolic disorders and systemic low-grade inflammation involving multiple organs. Recent findings have suggested that intestine is a key organ altered in response to high fat diet (HFD) feeding. Probiotics mainly lactobacillus strains have earlier been implicated in alleviating metabolic disorders. Here we aimed to examine the effects of a naturally occurring butyrate-producing probiotic clostridium butyricum CGMCC0313.1 (CB0313.1) in limiting the development of HFD-induced obesity. Mice treated with CB0313.1 exhibited reduced lipid accumulation in liver and serum, lower circulating insulin levels and improved glucose tolerance and insulin sensitivity. Furthermore, CB0313.1 administration reversed the HFD-induced colonic inflammation as evidenced by reduced tumor necrosis factor (TNF)-α level and increases the interleukin (IL)-10 and IL-22 levels in colon tissue. Additionally to colonic inflammation, CB0313.1 also reduced the colon permeability by upregulating the tight junction (TJ) proteins (claudin-1 and occludin) and contributed to a decreased circulating endotoxin level. In colon content, CB0313.1 administration restored the reduced production of butyrate and other short chain fatty acids (SCFAs) caused by HFD feeding. In adipose tissue, lower transcriptional levels of pro-inflammatory TNF-α, IL-6, IL-1β and monocyte chemotactic protein (MCP)-1 in adipose tissue were observed in CB0313.1-treated mice. Collectively, our data demonstrated that CB0313.1, targeting colon inflammation and permeability, ameliorated HFD-induced obesity, insulin resistance as well as adipose inflammation. PMID:27123997

  5. Food Components Modulate Obesity and Energy Metabolism via the Transcriptional Regulation of Lipid-Sensing Nuclear Receptors.

    PubMed

    Goto, Tsuyoshi; Takahashi, Nobuyuki; Kawada, Teruo

    2015-01-01

    Obesity is a major risk factor for chronic diseases such as diabetes, cardiovascular diseases, and hypertension. Many modern people have a tendency to overeat owing to stress and loosening of self-control. Moreover, energy expenditure varies greatly among individuals. Scientific reduction of obesity is important under these circumstances. Furthermore, recent research on molecular levels has clarified the differentiation of adipocytes, the level of subsequent fat accumulation, and the secretion of the biologically active adipokines by adipocytes. Adipose tissues and obesity have become the most important target for the prevention and treatment of many chronic diseases. We have identified various food-derived compounds modulating nuclear receptors, especially peroxisome proliferators-activated receptor(PPAR), in the regulation of energy metabolism and obesity. In this review, we discuss the PPARs that are most important in obesity and energy metabolism. PMID:26598824

  6. Enterostatin decreases postprandial pancreatic UCP2 mRNA levels and increases plasma insulin and amylin.

    PubMed

    Arsenijevic, Denis; Gallmann, Eva; Moses, William; Lutz, Thomas; Erlanson-Albertsson, Charlotte; Langhans, Wolfgang

    2005-07-01

    This study investigated the chronic effect of enterostatin on body weight and some of the associated changes in postprandial metabolism. Rats were adapted to 6 h of food access/day and a choice of low-fat and high-fat (HF) food and then given enterostatin or vehicle by an intraperitoneally implanted minipump delivering 160 nmol enterostatin/h continuously over a 5-day infusion period. Enterostatin resulted in a slight but significant reduction of HF intake and body weight. After the last 6-h food access period, enterostatin-treated animals had lower plasma triglyceride and free fatty acid but higher plasma glucose and lactate levels than control animals. Enterostatin infusion resulted in increased uncoupling protein-2 (UCP2) expression in various tissues, including epididymal fat and liver. UCP2 was reduced in the pancreas of enterostatin-treated animals, and this was associated with increased plasma levels of insulin and amylin. Whether these two hormones are involved in the observed decreased food intake due to enterostatin remains to be determined. As lipid metabolism appeared to be altered by enterostatin, we measured peroxisome proliferator-activated receptor (PPAR) expression in tissues and observed that PPARalpha, -beta, -gamma1, and -gamma2 expression were modified by enterostatin in epididymal fat, pancreas, and liver. This further links altered lipid metabolism with body weight loss. Our data suggest that alterations in UCP2 and PPARgamma2 play a role in the control of insulin and amylin release from the pancreas. This implies that enterostatin changes lipid and carbohydrate metabolic pathways in addition to its effects on food intake and energy expenditure. PMID:15713687

  7. Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors

    PubMed Central

    Chapman, M. John; Le Goff, Wilfried; Guerin, Maryse; Kontush, Anatol

    2010-01-01

    Subnormal plasma levels of high-density lipoprotein cholesterol (HDL-C) constitute a major cardiovascular risk factor; raising low HDL-C levels may therefore reduce the residual cardiovascular risk that frequently presents in dyslipidaemic subjects despite statin therapy. Cholesteryl ester transfer protein (CETP), a key modulator not only of the intravascular metabolism of HDL and apolipoprotein (apo) A-I but also of triglyceride (TG)-rich particles and low-density lipoprotein (LDL), mediates the transfer of cholesteryl esters from HDL to pro-atherogenic apoB-lipoproteins, with heterotransfer of TG mainly from very low-density lipoprotein to HDL. Cholesteryl ester transfer protein activity is elevated in the dyslipidaemias of metabolic disease involving insulin resistance and moderate to marked hypertriglyceridaemia, and is intimately associated with premature atherosclerosis and high cardiovascular risk. Cholesteryl ester transfer protein inhibition therefore presents a preferential target for elevation of HDL-C and reduction in atherosclerosis. This review appraises recent evidence for a central role of CETP in the action of current lipid-modulating agents with HDL-raising potential, i.e. statins, fibrates, and niacin, and compares their mechanisms of action with those of pharmacological agents under development which directly inhibit CETP. New CETP inhibitors, such as dalcetrapib and anacetrapib, are targeted to normalize HDL/apoA-I levels and anti-atherogenic activities of HDL particles. Further studies of these CETP inhibitors, in particular in long-term, large-scale outcome trials, will provide essential information on their safety and efficacy in reducing residual cardiovascular risk. PMID:19825813

  8. Single ingestion of soy β-conglycinin induces increased postprandial circulating FGF21 levels exerting beneficial health effects.

    PubMed

    Hashidume, Tsutomu; Kato, Asuka; Tanaka, Tomohiro; Miyoshi, Shoko; Itoh, Nobuyuki; Nakata, Rieko; Inoue, Hiroyasu; Oikawa, Akira; Nakai, Yuji; Shimizu, Makoto; Inoue, Jun; Sato, Ryuichiro

    2016-01-01

    Soy protein β-conglycinin has serum lipid-lowering and anti-obesity effects. We showed that single ingestion of β-conglycinin after fasting alters gene expression in mouse liver. A sharp increase in fibroblast growth factor 21 (FGF21) gene expression, which is depressed by normal feeding, resulted in increased postprandial circulating FGF21 levels along with a significant decrease in adipose tissue weights. Most increases in gene expressions, including FGF21, were targets for the activating transcription factor 4 (ATF4), but not for peroxisome proliferator-activated receptor α. Overexpression of a dominant-negative form of ATF4 significantly reduced β-conglycinin-induced increases in hepatic FGF21 gene expression. In FGF21-deficient mice, β-conglycinin effects were partially abolished. Methionine supplementation to the diet or primary hepatocyte culture medium demonstrated its importance for activating liver or hepatocyte ATF4-FGF21 signaling. Thus, dietary β-conglycinin intake can impact hepatic and systemic metabolism by increasing the postprandial circulating FGF21 levels. PMID:27312476

  9. Single ingestion of soy β-conglycinin induces increased postprandial circulating FGF21 levels exerting beneficial health effects

    PubMed Central

    Hashidume, Tsutomu; Kato, Asuka; Tanaka, Tomohiro; Miyoshi, Shoko; Itoh, Nobuyuki; Nakata, Rieko; Inoue, Hiroyasu; Oikawa, Akira; Nakai, Yuji; Shimizu, Makoto; Inoue, Jun; Sato, Ryuichiro

    2016-01-01

    Soy protein β-conglycinin has serum lipid-lowering and anti-obesity effects. We showed that single ingestion of β-conglycinin after fasting alters gene expression in mouse liver. A sharp increase in fibroblast growth factor 21 (FGF21) gene expression, which is depressed by normal feeding, resulted in increased postprandial circulating FGF21 levels along with a significant decrease in adipose tissue weights. Most increases in gene expressions, including FGF21, were targets for the activating transcription factor 4 (ATF4), but not for peroxisome proliferator-activated receptor α. Overexpression of a dominant-negative form of ATF4 significantly reduced β-conglycinin-induced increases in hepatic FGF21 gene expression. In FGF21-deficient mice, β-conglycinin effects were partially abolished. Methionine supplementation to the diet or primary hepatocyte culture medium demonstrated its importance for activating liver or hepatocyte ATF4-FGF21 signaling. Thus, dietary β-conglycinin intake can impact hepatic and systemic metabolism by increasing the postprandial circulating FGF21 levels. PMID:27312476

  10. Sterol Modulation of the Plasma Membrane H+-ATPase Activity from Corn Roots Reconstituted into Soybean Lipids.

    PubMed Central

    Grandmougin-Ferjani, A.; Schuler-Muller, I.; Hartmann, M. A.

    1997-01-01

    A partially purified H+-ATPase from the plasma membrane (PM) of corn (Zea mays L.) roots was inserted into vesicles prepared with soybean (Glycine max L.) phospholipids and various concentrations of individual sterols using either a freeze-thaw sonication or an octylglucoside dilution procedure. Both methods yielded a functional enzyme that retained its native characteristics. We have investigated the effects of typical plant sterols (i.e. sitosterol, stigmasterol, and 24-methylcholesterol) on both ATP hydrolysis and H+ pumping by the reconstituted corn root PM ATPase. We have also checked the influence of cholesterol and of two unusual sterols, 24-methylpollinastanol and 14[alpha],24-dimethylcholest-8-en-3[beta]-ol. Here we present evidence for a sterol modulation of the plant PM H+-ATPase activity. In particular, cholesterol and stigmasterol were found to stimulate the pump, especially when present at 5 mol%, whereas all of the other sterols tested behaved as inhibitors at any concentration in proteoliposomes. In all situations H+ pumping was shown to be more sensitive to a sterol environment than was ATP hydrolysis. Our results suggest the occurrence of binding sites for sterols on the plant PM H+-ATPase. PMID:12223599

  11. Alcohol, postprandial plasma glucose, and prognosis of hepatocellular carcinoma

    PubMed Central

    Abe, Hiroshi; Aida, Yuta; Ishiguro, Haruya; Yoshizawa, Kai; Miyazaki, Tamihiro; Itagaki, Munenori; Sutoh, Satoshi; Aizawa, Yoshio

    2013-01-01

    AIM: To identify factors associated with prognosis of hepatocellular carcinoma (HCC) after initial therapy. METHODS: A total of 377 HCC patients who were newly treated at Katsushika Medical Center, Japan from January 2000 to December 2009 and followed up for > 2 years, or died during follow-up, were enrolled. The factors related to survival were first analyzed in 377 patients with HCC tumor stage T1-T4 using multivariate Cox proportional hazards regression analysis. A similar analysis was performed in 282 patients with tumor stage T1-T3. Additionally, factors associated with the period between initial and subsequent therapy were examined in 144 patients who did not show local recurrence. Finally, 214 HCC stage T1-T3 patients who died during the observation period were classified into four groups according to their alcohol consumption and postprandial glucose levels, and differences in their causes of death were examined. RESULTS: On multivariate Cox proportional hazards regression analysis, the following were significantly associated with survival: underlying liver disease stage [non-cirrhosis/Child-Pugh A vs B/C, hazard ratio (HR): 0.603, 95% CI: 0.417-0.874, P = 0.0079], HCC stage (T1/T2 vs T3/T4, HR: 0.447, 95% CI: 0.347-0.576, P < 0.0001), and mean postprandial plasma glucose after initial therapy (< 200 vs ≥ 200 mg/dL, HR: 0.181, 95% CI: 0.067-0.488, P = 0.0008). In T1-T3 patients, uninterrupted alcohol consumption after initial therapy (no vs yes, HR: 0.641, 95% CI: 0.469-0.877, P = 0.0055) was significant in addition to underlying liver disease stage (non-cirrhosis/Child-Pugh A vs B/C, HR: 0649, 95% CI: 0.476-0.885, P = 0.0068), HCC stage (T1 vs T2/T3, HR: 0.788, 95% CI: 0.653-0.945, P = 0.0108), and mean postprandial plasma glucose after initial therapy (< 200 mg/dL vs ≥ 200 mg/dL, HR: 0.502, 95% CI: 0.337-0.747, P = 0.0005). In patients without local recurrence, time from initial to subsequent therapy for newly emerging HCC was significantly longer in

  12. A Randomized Cross-Over Trial of the Postprandial Effects of Three Different Diets in Patients with Type 2 Diabetes

    PubMed Central

    Bunjaku, Bekim; Rosenqvist, Ulf; Nystrom, Fredrik H.; Guldbrand, Hans

    2013-01-01

    Background In the clinic setting both fasting levels of glucose and the area under the curve (AUC) of glucose, by determination of HbA1c levels, are used for risk assessments, in type 2 diabetes (NIDDM). However little is known about postprandial levels, and hence AUC, regarding other traditional risk factors such as insulin and blood-lipids and how this is affected by different diets. Objective To study postprandial effects of three diets, during a single day, in NIDDM. Methods A low-fat diet (45–56 energy-% from carbohydrates), and a low-carbohydrate diet (16–24 energy-% from carbohydrates) was compared with a Mediterranean-style diet (black coffee for breakfast and the same total-caloric intake as the other two diets for lunch with red wine, 32–35 energy−% from carbohydrates) in a randomized cross-over design. Total-caloric intake/test-day at the clinic from food was 1025–1080 kCal in men and 905–984 kCal in women. The test meals were consumed at a diabetes ward under supervision. Results Twenty-one participants were recruited and 19 completed the studies. The low-carbohydrate diet induced lower insulin and glucose excursions compared with the low-fat diet (p<0.0005 for both AUC). The insulin-response following the single Mediterranean-style lunch-meal was more pronounced than during the low-fat diet lunch (insulin increase-ratio of the low-fat diet: 4.35±2.2, of Mediterranean-style diet: 8.12±5.2, p = 0.001) while postprandial glucose levels were similar. The increase-ratio of insulin correlated with the elevation of the incretin glucose-dependent insulinotropic-polypeptide following the Mediterranean-style diet lunch (Spearman, r = 0.64, p = 0.003). Conclusions The large Mediterranean-style lunch-meal induced similar postprandial glucose-elevations as the low-fat meal despite almost double amount of calories due to a pronounced insulin-increase. This suggests that accumulation of caloric intake from breakfast and lunch to a single

  13. Lipids and HCV.

    PubMed

    Bassendine, M F; Sheridan, D A; Bridge, S H; Felmlee, D J; Neely, R D G

    2013-01-01

    Chronic hepatitis C virus (HCV) infection is associated with an increase in hepatic steatosis and a decrease in serum levels of total cholesterol, low-density lipoprotein cholesterol (LDL) and apolipoprotein B (apoB), the main protein constituent of LDL and very low-density lipoprotein (VLDL). These changes are more marked in HCV genotype 3 infection, and effective treatment results in their reversal. Low lipid levels in HCV infection correlate not only with steatosis and more advanced liver fibrosis but also with non-response to interferon-based therapy. The clinical relevance of disrupted lipid metabolism reflects the fact that lipids play a crucial role in the life cycle of hepatitis C virus. HCV assembly and maturation in hepatocytes depend on microsomal triglyceride transfer protein and apoB in a manner that parallels the formation of VLDL. VLDL production from the liver occurs throughout the day with an estimated 10(18) particles produced every 24 h whilst the estimated hepatitis C virion production rate is 10(12) virions per day. HCV particles in the serum exist as a mixture of complete low-density infectious lipo-viral particles (LVP) and a vast excess of apoB-associated empty nucleocapsid-free sub-viral particles that are complexed with anti-HCV envelope antibodies. Apolipoprotein E (apoE) is also involved in HCV particle morphogenesis and is an essential apolipoprotein for HCV infectivity. ApoE is a critical ligand for the receptor-mediated removal of triglyceride rich lipoprotein (TRL) remnants by the liver. The dynamics of apoB-associated lipoproteins, including HCV-LVP, change post-prandially with an increase in large TRL remnants and very low density HCV-LVP which are rapidly cleared by the liver (at least three HCV receptors are cellular receptors for uptake of TRL remnants). In summary, HCV utilises triglyceride-rich lipoprotein pathways within the liver and the circulation to its advantage. PMID:23111699

  14. The conserved disulfide bond of human tear lipocalin modulates conformation and lipid binding in a ligand selective manner.

    PubMed

    Gasymov, Oktay K; Abduragimov, Adil R; Glasgow, Ben J

    2011-05-01

    The primary aim of this study is the elucidation of the mechanism of disulfide induced alteration of ligand binding in human tear lipocalin (TL). Disulfide bonds may act as dynamic scaffolds to regulate conformational changes that alter protein function including receptor-ligand interactions. A single disulfide bond, (Cys61-Cys153), exists in TL that is highly conserved in the lipocalin superfamily. Circular dichroism and fluorescence spectroscopies were applied to investigate the mechanism by which disulfide bond removal effects protein stability, dynamics and ligand binding properties. Although the secondary structure is not altered by disulfide elimination, TL shows decreased stability against urea denaturation. Free energy change (ΔG(0)) decreases from 4.9±0.2 to 2.1±0.3kcal/mol with removal of the disulfide bond. Furthermore, ligand binding properties of TL without the disulfide vary according to the type of ligand. The binding of a bulky ligand, NBD-cholesterol, has a decreased time constant (from 11.8±0.2 to 3.3s). In contrast, the NBD-labeled phospholipid shows a moderate decrease in the time constant for binding, from 33.2±0.2 to 22.2±0.4s. FRET experiments indicate that the hairpin CD is directly involved in modulation of both ligand binding and flexibility of TL. In TL complexed with palmitic acid (PA-TL), the distance between the residues 62 of strand D and 81 of loop EF is decreased by disulfide bond reduction. Consequently, removal of the disulfide bond boosts flexibility of the protein to reach a CD-EF loop distance (24.3Å, between residues 62 and 81), which is not accessible for the protein with an intact disulfide bond (26.2Å). The results suggest that enhanced flexibility of the protein promotes a faster accommodation of the ligand inside the cavity and an energetically favorable ligand-protein complex. PMID:21466861

  15. The conserved disulfide bond of human tear lipocalin modulates conformation and lipid binding in a ligand selective manner

    PubMed Central

    Gasymov, Oktay K.; Abduragimov, Adil R.; Glasgow, Ben J.

    2011-01-01

    The primary aim of this study is the elucidation of the mechanism of disulfide induced alteration of ligand binding in human tear lipocalin (TL). Disulfide bonds may act as dynamic scaffolds to regulate conformational changes that alter protein function including receptor-ligand interactions. A single disulfide bond, (Cys61-Cys153), exists in TL that is highly conserved in the lipocalin superfamily. Circular dichroism and fluorescence spectroscopies were applied to investigate the mechanism by which disulfide bond removal effects protein stability, dynamics and ligand binding properties. Although the secondary structure is not altered by disulfide elimination, TL shows decreased stability against urea denaturation. Free energy change (ΔG0) decreases from 4.9± 0.2 to 2.1± 0.3 kcal/mol with removal of the disulfide bond. Furthermore, ligand binding properties of TL without the disulfide vary according to the type of ligand. The binding of a bulky ligand, NBD-cholesterol, has a decreased time constant (from 11.8± 0.2 to 3.3 s). In contrast, the NBD-labeled phospholipid shows a moderate decrease in the time constant for binding, from 33.2± 0.2 to 22.2± 0.4 s. FRET experiments indicate that the hairpin CD is directly involved in modulation of both ligand binding and flexibility of TL. In TL complexed with palmitc acid (PA-TL), the distance between the residues 62 of strand D and 81 of loop EF is decreased by disulfide bond reduction. Consequently, removal of the disulfide bond boosts flexibility of the protein to reach a CD-EF loop distance (24.3 Å, between residues 62 and 81), which is not accessible for the protein with an intact disulfide bond (26.2 Å). The results suggest that enhanced flexibility of the protein promotes a faster accommodation of the ligand inside the cavity and energetically favorable ligand-protein complex. PMID:21466861

  16. Cross-linking of sodium caseinate-structured emulsion with transglutaminase alters postprandial metabolic and appetite responses in healthy young individuals.

    PubMed

    Juvonen, Kristiina R; Macierzanka, Adam; Lille, Martina E; Laaksonen, David E; Mykkänen, Hannu M; Niskanen, Leo K; Pihlajamäki, Jussi; Mäkelä, Kari A; Mills, Clare E N; Mackie, Alan R; Malcolm, Paul; Herzig, Karl-Heinz; Poutanen, Kaisa S; Karhunen, Leila J

    2015-08-14

    The physico-chemical and interfacial properties of fat emulsions influence lipid digestion and may affect postprandial responses. The aim of the present study was to determine the effects of the modification of the interfacial layer of a fat emulsion by cross-linking on postprandial metabolic and appetite responses. A total of fifteen healthy individuals (26.5 (sem 6.9) years and BMI 21.9 (sem 2.0) kg/m2) participated in a cross-over design experiment in which they consumed two isoenergetic (1924 kJ (460 kcal)) and isovolumic (250 g) emulsions stabilised with either sodium caseinate (Cas) or transglutaminase-cross-linked sodium caseinate (Cas-TG) in a randomised order. Blood samples were collected from the individuals at baseline and for 6 h postprandially for the determination of serum TAG and plasma NEFA, cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), glucose and insulin responses. Appetite was assessed using visual analogue scales. Postprandial TAG and NEFA responses and gastric emptying (GE) rates were comparable between the emulsions. CCK increased more after the ingestion of Cas-TG than after the ingestion of Cas (P< 0.05), while GLP-1 responses did not differ between the two test emulsions. Glucose and insulin profiles were lower after consuming Cas-TG than after consuming Cas (P< 0.05). The overall insulin, glucose and CCK responses, expressed as areas above/under the curve, did not differ significantly between the Cas and Cas-TG meal conditions. Satiety ratings were reduced and hunger, desire to eat and thirst ratings increased more after the ingestion of Cas-TG than after the ingestion of Cas (P< 0.05). The present results suggest that even a subtle structural modification of the interfacial layer of a fat emulsion can alter the early postprandial profiles of glucose, insulin, CCK, appetite and satiety through decreased protein digestion without affecting significantly on GE or overall lipid digestion. PMID:26159899

  17. A Sulfur Amino Acid–Free Meal Increases Plasma Lipids in Humans123

    PubMed Central

    Park, Youngja; Le, Ngoc-Anh; Yu, Tianwei; Strobel, Fred; Gletsu-Miller, Nana; Accardi, Carolyn J.; Lee, Kichun S.; Wu, Shaoxiong; Ziegler, Thomas R.; Jones, Dean P.

    2011-01-01

    The content of sulfur amino acid (SAA) in a meal affects postprandial plasma cysteine concentrations and the redox potential of cysteine/cystine. Because such changes can affect enzyme, transporter, and receptor activities, meal content of SAA could have unrecognized effects on metabolism during the postprandial period. This pilot study used proton NMR (1H-NMR) spectroscopy of human plasma to test the hypothesis that dietary SAA content changes macronutrient metabolism. Healthy participants (18–36 y, 5 males and 3 females) were equilibrated for 3 d to adequate SAA, fed chemically defined meals without SAA for 5 d (depletion), and then fed isoenergetic, isonitrogenous meals containing 56 mg·kg−1·d−1 SAA for 4.5 d (repletion). On the first and last day of consuming the chemically defined meals, a morning meal containing 60% of the daily food intake was given and plasma samples were collected over an 8-h postprandial time course for characterization of metabolic changes by 1H-NMR spectroscopy. SAA-free food increased peak intensity in the plasma 1H-NMR spectra in the postprandial period. Orthogonal signal correction/partial least squares-discriminant analysis showed changes in signals associated with lipids, some amino acids, and lactate, with notable increases in plasma lipid signals (TG, unsaturated lipid, cholesterol). Conventional lipid analyses confirmed higher plasma TG and showed an increase in plasma concentration of the lipoprotein lipase inhibitor, apoC-III. The results show that plasma 1H-NMR spectra can provide useful macronutrient profiling following a meal challenge protocol and that a single meal with imbalanced SAA content alters postprandial lipid metabolism. PMID:21677075

  18. Comparison of the effect of different intensity exercise on a bicycle ergometer on postprandial lipidemia in type II diabetic patients

    PubMed Central

    Argani, Narges; Sharifi, Gholamreza; Golshahi, Jafar

    2014-01-01

    BACKGROUND Postprandial lipid clearance failure and lipoprotein disorders, which are independent risk factors for cardiovascular diseases are well-recognized in type II diabetes. Reduction of fats through exercise has been proved, though the mechanism is not well-defined, and the effects of different intensity exercise on postprandial lipidemia in diabetes type II is unknown. This study aims to find these effects using a cycle ergometer. METHODS On three different days, 15 type II diabetics (10 women and 5 men, with a mean age 42.07 ± 6.05 years, weight 94.64 ± 4.37 kg, height 159.78 ± 9.09 cm, and body mass index29.83 ± 3.93 kg/m2), consumed a full fat breakfast (750-800 kcal, 85% fat), and 150 min later, blood samples were taken from them to measure their lipid profile. The 1st day was the control day, without any exercises. Seven days later, 90 min after enriched breakfast, they did 30 min of exercise on the cycle ergometer with intensity of 55-70% of maximum heart rate (HRmax), and 14 days later, 90 min after enriched breakfast, they did 30 min of exercise with intensity of 70-85% of HRmax. RESULTS According to Friedman non-parametric test, high-density lipoprotein (HDL) cholesterol serum level significantly increased after 30 min of moderate intensity exercise (P > 0.05, from 39.4 ± 5.2 to 48.6 ± 9.3), while this increase was insignificant after a higher intensity exercise. Neither intensity levels had any significant effects on triglyceride or on low-density lipoprotein cholesterol. CONCLUSION Results showed that moderate intensity exercise was more effective in increasing HDL cholesterol level in type II diabetics. PMID:25161685

  19. Impaired postprandial lipemic response in chronic kidney disease.

    PubMed

    Saland, Jeffrey M; Satlin, Lisa M; Zalsos-Johnson, Jeanna; Cremers, Serge; Ginsberg, Henry N

    2016-07-01

    Dyslipidemia in chronic kidney disease (CKD) is usually characterized by hypertriglyceridemia. Here we studied postprandial lipemia in children and young adults to determine whether an increasing degree of CKD results in a proportional increase in triglyceride and chylomicron concentration. Secondary goals were to determine whether subnephrotic proteinuria, apolipoprotein (apo)C-III and insulin resistance modify the CKD effect. Eighteen fasting participants (mean age of 15 years, mean glomerular filtration rate (GFR) of 50 ml/min/1.73 m(2)) underwent a postprandial challenge with a high fat milkshake. Triglycerides, apoB-48, insulin, and other markers were measured before and 2, 4, 6, and 8 hours afterward. Response was assessed by the incremental area under the curve of triglycerides and of apoB-48. The primary hypothesis was tested by correlation to estimated GFR. Significantly, for every 10 ml/min/1.73 m(2) lower estimated GFR, the incremental area under the curve of triglycerides was 17% greater while that of apoB-48 was 16% greater. Univariate analyses also showed that the incremental area under the curve of triglycerides and apoB-48 were significantly associated with subnephrotic proteinuria, apoC-III, and insulin resistance. In multivariate analysis, CKD and insulin resistance were independently associated with increased area under the curve and were each linked to increased levels of apoC-III. Thus, postprandial triglyceride and chylomicron plasma excursions are increased in direct proportion to the degree of CKD. Independent effects are associated with subclinical insulin resistance and increased apoC-III is linked to both CKD and insulin resistance. PMID:27162092

  20. Evidence for an Exaggerated Postprandial Lipemia in Chronic Paraplegia

    PubMed Central

    Nash, Mark S; deGroot, Joris; Martinez-Arizala, Alberto; Mendez, Armando J

    2005-01-01

    Background/Objective: Excessive delay in triglyceride (TG) metabolism after ingestion of dietary fat represents a significant cardiovascular disease (CVD) risk. The objective of this study was to compare the postprandial lipemic responses of individuals with paraplegia with those of healthy nondisabled individuals. Methods: The ability of 3 recreationally active individuals with paraplegia having normal fasting TG (mean = 103 mg/dL) to metabolize TG after ingestion of a high-fat test meal was compared with a previously published cohort of 21 recreationally active individuals without paraplegia (TG mean = 86 mg/dL) who underwent identical testing. The subjects with paraplegia had venous blood taken under fasting conditions, and then ingested a milkshake containing premium ice cream blended with heavy whipping cream (~92% of calories from fat). Additional blood samples were obtained at 2, 4, and 6 hours after ingestion. The area under the curve (AUC) for TG clearance for both subject groups was measured with an area planimeter. Results: TG uptake for both groups was almost identical for the first 2 hours after ingestion. At 4 and 6 hours after ingestion, the TG levels were 50 and 35 mg/dL higher, respectively, in subjects with paraplegia than in nondisabled subjects. When corrected for small baseline differences in TG concentrations (16 mg/dL), the AUC was 46.5% greater for the group with paraplegia than in the nondisabled group. A near mirror association across time was observed between postprandial serum high-density lipoprotein cholesterol (HDL-C) and TG levels in subjects with paraplegia. Conclusion: This case series finds an exaggerated postprandial lipemia (PPL) in persons with paraplegia with normal fasting TGs. This finding is the first evidence, in a small population, of an unreported potential CVD risk in persons with paraplegia. PMID:16396382

  1. Influence of olive oil on carotenoid absorption from tomato juice and effects on postprandial lipemia.

    PubMed

    Arranz, Sara; Martínez-Huélamo, Miriam; Vallverdu-Queralt, Anna; Valderas-Martinez, Palmira; Illán, Montse; Sacanella, Emilio; Escribano, Elvira; Estruch, Ramon; Lamuela-Raventos, Rosa Ma

    2015-02-01

    The potential benefits of tomato-rich diets for the cardiovascular system have been related to plasma concentrations of carotenoids. In addition, the bioavailability of carotenoids from foods depends on their chemical structure, processing and the food matrix. Our aim was to evaluate the effect of adding oil to tomato juice (not treated with heat) on the bioavailability of plasma carotenoids and postprandial lipid response. In a randomized, controlled, crossover feeding trial, eleven healthy volunteers were assigned to receive a single ingestion of 750g of tomato juice (TJ) containing 10% of refined olive oil/70kg body weight (BW) and 750g of TJ without oil/70kg BW on two different days. All lycopene isomers increased significantly in subjects consuming TJ with oil, reaching the maximum concentration at 24h. LDL cholesterol and total cholesterol decreased significantly 6h after the consumption of TJ with oil, which significantly correlated with an increase of trans-lycopene and 5-cis-lycopene, respectively. PMID:25172701

  2. The normal fasting and postprandial diisopropyl-IDA Tc 99m hepatobiliary study

    SciTech Connect

    Klingensmith, W.C.; Spitzer, V.M.; Fritzberg, A.R.; Kuni, C.C.

    1981-12-01

    Diisopropyl-IDA Tc 99m imaging studies were performed in 11 normal subjects in both the fasting and postprandial states. In 5- to 60-minute analog images obtained in both fasting and postprandial studies, the cardiac blood pool was almost never seen, renal pelvic radioactivity was commonly seen, the extrahepatic biliary tract was always seen, and the left hepatic duct was always more prominent than the right hepatic duct. The biliary tract was visualized by ten minutes in nine of 11 fasting studies and 10 of 11 postprandial studies. The gallbladder was visualized in all eleven fasting studies, but in only four postprandial studies. The gallbladder was visualized in all eleven fasting studies, but in only four postprandial studies (p less than 0.05). The zero- to sixty-minute digital data indicated a greater hepatocyte clearance, an earlier time of peak parenchymal radioactivity, and a faster parenchymal washout in the postprandial studies compared with fasting studies (p less than 0.05). Approximately nine percent of the injected dose was recovered in the urine during the first three hours in fasting and postprandial studies. The normal diisopropyl-IDA Tc 99m study in the fasting and postprandial states is defined; significant differences exist between the two states.

  3. Postprandial blood glucose response in relation to gastric emptying and satiety in healthy subjects.

    PubMed

    Hlebowicz, Joanna

    2009-10-01

    Glucostatic appetite regulation has numerous determinants, among others: cephalic phase digestion, gastric emptying and absorption, together influencing postprandial blood glucose responses and satiety. This short communication presents and reviews studies of gastric emptying, antral distension and postprandial glucose response and their relation to reports of satiety in healthy non-obese over night fasting subjects. PMID:19607867

  4. Postprandial thermogenesis and substrate oxidation are unaffected by sleep restriction

    PubMed Central

    Shechter, Ari; Rising, Russell; Wolfe, Scott; Albu, Jeanine B.; St-Onge, Marie-Pierre

    2014-01-01

    Background/Objectives The extent to which alterations in energy expenditure (EE) in response to sleep restriction contribute to the short sleep-obesity relationship is not clearly defined. Short sleep may induce changes in resting metabolic rate (RMR), thermic effect of food (TEF), and postprandial substrate oxidation. Subjects/Methods Ten females (age and BMI: 22-43 y and 23.4-28 kg/m2) completed a randomized, crossover study assessing the effects of short (4 h/night) and habitual (8 h/night) sleep duration on fasting and postprandial RMR and respiratory quotient (RQ). Measurements were taken after 3 nights using whole-room indirect calorimetry. The TEF was assessed over a 6-h period following consumption of a high-fat liquid meal. Results Short vs. habitual sleep did not affect RMR (1.01 ± 0.05 and 0.97 ± 0.04 kcal/min; p=0.23). Fasting RQ was significantly lower after short vs. habitual sleep (0.84 ± 0.01 and 0.88 ± 0.01; p=0.028). Postprandial EE (short: 1.13 ± 0.04 and habitual: 1.10 ± 0.04, p=0.09) and RQ (short: 0.88 ± 0.01 and habitual: 0.88 ± 0.01, p=0.50) after the high-fat meal were not different between conditions. TEF was similar between conditions (0.24 ± 0.02 kcal/min in both; p=0.98), as was the ~6-h incremental area under the curve (1.16 ± 0.10 and 1.17 ± 0.09 kcal/min x 356 min after short and habitual sleep, respectively; p=0.92). Conclusions Current findings observed in non-obese healthy premenopausal women do not support the hypothesis that alterations in TEF and postprandial substrate oxidation are major contributors to the higher rate of obesity observed in short sleepers. In exploring a role of sleep duration on EE, research should focus on potential alterations in physical activity to explain the increased obesity risk in short sleepers. PMID:24352294

  5. The postprandial plasma rye fingerprint includes benzoxazinoid-derived phenylacetamide sulfates.

    PubMed

    Hanhineva, Kati; Keski-Rahkonen, Pekka; Lappi, Jenni; Katina, Kati; Pekkinen, Jenna; Savolainen, Otto; Timonen, Oskari; Paananen, Jussi; Mykkänen, Hannu; Poutanen, Kaisa

    2014-07-01

    The bioavailability of whole-grain rye-derived phytochemicals has not yet been comprehensively characterized, and different baking and manufacturing processes can modulate the phytochemical composition of breads and other rye products. The aim of our study was to find key differences in the phytochemical profile of plasma after the consumption of 3 breads containing rye bran when compared with a plain white wheat bread control. Plasma metabolite profiles of 12 healthy middle-aged men and women were analyzed using LC quadrupole time-of-flight mass spectrometry metabolomics analysis while fasting and at 60 min, 120 min, 240 min, and 24 h after consuming a meal that contained either 100% whole-grain sourdough rye bread or white wheat bread enriched with native unprocessed rye bran or bioprocessed rye bran. White wheat bread was used as the control. The meals were served in random order after a 12-h overnight fast, with at least 3 d between each occasion. Two sulfonated phenylacetamides, hydroxy-N-(2-hydroxyphenyl) acetamide and N-(2-hydroxyphenyl) acetamide, potentially derived from the benzoxazinoid metabolites, were among the most discriminant postprandial plasma biomarkers distinguishing intake of breads containing whole-meal rye or rye bran from the control white wheat bread. Furthermore, subsequent metabolite profiling analysis of the consumed breads indicated that different bioprocessing/baking techniques involving exposure to microbial metabolism (e.g., sourdough fermentation) have a central role in modulating the phytochemical content of the whole-grain and bran-rich breads. PMID:24812068

  6. Development of electron spin echo envelope modulation spectroscopy to probe the secondary structure of recombinant membrane proteins in a lipid bilayer.

    PubMed

    Zhang, Rongfu; Sahu, Indra D; Gibson, Kaylee R; Muhammad, Nefertiti B; Bali, Avnika P; Comer, Raven G; Liu, Lishan; Craig, Andrew F; Mccarrick, Robert M; Dabney-Smith, Carole; Sanders, Charles R; Lorigan, Gary A

    2015-11-01

    Membrane proteins conduct many important biological functions essential to the survival of organisms. However, due to their inherent hydrophobic nature, it is very difficult to obtain structural information on membrane-bound proteins using traditional biophysical techniques. We are developing a new approach to probe the secondary structure of membrane proteins using the pulsed EPR technique of Electron Spin Echo Envelope Modulation (ESEEM) Spectroscopy. This method has been successfully applied to model peptides made synthetically. However, in order for this ESEEM technique to be widely applicable to larger membrane protein systems with no size limitations, protein samples with deuterated residues need to be prepared via protein expression methods. For the first time, this study shows that the ESEEM approach can be used to probe the local secondary structure of a (2) H-labeled d8 -Val overexpressed membrane protein in a membrane mimetic environment. The membrane-bound human KCNE1 protein was used with a known solution NMR structure to demonstrate the applicability of this methodology. Three different α-helical regions of KCNE1 were probed: the extracellular domain (Val21), transmembrane domain (Val50), and cytoplasmic domain (Val95). These results indicated α-helical structures in all three segments, consistent with the micelle structure of KCNE1. Furthermore, KCNE1 was incorporated into a lipid bilayer and the secondary structure of the transmembrane domain (Val50) was shown to be α-helical in a more native-like environment. This study extends the application of this ESEEM approach to much larger membrane protein systems that are difficult to study with X-ray crystallography and/or NMR spectroscopy. PMID:26355804

  7. Effect of meal volume and calorie load on postprandial gastric function and emptying: studies under physiological conditions by combined fiber-optic pressure measurement and MRI.

    PubMed

    Kwiatek, Monika A; Menne, Dieter; Steingoetter, Andreas; Goetze, Oliver; Forras-Kaufman, Zsofia; Kaufman, Elad; Fruehauf, Heiko; Boesiger, Peter; Fried, Michael; Schwizer, Werner; Fox, Mark R

    2009-11-01

    further passage of nutrients. The distinct early phase of gastric emptying with relatively rapid, uncontrolled passage of nutrients into the small bowel, modulated by meal volume but not nutrient composition, ensures that the delivery of nutrients in the later postprandial period is related to the overall calorie load of the meal. PMID:19779010

  8. Gain-of-function Lipoprotein Lipase variant rs13702 modulates lipid traits through disruption of a microRNA-410 seed site

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genome wide association studies (GWAS) have identified hundreds of genetic variants that are associated with lipid phenotypes. However, data supporting a functional role for these variants in the context of lipid metabolism are scarce. We investigated the association of the Lipoprotein Lipase (LPL...

  9. Postprandial nutrient-sensing and metabolic responses after partial dietary fishmeal replacement by soyabean meal in turbot (Scophthalmus maximus L.).

    PubMed

    Xu, Dandan; He, Gen; Mai, Kangsen; Zhou, Huihui; Xu, Wei; Song, Fei

    2016-02-14

    In this study, we chose a carnivorous fish, turbot (Scophthalmus maximus L.), to examine its nutrient-sensing and metabolic responses after ingestion of diets with fishmeal (FM), or 45% of FM replaced by soyabean meal (34·6% dry diet) balanced with or without essential amino acids (EAA) to match the amino acid profile of FM diet for 30 d. After a 1-month feeding trial, fish growth, feed efficiency and nutrient retention were markedly reduced by soyabean meal-incorporated (SMI) diets. Compared with the FM diet, SMI led to a reduction of postprandial influx of free amino acids, hypoactivated target of rapamycin signalling and a hyperactivated amino acid response pathway after refeeding, a status associated with reduced protein synthesis, impaired postprandial glycolysis and lipogenesis. These differential effects were not ameliorated by matching an EAA profile of soyabean meal to that of the FM diet through dietary amino acid supplementation. Therefore, this study demonstrated that the FM diet and SMI diets led to distinct nutrient-sensing responses, which in turn modulated metabolism and determined the utilisation efficiency of diets. Our results provide a new molecular explanation for the role of nutrient sensing in the inferior performance of aquafeeds in which FM is replaced by soyabean meal. PMID:26586314

  10. Effects of six carbohydrate sources on dog diet digestibility and post-prandial glucose and insulin response.

    PubMed

    Carciofi, A C; Takakura, F S; de-Oliveira, L D; Teshima, E; Jeremias, J T; Brunetto, M A; Prada, F

    2008-06-01

    The effects of six extruded diets with different starch sources (cassava flour, brewer's rice, corn, sorghum, peas or lentils) on dog total tract apparent digestibility and glycemic and insulinemic response were investigated. The experiment was carried out on thirty-six dogs with six dogs per diet in a completely randomized design. The diets containing brewer's rice and cassava flour presented the greatest digestibility of dry matter, organic matter and gross energy (p < 0.05), followed by corn and sorghum; pea and lentil diets had the lowest. Starch digestibility was greater than 98% in all diets and was greater for brewer's rice and cassava flour than for lentils and peas diets (p < 0.05). Dogs' immediate post-prandial glucose and insulin responses (AUC < or = 30 min) were greater for brewer's rice, corn, and cassava flour diets (p < 0.05), and later meal responses (AUC > or = 30 min) were greater for sorghum, lentil and pea diets (p < 0.05). Variations in diet digestibility and post-prandial response can be explained by differences in chemical composition of each starch source including fibre content and starch granule structure. The nutritional particularities of each starch ingredient can be explored through diet formulations designed to modulate glycemic response. However, more studies are required to support these. PMID:18477314

  11. Resting metabolic rate and postprandial thermogenesis in vegetarians and nonvegetarians.

    PubMed

    Poehlman, E T; Arciero, P J; Melby, C L; Badylak, S F

    1988-08-01

    Resting metabolic rate (RMR), thermic effect of a meal (TEM), and associated hormonal changes were studied in vegetarians and nonvegetarians. RMR was established by indirect calorimetry in 12 male vegetarians (VEG) and 11 nonvegetarians (NVEG) of similar body fat and aerobic fitness. Subjects ingested a liquid meal and TEM was measured for 180 min postprandially. Plasma concentrations of glucose, insulin and thyroid hormones (T3 and T4) were determined before and after meal ingestion. Absolute RMR was comparable between VEG and NVEG. However, TEM was lower (p less than 0.01) in VEG (55.8 +/- 3.3 kcal/180 min) vs NVEG (76.4 +/- 3.6). Plasma levels of glucose and insulin were similar between the two groups whereas plasma T3 was slightly but nonsignificantly lower in vegetarians. A vegetarian diet may decrease the postprandial thermic response; this does not support the supposition that an elevated TEM is a factor contributing to the lower body weight in vegetarians than in omnivores. PMID:3044062

  12. Loneliness predicts postprandial ghrelin and hunger in women.

    PubMed

    Jaremka, Lisa M; Fagundes, Christopher P; Peng, Juan; Belury, Martha A; Andridge, Rebecca R; Malarkey, William B; Kiecolt-Glaser, Janice K

    2015-04-01

    Loneliness is strongly linked to poor health. Recent research suggests that appetite dysregulation provides one potential pathway through which loneliness and other forms of social disconnection influence health. Obesity may alter the link between loneliness and appetite-relevant hormones, one unexplored possibility. We examined the relationships between loneliness and both postmeal ghrelin and hunger, and tested whether these links differed for people with a higher versus lower body mass index (BMI; kg/m(2)). During this double-blind randomized crossover study, women (N=42) ate a high saturated fat meal at the beginning of one full-day visit and a high oleic sunflower oil meal at the beginning of the other. Loneliness was assessed once with a commonly used loneliness questionnaire. Ghrelin was sampled before the meal and postmeal at 2 and 7h. Self-reported hunger was measured before the meal, immediately postmeal, and then 2, 4, and 7h later. Lonelier women had larger postprandial ghrelin and hunger increases compared with less lonely women, but only among participants with a lower BMI. Loneliness and postprandial ghrelin and hunger were unrelated among participants with a higher BMI. These effects were consistent across both meals. These data suggest that ghrelin, an important appetite-regulation hormone, and hunger may link loneliness to weight gain and its corresponding negative health effects among non-obese people. PMID:25725426

  13. The -256T>C Polymorphism in the Apolipoprotein A-II Gene Promoter Is Associated with Body Mass Index and Food Intake in the Genetics of Lipid Lowering Drugs and Diet Network Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: Apolipoprotein A-II (APOA2) plays an ambiguous role in lipid metabolism, obesity, and atherosclerosis. METHODS: We studied the association between a functional APOA2 promoter polymorphism (-265T>C) and plasma lipids (fasting and postprandial), anthropometric variables, and food intake in...

  14. Consumption of a high-fat meal containing cheese compared with a vegan alternative lowers postprandial C-reactive protein in overweight and obese individuals with metabolic abnormalities: a randomised controlled cross-over study.

    PubMed

    Demmer, Elieke; Van Loan, Marta D; Rivera, Nancy; Rogers, Tara S; Gertz, Erik R; German, J Bruce; Zivkovic, Angela M; Smilowitz, Jennifer T

    2016-01-01

    Dietary recommendations suggest decreased consumption of SFA to minimise CVD risk; however, not all foods rich in SFA are equivalent. To evaluate the effects of SFA in a dairy food matrix, as Cheddar cheese, v. SFA from a vegan-alternative test meal on postprandial inflammatory markers, a randomised controlled cross-over trial was conducted in twenty overweight or obese adults with metabolic abnormalities. Individuals consumed two isoenergetic high-fat mixed meals separated by a 1- to 2-week washout period. Serum was collected at baseline, and at 1, 3 and 6 h postprandially and analysed for inflammatory markers (IL-6, IL-8, IL-10, IL-17, IL-18, TNFα, monocyte chemotactic protein-1 (MCP-1)), acute-phase proteins C-reactive protein (CRP) and serum amyloid-A (SAA), cellular adhesion molecules and blood lipids, glucose and insulin. Following both high-fat test meals, postprandial TAG concentrations rose steadily (P < 0·05) without a decrease by 6 h. The incremental AUC (iAUC) for CRP was significantly lower (P < 0·05) in response to the cheese compared with the vegan-alternative test meal. A treatment effect was not observed for any other inflammatory markers; however, for both test meals, multiple markers significantly changed from baseline over the 6 h postprandial period (IL-6, IL-8, IL-18, TNFα, MCP-1, SAA). Saturated fat in the form of a cheese matrix reduced the iAUC for CRP compared with a vegan-alternative test meal during the postprandial 6 h period. The study is registered at clinicaltrials.gov under NCT01803633. PMID:27313852

  15. Normal fasting and postprandial diisopropyl-IDA Tc 99m hepatobiliary stud

    SciTech Connect

    Klingensmith, W.C.; Spitzer, W.M.; Fritzberg, A.R.; Kuni, C.C.

    1981-12-01

    Diisopropyl-IDA TC 99m imaging studies were performed in 11 normal subjects in both the fasting and postprandial states. In 5- to 60-minute analog images obtained in both fasting and postprandial studies, the cardiac blood pool was almost never seen, renal pelvic radioactivity was commonly seen, the extrahepatic biliary tract was always seen, and the left hepatic duct was always more prominent than the right hepatic duct. The billiary tract was visualized by ten minutes in nine of 11 fasting studies and 10 of 11 postprandial studies. The gallbladder was visualized in all eleven fasting studies, but in only four postprandial studies (p<0.05). The zero- to sixty-minute digital data indicated a greater hepatocyte clearance, an earlier time of peak parenchymal radioactivity, and a faster parenchymal washout in the postprandial studies compared with fasting studies (p<0.05). Approximately nine percent of the injected dose was recovered in the urine during the first three hours in fasting and postprandial studies. The normal diisopropyl-IDA Tc 99m study in the fasting and postprandial states is defined; significant differences exist between the two states.

  16. Coffee polyphenol consumption improves postprandial hyperglycemia associated with impaired vascular endothelial function in healthy male adults.

    PubMed

    Jokura, Hiroko; Watanabe, Isamu; Umeda, Mika; Hase, Tadashi; Shimotoyodome, Akira

    2015-10-01

    Epidemiological studies indicate that habitual coffee consumption lowers the risk of diabetes and cardiovascular diseases. Postprandial hyperglycemia is a direct and independent risk factor for cardiovascular diseases. We previously demonstrated that coffee polyphenol ingestion increased secretion of Glucagon-like peptide 1 (GLP-1), which has been shown to exhibit anti-diabetic and cardiovascular effects. We hypothesized coffee polyphenol consumption may improve postprandial hyperglycemia and vascular endothelial function by increasing GLP-1 release and/or reducing oxidative stress. To examine this hypothesis, we conducted a randomized, acute, crossover, intervention study in healthy male adults, measuring blood parameters and flow-mediated dilation (FMD) after ingestion of a meal with or without coffee polyphenol extract (CPE). Nineteen subjects consumed a test meal with either a placebo- or CPE-containing beverage. Blood biomarkers and FMD were measured at fasting and up to 180 minutes postprandially. The CPE beverage led to a significantly lower peak postprandial increase in blood glucose and diacron-reactive oxygen metabolite, and significantly higher postprandial FMD than the placebo beverage. Postprandial blood GLP-1 increase tended to be higher after ingestion of the CPE beverage, compared with placebo. Subclass analysis revealed that the CPE beverage significantly improved postprandial blood GLP-1 response and reduced blood glucose increase in the subjects with a lower insulinogenic index. Correlation analysis showed postprandial FMD was negatively associated with blood glucose increase after ingestion of the CPE beverage. In conclusion, these results suggest that coffee polyphenol consumption improves postprandial hyperglycemia and vascular endothelial function, which is associated with increased GLP-1 secretion and decreased oxidative stress in healthy humans. PMID:26337017

  17. The effect of food temperature on postprandial metabolism in albatrosses.

    PubMed

    Battam, H; Chappell, M A; Buttemer, W A

    2008-04-01

    Heat generated by the specific dynamic action (SDA) associated with feeding is known to substitute for the thermoregulatory costs of cold-exposed endotherms; however, the effectiveness of this depends on food temperature. When food is cooler than core body temperature, it is warmed by body heat and, consequently, imposes a thermoregulatory challenge to the animal. The degree to which this cost might be ;paid' by SDA depends on the relative timing of food heating and the SDA response. We investigated this phenomenon in two genera of endotherms, Diomedea and Thalassarche albatrosses, by measuring postprandial metabolic rate following ingestion of food at body temperature (40 degrees C) and cooler (0 and 20 degrees C). This permitted us to estimate potential contributions to food warming by SDA-derived heat, and to observe the effect of cold food on metabolic rate. For meal sizes that were approximately 20% of body mass, SDA was 4.22+/-0.37% of assimilated food energy, and potentially contributed 17.9+/-1.0% and 13.2+/-2.2% of the required heating energy of food at 0 degrees C for Diomedea and Thalassarche albatrosses, respectively, and proportionately greater quantities at higher food temperatures. Cold food increased the rate at which postprandial metabolic rate increased to 3.2-4.5 times that associated with food ingested at body temperature. We also found that albatrosses generated heat in excess by more than 50% of the estimated thermostatic heating demand of cold food, a probable consequence of time delays in physiological responses to afferent signals. PMID:18344483

  18. Comparison of Postprandial Lipemia between Women who are on Oral Contraceptive Methods and Those who are not

    PubMed Central

    Petto, Jefferson; Vasques, Leila Monique Reis; Pinheiro, Renata Leão; Giesta, Beatriz de Almeida; dos Santos, Alan Carlos Nery; Gomes Neto, Mansueto; Ladeia, Ana Marice Teixeira

    2014-01-01

    Background: Postprandial Lipemia (PPL) is a physiological process that reflects the ability of the body to metabolize lipids. Even though the influence of oral contraceptives (OC) on PPL is not known, it is a known fact that their use increases fasting lipid values. Objective: To compare the PPL between women who are on OC and those who are not. Methods: A prospective analytical study which assessed eutrophic women, aged between 18 and 28 years old, who were irregularly active and with fasting triglycerides ≤150 mg/dL. They were divided into two groups: oral contraceptive group (COG) and non-oral contraceptive group (NCOG). Volunteers were submitted to the PPL test, in which blood samples were collected in time 0 (12-hour fasting) and after the intake of lipids in times 180 and 240 minutes. In order to compare the triglyceride deltas, which reflect PPL, the two-tailed Mann-Whitney test was used for independent samples between fasting collections and 180 minutes (∆1) and between fasting and 240 minutes (∆2). Results: Forty women were assessed and equally divided between groups. In the fasting lipid profile, it was observed that HDL did not present significant differences and that triglycerides in COG were twice as high in comparison to NCOG. Medians of ∆1 and ∆2 presented significant differences in both comparisons (p ≤0.05). Conclusion: The results point out that women who are irregularly active and use OC present more PPL in relation to those who do not use OC, which suggests that in this population, its chronic use increases the risk of heart conditions. PMID:25317941

  19. Postprandial insulin action relies on meal composition and hepatic parasympathetics: dependency on glucose and amino acids: Meal, parasympathetics & insulin action.

    PubMed

    Afonso, Ricardo A; Gaspar, Joana M; Lamarão, Iva; Lautt, W Wayne; Macedo, M Paula

    2016-01-01

    Insulin sensitivity (IS) increases following a meal. Meal composition affects postprandial glucose disposal but still remains unclear which nutrients and mechanisms are involved. We hypothesized that gut-absorbed glucose and amino acids stimulate hepatic parasympathetic nerves, potentiating insulin action. Male Sprague-Dawley rats were 24 h fasted and anesthetized. Two series of experiments were performed. (A) IS was assessed before and after liquid test meal administration (10 ml.kg(-1), intraenteric): glucose + amino acids + lipids (GAL, n=6); glucose (n=5); amino acids (n=5); lipids (n=3); glucose + amino acids (GA, n=9); amino acids + lipids (n=3); and glucose + lipids (n=4). (B) Separately, fasted animals were submitted to hepatic parasympathetic denervation (DEN); IS was assessed before and after GAL (n=4) or GA administration (n=4). (A) Both GAL and GA induced significant insulin sensitization. GAL increased IS from 97.9±6.2 mg glucose/kg bw (fasting) to 225.4±18.3 mg glucose/kg bw (P<0.001; 143.6±26.0% potentiation of IS); GA increased IS from 109.0±6.6 to 240.4±18.0 mg glucose/kg bw (P<0.001; 123.1±13.4% potentiation). None of the other meals potentiated IS. (B) GAL and GA did not induce a significant insulin sensitization in DEN animal. To achieve maximal insulin sensitization following a meal, it is required that gut-absorbed glucose and amino acids trigger a vagal reflex that involves hepatic parasympathetic nerves. PMID:26410344

  20. Addition of a dairy fraction rich in milk fat globule membrane to a high-saturated fat meal reduces the postprandial insulinaemic and inflammatory response in overweight and obese adults.

    PubMed

    Demmer, Elieke; Van Loan, Marta D; Rivera, Nancy; Rogers, Tara S; Gertz, Erik R; German, J Bruce; Smilowitz, Jennifer T; Zivkovic, Angela M

    2016-01-01

    Meals high in SFA, particularly palmitate, are associated with postprandial inflammation and insulin resistance. Milk fat globule membrane (MFGM) has anti-inflammatory properties that may attenuate the negative effects of SFA-rich meals. Our objective was to examine the postprandial metabolic and inflammatory response to a high-fat meal composed of palm oil (PO) compared with PO with an added dairy fraction rich in MFGM (PO+MFGM) in overweight and obese men and women (n 36) in a randomised, double-blinded, cross-over trial. Participants consumed two isoenergetic high-fat meals composed of a smoothie enriched with PO with v. without a cream-derived complex milk lipid fraction ( dairy fraction rich in MFGM) separated by a washout of 1-2 weeks. Serum cytokines, adhesion molecules, cortisol and markers of inflammation were measured at fasting, and at 1, 3 and 6 h postprandially. Glucose, insulin and lipid profiles were analysed in plasma. Consumption of the PO + MFGM v. PO meal resulted in lower total cholesterol (P = 0·021), LDL-cholesterol (P = 0·046), soluble intracellular adhesion molecule (P = 0·005) and insulin (P = 0·005) incremental AUC, and increased IL-10 (P = 0·013). Individuals with high baseline C-reactive protein (CRP) concentrations (≥3 mg/l, n 17) had higher (P = 0·030) insulin at 1 h after the PO meal than individuals with CRP concentrations <3 mg/l (n 19). The addition of MFGM attenuated this difference between CRP groups. The addition of a dairy fraction rich in MFGM attenuated the negative effects of a high-SFA meal by reducing postprandial cholesterol, inflammatory markers and insulin response in overweight and obese individuals, particularly in those with elevated CRP. PMID:27313850

  1. Salacia oblonga root improves postprandial hyperlipidemia and hepatic steatosis in Zucker diabetic fatty rats: Activation of PPAR-{alpha}

    SciTech Connect

    Hsun-Wei Huang, Tom; Peng Gang; Qian Li, George; Yamahara, Johji; Roufogalis, Basil D.; Li Yuhao . E-mail: yuhao@pharm.usyd.edu.au

    2006-02-01

    Salacia oblonga (SO) root is an Ayurvedic medicine with anti-diabetic and anti-obese properties. Peroxisome proliferator-activated receptor (PPAR)-{alpha}, a nuclear receptor, plays an important role in maintaining the homeostasis of lipid metabolism. Here, we demonstrate that chronic oral administration of the water extract from the root of SO to Zucker diabetic fatty (ZDF) rats, a genetic model of type 2 diabetes and obesity, lowered plasma triglyceride and total cholesterol (TC) levels, increased plasma high-density lipoprotein levels and reduced the liver contents of triglyceride, non-esterified fatty acids (NEFA) and the ratio of fatty droplets to total tissue. By contrast, the extract had no effect on plasma triglyceride and TC levels in fasted ZDF rats. After olive oil administration to ZDF the extract also inhibited the increase in plasma triglyceride levels. These results suggest that SO extract improves postprandial hyperlipidemia and hepatic steatosis in ZDF rats. Additionally, SO treatment enhanced hepatic expression of PPAR-{alpha} mRNA and protein, and carnitine palmitoyltransferase-1 and acyl-CoA oxidase mRNAs in ZDF rats. In vitro, SO extract and its main component mangiferin activated PPAR-{alpha} luciferase activity in human embryonic kidney 293 cells and lipoprotein lipase mRNA expression and enzyme activity in THP-1 differentiated macrophages; these effects were completely suppressed by a selective PPAR-{alpha} antagonist MK-886. The findings from both in vivo and in vitro suggest that SO extract functions as a PPAR-{alpha} activator, providing a potential mechanism for improvement of postprandial hyperlipidemia and hepatic steatosis in diabetes and obesity.

  2. Effect and potential mechanism of action of sea cucumber saponins on postprandial blood glucose in mice.

    PubMed

    Fu, Xueyuan; Wen, Min; Han, Xiuqing; Yanagita, Teruyoshi; Xue, Yong; Wang, Jingfeng; Xue, Changhu; Wang, Yuming

    2016-06-01

    Postprandial blood glucose control is the major goal in the treatment of diabetes. Here, we investigated the effect of sea cucumber saponins (SCSs) on postprandial blood glucose levels. SCS inhibited yeast as well as rat intestinal α-glucosidase activity in a dose-dependent manner and showed better inhibition of yeast α-glucosidases compared to the positive control. Further studies were performed using ICR mice treated with SCS and starch or SCS alone by oral gavage. Unexpectedly, SCS increased postprandial blood glucose levels a short time (1 h) after oral gavage. The serum corticosterone (CORT) level showed a consistent correlation with glucose levels. In vitro experiments confirmed that SCS treatment increased the secretion of CORT in the Y1 adrenal cell line. Overall, these studies demonstrated that SCS gavage could inhibit α-glucosidase activity but cannot attenuate postprandial blood glucose level within short time periods. The underlying mechanisms are probably related to increased serum CORT levels. PMID:26932154

  3. Postprandial blood glucose control in type 1 diabetes for carbohydrates with varying glycemic index foods.

    PubMed

    Hashimoto, Shogo; Noguchi, Claudia Cecilia Yamamoto; Furutani, Eiko

    2014-01-01

    Treatment of type 1 diabetes consists of maintaining postprandial normoglycemia using the correct prandial insulin dose according to food intake. Nonetheless, it is hardly achieved in practice, which results in several diabetes-related complications. In this study we present a feedforward plus feedback blood glucose control system that considers the glycemic index of foods. It consists of a preprandial insulin bolus whose optimal bolus dose and timing are stated as a minimization problem, which is followed by a postprandial closed-loop control based on model predictive control. Simulation results show that, for a representative carbohydrate intake of 50 g, the present control system is able to maintain postprandial glycemia below 140 mg/dL while preventing postprandial hypoglycemia as well. PMID:25571074

  4. Altering the Mitochondrial Fatty Acid Synthesis (mtFASII) Pathway Modulates Cellular Metabolic States and Bioactive Lipid Profiles as Revealed by Metabolomic Profiling

    PubMed Central

    Clay, Hayley B.; Parl, Angelika K.; Mitchell, Sabrina L.; Singh, Larry; Bell, Lauren N.; Murdock, Deborah G.

    2016-01-01

    Despite the presence of a cytosolic fatty acid synthesis pathway, mitochondria have retained their own means of creating fatty acids via the mitochondrial fatty acid synthesis (mtFASII) pathway. The reason for its conservation has not yet been elucidated. Therefore, to better understand the role of mtFASII in the cell, we used thin layer chromatography to characterize the contribution of the mtFASII pathway to the fatty acid composition of selected mitochondrial lipids. Next, we performed metabolomic analysis on HeLa cells in which the mtFASII pathway was either hypofunctional (through knockdown of mitochondrial acyl carrier protein, ACP) or hyperfunctional (through overexpression of mitochondrial enoyl-CoA reductase, MECR). Our results indicate that the mtFASII pathway contributes little to the fatty acid composition of mitochondrial lipid species examined. Additionally, loss of mtFASII function results in changes in biochemical pathways suggesting alterations in glucose utilization and redox state. Interestingly, levels of bioactive lipids, including lysophospholipids and sphingolipids, directly correlate with mtFASII function, indicating that mtFASII may be involved in the regulation of bioactive lipid levels. Regulation of bioactive lipid levels by mtFASII implicates the pathway as a mediator of intracellular signaling. PMID:26963735

  5. Cyanogenic Lipids

    PubMed Central

    Selmar, Dirk; Grocholewski, Sabine; Seigler, David S.

    1990-01-01

    Large amounts of cyanogenic lipids (esters of 1 cyano-2-methylprop-2-ene-1-ol with C:20 fatty acids) are stored in the seeds of Ungnadia speciosa. During seedling development, these lipids are completely consumed without liberation of free HCN to the atmosphere. At the same time, cyanogenic glycosides are synthesized, but the total amount is much lower (about 26%) than the quantity of cyanogenic lipids formerly present in the seeds. This large decrease in the total content of cyanogens (HCN-potential) demonstrates that at least 74% of cyanogenic lipids are converted to noncyanogenic compounds. Whether the newly synthesized cyanogenic glycosides are derived directly from cyanogenic lipids or produced by de novo synthesis is still unknown. Based on the utilization of cyanogenic lipids for the synthesis of noncyanogenic compounds, it is concluded that these cyanogens serve as storage for reduced nitrogen. The ecophysiological significance of cyanolipids based on multifunctional aspects is discussed. PMID:16667514

  6. The effects of sex, metabolic syndrome and exercise on postprandial lipemia

    PubMed Central

    Cox-York, Kimberly A.; Sharp, Teresa A.; Stotz, Sarah A.; Bessesen, Daniel H.; Pagliassotti, Michael J.; Horton, Tracy J.

    2012-01-01

    Objective Exercise has been suggested to have cardio protective benefits due to a lowering of postprandial triglycerides (PPTG). We hypothesized that a morning exercise bout would significantly lower PPTG measured over a full day, in response to moderate fat meals (35% energy) in men more so than women, and in metabolic syndrome (MetS) relative to normal weight (NW) individuals. Materials/Methods Participants completed two randomized study days; one control and one exercise day (60 min of morning exercise, 60% VO2peak). Meals were consumed at breakfast, lunch and dinner with the energy expended during exercise replaced on the active day. The areas (AUC) and incremental areas (IAUC) under the curve were calculated for total triglycerides, total cholesterol and other metabolites. Results Exercise did not significantly change the PPTG AUC & IAUC overall, nor within, or between, each sex or group (NW and MetS). Exercise induced a 30% decrease in total cholesterol IAUC (p = 0.003) in NW subjects. Overall, women had a lower IAUC for PPTG compared to men (p = 0.037), with the greatest difference between MetS women and MetS men, due to a sustained drop in TG after lunch in the women. This suggests that PP, rather than fasting, lipid analyses may be particularly important when evaluating sex differences in metabolic risk. Conclusions With energy replacement, moderate morning exercise did not result in a significant decrease in PPTG excursions. Exercise did elicit a significant decrease in PP cholesterol levels in NW subjects, suggesting a potential mechanism for the cardio protective effects of exercise. PMID:22974968

  7. Lipid metabolism, apoptosis and cancer therapy.

    PubMed

    Huang, Chunfa; Freter, Carl

    2015-01-01

    Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules. These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways. Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases. In this review, we discuss recent data in the fields of lipid metabolism, lipid-mediated apoptosis, and cancer therapy. In conclusion, understanding the underlying molecular mechanism of lipid metabolism and the function of different lipid molecules could provide the basis for cancer cell death rationale, discover novel and potential targets, and develop new anticancer drugs for cancer therapy. PMID:25561239

  8. Sodium nitrate co-ingestion with protein does not augment postprandial muscle protein synthesis rates in older, type 2 diabetes patients.

    PubMed

    Kouw, Imre W K; Cermak, Naomi M; Burd, Nicholas A; Churchward-Venne, Tyler A; Senden, Joan M; Gijsen, Annemarie P; van Loon, Luc J C

    2016-08-01

    The age-related anabolic resistance to protein ingestion is suggested to be associated with impairments in insulin-mediated capillary recruitment and postprandial muscle tissue perfusion. The present study investigated whether dietary nitrate co-ingestion with protein improves muscle protein synthesis in older, type 2 diabetes patients. Twenty-four men with type 2 diabetes (72 ± 1 yr, 26.7 ± 1.4 m/kg(2) body mass index, 7.3 ± 0.4% HbA1C) received a primed continuous infusion of l-[ring-(2)H5]phenylalanine and l-[1-(13)C]leucine and ingested 20 g of intrinsically l-[1-(13)C]phenylalanine- and l-[1-(13)C]leucine-labeled protein with (PRONO3) or without (PRO) sodium nitrate (0.15 mmol/kg). Blood and muscle samples were collected to assess protein digestion and absorption kinetics and postprandial muscle protein synthesis rates. Upon protein ingestion, exogenous phenylalanine appearance rates increased in both groups (P < 0.001), resulting in 55 ± 2% and 53 ± 2% of dietary protein-derived amino acids becoming available in the circulation over the 5h postprandial period in the PRO and PRONO3 groups, respectively. Postprandial myofibrillar protein synthesis rates based on l-[ring-(2)H5]phenylalanine did not differ between groups (0.025 ± 0.004 and 0.021 ± 0.007%/h over 0-2 h and 0.032 ± 0.004 and 0.030 ± 0.003%/h over 2-5 h in PRO and PRONO3, respectively, P = 0.7). No differences in incorporation of dietary protein-derived l-[1-(13)C]phenylalanine into de novo myofibrillar protein were observed at 5 h (0.016 ± 0.002 and 0.014 ± 0.002 mole percent excess in PRO and PRONO3, respectively, P = 0.8). Dietary nitrate co-ingestion with protein does not modulate protein digestion and absorption kinetics, nor does it further increase postprandial muscle protein synthesis rates or the incorporation of dietary protein-derived amino acids into de novo myofibrillar protein in older, type 2 diabetes patients. PMID:27221118

  9. Pycnogenol® inhibits lipid accumulation in 3T3-L1 adipocytes with the modulation of reactive oxygen species (ROS) production associated with antioxidant enzyme responses.

    PubMed

    Lee, Ok-Hwan; Seo, Min-Jung; Choi, Hyeon-Son; Lee, Boo-Yong

    2012-03-01

    Pycnogenol® is a group of flavonoids with antioxidant effects. Adipogenesis is the process of adipocyte differentiation. It causes the increase of lipids as well as ROS (reactive oxygen species). Lipid accumulation and ROS production were determined in 3 T3-L1 adipocyte, and the effect of Pycnogenol® was evaluated. Lipid accumulation was elevated in adipocyte treated with hydrogen peroxide, one of the ROS. Pycnogenol® showed an inhibitory effect on the lipid accumulation and ROS production during the adipogenesis. We also investigated the molecular events associated with ROS production and lipid accumulation. Our results showed that Pycnogenol® inhibited the mRNA expression of pro-oxidant enzymes, such as NOX4 (NADPH (nicotinamide adenine dinucleotide phosphate hydrogen) oxidase 4), and the NADPH-producing G6PDH (glucose-6-phosphate dehydrogenase) enzyme. In addition, Pycnogenol® suppressed the mRNA abundance of adipogenic transcription factors, PPAR-γ (peroxisome proliferator-activated receptor γ) and C/EBP-α (CCAAT/enhancer binding protein α), and their target gene, aP2 (adipocyte protein 2) responsible for fatty acid transportation. On the other hand, Pycnogenol® increased the abundance of antioxidant proteins such as Cu/Zn-SOD (copper-zinc superoxide dismutase), Mn-SOD (manganese superoxide dismutase), GPx (glutathione peroxidase) and GR (glutathione reductase). Our results suggest that Pycnogenol® inhibits lipid accumulation and ROS production by regulating adipogenic gene expression and pro-/antioxidant enzyme responses in adipocytes. PMID:21796705

  10. The V227A polymorphism at the PPARA locus is associated with serum lipid concentrations and modulates the association between dietary polyunsaturated fatty acid intake and serum high density lipoprotein concentrations in Chinese women.

    PubMed

    Chan, Edmund; Tan, Chuen Seng; Deurenberg-Yap, Mabel; Chia, Kee Seng; Chew, Suok Kai; Tai, E Shyong

    2006-08-01

    Peroxisome proliferators activated receptor alpha (PPARalpha) regulates the transcription of several proteins involved in human lipoprotein metabolism. We screened the PPARA locus for polymorphisms in 20 unrelated subjects from each of three ethnic groups (Chinese, Malays and Asian Indians). Only the V227A polymorphism was observed. We genotyped 4248 subjects (2899 Chinese, 761 Malay and 588 Asian Indians) and found allele frequencies for the A227 allele of 0.04 in Chinese, 0.006 in Malays and 0.003 in Asian Indians. We examined the associations between this polymorphism and serum lipid concentrations in Chinese. In women, but not in men, the presence of the A227 allele was associated with lower serum concentrations of total cholesterol [5.38mmol/l (95%CI: 5.22-5.54) versus 5.21mmol/l (95%CI: 4.99-5.43), p=0.047] and triglycerides [1.19mmol/l (95%CI: 1.10-1.28) versus 1.09mmol/l (95%CI: 0.98-1.21), p=0.048]. We also found that the V227A polymorphism modulates the association between dietary polyunsaturated fatty acid intake and serum high density lipoprotein concentration (p-value for interaction=0.049). Our findings implicate PPARalpha in the lipid lowering associated with diets high in PUFA and suggests that genetic variation at the PPARA locus may determine the lipid response to changes in PUFA intake. PMID:16288935

  11. Postprandial Levels of Branch Chained and Aromatic Amino Acids Associate with Fasting Glycaemia.

    PubMed

    Ottosson, Filip; Ericson, Ulrika; Almgren, Peter; Nilsson, Jeanette; Magnusson, Martin; Fernandez, Céline; Melander, Olle

    2016-01-01

    High fasting plasma concentrations of isoleucine, phenylalanine, and tyrosine have been associated with increased risk of hyperglycaemia and incidence of type 2 diabetes. Whether these associations are diet or metabolism driven is unknown. We examined how the dietary protein source affects the postprandial circulating profile of these three diabetes associated amino acids (DMAAs) and tested whether the postprandial DMAA profiles are associated with fasting glycaemia. We used a crossover design with twenty-one healthy individuals and four different isocaloric test meals, containing proteins from different dietary sources (dairy, fish, meat, and plants). Analysis of the postprandial DMAAs concentrations was performed using targeted mass spectrometry. A DMAA score was defined as the sum of all the three amino acid concentrations. The postprandial area under the curve (AUC) of all the three amino acids and the DMAA score was significantly greater after intake of the meal with dairy protein compared to intake of the three other meals. The postprandial AUC for the DMAA score and all the three amino acids strongly associated with fasting glucose level and insulin resistance. This indicates the importance of the postprandial kinetics and metabolism of DMAAs in understanding the overall association between DMAAs and glycaemia. PMID:27274867

  12. Postprandial Levels of Branch Chained and Aromatic Amino Acids Associate with Fasting Glycaemia

    PubMed Central

    Ottosson, Filip; Ericson, Ulrika; Almgren, Peter; Nilsson, Jeanette; Magnusson, Martin; Fernandez, Céline; Melander, Olle

    2016-01-01

    High fasting plasma concentrations of isoleucine, phenylalanine, and tyrosine have been associated with increased risk of hyperglycaemia and incidence of type 2 diabetes. Whether these associations are diet or metabolism driven is unknown. We examined how the dietary protein source affects the postprandial circulating profile of these three diabetes associated amino acids (DMAAs) and tested whether the postprandial DMAA profiles are associated with fasting glycaemia. We used a crossover design with twenty-one healthy individuals and four different isocaloric test meals, containing proteins from different dietary sources (dairy, fish, meat, and plants). Analysis of the postprandial DMAAs concentrations was performed using targeted mass spectrometry. A DMAA score was defined as the sum of all the three amino acid concentrations. The postprandial area under the curve (AUC) of all the three amino acids and the DMAA score was significantly greater after intake of the meal with dairy protein compared to intake of the three other meals. The postprandial AUC for the DMAA score and all the three amino acids strongly associated with fasting glucose level and insulin resistance. This indicates the importance of the postprandial kinetics and metabolism of DMAAs in understanding the overall association between DMAAs and glycaemia. PMID:27274867

  13. The Apolipoprotein C-I Content of Very-Low-Density Lipoproteins Is Associated with Fasting Triglycerides, Postprandial Lipemia, and Carotid Atherosclerosis

    PubMed Central

    Hansen, John-Bjarne; Fernández, José A.; Notø, Ann-Trude With; Deguchi, Hiroshi; Björkegren, Johan; Mathiesen, Ellisiv B.

    2011-01-01

    Background. Experimental studies in animals suggest that apolipoprotein (apo) C-I is an important regulator of triglycerides in fasting and postprandial conditions and associated with carotid atherosclerosis. Methods. A cross-sectional study was conducted with 81 subjects, aged 56–80 years recruited from a population health survey. The participants underwent a fat tolerance test (1 g fat per Kg body weight) and carotid atherosclerosis was determined by ultrasound examination. VLDL particles, Sf 20–400, were isolated and their lipid composition and apoC-I content determined. Results. The carotid plaque area increased linearly with the number of apoC-I molecules per VLDL particles (P = 0.048) under fasting conditions. Fasting triglycerides increased across tertiles of apoC-I per VLDL particle in analyses adjusted for apoC-II and -C-III, apoE genotype and traditional cardiovascular risk factors (P = 0.011). The relation between apoC-I in VLDL and serum triglycerides was conveyed by triglyceride enrichment of VLDL particles (P for trend <0.001. The amount of apoC-I molecules per VLDL was correlated with the total (r = 0.41, P < 0.0001) and incremental (r = 0.35, P < 0.001) area under the postprandial triglyceride curve. Conclusions. Our findings support the concept that the content of apoC-I per VLDL particle is an important regulator of triglyceride metabolism in the fasting and postprandial state and associated with carotid athrosclerosis. PMID:21776394

  14. Milk lipids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Milk fat conveys a number of desirable qualities to food, and various lipid components contribute to human nutrition and health. Over 96% of milk lipids consist of triacylglycerols, which contain a variety of fatty acids. Di- and monoacylglycerols, free fatty acids, sterols, and phospho-, glyco-,...

  15. Postprandial metabolism of Pacific bluefin tuna (Thunnus orientalis).

    PubMed

    Clark, T D; Brandt, W T; Nogueira, J; Rodriguez, L E; Price, M; Farwell, C J; Block, B A

    2010-07-15

    Specific dynamic action (SDA) is defined as the energy expended during ingestion, digestion, absorption and assimilation of a meal. This study presents the first data on the SDA response of individual tunas of any species. Juvenile Pacific bluefin tunas (Thunnus orientalis; body mass 9.7-11.0 kg; N=7) were individually fed known quantities of food consisting primarily of squid and sardine (meal energy range 1680-8749 kJ, approximately 4-13% of tuna body mass). Oxygen consumption rates (M(O2)) were measured in a swim tunnel respirometer during the postprandial period at a swimming speed of 1 body length (BL) s(-1) and a water temperature of 20 degrees C. was markedly elevated above routine levels in all fish following meal consumption [routine metabolic rate (RMR)=174+/-9 mg kg(-1) h(-1)]. The peak M(O2) during the SDA process ranged from 250 to 440 mg kg(-1) h(-1) (1.5-2.3 times RMR) and was linearly related to meal energy content. The duration of the postprandial increment in M(O2) ranged from 21 h to 33 h depending upon meal energy content. Consequently, the total energy used in SDA increased linearly with meal energy and ranged from 170 kJ to 688 kJ, such that the SDA process accounted for 9.2+/-0.7% of ingested energy across all experiments. These values suggest rapid and efficient food conversion in T. orientalis in comparison with most other fishes. Implanted archival temperature tags recorded the increment in visceral temperature (T(V)) in association with SDA. M(O2) returned to routine levels at the end of the digestive period 2-3 h earlier than T(V). The qualitative patterns in M(O2) and T(V) during digestion were similar, strengthening the possibility that archival measurements of T(V) can provide new insight into the energetics and habitat utilization of free-swimming bluefin in the natural environment. Despite efficient food conversion, SDA is likely to represent a significant component of the daily energy budget of wild bluefin tunas due to a regular

  16. Post-prandial regulation of hepatic glucokinase and lipogenesis requires the activation of TORC1 signalling in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Dai, Weiwei; Panserat, Stéphane; Mennigen, Jan A; Terrier, Frédéric; Dias, Karine; Seiliez, Iban; Skiba-Cassy, Sandrine

    2013-12-01

    To assess the potential involvement of TORC1 (target of rapamycin complex 1) signalling in the regulation of post-prandial hepatic lipid and glucose metabolism-related gene expression in trout, we employed intraperitoneal administration of rapamycin to achieve an acute inhibition of the TOR pathway. Our results reveal that rapamycin inhibits the phosphorylation of TORC1 and its downstream effectors (S6K1, S6 and 4E-BP1), without affecting Akt and the Akt substrates Forkhead-box Class O1 (FoxO1) and glycogen synthase kinase 3α/β (GSK 3α/β). These results indicate that acute administration of rapamycin in trout leads to the inhibition of TORC1 activation. No effect is observed on the expression of genes involved in gluconeogenesis, glycolysis and fatty acid oxidation, but hepatic TORC1 inhibition results in decreased sterol regulatory element binding protein 1c (SREBP1c) gene expression and suppressed fatty acid synthase (FAS) and glucokinase (GK) at gene expression and activity levels, indicating that FAS and GK activity is controlled at a transcriptional level in a TORC1-dependent manner. This study demonstrates for the first time in fish that post-prandial regulation of hepatic lipogenesis and glucokinase in rainbow trout requires the activation of TORC1 signalling. PMID:24031053

  17. Genome-wide association study of triglyceride response to a high-fat meal among participants of the NHLBI genetics of lipid lowering drugs and diet network (GOLDN)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: The triglyceride (TG) response to a high-fat meal (postprandial lipemia, PPL) affects cardiovascular disease risk and is influenced by genes and environment. Genes involved in lipid metabolism have dominated genetic studies of PPL TG response. We sought to elucidate common genetic variant...

  18. Important Aspects of Post-Prandial Antidiabetic Drug, Acarbose.

    PubMed

    Singla, Rajeev Kumar; Singh, Radha; Dubey, Ashok Kumar

    2016-01-01

    Acarbose, a well known and efficacious α-amylase and α-glucosidase inhibitor, is a postprandial acting antidiabetic drug. DNS-based α-amylase inhibitory assays showed that use of acarbose at concentrations above 125 µg/ml resulted in release of reducing sugar in the reaction, an unexpected observation. Objective of the present study was to design experimental strategies to address this unusual finding. Acarbose was found to be susceptible to thermo-lysis. Further, besides being an inhibitor, it could also be hydrolyzed by porcine pancreatic α-amylase, but had weaker affinity for α - amylase compared to starch. GRIP docking was done for the mechanistic analysis of the active site in the enzyme for substrate, inhibitor and, inhibitor's metabolite (K2). Interaction between acarbose and α-amylase involved significant hydrogen binding compared to that of starch, producing a stronger enzyme-inhibitor complex. Further, docking analysis led us to predict the site on α-amylase where the inhibitor (acarbose) bound more tightly, which possibly affected the binding and hydrolysis of starch exerting its effective anti-diabetic function. PMID:27086787

  19. Influence of various carbohydrate sources on postprandial glucose, insulin and NEFA concentrations in obese cats.

    PubMed

    Mori, A; Ueda, K; Lee, P; Oda, H; Ishioka, K; Sako, T

    2016-01-01

    Carbohydrate is an important source of energy, which can significantly affect postprandial blood glucose and insulin levels in cats. In healthy animals, this is not a big concern; however, in obese and diabetic animals, this is an important detail. In the present study, the impact of four different carbohydrate sources (glucose, maltose, corn starch, and trehalose) on short-term post-prandial serum glucose, insulin, and non-esterified fatty acid (NEFA) concentrations was investigated with four obese cats. Each of the carbohydrate sources was added to a commercial wet food diet for feeding the animals. A significant difference was observed in postprandial glucose, insulin, and NEFA area under the curve (AUC) values between each carbohydrate source in obese cats. Furthermore, glucose and maltose induced the highest postprandial glucose and insulin AUC values, whereas trehalose induced the lowest postprandial glucose and insulin AUC value amongst all carbohydrate sources, respectively, in obese cats. However, trehalose has a higher risk of inducing side effects, such as diarrhea, as compared to other carbohydrate sources. As such, different carbohydrate sources appear to have a very significant impact on post-prandial glycemia and subsequent insulin requirement levels in obese cats. These results might be useful when selecting a prescription diet for obese or diabetic cats. In addition, maltose appears to be capable of inducing experimentally evoked postprandial hyperglycemia in obese cats, which may serve as a good tool for use to check the impact and effectiveness of newly developed oral hypoglycemic drugs or supplements for cats in future experiments. PMID:27487514

  20. Pathogenesis and management of postprandial hyperglycemia: role of incretin-based therapies

    PubMed Central

    Gerich, John

    2013-01-01

    Postprandial plasma glucose concentrations are an important contributor to glycemic control. There is evidence suggesting that postprandial hyperglycemia may be an independent risk factor for cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are antidiabetic agents that predominantly reduce postprandial plasma glucose levels. DPP-4 inhibitors are associated with fewer gastrointestinal side effects than GLP-1 receptor agonists and are administered orally, unlike GLP-1 analogs, which are administered as subcutaneous injections. GLP-1 receptor agonists are somewhat more effective than DPP-4 inhibitors in reducing postprandial plasma glucose and are usually associated with significant weight loss. For these reasons, GLP-1 receptor agonists are generally preferred over DPP-4 inhibitors as part of combination treatment regimens in patients with glycated hemoglobin levels above 8.0%. This article reviews the pathogenesis of postprandial hyperglycemia, the mechanisms by which GLP-1 receptor agonists and DPP-4 inhibitors reduce postprandial plasma glucose concentrations, and the results of recent clinical trials (ie, published 2008 to October 2012) that evaluated the effects of these agents on postprandial plasma glucose levels when evaluated as monotherapy compared with placebo or as add-on therapy to metformin, a sulfonylurea, or insulin. Findings from recent clinical studies suggest that both GLP-1 receptor agonists and DPP-4 inhibitors could become valuable treatment options for optimizing glycemic control in patients unable to achieve glycated hemoglobin goals on basal insulin, with the added benefits of weight loss and a low risk of hypoglycemia. PMID:24403842

  1. Manipulation of starch bioaccessibility in wheat endosperm to regulate starch digestion, postprandial glycemia, insulinemia, and gut hormone responses: a randomized controlled trial in healthy ileostomy participants12

    PubMed Central

    Edwards, Cathrina H; Grundy, Myriam ML; Grassby, Terri; Vasilopoulou, Dafni; Frost, Gary S; Butterworth, Peter J; Berry, Sarah EE; Sanderson, Jeremy; Ellis, Peter R

    2015-01-01

    Background: Cereal crops, particularly wheat, are a major dietary source of starch, and the bioaccessibility of starch has implications for postprandial glycemia. The structure and properties of plant foods have been identified as critical factors in influencing nutrient bioaccessibility; however, the physical and biochemical disassembly of cereal food during digestion has not been widely studied. Objectives: The aims of this study were to compare the effects of 2 porridge meals prepared from wheat endosperm with different degrees of starch bioaccessibility on postprandial metabolism (e.g., glycemia) and to gain insight into the structural and biochemical breakdown of the test meals during gastroileal transit. Design: A randomized crossover trial in 9 healthy ileostomy participants was designed to compare the effects of 55 g starch, provided as coarse (2-mm particles) or smooth (<0.2-mm particles) wheat porridge, on postprandial changes in blood glucose, insulin, C-peptide, lipids, and gut hormones and on the resistant starch (RS) content of ileal effluent. Undigested food in the ileal output was examined microscopically to identify cell walls and encapsulated starch. Results: Blood glucose, insulin, C-peptide, and glucose-dependent insulinotropic polypeptide concentrations were significantly lower (i.e., 33%, 43%, 40%, and 50% lower 120-min incremental AUC, respectively) after consumption of the coarse porridge than after the smooth porridge (P < 0.01). In vitro, starch digestion was slower in the coarse porridge than in the smooth porridge (33% less starch digested at 90 min, P < 0.05, paired t test). In vivo, the structural integrity of coarse particles (∼2 mm) of wheat endosperm was retained during gastroileal transit. Microscopic examination revealed a progressive loss of starch from the periphery toward the particle core. The structure of the test meal had no effect on the amount or pattern of RS output. Conclusion: The structural integrity of wheat

  2. Gain-of-Function Lipoprotein Lipase Variant rs13702 Modulates Lipid Traits through Disruption of a MicroRNA-410 Seed Site

    PubMed Central

    Richardson, Kris; Nettleton, Jennifer A.; Rotllan, Noemi; Tanaka, Toshiko; Smith, Caren E.; Lai, Chao-Qiang; Parnell, Laurence D.; Lee, Yu-Chi; Lahti, Jari; Lemaitre, Rozenn N.; Manichaikul, Ani; Keller, Margaux; Mikkilä, Vera; Ngwa, Julius; van Rooij, Frank J.A.; Ballentyne, Christie M.; Borecki, Ingrid B.; Cupples, L. Adrienne; Garcia, Melissa; Hofman, Albert; Ferrucci, Luigi; Mozaffarian, Dariush; Perälä, Mia-Maria; Raitakari, Olli; Tracy, Russell P.; Arnett, Donna K.; Bandinelli, Stefania; Boerwinkle, Eric; Eriksson, Johan G.; Franco, Oscar H.; Kähönen, Mika; Nalls, Michael; Siscovick, David S.; Houston, Denise K.; Psaty, Bruce M.; Viikari, Jorma; Witteman, Jacqueline C.M.; Goodarzi, Mark O.; Lehtimäki, Terho; Liu, Yongmei; Zillikens, M. Carola; Chen, Yii-Der I.; Uitterlinden, André G.; Rotter, Jerome I.; Fernandez-Hernando, Carlos; Ordovas, Jose M.

    2013-01-01

    Genome-wide association studies (GWAS) have identified hundreds of genetic variants that are associated with lipid phenotypes. However, data supporting a functional role for these variants in the context of lipid metabolism are scarce. We investigated the association of the lipoprotein lipase (LPL) variant rs13702 with plasma lipids and explored its potential for functionality. The rs13702 minor allele had been predicted to disrupt a microRNA (miR) recognition element (MRE) seed site (MRESS) for the human microRNA-410 (miR-410). Furthermore, rs13702 is in linkage disequilibrium (LD) with several SNPs identified by GWAS. We performed a meta-analysis across ten cohorts of participants that showed a statistically significant association of rs13702 with triacylglycerols (TAG) (p = 3.18 × 10−42) and high-density lipoprotein cholesterol (HDL-C) (p = 1.35 × 10−32) with each copy of the minor allele associated with 0.060 mmol/l lower TAG and 0.041 mmol/l higher HDL-C. Our data showed that an LPL 3′ UTR luciferase reporter carrying the rs13702 major T allele was reduced by 40% in response to a miR-410 mimic. We also evaluated the interaction between intake of dietary fatty acids and rs13702. Meta-analysis demonstrated a significant interaction between rs13702 and dietary polyunsaturated fatty acid (PUFA) with respect to TAG concentrations (p = 0.00153), with the magnitude of the inverse association between dietary PUFA intake and TAG concentration showing −0.007 mmol/l greater reduction. Our results suggest that rs13702 induces the allele-specific regulation of LPL by miR-410 in humans. This work provides biological and potential clinical relevance for previously reported GWAS variants associated with plasma lipid phenotypes. PMID:23246289

  3. Oncoprotein HBXIP Modulates Abnormal Lipid Metabolism and Growth of Breast Cancer Cells by Activating the LXRs/SREBP-1c/FAS Signaling Cascade.

    PubMed

    Zhao, Yu; Li, Hang; Zhang, Yingyi; Li, Leilei; Fang, Runping; Li, Yinghui; Liu, Qian; Zhang, Weiying; Qiu, Liyan; Liu, Fabao; Zhang, Xiaodong; Ye, Lihong

    2016-08-15

    Abnormal lipid metabolism is a hallmark of tumorigenesis. Accumulating evidence demonstrates that fatty acid synthase (FAS, FASN) is a metabolic oncogene that supports the growth and survival of tumor cells and is highly expressed in many cancers. Here, we report that the oncoprotein, hepatitis B X-interacting protein (HBXIP, LAMTOR5) contributes to abnormal lipid metabolism. We show that high expression of HBXIP in 236 breast cancer patients was significantly associated with decreased overall survival and progression-free survival. Interestingly, the expression of HBXIP was positively related to that of FAS in clinical breast cancer tissues, and HBXIP overexpression in breast cancer cells resulted in FAS upregulation. Mechanistically, HBXIP upregulated SREBP-1c (SREBF1), which activates the transcription of FAS, by directly interacting with and coactivating nuclear receptor (NR) liver X receptors (LXR). Physiologically, LXRs are activated via a coactivator containing NR motif in a ligand-dependent manner. However, in breast cancer cells, HBXIP containing the corepressor/nuclear receptor motif with special flanking sequence could coactivate LXRs independent of ligand. Moreover, overexpressed SREBP-1c was able to activate the transcription of HBXIP, forming a positive-feedback loop. Functionally, HBXIP enhanced lipogenesis, resulting in the growth of breast cancer cells in vitro and in vivo Thus, we conclude that the oncoprotein HBXIP contributes to the abnormal lipid metabolism in breast cancer through LXRs/SREBP-1c/FAS signaling, providing new insights into the mechanisms by which cancer cells reprogram lipid metabolism in their favor. Cancer Res; 76(16); 4696-707. ©2016 AACR. PMID:26980761

  4. Nanomechanical properties of lipid bilayer: Asymmetric modulation of lateral pressure and surface tension due to protein insertion in one leaflet of a bilayer

    NASA Astrophysics Data System (ADS)

    Maftouni, Negin; Amininasab, Mehriar; Ejtehadi, Mohammad Reza; Kowsari, Farshad; Dastvan, Reza

    2013-02-01

    The lipid membranes of living cells form an integral part of biological systems, and the mechanical properties of these membranes play an important role in biophysical investigations. One interesting problem to be evaluated is the effect of protein insertion in one leaflet of a bilayer on the physical properties of lipid membrane. In the present study, an all atom (fine-grained) molecular dynamics simulation is used to investigate the binding of cytotoxin A3 (CTX A3), a cytotoxin from snake venom, to a phosphatidylcholine lipid bilayer. Then, a 5-microsecond coarse-grained molecular dynamics simulation is carried out to compute the pressure tensor, lateral pressure, surface tension, and first moment of lateral pressure in each monolayer. Our simulations reveal that the insertion of CTX A3 into one monolayer results in an asymmetrical change in the lateral pressure and corresponding spatial distribution of surface tension of the individual bilayer leaflets. The relative variation in the surface tension of the two monolayers as a result of a change in the contribution of the various intermolecular forces may potentially be expressed morphologically.

  5. Nanomechanical properties of lipid bilayer: asymmetric modulation of lateral pressure and surface tension due to protein insertion in one leaflet of a bilayer.

    PubMed

    Maftouni, Negin; Amininasab, Mehriar; Ejtehadi, Mohammad Reza; Kowsari, Farshad; Dastvan, Reza

    2013-02-14

    The lipid membranes of living cells form an integral part of biological systems, and the mechanical properties of these membranes play an important role in biophysical investigations. One interesting problem to be evaluated is the effect of protein insertion in one leaflet of a bilayer on the physical properties of lipid membrane. In the present study, an all atom (fine-grained) molecular dynamics simulation is used to investigate the binding of cytotoxin A3 (CTX A3), a cytotoxin from snake venom, to a phosphatidylcholine lipid bilayer. Then, a 5-microsecond [corrected] coarse-grained molecular dynamics simulation is carried out to compute the pressure tensor, lateral pressure, surface tension, and first moment of lateral pressure in each monolayer. Our simulations reveal that the insertion of CTX A3 into one monolayer results in an asymmetrical change in the lateral pressure and corresponding spatial distribution of surface tension of the individual bilayer leaflets. The relative variation in the surface tension of the two monolayers as a result of a change in the contribution of the various intermolecular forces may potentially be expressed morphologically. PMID:23425492

  6. Free Fatty Acids Increase Intracellular Lipid Accumulation and Oxidative Stress by Modulating PPARα and SREBP-1c in L-02 Cells.

    PubMed

    Qin, Shumin; Yin, Jinjin; Huang, Keer

    2016-07-01

    Excessive fat accumulation and increased oxidative stress contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the development of steatosis are not entirely understood. The present study was undertaken to establish an experimental model of hepatocellular steatosis with a fat overaccumulation profile in which the effects of oxidative stress could be studied in L-02 cells. We investigated the effects of free fatty acids (FFA) (palmitate:oleate, 1:2) on lipid accumulation and oxidative stress and their possible mechanisms in L-02 cells. High concentrations of fatty acids significantly induced excessive lipid accumulation and oxidative stress in L-02 cells, which could only be reversed with 50 μΜ WY14643 (the PPARα agonist). Immunoblotting and qPCR analyses revealed that FFA downregulated the expression of proliferator-activated receptor alpha (PPARα), which contributed to the increased activation of sterol regulatory element binding protein-1c (SREBP-1c). These results suggest that FFA induce lipid accumulation and oxidative stress in L-02 cells by upregulating SREBP-1c expression through the suppression of PPARα. PMID:27270405

  7. Modulation of Human Mitochondrial Voltage-dependent Anion Channel 2 (hVDAC-2) Structural Stability by Cysteine-assisted Barrel-lipid Interactions*

    PubMed Central

    Maurya, Svetlana Rajkumar; Mahalakshmi, Radhakrishnan

    2013-01-01

    Human mitochondrial voltage-dependent anion channel 2 (hVDAC-2), the most predominant isoform seen in brain mitochondria, is not only crucial for cell survival but is also implicated in Alzheimer disease. The abundance of cysteines in this isoform is particularly fascinating, as hVDAC-1 cysteines have no associated functional role. We report a detailed biophysical examination of a Cys-less mutant of hVDAC-2, and its behavioral comparison with the wild type protein. Our findings suggest that cysteine mutation results in the formation of a better barrel at the expense of weakened protein-lipid interactions. The wild type protein displays stronger lipid association, despite being less structured. A reversal in behavior of both proteins is observed in the case of chemical denaturation, with the Cys-less mutant exhibiting lowered unfolding free energies. In bicellar systems comprising 14-C phosphocholines, we observe that protein-lipid interactions are weakened in both constructs, resulting in barrel structure destabilization. Our biochemical and biophysical studies together reveal key structural roles for the cysteine residues. We find that minor conformational variations in local residues are sufficient to define the membrane protein dynamics in hVDAC-2. Such subtle sequence variations contribute to differential stability of VDACs and may have implications in their in vivo regulation and recycling. PMID:23873934

  8. Molecular confinement of human amylin in lipidic nanoparticles.

    PubMed

    Braga, Raquel Rennó; Almeida, Luciana; Guerreiro, Luiz Henrique; Tinoco, Priscilla; Miranda, Kildare R; Braga, Carolina A; Gadelha, Ana Paula; Garcia, Sheila; Lima, Luis Mauricio T R

    2016-09-01

    Amylin is a pancreatic hormone involved in the regulation of glucose metabolism and homeostasis. Restoration of the post-prandial and basal levels of human amylin in diabetic individuals is a key in controlling glycemia, controlling glucagon, reducing the insulin dose and increasing satiety, among other physiologic functions. Human amylin has a high propensity to aggregate. We have addressed this issue by designing a liposomal human amylin formulation. Nanoparticles of multilamellar liposomes comprising human amylin were obtained with 53% encapsulation efficiency. The in vitro kinetic release assay shows a biphasic profile. The stabilization of the lipidic nanoparticle against freeze-drying was achieved by using mannitol as a cryoprotectant, as evidenced by morphological characterization. The effectiveness of the human amylin entrapped in lipidic nanoparticles was tested by the measurement of its pharmacological effect in vivo after subcutaneous administration in mice. Collectively these results demonstrate the compatibility of human amylin with the lipidic interface as an effective pharmaceutical delivery system. PMID:26340033

  9. Cereal Processing Influences Postprandial Glucose Metabolism as Well as the GI Effect

    PubMed Central

    Vinoy, Sophie; Normand, Sylvie; Meynier, Alexandra; Sothier, Monique; Louche-Pelissier, Corinne; Peyrat, Jocelyne; Maitrepierre, Christine; Nazare, Julie-Anne; Brand-Miller, Jeannie; Laville, Martine

    2013-01-01

    Objective: Technological processes may influence the release of glucose in starch. The aim of this study was to compare the metabolic response and the kinetics of appearance of exogenous glucose from 2 cereal products consumed at breakfast. Methods: Twenty-five healthy men were submitted to a randomized, open, crossover study that was divided into 2 parts: 12 of the 25 subjects were included in the “isotope part,” and the 13 other subjects were included in the “glycemic part.” On test days, subjects received biscuits (low glycemic index [GI], high slowly available glucose [SAG]) or extruded cereals (medium GI, low SAG) as part of a breakfast similar in terms of caloric and macronutrient content. The postprandial phase lasted 270 minutes. Results: The rate of appearance (RaE) of exogenous glucose was significantly lower after consumption of biscuits in the first part of the morning (90–150 minutes) than after consumption of extruded cereals (p ≤ 0.05). Conversely, at 210 minutes, it was significantly higher with biscuits (p ≤ 0.01). For the first 2 hours, plasma glucose and insulin were significantly lower after biscuits during the glycemic part. C-peptide plasma concentrations were significantly lower at 90, 120, and 150 minutes after ingestion of the biscuits (p ≤ 0.05). Conclusion: The consumption of biscuits with a high content of slowly digestible starch reduces the appearance rate of glucose in the first part of the morning and prolongs this release in the late phase of the morning (210 minutes). Our results also emphasize that modulation of glucose availability at breakfast is an important factor for metabolic control throughout the morning in healthy subjects due to the lowering of blood glucose and insulin excursions. PMID:24015715

  10. Impact of Diabetes-Specific Nutritional Formulas versus Oatmeal on Postprandial Glucose, Insulin, GLP-1 and Postprandial Lipidemia.

    PubMed

    Mottalib, Adham; Mohd-Yusof, Barakatun-Nisak; Shehabeldin, Mohamed; Pober, David M; Mitri, Joanna; Hamdy, Osama

    2016-01-01

    Diabetes-specific nutritional formulas (DSNFs) are frequently used as part of medical nutrition therapy for patients with diabetes. This study aims to evaluate postprandial (PP) effects of 2 DSNFs; Glucerna (GL) and Ultra Glucose Control (UGC) versus oatmeal (OM) on glucose, insulin, glucagon-like peptide-1 (GLP-1), free fatty acids (FFA) and triglycerides (TG). After an overnight fast, 22 overweight/obese patients with type 2 diabetes were given 200 kcal of each of the three meals on three separate days in random order. Blood samples were collected at baseline and at 30, 60, 90, 120, 180 and 240 min. Glucose area under the curve (AUC0-240) after GL and UGC was lower than OM (p < 0.001 for both). Insulin positive AUC0-120 after UGC was higher than after OM (p = 0.02). GLP-1 AUC0-120 and AUC0-240 after GL and UGC was higher than after OM (p < 0.001 for both). FFA and TG levels were not different between meals. Intake of DSNFs improves PP glucose for 4 h in comparison to oatmeal of similar caloric level. This is achieved by either direct stimulation of insulin secretion or indirectly by stimulating GLP-1 secretion. The difference between their effects is probably related to their unique blends of amino acids, carbohydrates and fat. PMID:27455318

  11. Impact of Diabetes-Specific Nutritional Formulas versus Oatmeal on Postprandial Glucose, Insulin, GLP-1 and Postprandial Lipidemia

    PubMed Central

    Mottalib, Adham; Mohd-Yusof, Barakatun-Nisak; Shehabeldin, Mohamed; Pober, David M.; Mitri, Joanna; Hamdy, Osama

    2016-01-01

    Diabetes-specific nutritional formulas (DSNFs) are frequently used as part of medical nutrition therapy for patients with diabetes. This study aims to evaluate postprandial (PP) effects of 2 DSNFs; Glucerna (GL) and Ultra Glucose Control (UGC) versus oatmeal (OM) on glucose, insulin, glucagon-like peptide-1 (GLP-1), free fatty acids (FFA) and triglycerides (TG). After an overnight fast, 22 overweight/obese patients with type 2 diabetes were given 200 kcal of each of the three meals on three separate days in random order. Blood samples were collected at baseline and at 30, 60, 90, 120, 180 and 240 min. Glucose area under the curve (AUC0–240) after GL and UGC was lower than OM (p < 0.001 for both). Insulin positive AUC0–120 after UGC was higher than after OM (p = 0.02). GLP-1 AUC0–120 and AUC0–240 after GL and UGC was higher than after OM (p < 0.001 for both). FFA and TG levels were not different between meals. Intake of DSNFs improves PP glucose for 4 h in comparison to oatmeal of similar caloric level. This is achieved by either direct stimulation of insulin secretion or indirectly by stimulating GLP-1 secretion. The difference between their effects is probably related to their unique blends of amino acids, carbohydrates and fat. PMID:27455318

  12. Berries reduce postprandial insulin responses to wheat and rye breads in healthy women.

    PubMed

    Törrönen, Riitta; Kolehmainen, Marjukka; Sarkkinen, Essi; Poutanen, Kaisa; Mykkänen, Hannu; Niskanen, Leo

    2013-04-01

    Starch in white wheat bread (WB) induces high postprandial glucose and insulin responses. For rye bread (RB), the glucose response is similar, whereas the insulin response is lower. In vitro studies suggest that polyphenol-rich berries may reduce digestion and absorption of starch and thereby suppress postprandial glycemia, but the evidence in humans is limited. We investigated the effects of berries consumed with WB or RB on postprandial glucose and insulin responses. Healthy females (n = 13-20) participated in 3 randomized, controlled, crossover, 2-h meal studies. They consumed WB or RB, both equal to 50 g available starch, with 150 g whole-berry purée or the same amount of bread without berries as reference. In study 1, WB was served with strawberries, bilberries, or lingonberries and in study 2 with raspberries, cloudberries, or chokeberries. In study 3, WB or RB was served with a mixture of berries consisting of equal amounts of strawberries, bilberries, cranberries, and blackcurrants. Strawberries, bilberries, lingonberries, and chokeberries consumed with WB and the berry mixture consumed with WB or RB significantly reduced the postprandial insulin response. Only strawberries (36%) and the berry mixture (with WB, 38%; with RB, 19%) significantly improved the glycemic profile of the breads. These results suggest than when WB is consumed with berries, less insulin is needed for maintenance of normal or slightly improved postprandial glucose metabolism. The lower insulin response to RB compared with WB can also be further reduced by berries. PMID:23365108

  13. Coffee bean polyphenols ameliorate postprandial endothelial dysfunction in healthy male adults.

    PubMed

    Ochiai, Ryuji; Sugiura, Yoko; Otsuka, Kazuhiro; Katsuragi, Yoshihisa; Hashiguchi, Teruto

    2015-05-01

    To reveal the effect of coffee bean polyphenols (CBPs) on blood vessels, this study aimed to investigate the effect of CBPs on acute postprandial endothelial dysfunction. Thirteen healthy non-diabetic men (mean age, 44.9 ± 1.4 years) consumed a test beverage (active: containing CBPs, placebo: no CBPs) before a 554-kcal test meal containing 14 g of protein, 30 g of fat and 58 g of carbohydrates. Then, a crossover analysis was performed to investigate the time-dependent changes in flow-mediated dilation (FMD) in the brachial artery. In the active group, the postprandial impairment of FMD was significantly improved, the two-hour postprandial nitric oxide metabolite levels were significantly increased and the six-hour postprandial urinary 8-epi-prostaglandin F2α levels were significantly reduced compared to the placebo group. The test meal increased the levels of blood glucose, insulin and triglycerides in both groups with no significant intergroup differences. These findings indicate that CBPs intake ameliorates postprandial endothelial dysfunction in healthy men. PMID:25666414

  14. Peripheral arterial disease, type 2 diabetes and postprandial lipidaemia: Is there a link?

    PubMed

    Valdivielso, Pedro; Ramírez-Bollero, José; Pérez-López, Carmen

    2014-10-15

    Peripheral arterial disease, manifested as intermittent claudication or critical ischaemia, or identified by an ankle/brachial index < 0.9, is present in at least one in every four patients with type 2 diabetes mellitus. Several reasons exist for peripheral arterial disease in diabetes. In addition to hyperglycaemia, smoking and hypertension, the dyslipidaemia that accompanies type 2 diabetes and is characterised by increased triglyceride levels and reduced high-density lipoprotein cholesterol concentrations also seems to contribute to this association. Recent years have witnessed an increased interest in postprandial lipidaemia, as a result of various prospective studies showing that non-fasting triglycerides predict the onset of arteriosclerotic cardiovascular disease better than fasting measurements do. Additionally, the use of certain specific postprandial particle markers, such as apolipoprotein B-48, makes it easier and more simple to approach the postprandial phenomenon. Despite this, only a few studies have evaluated the role of postprandial triglycerides in the development of peripheral arterial disease and type 2 diabetes. The purpose of this review is to examine the epidemiology and risk factors of peripheral arterial disease in type 2 diabetes, focusing on the role of postprandial triglycerides and particles. PMID:25317236

  15. Effect of high-intensity intermittent exercise on postprandial plasma triacylglycerol in sedentary young women.

    PubMed

    Tan, Martin; Chan Moy Fat, Rachel; Boutcher, Yati N; Boutcher, Stephen H

    2014-02-01

    High-intensity intermittent exercise (HIIE) such as the 30-s Wingate test attenuates postprandial triacylglycerol (TG), however, the ability of shorter versions of HIIE to reduce postprandial TG is undetermined. Thus, the effect of 8-s sprinting bouts of HIIE on blood TG levels of 12 females after consumption of a high-fat meal (HFM) was examined. Twelve young, sedentary women (BMI 25.1 ± 2.3 kg/m²; age 21.3 ± 2.1 years) completed a maximal oxygen uptake test and then on different days underwent either an exercise or a no-exercise postprandial TG condition. Both conditions involved consuming a HFM after a 12-hr fast. The HFM, in milkshake form provided 4170 kJ (993 Kcal) of energy and 98 g fat. Order was counter-balanced. In the exercise condition participants completed 20-min of HIIE cycling consisting of repeated bouts of 8 s sprint cycling (100-115 rpm) and 12 s of active rest (easy pedaling) 14 hr before consuming the HFM. Blood samples were collected hourly after the HFM for 4 hr. Total postprandial TG was 13% lower, p = .004, in the exercise (5.84 ± 1.08 mmol L⁻¹ 4 h⁻¹) compared with the no-exercise condition (6.71 ± 1.63 mmol L⁻¹ 4 h⁻¹). In conclusion, HIIE significantly attenuated postprandial TG in sedentary young women. PMID:24092770

  16. Peripheral arterial disease, type 2 diabetes and postprandial lipidaemia: Is there a link?

    PubMed Central

    Valdivielso, Pedro; Ramírez-Bollero, José; Pérez-López, Carmen

    2014-01-01

    Peripheral arterial disease, manifested as intermittent claudication or critical ischaemia, or identified by an ankle/brachial index < 0.9, is present in at least one in every four patients with type 2 diabetes mellitus. Several reasons exist for peripheral arterial disease in diabetes. In addition to hyperglycaemia, smoking and hypertension, the dyslipidaemia that accompanies type 2 diabetes and is characterised by increased triglyceride levels and reduced high-density lipoprotein cholesterol concentrations also seems to contribute to this association. Recent years have witnessed an increased interest in postprandial lipidaemia, as a result of various prospective studies showing that non-fasting triglycerides predict the onset of arteriosclerotic cardiovascular disease better than fasting measurements do. Additionally, the use of certain specific postprandial particle markers, such as apolipoprotein B-48, makes it easier and more simple to approach the postprandial phenomenon. Despite this, only a few studies have evaluated the role of postprandial triglycerides in the development of peripheral arterial disease and type 2 diabetes. The purpose of this review is to examine the epidemiology and risk factors of peripheral arterial disease in type 2 diabetes, focusing on the role of postprandial triglycerides and particles. PMID:25317236

  17. Postprandial Administration of Intranasal Insulin Intensifies Satiety and Reduces Intake of Palatable Snacks in Women

    PubMed Central

    Hallschmid, Manfred; Higgs, Suzanne; Thienel, Matthias; Ott, Volker; Lehnert, Hendrik

    2012-01-01

    The role of brain insulin signaling in the control of food intake in humans has not been thoroughly defined. We hypothesized that the hormone contributes to the postprandial regulation of appetite for palatable food, and assessed the effects on appetite and snack intake of postprandial versus fasted intranasal insulin administration to the brain in healthy women. Two groups of subjects were intranasally administered 160 IU insulin or vehicle after lunch. Two hours later, consumption of cookies of varying palatability was measured under the pretext of a taste test. In a control study, the effects of intranasal insulin administered to fasted female subjects were assessed. Compared with placebo, insulin administration in the postprandial but not in the fasted state decreased appetite as well as intake and rated palatability of chocolate chip cookies (the most palatable snack offered). In both experiments, intranasal insulin induced a slight decrease in plasma glucose but did not affect serum insulin concentrations. Data indicate that brain insulin acts as a relevant satiety signal during the postprandial period, in particular reducing the intake of highly palatable food, and impacts peripheral glucose homeostasis. Postprandial intranasal insulin administration might be useful in curtailing overconsumption of snacks with accentuated rewarding value. PMID:22344561

  18. Postprandial administration of intranasal insulin intensifies satiety and reduces intake of palatable snacks in women.

    PubMed

    Hallschmid, Manfred; Higgs, Suzanne; Thienel, Matthias; Ott, Volker; Lehnert, Hendrik

    2012-04-01

    The role of brain insulin signaling in the control of food intake in humans has not been thoroughly defined. We hypothesized that the hormone contributes to the postprandial regulation of appetite for palatable food, and assessed the effects on appetite and snack intake of postprandial versus fasted intranasal insulin administration to the brain in healthy women. Two groups of subjects were intranasally administered 160 IU insulin or vehicle after lunch. Two hours later, consumption of cookies of varying palatability was measured under the pretext of a taste test. In a control study, the effects of intranasal insulin administered to fasted female subjects were assessed. Compared with placebo, insulin administration in the postprandial but not in the fasted state decreased appetite as well as intake and rated palatability of chocolate chip cookies (the most palatable snack offered). In both experiments, intranasal insulin induced a slight decrease in plasma glucose but did not affect serum insulin concentrations. Data indicate that brain insulin acts as a relevant satiety signal during the postprandial period, in particular reducing the intake of highly palatable food, and impacts peripheral glucose homeostasis. Postprandial intranasal insulin administration might be useful in curtailing overconsumption of snacks with accentuated rewarding value. PMID:22344561

  19. Post-prandial changes in protein synthesis in red drum (Sciaenops ocellatus) larvae.

    PubMed

    McCarthy, Ian D; Fuiman, Lee A

    2011-06-01

    Protein synthesis is one of the major energy-consuming processes in all living organisms. Post-prandial changes in protein synthesis have been studied in a range of animal taxa but have been little studied in fish larvae. Using the flooding-dose method, we measured post-prandial changes in whole-body rates of protein synthesis in regularly fed red drum Sciaenops ocellatus (Linnaeus) larvae for 24-28 h following their daily meal. Fractional rates of protein synthesis increased from a baseline (pre-feeding) rate of 16% day(-1) to a post-prandial peak of 48% day(-1) ca. 8 h after feeding before declining to 12% day(-1) after 24-28 h. The overall mean daily rate of protein synthesis was calculated as 27% day(-1). Although suggested as energetically impossible in larval poikilotherms, our results show that rates in excess of 30% day(-1) can be attained by larval fishes for a few hours but are not sustained. The average daily energetic cost of protein synthesis was estimated as 34% of daily total oxygen consumption, ranging from 19% immediately before feeding to 61% during the post-prandial peak in protein synthesis. This suggests that during the post-prandial peak, protein synthesis will require a large proportion of the hourly energy production, which, given the limited metabolic scope in fish larvae, may limit the energy that could otherwise be allocated to other energy-costly functions, such as foraging and escape responses. PMID:21562168

  20. Evaluation of a high nutritional quality snack based on oat flakes and inulin: effects on postprandial glucose, insulin and ghrelin responses of healthy subjects.

    PubMed

    Stamataki, Nikoleta S; Nikolidaki, Eirini K; Yanni, Amalia E; Stoupaki, Maria; Konstantopoulos, Panagiotis; Tsigkas, Alexandros-Pantelis; Perrea, Despoina; Tentolouris, Nikolaos; Karathanos, Vaios T

    2016-07-13

    The consumption of high nutritional value snacks may favorably affect the diet quality. Biscuits manufactured with oat flakes and maltitol were assessed for glycemic, insulinemic and ghrelin responses. Enrichment with inulin, a fructooligosachararide (FOS) which acts as soluble fiber, was performed in an attempt to further increase the dietary fiber content and examine potential additional postprandial benefits. Eleven healthy subjects participated in the study and consumed either 80 g oat biscuits (OB) or 81 g oat biscuits with 4% inulin (OBIN) or a solution containing 50 g of glucose (reference food), each yielding 50 g of available carbohydrates. Venous blood samples were collected before consumption and at 15, 30, 45, 60, 90, 120 and 180 min postprandially. The developed products were also evaluated for physicochemical properties, including porosity, density, texture, color, sensory attributes and microstructure (by scanning electron microscopy). Both biscuits demonstrated a low glycemic index (GI), which was found to be 32.82 ± 8.07 for OB and 45.68 ± 9.64 for OBIN. Compared to OB, OBIN demonstrated higher insulin response at 45 and 60 min and higher ghrelin suppression at 60 and 120 min postprandially (P < 0.05). Furthermore, OBIN demonstrated increased hardness and color values, lower porosity, and higher rate of starch granule gelatinization, without significantly altering the sensory attributes. Biscuits formulated with oat flakes and maltitol with or without 4% inulin can be classified as low GI foods. Inulin addition significantly lowered the ghrelin response to OBIN, suggesting an advantage of OBIN in the modulation of satiety; however, no further benefits regarding glucose and insulin responses were observed. PMID:27381507

  1. (p)ppGpp modulates cell size and the initiation of DNA replication in Caulobacter crescentus in response to a block in lipid biosynthesis.

    PubMed

    Stott, Kristina V; Wood, Shannon M; Blair, Jimmy A; Nguyen, Bao T; Herrera, Anabel; Mora, Yannet G Perez; Cuajungco, Math P; Murray, Sean R

    2015-03-01

    Stress conditions, such as a block in fatty acid synthesis, signal bacterial cells to exit the cell cycle. Caulobacter crescentus FabH is a cell-cycle-regulated β-ketoacyl-acyl carrier protein synthase that initiates lipid biosynthesis and is essential for growth in rich media. To explore how C. crescentus responds to a block in lipid biosynthesis, we created a FabH-depletion strain. We found that FabH depletion blocks lipid biosynthesis in rich media and causes a cell cycle arrest that requires the alarmone (p)ppGpp for adaptation. Notably, basal levels of (p)ppGpp coordinate both a reduction in cell volume and a block in the over-initiation of DNA replication in response to FabH depletion. The gene ctrA encodes a master transcription factor that directly regulates 95 cell-cycle-controlled genes while also functioning to inhibit the initiation of DNA replication. Here, we demonstrate that ctrA transcription is (p)ppGpp-dependent during fatty acid starvation. CtrA fails to accumulate when FabH is depleted in the absence of (p)ppGpp due to a substantial reduction in ctrA transcription. The (p)ppGpp-dependent maintenance of ctrA transcription during fatty acid starvation initiated from only one of the two ctrA promoters. In the absence of (p)ppGpp, the majority of FabH-depleted cells enter a viable but non-culturable state, with multiple chromosomes, and are unable to recover from the miscoordination of cell cycle events. Thus, basal levels of (p)ppGpp facilitate C. crescentus' re-entry into the cell cycle after termination of fatty acid starvation. PMID:25573769

  2. Modulation of cellulase activity by charged lipid bilayers with different acyl chain properties for efficient hydrolysis of ionic liquid-pretreated cellulose.

    PubMed

    Mihono, Kai; Ohtsu, Takeshi; Ohtani, Mai; Yoshimoto, Makoto; Kamimura, Akio

    2016-10-01

    The stability of cellulase activity in the presence of ionic liquids (ILs) is critical for the enzymatic hydrolysis of insoluble cellulose pretreated with ILs. In this work, cellulase was incorporated in the liposomes composed of negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) and zwitterionic phosphatidylcholines (PCs) with different length and degree of unsaturation of the acyl chains. The liposomal cellulase-catalyzed reaction was performed at 45°C in the acetate buffer solution (pH 4.8) with 2.0g/L CC31 as cellulosic substrate. The crystallinity of CC31 was reduced by treating with 1-butyl-3-methylimidazolium chloride ([Bmim]Cl) at 120°C for 30min. The liposomal cellulase continuously catalyzed hydrolysis of the pretreated CC31 for 48h producing glucose in the presence of 15wt% [Bmim]Cl. The charged lipid membranes were interactive with [Bmim](+), as elucidated by the [Bmim]Cl-induced alterations in fluorescence polarization of the membrane-embedded 1,6-diphenyl-1,3,5-hexatriene (DPH) molecules. The charged membranes offered the microenvironment where inhibitory effects of [Bmim]Cl on the cellulase activity was relieved. The maximum glucose productivity GP of 10.8 mmol-glucose/(hmol-lipid) was obtained at the reaction time of 48h with the cellulase incorporated in the liposomes ([lipid]=5.0mM) composed of 50mol% POPG and 1,2-dilauroyl-sn-glycero-3-phosohocholine (DLPC) with relatively short and saturated acyl chains. PMID:27318965

  3. Effect of low glycemic index food and postprandial exercise on blood glucose level, oxidative stress and antioxidant capacity

    PubMed Central

    KASUYA, NORIAKI; OHTA, SHOICHIRO; TAKANAMI, YOSHIKAZU; KAWAI, YUKARI; INOUE, YUTAKA; MURATA, ISAMU; KANAMOTO, IKUO

    2015-01-01

    Low glycemic index (GI) food and postprandial exercise are non-drug therapies for improving postprandial hyperglycemia. The present randomized, crossover study investigated the effect of low GI food combined with postprandial exercise on postprandial blood glucose level, oxidative stress and antioxidant capacity. A total of 13 healthy subjects were each used in four experiments: i) rice only (control), ii) salad prior to rice (LGI), iii) exercise following rice (EX) and iv) salad prior to rice and exercise following rice (MIX). The blood glucose level, oxidative stress and antioxidant capacity were then measured. At 60 min after the meal, the blood glucose level was observed to be increased in the MIX group compared with that in the LGI group. Furthermore, at 180 min, the antioxidant capacity was found to be reduced in the MIX group compared with those of the LGI and EX groups. These findings suggest that low GI food combined with postprandial exercise does not improve postprandial hyperglycemia. It may be necessary to establish optimal timing and intensity when combining low GI food with postprandial exercise to improve postprandial hyperglycemia. PMID:25780409

  4. Differential modulation of the lipid metabolism as a model for cellular resistance to fumonisin B1-induced cytotoxic effects in vitro.

    PubMed

    Riedel, S; Abel, S; Burger, H-M; van der Westhuizen, L; Swanevelder, S; Gelderblom, W C A

    2016-06-01

    Differential sensitivity of primary hepatocytes and Chang cells to the cancer promoter fumonisin B1 (FB1)-induced cytotoxic effects were investigated in relation to changes in membrane lipid distribution. In contrast to primary hepatocytes, Chang cells were resistant to FB1-induced cytotoxic effects. This was associated with a high cholesterol (Chol) and sphingomyelin (SM) and low phosphatidylcholine (PC) content, resulting in a significant (P<0.05) decrease in phosphatidylethanolamine (PE)/PC ratio, increased Chol/total phosphoglyceride (TPG) ratios and low total polyunsaturated fatty acids (PUFA) content in PC and PE, suggesting a more rigid membrane structure. High levels of C18:1 and reduced polyunsaturated fatty acid (PUFA) levels are likely to provide selective resistance to FB1-induced oxidative stress. FB1-associated lipid changes included decreases in SM and Chol, increases in sphinganine (Sa) and PE with the increases in key saturated, monounsaturated, and PUFAs in PE as key role players in the differential responses to FB1-induced cell growth responses in cells. PMID:27269712

  5. Bidens pilosa and its active compound inhibit adipogenesis and lipid accumulation via down-modulation of the C/EBP and PPARγ pathways

    PubMed Central

    Liang, Yu-Chuan; Yang, Meng-Ting; Lin, Chuan-Ju; Chang, Cicero Lee-Tian; Yang, Wen-Chin

    2016-01-01

    Obesity and its complications are a major global health problem. In this study, we investigated the anti-obesity effect and mechanism of an edible plant, Bidens pilosa, and its active constituent. We first assessed the long-term effect of B. pilosa on body composition, body weight, blood parameters in ICR mice. We observed that it significantly decreased fat content and increased protein content in ICR mice. Next, we verified the anti-obesity effect of B. pilosa in ob/ob mice. It effectively and dose-dependently reduced fat content, adipocyte size and/or body weight in mice. Moreover, mechanistic studies showed that B. pilosa inhibited the expression of peroxisome proliferator activated receptor γ (PPARγ), CCAAT/enhancer binding proteins (C/EBPs) and Egr2 in adipose tissue. Finally, we examined the effect of 2-β-D-glucopyranosyloxy-1-hydroxytrideca-5,7,9,11-tetrayne (GHT) on adipogenesis in adipocytes. We found that B. pilosa significantly decreased the adipogenesis and lipid accumulation. This decrease was associated with the down-regulation of expression of Egr2, C/EBPs, PPARγ, adipocyte Protein 2 (aP2) and adiponectin. In summary, this work demonstrated that B. pilosa and GHT suppressed adipogenesis and lipid content in adipocytes and/or animals via the down-regulation of the Egr2, C/EBPs and PPARγ pathways, suggesting a novel application of B. pilosa and GHT against obesity. PMID:27063434

  6. D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol alters cellular cholesterol homeostasis by modulating the endosome lipid domains.

    PubMed

    Makino, Asami; Ishii, Kumiko; Murate, Motohide; Hayakawa, Tomohiro; Suzuki, Yusuke; Suzuki, Minoru; Ito, Kazuki; Fujisawa, Tetsuro; Matsuo, Hirotami; Ishitsuka, Reiko; Kobayashi, Toshihide

    2006-04-11

    D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) is a frequently used inhibitor of glycosphingolipid biosynthesis. However, some interesting characteristics of D-PDMP cannot be explained by the inhibition of glycolipid synthesis alone. In the present study, we showed that d-PDMP inhibits the activation of lysosomal acid lipase by late endosome/lysosome specific lipid, bis(monoacylglycero)phosphate (also called as lysobisphosphatidic acid), through alteration of membrane structure of the lipid. When added to cultured fibroblasts, D-PDMP inhibits the degradation of low-density lipoprotein (LDL) and thus accumulates both cholesterol ester and free cholesterol in late endosomes/lysosomes. This accumulation results in the inhibition of LDL-derived cholesterol esterification and the decrease of cell surface cholesterol. We showed that D-PDMP alters cellular cholesterol homeostasis in a glycosphingolipid-independent manner using L-PDMP, a stereoisomer of D-PDMP, which does not inhibit glycosphingolipid synthesis, and mutant melanoma cell which is defective in glycolipid synthesis. Altering cholesterol homeostasis by D-PDMP explains the unique characteristics of sensitizing multidrug resistant cells by this drug. PMID:16584188

  7. Thermophile-fermented compost as a fish feed additive modulates lipid peroxidation and free amino acid contents in the muscle of the carp, Cyprinus carpio.

    PubMed

    Tanaka, Ryusuke; Miyamoto, Hirokuni; Inoue, Shin-Ichi; Shigeta, Kazuhiro; Kondo, Masakazu; Ito, Toshiyuki; Kodama, Hiroaki; Miyamoto, Hisashi; Matsushita, Teruo

    2016-05-01

    Recently, a compost fermented with marine animals with thermophilic Bacillaceae in a clean and exclusive process at high temperature was reported as a possible feed additive to improve the healthy balance in sea fish and mammals (i.e., pigs and rodents). Here, the effects of the oral administration of the compost on the muscle and internal organs of carp (Cyprinus carpio) as a freshwater fish model were investigated. The fatty acid composition was different in the muscle of the carp fed with or without the compost extract, but there was little difference in the hepatopancreas. The accumulation of triacylglycerols, cholesterol, lipid peroxide and hydroxyl lipids decreased in the muscle after the oral administration of the compost extract in the carps over 12 weeks, but the accumulation did not always decrease in the hepatopancreas. In contrast, free-radical-scavenging activities and the concentrations of free amino acids in the muscle did not always increase and was dependent on the dose of the compost at 12 weeks. The scavenging activities and part of free amino acid levels in the muscle of the carp were improved at 24 weeks after a high dose of compost exposure, and then the survival rates of the carp were maintained. Thus, the oral administration of thermophile-fermented compost can prevent peroxidation and increase the content of free amino acids in the muscle of the freshwater fish, depending on the dose and term of the administration, and may be associated with the viability of the fish. PMID:26702954

  8. The pecan nut (Carya illinoinensis) and its oil and polyphenolic fractions differentially modulate lipid metabolism and the antioxidant enzyme activities in rats fed high-fat diets.

    PubMed

    Domínguez-Avila, Jesús A; Alvarez-Parrilla, Emilio; López-Díaz, José A; Maldonado-Mendoza, Ignacio E; Gómez-García, María Del Consuelo; de la Rosa, Laura A

    2015-02-01

    Tree nuts such as pecans (Carya illinoinensis) contain mostly oil but are also a source of polyphenols. Nut consumption has been linked to a reduction in serum lipid levels and oxidative stress. These effects have been attributed to the oil while overlooking the potential contribution of the polyphenols. Because the evidence regarding each fraction's bioactivity is scarce, we administered high-fat (HF) diets to male Wistar rats, supplementing them with pecan oil (HF+PO), pecan polyphenols (HF+PP) or whole pecans (HF+WP), and analysed the effects of each fraction. The HF diet increased the serum leptin and total cholesterol (TC) with respect to the control levels. The HF+WP diet prevented hyperleptinemia and decreased the TC compared with the control. The HF+WP diet upregulated the hepatic expression of apolipoprotein B and LDL receptor mRNAs with respect to the HF levels. The HF+PO diet reduced the level of triacylglycerols compared with the control. The HF+PP diet stimulated the hepatic expression of liver X receptor alpha mRNA. The HF+WP diet increased the activities of hepatic catalase, glutathione peroxidase and glutathione S transferase compared with the control, and decreased the degree of lipid peroxidation compared with the HF diet. The most bioactive diet was the WP diet. PMID:25172744

  9. Bidens pilosa and its active compound inhibit adipogenesis and lipid accumulation via down-modulation of the C/EBP and PPARγ pathways.

    PubMed

    Liang, Yu-Chuan; Yang, Meng-Ting; Lin, Chuan-Ju; Chang, Cicero Lee-Tian; Yang, Wen-Chin

    2016-01-01

    Obesity and its complications are a major global health problem. In this study, we investigated the anti-obesity effect and mechanism of an edible plant, Bidens pilosa, and its active constituent. We first assessed the long-term effect of B. pilosa on body composition, body weight, blood parameters in ICR mice. We observed that it significantly decreased fat content and increased protein content in ICR mice. Next, we verified the anti-obesity effect of B. pilosa in ob/ob mice. It effectively and dose-dependently reduced fat content, adipocyte size and/or body weight in mice. Moreover, mechanistic studies showed that B. pilosa inhibited the expression of peroxisome proliferator activated receptor γ (PPARγ), CCAAT/enhancer binding proteins (C/EBPs) and Egr2 in adipose tissue. Finally, we examined the effect of 2-β-D-glucopyranosyloxy-1-hydroxytrideca-5,7,9,11-tetrayne (GHT) on adipogenesis in adipocytes. We found that B. pilosa significantly decreased the adipogenesis and lipid accumulation. This decrease was associated with the down-regulation of expression of Egr2, C/EBPs, PPARγ, adipocyte Protein 2 (aP2) and adiponectin. In summary, this work demonstrated that B. pilosa and GHT suppressed adipogenesis and lipid content in adipocytes and/or animals via the down-regulation of the Egr2, C/EBPs and PPARγ pathways, suggesting a novel application of B. pilosa and GHT against obesity. PMID:27063434

  10. Postprandial hyperglycemia in patients with noninsulin-dependent diabetes mellitus. Role of hepatic and extrahepatic tissues.

    PubMed Central

    Firth, R G; Bell, P M; Marsh, H M; Hansen, I; Rizza, R A

    1986-01-01

    Patients with noninsulin-dependent diabetes mellitus (NIDDM) have both preprandial and postprandial hyperglycemia. To determine the mechanism responsible for the postprandial hyperglycemia, insulin secretion, insulin action, and the pattern of carbohydrate metabolism after glucose ingestion were assessed in patients with NIDDM and in matched nondiabetic subjects using the dual isotope and forearm catheterization techniques. Prior to meal ingestion, hepatic glucose release was increased (P less than 0.001) in the diabetic patients measured using [2-3H] or [3-3H] glucose. After meal ingestion, patients with NIDDM had excessive rates of systemic glucose entry (1,316 +/- 56 vs. 1,018 +/- 65 mg/kg X 7 h, P less than 0.01), primarily owing to a failure to suppress adequately endogenous glucose release (680 +/- 50 vs. 470 +/- 32 mg/kg X 7 h, P less than 0.01) from its high preprandial level. Despite impaired suppression of endogenous glucose production during a hyperinsulinemic glucose clamp (P less than 0.001) and decreased postprandial C-peptide response (P less than 0.05) in NIDDM, percent suppression of hepatic glucose release after oral glucose was comparable in the diabetic and nondiabetic subjects (45 +/- 3 vs. 39 +/- 2%). Although new glucose formation from meal-derived three-carbon precursors (53 +/- 3 vs. 40 +/- 7 mg/kg X 7 h, P less than 0.05) was greater in the diabetic patients, it accounted for only a minor part of this excessive postprandial hepatic glucose release. Postprandial hyperglycemia was exacerbated by the lack of an appropriate increase in glucose uptake whether measured isotopically or by forearm glucose uptake. Thus as has been proposed for fasting hyperglycemia, excessive hepatic glucose release and impaired glucose uptake are involved in the pathogenesis of postprandial hyperglycemia in patients with NIDDM. Images PMID:3517067

  11. A single session of neuromuscular electrical stimulation does not augment postprandial muscle protein accretion.

    PubMed

    Dirks, Marlou L; Wall, Benjamin T; Kramer, Irene Fleur; Zorenc, Antoine H; Goessens, Joy P B; Gijsen, Annemie P; van Loon, Luc J C

    2016-07-01

    The loss of muscle mass and strength that occurs with aging, termed sarcopenia, has been (at least partly) attributed to an impaired muscle protein synthetic response to food intake. Previously, we showed that neuromuscular electrical stimulation (NMES) can stimulate fasting muscle protein synthesis rates and prevent muscle atrophy during disuse. We hypothesized that NMES prior to protein ingestion would increase postprandial muscle protein accretion. Eighteen healthy elderly (69 ± 1 yr) males participated in this study. After a 70-min unilateral NMES protocol was performed, subjects ingested 20 g of intrinsically l-[1-(13)C]phenylalanine-labeled casein. Plasma samples and muscle biopsies were collected to assess postprandial mixed muscle and myofibrillar protein accretion as well as associated myocellular signaling during a 4-h postprandial period in both the control (CON) and stimulated (NMES) leg. Protein ingestion resulted in rapid increases in both plasma phenylalanine concentrations and l-[1-(13)C]phenylalanine enrichments, which remained elevated during the entire 4-h postprandial period (P < 0.05). Mixed-muscle protein-bound l-[1-(13)C]phenylalanine enrichments increased significantly over time following protein ingestion, with no differences between the CON (0.0164 ± 0.0019 MPE) and NMES (0.0164 ± 0.0019 MPE) leg (P > 0.05). In agreement, no differences were observed in the postprandial rise in myofibrillar protein bound l-[1-(13)C]phenylalanine enrichments between the CON and NMES legs (0.0115 ± 0.0014 vs. 0.0133 ± 0.0013 MPE, respectively, P > 0.05). Significant increases in mTOR and P70S6K phosphorylation status were observed in the NMES-stimulated leg only (P < 0.05). We conclude that a single session of NMES prior to food intake does not augment postprandial muscle protein accretion in healthy older men. PMID:27279248

  12. Mechanisms of lipid regulation and lipid gating in TRPC channels.

    PubMed

    Svobodova, Barbora; Groschner, Klaus

    2016-06-01

    TRPC proteins form cation channels that integrate and relay cellular signals by mechanisms involving lipid recognition and lipid-dependent gating. The lipohilic/amphiphilic molecules that function as cellular activators or modulators of TRPC proteins span a wide range of chemical structures. In this context, cellular redox balance is likely linked to the lipid recognition/gating features of TRPC channels. Both classical ligand-protein interactions as well as indirect and promiscuous sensory mechanisms have been proposed. Some of the recognition processes are suggested to involve ancillary lipid-binding scaffolds or regulators as well as dynamic protein-protein interactions determined by bilayer architecture. A complex interplay of protein-protein and protein-lipid interactions is likely to govern the gating and/or plasma membrane recruitment of TRPC channels, thereby providing a distinguished platform for signal integration and coincident signal detection. Both the primary molecular event(s) of lipid recognition by TRPC channels as well as the transformation of these events into distinct gating movements is poorly understood at the molecular level, and it remains elusive whether lipid sensing in TRPCs is conferred to a distinct sensor domain. Recent structural information on the molecular action of lipophilic activators in distantly related members of the TRP superfamily encourages speculations on TRPC gating mechanisms involved in lipid recognition/gating. This review aims to provide an update on the current understanding of the lipid-dependent control of TRPC channels with focus on the TRPC lipid sensing, signal-integration hub and a short discussion of potential links to redox signaling. PMID:27125985

  13. Genome-wide association studies identified novel loci for non-high-density lipoprotein cholesterol and its postprandial lipemic response

    PubMed Central

    An, Ping; Straka, Robert J.; Pollin, Toni I.; Feitosa, Mary F.; Wojczynski, Mary K.; Daw, E. Warwick; O'Connell, Jeffrey R.; Gibson, Quince; Ryan, Kathleen A.; Hopkins, Paul N.; Tsai, Michael Y.; Lai, Chao-Qiang; Province, Michael A.; Ordovas, Jose M.; Shuldiner, Alan R; Arnett, Donna K.; Borecki, Ingrid B.

    2014-01-01

    Non-high-density lipoprotein cholesterol (NHDL) is an independent and superior predictor of CVD risk as compared to LDL alone. It represents a spectrum of atherogenic lipid fractions with possibly a distinct genomic signature. We performed genome-wide association studies (GWAS) to identify loci influencing baseline NHDL and its postprandial lipemic (PPL) response. We carried out GWAS in 4,241 participants of European descent. Our discovery cohort included 928 subjects from the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) Study. Our replication cohorts included 3,313 subjects from the Heredity and Phenotype Intervention (HAPI) Heart Study and Family Heart Study (FamHS). A linear mixed model using the kinship matrix was used for association tests. The best association signal was found in a tri-genic region at RHOQ-PIGF-CRIPT for baseline NHDL (lead SNP rs6544903, discovery p = 7e-7, MAF = 2%; validation p = 6e-4 at 0.1 kb upstream neighboring SNP rs3768725, and 5e-4 at 0.7 kb downstream neighboring SNP rs6733143, MAF = 10%). The lead and neighboring SNPs were not perfect surrogate proxies to each other (D′ = 1, r2 = 0.003) but they seemed to be partially dependent (likelihood ration test p = 0.04). Other suggestive loci (discovery p < 1e-6) included LOC100419812 and LOC100288337 for baseline NHDL, and LOC100420502 and CDH13 for NHDL PPL response that were not replicated (p > 0.01). The current and first GWAS of NHDL yielded an interesting common variant in RHOQ-PIGF-CRIPT influencing baseline NHDL levels. Another common variant in CDH13 for NHDL response to dietary high fat intake challenge was also suggested. Further validations for both loci from large independent studies, especially interventional studies, are warranted. PMID:24604477

  14. Resistance Exercise Attenuates High-Fructose, High-Fat-Induced Postprandial Lipemia

    PubMed Central

    Wilburn, Jessie R; Bourquin, Jeffrey; Wysong, Andrea; Melby, Christopher L

    2015-01-01

    INTRODUCTION Meals rich in both fructose and fat are commonly consumed by many Americans, especially young men, which can produce a significant postprandial lipemic response. Increasing evidence suggests that aerobic exercise can attenuate the postprandial increase in plasma triacylglycerols (TAGs) in response to a high-fat or a high-fructose meal. However, it is unknown if resistance exercise can dampen the postprandial lipemic response to a meal rich in both fructose and fat. METHODS Eight apparently healthy men (Mean ± SEM; age = 27 ± 2 years) participated in a crossover study to examine the effects of acute resistance exercise on next-day postprandial lipemia resulting from a high-fructose, high-fat meal. Participants completed three separate two-day conditions in a random order: (1) EX-COMP: a full-body weightlifting workout with the provision of additional kilocalories to compensate for the estimated net energy cost of exercise on day 1, followed by the consumption of a high-fructose, high-fat liquid test meal the next morning (day 2) (~600 kcal) and the determination of the plasma glucose, lactate, insulin, and TAG responses during a six-hour postprandial period; (2) EX-DEF: same condition as EX-COMP but without exercise energy compensation on day 1; and (3) CON: no exercise control. RESULTS The six-hour postprandial plasma insulin and lactate responses did not differ between conditions. However, the postprandial plasma TAG concentrations were 16.5% and 24.4% lower for EX-COMP (551.0 ± 80.5 mg/dL × 360 minutes) and EX-DEF (499.4 ± 73.5 mg/dL × 360 minutes), respectively, compared to CON (660.2 ± 95.0 mg/dL × 360 minutes) (P < 0.05). CONCLUSIONS A single resistance exercise bout, performed ~15 hours prior to a high-fructose, high-fat meal, attenuated the postprandial TAG response, as compared to a no-exercise control condition, in healthy, resistance-trained men. PMID:26508874

  15. Lipid Nanotechnology

    PubMed Central

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

    2013-01-01

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

  16. Modulation of Membrane Lipid Composition and Homeostasis in Salmon Hepatocytes Exposed to Hypoxia and Perfluorooctane Sulfonamide, Given Singly or in Combination

    PubMed Central

    Olufsen, Marianne; Cangialosi, Maria V.; Arukwe, Augustine

    2014-01-01

    The relative importance of environmental hypoxia due to global climate change on organismal ability to adapt to chemical insult and/or mechanisms of these responses is not well understood. Therefore, we have studied the effects of combined exposure to perfluorooctane sulfonamide (PFOSA) and chemically induced hypoxia on membrane lipid profile and homeostasis. Primary salmon hepatocytes were exposed to PFOSA at 0, 25 and 50 µM singly or in combination with either cobalt chloride (CoCl2: 0 and 150 µM) or deferroxamine (DFO: 0 and 100 µM) for 24 and 48 h. CoCl2 and DFO were used to induce cellular hypoxia because these two chemicals have been commonly used in animal experiments for this purpose and have been shown to increase hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF) levels. Fatty acid (FA) profiles were determined by GC-MS, while gene expression patterns were determined by quantitative PCR. Hypoxic condition was confirmed with time-related increases of HIF-1α mRNA levels in CoCl2 and DFO exposed cells. In general, significant alterations of genes involved in lipid homeostasis were predominantly observed after 48 h exposure. Gene expression analysis showed that biological responses related to peroxisome proliferation (peroxisome proliferator-activated receptors (PPARs) and acyl coenzyme A (ACOX)) and FA desaturation (Δ5- and Δ6-desaturases: FAD5 and FAD6, respectively) and elongation (FAE) were elevated slightly by single exposure (i.e. either PFOSA, CoCl2 or DFO exposure alone), and these responses were potentiated in combined exposure conditions. Principal component analysis (PCA) showed a clustering of peroxisome proliferation responses at transcript levels and FA desaturation against membrane FAs levels whose changes were explained by PFOSA and chemically induced hypoxia exposures. Overall, our data show that most of the observed responses were stronger in combined stressor exposure conditions, compared to

  17. Tryptophan metabolism, growth responses, and postprandial insulin metabolism in weaned piglets according to the dietary provision of niacin (vitamin B) and tryptophan.

    PubMed

    Matte, J Jacques; Corrent, Etienne; Simongiovanni, Aude; Le Floc'h, Nathalie

    2016-05-01

    The present experiment aimed to determine if Trp metabolism and growth responses to dietary Trp are modulated by dietary niacin (B) in weanling piglets. Piglets weaned at 3 wk of age were distributed 1 wk later (7.6 kg of BW, SEM = 0.1) in 52 pens of 2 animals each. Pens were assigned to factorial dietary treatments with 2 additions of B, 15 mg/kg (LB3) vs. 45 mg/kg (HB3) and 2 additions of Trp, 0 mg/kg (-Trp) vs. 1 mg/kg (+Trp) for Trp to Lys ratios of 0.16 vs. 0.24, respectively. Growth performance was recorded every week from 4 to 10 wk of age. Fasting blood samples were taken at 4, 6, 8, and 10 wk of age. From 4 to 10 wk of age, ADFI tended to be greater ( = 0.10) in HB3 than in LB3 (1,031 vs. 1,003 g, SEM = 7), and this was reflected ( = 0.06) by ADG (642 vs. 623 g, SEM = 7). No treatment effect was observed on plasma Trp or kynurenine (Kyn), an intermediate metabolite of Trp catabolism. The response of plasma nicotinamide (Nam), a product of Trp catabolism and an indicator of B status, to dietary B differed according to treatments (interaction Trp × B, < 0.01) with values of 1.4, 3.3, 4.1, and 5.3 μM (SEM = 0.1) in LB3-Trp, HB3-Trp, LB3+Trp, and HB3+Trp, respectively. At 11 wk of age, postprandial blood samples were collected from 6 piglets per treatment for measurements of Trp and insulin metabolism. Postprandial plasma Trp (96.4 vs. 72.2 μ, SEM = 3.4) and Kyn (1.7 vs. 1.3 μ, SEM = 0.1) were greater ( < 0.01) in +Trp vs. -Trp. Postprandial plasma Nam was greater ( < 0.01) in +Trp vs. -Trp (3.4 vs. 1.9 µ, SEM = 0.3) and in HB3 vs. LB3 piglets (3.4 vs. 1.9 µ, SEM = 0.3). Postprandial peaks and areas under curves of C-peptide and glucose were not affected by treatments. However, for insulin, the postprandial peak was lower in +Trp vs. -Trp piglets in the LB3 group (interaction Trp × B, < 0.05); values were 1.3, 1.0, 0.7, and 1.0 n (SEM = 0.1) in LB3-Trp, HB3-Trp, LB3+Trp, and HB3+Trp, respectively. The peak value of the molar ratio insulin:C-peptide was

  18. Lipid-induced Muscle Insulin Resistance Is Mediated by GGPPS via Modulation of the RhoA/Rho Kinase Signaling Pathway.

    PubMed

    Tao, Weiwei; Wu, Jing; Xie, Bing-Xian; Zhao, Yuan-Yuan; Shen, Ning; Jiang, Shan; Wang, Xiu-Xing; Xu, Na; Jiang, Chen; Chen, Shuai; Gao, Xiang; Xue, Bin; Li, Chao-Jun

    2015-08-14

    Elevated circulating free fatty acid levels are important contributors to insulin resistance in the muscle and liver, but the underlying mechanisms require further elucidation. Here, we show that geranylgeranyl diphosphate synthase 1 (GGPPS), which is a branch point enzyme in the mevalonic acid pathway, promotes lipid-induced muscle insulin resistance through activation of the RhoA/Rho kinase signaling pathway. We have found that metabolic perturbation would increase GGPPS expression in the skeletal muscles of db/db mice and high fat diet-fed mice. To address the metabolic effects of GGPPS activity in skeletal muscle, we generated mice with specific GGPPS deletions in their skeletal muscle tissue. Heterozygous knock-out of GGPPS in the skeletal muscle improved systemic insulin sensitivity and glucose homeostasis in mice fed both normal chow and high fat diets. These metabolic alterations were accompanied by activated PI3K/Akt signaling and enhanced glucose uptake in the skeletal muscle. Further investigation showed that the free fatty acid-stimulated GGPPS expression in the skeletal muscle was able to enhance the geranylgeranylation of RhoA, which further induced the inhibitory phosphorylation of IRS-1 (Ser-307) by increasing Rho kinase activity. These results implicate a crucial role of the GGPPS/RhoA/Rho kinase/IRS-1 pathway in skeletal muscle, in which it mediates lipid-induced systemic insulin resistance in obese mice. Therefore, skeletal muscle GGPPS may represent a potential pharmacological target for the prevention and treatment of obesity-related type 2 diabetes. PMID:26112408

  19. Modulation of the Host Lipid Landscape to Promote RNA Virus Replication: The Picornavirus Encephalomyocarditis Virus Converges on the Pathway Used by Hepatitis C Virus

    PubMed Central

    Dorobantu, Cristina M.; Albulescu, Lucian; Harak, Christian; Feng, Qian; van Kampen, Mirjam; Strating, Jeroen R. P. M.; Gorbalenya, Alexander E.; Lohmann, Volker

    2015-01-01

    Cardioviruses, including encephalomyocarditis virus (EMCV) and the human Saffold virus, are small non-enveloped viruses belonging to the Picornaviridae, a large family of positive-sense RNA [(+)RNA] viruses. All (+)RNA viruses remodel intracellular membranes into unique structures for viral genome replication. Accumulating evidence suggests that picornaviruses from different genera use different strategies to generate viral replication organelles (ROs). For instance, enteroviruses (e.g. poliovirus, coxsackievirus, rhinovirus) rely on the Golgi-localized phosphatidylinositol 4-kinase III beta (PI4KB), while cardioviruses replicate independently of the kinase. By which mechanisms cardioviruses develop their ROs is currently unknown. Here we show that cardioviruses manipulate another PI4K, namely the ER-localized phosphatidylinositol 4-kinase III alpha (PI4KA), to generate PI4P-enriched ROs. By siRNA-mediated knockdown and pharmacological inhibition, we demonstrate that PI4KA is an essential host factor for EMCV genome replication. We reveal that the EMCV nonstructural protein 3A interacts with and is responsible for PI4KA recruitment to viral ROs. The ensuing phosphatidylinositol 4-phosphate (PI4P) proved important for the recruitment of oxysterol-binding protein (OSBP), which delivers cholesterol to EMCV ROs in a PI4P-dependent manner. PI4P lipids and cholesterol are shown to be required for the global organization of the ROs and for viral genome replication. Consistently, inhibition of OSBP expression or function efficiently blocked EMCV RNA replication. In conclusion, we describe for the first time a cellular pathway involved in the biogenesis of cardiovirus ROs. Remarkably, the same pathway was reported to promote formation of the replication sites of hepatitis C virus, a member of the Flaviviridae family, but not other picornaviruses or flaviviruses. Thus, our results highlight the convergent recruitment by distantly related (+)RNA viruses of a host lipid

  20. Isovaleric, methylmalonic, and propionic acid decrease anesthetic EC50 in tadpoles, modulate glycine receptor function, and interact with the lipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine

    PubMed Central

    Weng, Yun; Hsu, Tienyi Theresa; Zhao, Jing; Nishimura, Stefanie; Fuller, Gerald G.; Sonner, James M.

    2010-01-01

    Introduction Elevated concentrations of isovaleric, methylmalonic, and propionic acid are associated with impaired consciousness in genetic diseases (organic acidemias). We conjectured that part of the central nervous system depression observed in these disorders was due to anesthetic effects of these metabolites. We tested three hypotheses. First, that these metabolites would have anesthetic-sparing effects, possibly being anesthetics by themselves. Second, that these compounds would modulate glycine and GABAA receptor function, increasing chloride currents through these channels as potent clinical inhaled anesthetics do. Third, that these compounds would affect physical properties of lipids. Methods Anesthetic EC50’s were measured in Xenopus laevis tadpoles. Glycine and GABAA receptors were expressed in Xenopus laevis oocytes and studied using two-electrode voltage clamping. Pressure-area isotherms of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayers were measured with and without added organic acids. Results Isovaleric acid was an anesthetic in tadpoles, while methylmalonic and propionic acid decreased isoflurane’s EC50 by half. All three organic acids concentration-dependently increased current through α1 glycine receptors. There were minimal effects on α1β2γ2s GABAA receptors. The organic acids increased total lateral pressure (surface pressure) of DPPC monolayers, including at mean molecular areas typical of bilayers. Conclusion Isovaleric, methylmalonic, and propionic acid have anesthetic affects in tadpoles, positively modulate glycine receptor fuction, and affect physical properties of DPPC monolayers. PMID:19372333

  1. Lipid Storage Diseases

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Lipid Storage Diseases Information Page Condensed from Lipid Storage ... en Español Additional resources from MedlinePlus What are Lipid Storage Diseases? Lipid storage diseases are a group ...

  2. Evaluating Crossbred Red Rice Variants for Postprandial Glucometabolic Responses: A Comparison with Commercial Varieties.

    PubMed

    Se, Chee-Hee; Chuah, Khun-Aik; Mishra, Ankitta; Wickneswari, Ratnam; Karupaiah, Tilakavati

    2016-01-01

    Consumption of white rice predisposes some Asian populations to increased risk of type 2 diabetes. We compared the postprandial glucometabolic responses to three newly-developed crossbred red rice variants (UKMRC9, UKMRC10, UKMRC11) against three selected commercial rice types (Thai red, Basmati white, Jasmine white) using 50-g carbohydrate equivalents provided to 12 normoglycaemic adults in a crossover design. Venous blood was drawn fasted and postprandially for three hours. Glycaemic (GI) and insulin (II) indices, incremental areas-under-the-curves for glucose and insulin (IAUCins), indices of insulin sensitivity and secretion, lactate and peptide hormones (motilin, neuropeptide-Y, orexin-A) were analyzed. The lowest to highest trends for GI and II were similar i.e., UKMRC9 < Basmati < Thai red < UKMRC10 < UKMRC11 < Jasmine. Postprandial insulinaemia and IAUCins of only UKMRC9 were significantly the lowest compared to Jasmine. Crude protein and fiber content correlated negatively with the GI values of the test rice. Although peptide hormones were not associated with GI and II characteristics of test rice, early and late phases of prandial neuropeptide-Y changes were negatively correlated with postprandial insulinaemia. This study indicated that only UKMRC9 among the new rice crossbreeds could serve as an alternative cereal option to improve diet quality of Asians with its lowest glycaemic and insulinaemic burden. PMID:27213446

  3. Pre and postprandial changes in orexigenic and anorexigenic factors in channel catfish Ictalurus punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We examined pre- and postprandial changes in the expression of plasma ghrelin (GHRL) and mRNAs encoding GRLN, cocaine and amphetamine regulated transcript (CART), neuropeptide Y (NPY), and cholecystokinin (CCK) in channel catfish. Fish were either offered feed (Fed) or fasted (Unfed). Feeding incr...

  4. Pre and postprandial changes in orexigenic and anorexigenic factors in channel catfish Ictalurus punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ghrelin (GRLN), cocaine and amphetamine regulated transcript (CART), neuropeptide Y (NPY), and cholecystokinin (CCK) are neuropeptides involved in the regulation of appetite and feeding in vertebrates. We examined pre- and postprandial changes in the expression of plasma GHRL and mRNAs encoding GRL...

  5. Gastric emptying and postprandial glucose excursions in adolescents with type 1 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Because amylin is co-secreted with insulin from beta cells, patients with type 1 diabetes (T1DM) are deficient in both insulin and amylin. Amylin delays gastric emptying and suppresses glucagon in the postprandial period. Hence, we hypothesized that children with complication-naive T1DM have acceler...

  6. Evaluating Crossbred Red Rice Variants for Postprandial Glucometabolic Responses: A Comparison with Commercial Varieties

    PubMed Central

    Se, Chee-Hee; Chuah, Khun-Aik; Mishra, Ankitta; Wickneswari, Ratnam; Karupaiah, Tilakavati

    2016-01-01

    Consumption of white rice predisposes some Asian populations to increased risk of type 2 diabetes. We compared the postprandial glucometabolic responses to three newly-developed crossbred red rice variants (UKMRC9, UKMRC10, UKMRC11) against three selected commercial rice types (Thai red, Basmati white, Jasmine white) using 50-g carbohydrate equivalents provided to 12 normoglycaemic adults in a crossover design. Venous blood was drawn fasted and postprandially for three hours. Glycaemic (GI) and insulin (II) indices, incremental areas-under-the-curves for glucose and insulin (IAUCins), indices of insulin sensitivity and secretion, lactate and peptide hormones (motilin, neuropeptide-Y, orexin-A) were analyzed. The lowest to highest trends for GI and II were similar i.e., UKMRC9 < Basmati < Thai red < UKMRC10 < UKMRC11 < Jasmine. Postprandial insulinaemia and IAUCins of only UKMRC9 were significantly the lowest compared to Jasmine. Crude protein and fiber content correlated negatively with the GI values of the test rice. Although peptide hormones were not associated with GI and II characteristics of test rice, early and late phases of prandial neuropeptide-Y changes were negatively correlated with postprandial insulinaemia. This study indicated that only UKMRC9 among the new rice crossbreeds could serve as an alternative cereal option to improve diet quality of Asians with its lowest glycaemic and insulinaemic burden. PMID:27213446

  7. Occurrence and relevance of postprandial hypotension in patients with essential hypertension.

    PubMed

    Mitro, P; Feterik, K; Cvercková, A; Trejbal, D

    1999-04-23

    The aim of this study was to determine the occurrence of postprandial hypotension (PPH) in patients with arterial hypertension, identify its risk factors and evaluate the importance of postprandial blood pressure reduction in relation to the management of hypertension. Forty-nine patients (23 male; 26 female; mean age 65.6 +/- 12 years) with diagnosed hypertension underwent measurement of blood pressure and pulse rate before intake of a standardised breakfast (1821 kJ) and at 15-minute intervals until 1 hour thereafter. The orthostatic test for detection of orthostatic hypotension was performed before the ingestion of food. PPH was detected in 22 patients (45%) with arterial hypertension. Patients treated with diuretics had significantly greater postprandial reductions in blood pressure compared to those who received no diuretic treatment. Levels of premeal systolic blood pressure, age, orthostatic hypotension, history of syncope cardiovascular disease or stroke were not associated with a more severe decline in postprandial blood pressure. Maximal reductions in blood pressure were recorded approximately 33 +/- 15 minutes after ingestion of food. Therefore, recent intake of food should be taken into account in the evaluation of hypertension and the effect of antihypertensive drugs when blood pressure is measured within one hour after a meal. PMID:10378313

  8. The effects of caffeine on the postprandial fall of blood pressure in the elderly.

    PubMed

    Lenders, J W; Morre, H L; Smits, P; Thien, T

    1988-07-01

    In a double-blind placebo-controlled study, we examined the effect of caffeine pretreatment on the haemodynamic and humoral changes after a standardized breakfast in 15 healthy elderly subjects (mean age 75.4 +/- 6.6 years). After placebo, the preprandial blood pressure did not change and the postprandial blood pressure declined by a maximum of 6.1%. After oral ingestion of 250 mg caffeine, 60 min before breakfast, the preprandial blood pressure increased by 12.5%. Although the decrease of the postprandial blood pressure was not altered, blood pressure remained above its basal value. The increase in plasma noradrenaline after the meal was similar in the placebo and the caffeine tests. Plasma adrenaline decreased after placebo (-19%) but did not change after caffeine. Thus, despite the unchanged decrease of the postprandial blood pressure, the preprandial pressor effect of caffeine prevented the decline of the postprandial blood pressure below its baseline value. The clinical relevance of this finding has still to be determined. PMID:3177083

  9. Effects of Diet Composition on Postprandial Energy Availability during Weight Loss Maintenance

    PubMed Central

    Walsh, Carolyn O.; Ebbeling, Cara B.; Swain, Janis F.; Markowitz, Robert L.; Feldman, Henry A.; Ludwig, David S.

    2013-01-01

    Background The major circulating metabolic fuels regulate hunger, and each is affected by dietary composition. An integrated measure of postprandial energy availability from circulating metabolic fuels may help inform dietary recommendations for weight maintenance after weight loss. Aim We examined the effect of low-fat (LF, 60% of energy from carbohydrate, 20% fat, 20% protein), low-glycemic index (LGI, 40%–40%-20%), and very low-carbohydrate (VLC, 10%–60%-30%) diets on total postprandial metabolic fuel energy availability (EA) during weight loss maintenance. Methods Eight obese young adults were fed a standard hypocaloric diet to produce 10–15% weight loss. They were then provided isocaloric LF, LGI, and VLC diets in a randomized crossover design, each for a 4-week period of weight loss maintenance. At the end of each dietary period, a test meal representing the respective diet was provided, and blood samples were obtained every 30 minutes for 5 hours. The primary outcome was EA, defined as the combined energy density (circulating level×relative energy content) of glucose, free fatty acids, and β-hydroxybutyrate. Secondary outcomes were individual metabolic fuels, metabolic rate, insulin, glucagon, cortisol, epinephrine, and hunger ratings. Respiratory quotient was a process measure. Data were analyzed by repeated-measures analysis of variance, with outcomes compared in the early (30 to 150 min) and late (180 to 300 min) postprandial periods. Results EA did not differ between the test meals during the early postprandial period (p = 0.99). However, EA in the late postprandial period was significantly lower after the LF test meal than the LGI (p<0.0001) and VLC (p<0.0001) test meals. Metabolic rate also differed in the late postprandial period (p = 0.0074), with higher values on the VLC than LF (p = 0.0064) and LGI (p = 0.0066) diets. Conclusion These findings suggest that an LF diet may adversely affect postprandial EA and risk for weight

  10. Postprandial Differences in the Amino Acid and Biogenic Amines Profiles of Impaired Fasting Glucose Individuals after Intake of Highland Barley

    PubMed Central

    Liu, Liyan; Wang, Xinyang; Li, Ying; Sun, Changhao

    2015-01-01

    The aim of this study was to measure the postprandial changes in amino acid and biogenic amine profiles in individuals with impaired fasting glucose (IFG) and to investigate the changes of postprandial amino acid and biogenic amine profiles after a meal of highland barley (HB). Firstly, 50 IFG and 50 healthy individuals were recruited for the measurement of 2 h postprandial changes of amino acid and biogenic amine profiles after a glucose load. Secondly, IFG individuals received three different loads: Glucose (GL), white rice (WR) and HB. Amino acid and biogenic amine profiles, glucose and insulin were assayed at time zero and 30, 60, 90 and 120 min after the test load. The results showed fasting and postprandial amino acid and biogenic amine profiles were different between the IFG group and the controls. The level of most amino acids and their metabolites decreased after an oral glucose tolerance test, while the postprandial level of γ-aminobutyric acid (GABA) increased significantly in IFG individuals. After three different test loads, the area under the curve for glucose, insulin, lysine and GABA after a HB load decreased significantly compared to GL and WR loads. Furthermore, the postprandial changes in the level of GABA between time zero and 120 min during a HB load were associated positively with 2 h glucose and fasting insulin secretion in the IFG individuals. Thus, the HB load produced low postprandial glucose and insulin responses, which induced changes in amino acid and biogenic amine profiles and improved insulin sensitivity. PMID:26184292

  11. Model-Based Quantification of the Systemic Interplay between Glucose and Fatty Acids in the Postprandial State

    PubMed Central

    Sips, Fianne L. P.; Nyman, Elin; Adiels, Martin; Hilbers, Peter A. J.; Strålfors, Peter; van Riel, Natal A. W.; Cedersund, Gunnar

    2015-01-01

    In metabolic diseases such as Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease, the systemic regulation of postprandial metabolite concentrations is disturbed. To understand this dysregulation, a quantitative and temporal understanding of systemic postprandial metabolite handling is needed. Of particular interest is the intertwined regulation of glucose and non-esterified fatty acids (NEFA), due to the association between disturbed NEFA metabolism and insulin resistance. However, postprandial glucose metabolism is characterized by a dynamic interplay of simultaneously responding regulatory mechanisms, which have proven difficult to measure directly. Therefore, we propose a mathematical modelling approach to untangle the systemic interplay between glucose and NEFA in the postprandial period. The developed model integrates data of both the perturbation of glucose metabolism by NEFA as measured under clamp conditions, and postprandial time-series of glucose, insulin, and NEFA. The model can describe independent data not used for fitting, and perturbations of NEFA metabolism result in an increased insulin, but not glucose, response, demonstrating that glucose homeostasis is maintained. Finally, the model is used to show that NEFA may mediate up to 30–45% of the postprandial increase in insulin-dependent glucose uptake at two hours after a glucose meal. In conclusion, the presented model can quantify the systemic interactions of glucose and NEFA in the postprandial state, and may therefore provide a new method to evaluate the disturbance of this interplay in metabolic disease. PMID:26356502

  12. Oral supplementation with troxerutin (trihydroxyethylrutin), modulates lipid peroxidation and antioxidant status in 1,2-dimethylhydrazine-induced rat colon carcinogenesis.

    PubMed

    Vinothkumar, R; Vinoth Kumar, R; Karthikkumar, V; Viswanathan, P; Kabalimoorthy, J; Nalini, N

    2014-01-01

    The present study was aimed to investigate the chemopreventive potential of troxerutin on 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis by evaluating the antioxidant and lipid peroxidation (LPO) status. Rats were randomly divided into six groups. Group I rats served as control. Group II rats received troxerutin (50 mg/kgb.w., p.o.) for 16 weeks. Groups III-VI rats received subcutaneous injections of DMH (20 mg/kgb.w., s.c.) once a week, for the first 4 weeks. In addition to DMH, groups IV-VI rats received troxerutin at the doses of 12.5, 25 and 50 mg/kgb.w., respectively. In DMH treated rats, our results showed decreased activities of antioxidants and increased levels of LPO in the liver. Moreover, LPO and antioxidants in the colon were found to be significantly diminished in DMH the treated rats. Furthermore, enhanced activity of colonic vitamin C and vitamin E levels were observed in DMH alone treated rats (group III), which was significantly reversed on troxerutin supplementation. Troxerutin at the dose of 25 mg/kgb.w. had shown profound beneficial effects by exhibiting near normal biochemical profile and well-preserved colon histology as compared to the other two tested doses (12.5 and 50 mg/kgb.w.). These findings suggest that troxerutin could serve as a novel agent for colon cancer chemoprevention. PMID:24355798

  13. Hepatitis C Virus Hijacks Host Lipid Metabolism

    PubMed Central

    Syed, Gulam H; Amako, Yutaka; Siddiqui, Aleem

    2009-01-01

    Hepatitis C virus (HCV) modulates cellular lipid metabolism to enhance its replication. HCV circulates in the blood in association with lipoproteins. HCV infection is associated with enhanced lipogenesis, reduced secretion and β-oxidation of lipids. HCV-induced imbalance in lipid homeostasis leads to steatosis. Many lipids are crucial for viral life cycle, and inhibitors of cholesterol/fatty acid biosynthetic pathways inhibit viral replication, maturation and secretion. HCV negatively modulates the synthesis and secretion of very low-density lipoproteins (VLDL). The components involved in VLDL assembly are also required for HCV morphogenesis/secretion, suggesting that HCV coopts the VLDL secretory pathway for its own secretion. This review highlights HCV-altered lipid metabolic events that aid in the viral life cycle and ultimately promote liver disease pathogenesis. PMID:19854061

  14. Two independent apolipoprotein A5 haplotypes modulate postprandial lipoprotein metabolism in a healthy Caucasian population

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Apolipoprotein A5 (APOA5) plays an important role in plasma triacylglycerol (TG) homeostasis. Five polymorphisms (1131T>C, c.-3A>G, c.56C>G, IVS3+476G>A, c.1259T>C) in the APOA5 gene define three common haplotypes (APOA5'1, APOA5'2 and APOA5'3) in Caucasian individuals. Our aim was to de...

  15. Polyunsaturated fatty acids modulate the effect of TCF7L2 gene variants on postprandial lipemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The transcription factor 7-like 2 (TCF7L2) has been recently associated with diabetes risk and it may exert its effect through metabolic syndrome (MetS) related traits and subjected to modification by environmental factors. We investigated the effect of single nucleotide polymorphisms (SNP), rs79031...

  16. Suspected postprandial hypoglycemia is associated with beta-adrenergic hypersensitivity and emotional distress.

    PubMed

    Berlin, I; Grimaldi, A; Landault, C; Cesselin, F; Puech, A J

    1994-11-01

    Suspected postprandial (reactive or idiopathic) hypoglycemia is characterized by predominantly adrenergic symptoms appearing after meals rich in carbohydrates and by their rare association with low blood glucose level (< 2.77 mmol/L). We studied heart rate, blood pressure, plasma insulin, C-peptide, and catecholamine responses during a 5-h oral glucose tolerance test in eight patients with suspected postprandial hypoglycemia and eight age-, sex-, and body mass index-matched healthy controls. We also evaluated beta-adrenergic sensitivity by using the isoproterenol sensitivity test. Psychological profile was assessed by the Symptom Checklist (SCL-90R) self-report symptom inventory. Patients with suspected postprandial hypoglycemia had higher beta-adrenergic sensitivity (defined as the dose of isoproterenol required to increase the resting heart rate by 25 beats/min) than controls (mean +/- SEM, 0.8 +/- 0.13 vs. 1.86 +/- 0.25 microgram isoproterenol; P = 0.002). After administration of glucose (75 g) blood glucose, plasma C-peptide, plasma epinephrine, and plasma norepinephrine responses were identical in the two groups, but plasma insulin was higher in the patients (group effect, P = 0.02; group by time interaction, P = 0.0001). Both heart rate and systolic blood pressure were significantly higher (but remained in the normal range) after glucose administration in patients with suspected postprandial hypoglycemia than in controls (group by time interactions, P = 0.004 and 0.0007, respectively). After glucose intake, seven patients had symptoms (palpitations, headache, tremor, generalized sweating, hunger, dizziness, sweating of the palms, flush, nausea, and fatigue), whereas in the control group, one subject reported flush and another palpitations, tremor, and hunger. Analysis of the SCL-90R questionnaire revealed that patients had emotional distress and significantly higher anxiety, somatization, depression, and obsessive-compulsive scores than controls. We may

  17. Effect of green tea catechins on the postprandial glycemic response to starches differing in amylose content.

    PubMed

    Liu, Jie; Wang, Mingzhu; Peng, Shanli; Zhang, Genyi

    2011-05-11

    The effect of tea polyphenols (TPLs), specifically tea catechins, on the postprandial glycemic response to cooked starches differing in amylose contents was investigated. The in vivo test using a mouse model showed a moderate reduction of the postprandial glycemic response to co-cooked normal (containing 27.8% amylose) or waxy corn starch with 10% TPLs (dry weight of starch), while an augmented glycemic response with a delayed blood glucose peak was observed when high amylose corn starch (HAC, containing 79.4% amylose) was used as the starch component. Enzyme kinetics results demonstrated that TPLs noncompetitively inhibit the digestion of waxy or normal corn starch, while the digestion rate of HAC starch was increased in the presence of TPLs, which supports the observed postprandial glycemic responses. Further studies using X-ray powder diffraction showed that the diffraction intensity (area under the diffraction curves) of normal and HAC starch was increased by 45% and 74%, respectively, whereas no change was observed for waxy corn starch. Consistently, dynamic laser light scattering studies using a solution of pure amylose showed an increased hydrodynamic radius of amylose molecules from ∼54 nm to ∼112 nm in the presence of TPLs. These experimental results indicate that there might exist an interaction between TPLs and amylose, which facilitates the association of amylose molecules to form a special nonordered structure that can produce a high and sustained postprandial glycemic response. Thus, a combination of tea polyphenols and specific starches could be used to manipulate postprandial glycemic response for glycemic control and optimal health. PMID:21401210

  18. START ships lipids across interorganelle space.

    PubMed

    Alpy, Fabien; Tomasetto, Catherine

    2014-01-01

    The family of StAR related lipid transfer proteins (START) is so-named based on the distinctive capacity for these proteins to transport lipids between membranes. The START domain is a module of about 210 residues, which binds lipids such as glycerolipids, sphingolipids and sterols. This domain has a deep lipid-binding pocket - which shields the hydrophic ligand from the external aqueous environment - covered by a lid. Based on their homology, the fifteen START proteins in mammals have been allocated to six distinct subfamilies, each subfamily being more specialized in the transport and/or sensing of a lipid ligand species. However within the same subgroup, their expression profile and their subcellular localization distinguish them and are critical for their different biological functions. Indeed, START proteins act in a variety of distinct physiological processes, such as lipid transfer between intracellular compartments, lipid metabolism and modulation of signaling events. Mutation or deregulated expression of START proteins is linked to pathological processes, including genetic disorders, autoimmune diseases and cancers. Besides the common single START domain, which is always located at the carboxy-terminal end in mammals, most START proteins harbor additional domains predicted to be critical in favoring lipid exchange. Evidence from well characterized START proteins indicates that these additional domains might be tethering machineries able to bring distinct organelles together and create membrane contact sites prone to lipid exchange via the START domain. PMID:24076129

  19. Lipid regulation of BK channel function

    PubMed Central

    Dopico, Alex M.; Bukiya, Anna N.

    2014-01-01

    This mini-review focuses on lipid modulation of BK (MaxiK, BKCa) current by a direct interaction between lipid and the BK subunits and/or their immediate lipid environment. Direct lipid-BK protein interactions have been proposed for fatty and epoxyeicosatrienoic acids, phosphoinositides and cholesterol, evidence for such action being less clear for other lipids. BK α (slo1) subunits are sufficient to support current perturbation by fatty and epoxyeicosatrienoic acids, glycerophospholipids and cholesterol, while distinct BK β subunits seem necessary for current modulation by most steroids. Subunit domains or amino acids that participate in lipid action have been identified in a few cases: hslo1 Y318, cerebral artery smooth muscle (cbv1) R334,K335,K336, cbv1 seven cytosolic CRAC domains, slo1 STREX and β1 T169,L172,L173 for docosahexaenoic acid, PIP2, cholesterol, sulfatides, and cholane steroids, respectively. Whether these protein motifs directly bind lipids or rather transmit the energy of lipid binding to other areas and trigger protein conformation change remains unresolved. The impact of direct lipid-BK interaction on physiology is briefly discussed. PMID:25202277

  20. n-3 LC-PUFA deposition efficiency and appetite-regulating hormones are modulated by the dietary lipid source during rainbow trout grow-out and finishing periods.

    PubMed

    Francis, D S; Thanuthong, T; Senadheera, S P S D; Paolucci, M; Coccia, E; De Silva, S S; Turchini, G M

    2014-04-01

    Largely attributable to concerns surrounding sustainability, the utilisation of omega-3 long-chain polyunsaturated fatty acid-rich (n-3 LC-PUFA) fish oils in aquafeeds for farmed fish species is an increasingly concerning issue. Therefore, strategies to maximise the deposition efficiency of these key health beneficial fatty acids are being investigated. The present study examined the effects of four vegetable-based dietary lipid sources (linseed, olive, palm and sunflower oil) on the deposition efficiency of n-3 LC-PUFA and the circulating blood plasma concentrations of the appetite-regulating hormones, leptin and ghrelin, during the grow-out and finishing phases in rainbow trout culture. Minimal detrimental effects were noted in fish performance; however, major modifications were apparent in tissue fatty acid compositions, which generally reflected that of the diet. These modifications diminished somewhat following the fish oil finishing phase, but longer-lasting effects remained evident. The fatty acid composition of the alternative oils was demonstrated to have a modulatory effect on the deposition efficiency of n-3 LC-PUFA and on the key endocrine hormones involved in appetite regulation, growth and feed intake during both the grow-out and finishing phases. In particular, n-6 PUFA (sunflower oil diet) appeared to 'spare' the catabolism of n-3 LC-PUFA and, as such, resulted in the highest retention of these fatty acids, ultimately highlighting new nutritional approaches to maximise the maintenance of the qualitative benefits of fish oils when they are used in feeds for aquaculture species. PMID:24078221

  1. Solid lipid nanoparticles of amphotericin B (AmbiOnp): in vitro and in vivo assessment towards safe and effective oral treatment module.

    PubMed

    Chaudhari, Manisha B; Desai, Preshita P; Patel, Pratikkumar A; Patravale, Vandana B

    2016-08-01

    Amphotericin B, a gold standard broad spectrum antibiotic used in treatment of systemic fungal infections and visceral leishmaniasis, though is effective parenterally offers severe nephrotoxicity whereas the oral delivery is reported to give very meager oral bioavailability. Thus, to alleviate the toxicity and to improve oral bioavailability, an effective oral delivery approach in the form of solid lipid nanoparticles of amphotericin B (AmbiOnp) was reported earlier by our group. In this investigation, we report the predominant formation of nontoxic superaggregated form of amphotericin B, resulting from the probe sonication-assisted nanoprecipitation technique. The developed formulation was further confirmed to retain this nontoxic form and was found to be stable over the varied gastrointestinal conditions. Further, in vitro antifungal activity of AmbiOnp against Candida albicans showed minimum inhibitory concentration value of 7.812 μg/mL attributed to controlled release of drug from nanoparticulate matrix. In vivo pharmacokinetic studies revealed a relative bioavailability of AmbiOnp to be 1.05-fold with a Cmax of 1109.31 ± 104.79 ng/mL at the end of 24 h which was comparable to Cmax of 1417.49 ± 85.52 ng/mL achieved with that of marketed formulation (Fungizone®) given intravenously establishing efficacy of AmbiOnp. In vivo biodistribution studies indicated very low levels of Amphotericin B in kidneys when given as AmbiOnp as compared to that of marketed formulation proving its safety and was further corroborated by renal toxicity studies. Further, the formulations were found to be stable under refrigeration condition over a period of 3 months. PMID:26712123

  2. Effects of rs7903146 Variation in the Tcf7l2 Gene in the Lipid Metabolism of Three Different Populations

    PubMed Central

    Garcia-Rios, Antonio; Yubero-Serrano, Elena M.; Camargo, Antonio; Gomez-Luna, Maria J.; Marin, Carmen; Gomez-Luna, Purificacion; Dembinska-Kiec, Aldona; Rodriguez-Cantalejo, Fernando; Tinahones, Francisco J.; Roche, Helen M.; Perez-Jimenez, Francisco; Lopez-Miranda, Jose; Delgado-Lista, Javier

    2012-01-01

    Background TCF7L2 rs7903146 is an important genetic factor predicting type 2 diabetes (T2DM) which has also been linked to higher cardiovascular risk. To date, there is little information about the additional impact of this single nucleotide polymorphism (SNP) beyond glucose metabolism. Methodology/Principal Findings We studied whether rs7903146 influenced postprandial lipid metabolism in three different populations (healthy young men, metabolic syndrome (MetS) patients and elderly persons). Eighty-eight healthy males were submitted to a single saturated fatty acid-rich test meal. Additionally, 110 middle-aged MetS patients and 20 healthy elderly persons (≥65 years) were submitted to three different dietary models followed by test meals. Minor allele homozygotes for rs7903146 showed a worse postprandial lipemia profile in young males, as seen by a lower HDL-cholesterol and Apo A1 concentration during the postprandial lipemia and a trend towards higher triglycerides (TG), than the other genotypes. In healthy elderly persons, carriers of the minor allele showed higher total cholesterol, LDL-cholesterol, Apo B and TG in the fasting state, and a higher postprandial area under the curve for total cholesterol, Apo B, small-triglyceride rich lipoprotein (TRL) cholesterol and small-(TRL) triglycerides. These results were accompanied by differential changes in adipokines. We did not observe any influence of rs7903146 on the postprandium of MetS patients. Conclusions/Significance Healthy young males and elderly persons who are carriers of the mutant allele for rs7903146 have an impaired postprandial lipid metabolism that may be mediated by an alteration in adipokine regulation, and may be related to the higher cardiovascular risk observed in these persons. Trial Registration ClinicalTrials.gov NCT00429195 PMID:22916254

  3. Circulating intestinal fibroblast growth factor 19 has a pronounced diurnal variation and modulates hepatic bile acid synthesis in man.

    PubMed

    Lundåsen, T; Gälman, C; Angelin, B; Rudling, M

    2006-12-01

    Bile acids (BAs) traversing the enterohepatic circulation exert several important metabolic effects. Their hepatic synthesis, controlled by the enzyme cholesterol 7alpha-hydroxylase (CYP7A1), has a unique diurnal variation in man. Here we provide evidence that the transintestinal flux of BAs regulates serum levels of intestinal fibroblast growth factor 19 (FGF19) that in turn modulate BA production in human liver. Basal FGF19 levels varied by 10-fold in normal subjects, and were reduced following treatment with a BA-binding resin and increased upon feeding the BA chenodeoxycholic acid. Serum FGF19 levels exhibited a pronounced diurnal rhythm with peaks occurring 90-120 min after the postprandial rise in serum BAs. The FGF19 peaks in turn preceded the declining phase of BA synthesis. The diurnal rhythm of serum FGF19 was abolished upon fasting. We conclude that, in humans, circulating FGF19 has a diurnal rhythm controlled by the transintestinal BA flux, and that FGF19 modulates hepatic BA synthesis. Through its systemic effects, circulating FGF19 may also mediate other known BA-dependent effects on lipid and carbohydrate metabolism. PMID:17116003

  4. Differential Acute Postprandial Effects of Processed Meat and Isocaloric Vegan Meals on the Gastrointestinal Hormone Response in Subjects Suffering from Type 2 Diabetes and Healthy Controls: A Randomized Crossover Study

    PubMed Central

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

    2014-01-01

    Background The intake of meat, particularly processed meat, is a dietary risk factor for diabetes. Meat intake impairs insulin sensitivity and leads to increased oxidative stress. However, its effect on postprandial gastrointestinal hormone (GIH) secretion is unclear. We aimed to investigate the acute effects of two standardized isocaloric meals: a processed hamburger meat meal rich in protein and saturated fat (M-meal) and a vegan meal rich in carbohydrates (V-meal). We hypothesized that the meat meal would lead to abnormal postprandial increases in plasma lipids and oxidative stress markers and impaired GIH responses. Methods In a randomized crossover study, 50 patients suffering from type 2 diabetes (T2D) and 50 healthy subjects underwent two 3-h meal tolerance tests. For statistical analyses, repeated-measures ANOVA was performed. Results The M-meal resulted in a higher postprandial increase in lipids in both groups (p<0.001) and persistent postprandial hyperinsulinemia in patients with diabetes (p<0.001). The plasma glucose levels were significantly higher after the V-meal only at the peak level. The plasma concentrations of glucose-dependent insulinotropic peptide (GIP), peptide tyrosine-tyrosine (PYY) and pancreatic polypeptide (PP) were higher (p<0.05, p<0.001, p<0.001, respectively) and the ghrelin concentration was lower (p<0.001) after the M-meal in healthy subjects. In contrast, the concentrations of GIP, PYY and PP were significantly lower after the M-meal in T2D patients (p<0.001). Compared with the V-meal, the M-meal was associated with a larger increase in lipoperoxidation in T2D patients (p<0.05). Conclusion/Interpretation Our results suggest that the diet composition and the energy content, rather than the carbohydrate count, should be important considerations for dietary management and demonstrate that processed meat consumption is accompanied by impaired GIH responses and increased oxidative stress marker levels in diabetic patients. Trial

  5. Fasting and postprandial regulation of the intracellular localization of adiponectin and of adipokines secretion by dietary fat in rats

    PubMed Central

    Olivares-García, V; Torre-Villalvazo, I; Velázquez-Villegas, L; Alemán, G; Lara, N; López-Romero, P; Torres, N; Tovar, A R; Díaz-Villaseñor, A

    2015-01-01

    Background/Objective: Dietary fat sources modulate fasting serum concentration of adipokines, particularly adiponectin. However, previous studies utilized obese animals in which adipose tissue function is severely altered. Thus, the present study aimed to assess the postprandial regulation of adipokine secretion in nonobese rats that consumed high-fat diet (HFD) composed of different types of fat for a short time. Methods: The rats were fed a control diet or a HFD containing coconut, safflower or soybean oil (rich in saturated fatty acid, monounsaturated fatty acid or polyunsaturated fatty acid, respectively) for 21 days. The serum concentrations of adiponectin, leptin, retinol, retinol-binding protein-4 (RBP-4), visfatin and resistin were determined at fasting and after refeeding. Adiponectin multimerization and intracellular localization, as well as the expression of endoplasmic reticulum (ER) chaperones and transcriptional regulators, were evaluated in epididymal white adipose tissue. Results: In HFD-fed rats, serum adiponectin was significantly decreased 30 min after refeeding. With coconut oil, all three multimeric forms were reduced; with safflower oil, only the high-molecular-weight (HMW) and medium-molecular-weight (MMW) forms were decreased; and with soybean oil, only the HMW form was diminished. These reductions were due not to modifications in mRNA abundance or adiponectin multimerization but rather to an increment in intracellular localization at the ER and plasma membrane. Thus, when rats consumed a HFD, the type of dietary fat differentially affected the abundance of endoplasmic reticulum resident protein 44 kDa (ERp44), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ (PPARγ) mRNAs, all of which are involved in the post-translational processing of adiponectin required for its secretion. Leptin, RBP-4, resistin and visfatin serum concentrations did not change during fasting, whereas modest alterations were observed after

  6. Association of Genetic Variants with Isolated Fasting Hyperglycaemia and Isolated Postprandial Hyperglycaemia in a Han Chinese Population

    PubMed Central

    Chen, Ying; Chen, Li; Zhao, Zhigang; Li, Qiang; Ge, Jiapu; Chen, Gang; Guo, Xiaohui; Lu, Juming; Weng, Jianping; Jia, Weiping; Ji, Linong; Xiao, Jianzhong; Shan, Zhongyan; Liu, Jie; Tian, Haoming; Ji, Qiuhe; Zhu, Dalong; Zhou, Zhiguang; Shan, Guangliang; Yang, Wenying

    2013-01-01

    Background Though multiple single nucleotide polymorphisms (SNPs) associated with type 2 diabetes have been identified, the genetic bases of isolated fasting hyperglycaemia (IFH) and isolated postprandial hyperglycaemia (IPH) were still unclear. In present study, we aimed to investigate the association of genome-wide association study-validated genetic variants and IFH or IPH in Han Chinese. Methods/Principal Findings We genotyped 27 validated SNPs in 6,663 unrelated individuals comprising 341 IFH, 865 IPH, 1,203 combined fasting hyperglycaemia and postprandial hyperglycaemia, and 4,254 normal glycaemic subjects of Han ancestry. The distributions of genotype frequencies of FTO, CDKAL1 and GCKR were significant different between individuals with IFH and those with IPH (SNP(ptrend): rs8050136(0.0024), rs9939609(0.0049), rs7756992(0.0122), rs780094(0.0037)). Risk allele of FTO specifically increased the risk of IFH (rs8050136: OR 1.403 [95% CI 1.125–1.750], p = 0.0027; rs9939609: 1.398 [1.120–1.744], p = 0.0030). G allele of CDKAL1 specifically increased the risk of IPH (1.217 [1.092–1.355], p = 0.0004). G allele of GCKR increased the risk of IFH (1.167 [0.999–1.362], p = 0.0513), but decreased the risk of IPH (0.891 [0.801–0.991], p = 0.0331). In addition, TCF7L2 and KCNQ1 increased the risk of both IFH and IPH. When combined, each additional risk allele associated with IFH increased the risk for IFH by 1.246-fold (p<0.0001), while each additional risk allele associated with IPH increased the risk for IPH by 1.190-fold (p<0.0001). Conclusion/Significance Our results indicate that genotype distributions of variants from FTO, GCKR, CDKAL1 were different between IPH and IFH in Han Chinese. Variants of genes modulating insulin sensitivity (FTO, GCKR) contributed to the risk of IFH, while variants of genes related to beta cell function (CDKAL1) increase the risk of IPH. PMID:23990951

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  9. Postprandial oxidative stress is increased after a phytonutrient-poor food but not after a kilojoule-matched phytonutrient-rich food.

    PubMed

    Khor, Amanda; Grant, Ross; Tung, Chin; Guest, Jade; Pope, Belinda; Morris, Margaret; Bilgin, Ayse

    2014-05-01

    Research indicates that energy-dense foods increase inflammation and oxidative activity, thereby contributing to the development of vascular disease. However, it is not clear whether the high kilojoule load alone, irrespective of the nutritional content of the ingested food, produces the postprandial oxidative and inflammatory activity. This study investigated the hypothesis that ingestion of a high-fat, high-sugar, phytonutrient-reduced food (ice cream) would increase oxidative and inflammatory activity greater than a kilojoule-equivalent meal of a phytonutrient-rich whole food (avocado). The individual contributions of the fat/protein and sugar components of the ice cream meal to postprandial inflammation and oxidative stress were also quantified. Using a randomized, crossover design, 11 healthy participants ingested 4 test meals: ice cream, avocado, the fat/protein component in ice cream, and the sugar equivalent component in ice cream. Plasma glucose, cholesterol, triglycerides, and inflammatory and oxidative stress markers were measured at baseline and 1, 2, and 4 hours (t1, t2, t4) after ingestion. Lipid peroxidation was increased at 2 hours after eating fat/protein (t0-t2, P < .05) and sugar (t1-t2, P < .05; t1-t4, P < .05). Antioxidant capacity was decreased at 4 hours after eating ice cream (t0-t4, P < .01) and sugar (t0-t4, P < .01). Ingestion of a kilojoule-equivalent avocado meal did not produce any changes in either inflammatory or oxidative stress markers. These data indicate that the ingestion of a phytonutrient-poor food and its individual fat/protein or sugar components increase plasma oxidative activity. This is not observed after ingestion of a kilojoule-equivalent phytonutrient-rich food. PMID:24916552

  10. Dietary Fatty Acid Metabolism is Affected More by Lipid Level than Source in Senegalese Sole Juveniles: Interactions for Optimal Dietary Formulation.

    PubMed

    Bonacic, Kruno; Estévez, Alicia; Bellot, Olga; Conde-Sieira, Marta; Gisbert, Enric; Morais, Sofia

    2016-01-01

    This study analyses the effects of dietary lipid level and source on lipid absorption and metabolism in Senegalese sole (Solea senegalensis). Juvenile fish were fed 4 experimental diets containing either 100 % fish oil (FO) or 25 % FO and 75 % vegetable oil (VO; rapeseed, linseed and soybean oils) at two lipid levels (~8 or ~18 %). Effects were assessed on fish performance, body proximate composition and lipid accumulation, activity of hepatic lipogenic and fatty acid oxidative enzymes and, finally, on the expression of genes related to lipid metabolism in liver and intestine, and to intestinal absorption, both pre- and postprandially. Increased dietary lipid level had no major effects on growth and feeding performance (FCR), although fish fed FO had marginally better growth. Nevertheless, diets induced significant changes in lipid accumulation and metabolism. Hepatic lipid deposits were higher in fish fed VO, associated to increased hepatic ATP citrate lyase activity and up-regulated carnitine palmitoyltransferase 1 (cpt1) mRNA levels post-prandially. However, lipid level had a larger effect on gene expression of metabolic (lipogenesis and β-oxidation) genes than lipid source, mostly at fasting. High dietary lipid level down-regulated fatty acid synthase expression in liver and intestine, and increased cpt1 mRNA in liver. Large lipid accumulations were observed in the enterocytes of fish fed high lipid diets. This was possibly a result of a poor capacity to adapt to high dietary lipid level, as most genes involved in intestinal absorption were not regulated in response to the diet. PMID:26563870

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

    PubMed

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

    2016-06-01

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

  12. Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages.

    PubMed

    Allegra, M; D'Acquisto, F; Tesoriere, L; Attanzio, A; Livrea, M A

    2014-01-01

    Macrophages come across active prostaglandin (PG) metabolism during inflammation, shunting early production of pro-inflammatory towards anti-inflammatory mediators terminating the process. This work for the first time provides evidence that a phytochemical may modulate the arachidonate (AA) metabolism in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, promoting the ultimate formation of anti-inflammatory cyclopentenone 15deoxy-PGJ2. Added 1 h before LPS, indicaxanthin from Opuntia Ficus Indica prevented activation of nuclear factor-κB (NF-κB) and over-expression of PGE2 synthase-1 (mPGES-1), but up-regulated cyclo-oxygenase-2 (COX-2) and PGD2 synthase (H-PGDS), with final production of the anti-inflammatory cyclopentenone. The effects were positively related with concentration between 50 and 100 µM. Indicaxanthin did not have any effect in the absence of LPS. A kinetic study investigating the redox status of LPS-stimulated macrophages between 0.5 and 12 h, either in the absence or in the presence of 50-100 µM indicaxanthin, revealed a differential control of ROS production, with early (0.5-3 h) modest inhibition, followed by a progressive (3-12 h) concentration-dependent enhancement over the level induced by LPS alone. In addition, indicaxanthin caused early (0.5-3 h) concentration-dependent elevation of conjugated diene lipid hydroperoxides, and production of hydroxynonenal-protein adducts, over the amount induced by LPS. In LPS-stimulated macrophages indicaxanthin did not affect PG metabolism when co-incubated with either an inhibitor of NADPH oxidase or vitamin E. It is concluded that LPS-induced pro-oxidant activity of indicaxanthin at the membrane level allows formation of signaling intermediates whose accumulation modulates PG biosynthetic pathway in inflamed macrophages. PMID:25180166

  13. Pathways for Modulating Exosome Lipids Identified By High-Density Lipoprotein-Like Nanoparticle Binding to Scavenger Receptor Type B-1.

    PubMed

    Angeloni, Nicholas L; McMahon, Kaylin M; Swaminathan, Suchitra; Plebanek, Michael P; Osman, Iman; Volpert, Olga V; Thaxton, C Shad

    2016-01-01

    Exosomes are produced by cells to mediate intercellular communication, and have been shown to perpetuate diseases, including cancer. New tools are needed to understand exosome biology, detect exosomes from specific cell types in complex biological media, and to modify exosomes. Our data demonstrate a cellular pathway whereby membrane-bound scavenger receptor type B-1 (SR-B1) in parent cells becomes incorporated into exosomes. We tailored synthetic HDL-like nanoparticles (HDL NP), high-affinity ligands for SR-B1, to carry a fluorescently labeled phospholipid. Data show SR-B1-dependent transfer of the fluorescent phospholipid from HDL NPs to exosomes. Modified exosomes are stable in serum and can be directly detected using flow cytometry. As proof-of-concept, human serum exosomes were found to express SR-B1, and HDL NPs can be used to label and isolate them. Ultimately, we discovered a natural cellular pathway and nanoparticle-receptor pair that enables exosome modulation, detection, and isolation. PMID:26964503

  14. Pathways for Modulating Exosome Lipids Identified By High-Density Lipoprotein-Like Nanoparticle Binding to Scavenger Receptor Type B-1

    PubMed Central

    Angeloni, Nicholas L.; McMahon, Kaylin M.; Swaminathan, Suchitra; Plebanek, Michael P.; Osman, Iman; Volpert, Olga V.; Thaxton, C. Shad

    2016-01-01

    Exosomes are produced by cells to mediate intercellular communication, and have been shown to perpetuate diseases, including cancer. New tools are needed to understand exosome biology, detect exosomes from specific cell types in complex biological media, and to modify exosomes. Our data demonstrate a cellular pathway whereby membrane-bound scavenger receptor type B-1 (SR-B1) in parent cells becomes incorporated into exosomes. We tailored synthetic HDL-like nanoparticles (HDL NP), high-affinity ligands for SR-B1, to carry a fluorescently labeled phospholipid. Data show SR-B1-dependent transfer of the fluorescent phospholipid from HDL NPs to exosomes. Modified exosomes are stable in serum and can be directly detected using flow cytometry. As proof-of-concept, human serum exosomes were found to express SR-B1, and HDL NPs can be used to label and isolate them. Ultimately, we discovered a natural cellular pathway and nanoparticle-receptor pair that enables exosome modulation, detection, and isolation. PMID:26964503

  15. Insoluble Fiber in Young Barley Leaf Suppresses the Increment of Postprandial Blood Glucose Level by Increasing the Digesta Viscosity

    PubMed Central

    Kamiya, Tomoyasu; Tomozawa, Hiroshi; Ueno, Shiori; Tsubata, Masahito; Ikeguchi, Motoya; Takagaki, Kinya; Okushima, Ayaka; Miyata, Yu; Tamaru, Shizuka; Tanaka, Kazunari; Takahashi, Toru

    2013-01-01

    Barley (Hordeum vulgare L.) is a well-known cereal plant. Young barley leaf is consumed as a popular green-colored drink, which is named “Aojiru” in Japan. We examined the effects of barley leaf powder (BLP) and insoluble fibers derived from BLP on postprandial blood glucose in rats and healthy Japanese volunteers. BLP and insoluble fibers derived from BLP suppressed the increment of postprandial blood glucose levels in rats (P < 0.01), and increased the viscosity of their digesta. The insoluble fibers present in BLP might play a role in controlling blood glucose level by increasing digesta viscosity. In human, BLP suppressed the increment of postprandial blood glucose level only in those which exhibited higher blood glucose levels after meals (P < 0.01). BLP might suppress the increment of postprandial blood glucose level by increasing digesta viscosity in both of rats and humans who require blood glucose monitoring. PMID:24348688

  16. Dividing Cells Regulate Their Lipid Composition and Localization

    PubMed Central

    Atilla-Gokcumen, G. Ekin; Muro, Eleonora; Relat-Goberna, Josep; Sasse, Sofia; Bedigian, Anne; Coughlin, Margaret L.; Garcia-Manyes, Sergi; Eggert, Ulrike S.

    2014-01-01

    Summary Although massive membrane rearrangements occur during cell division, little is known about specific roles that lipids might play in this process. We report that the lipidome changes with the cell cycle. LC-MS-based lipid profiling shows that 11 lipids with specific chemical structures accumulate in dividing cells. Using AFM, we demonstrate differences in the mechanical properties of live dividing cells and their isolated lipids relative to nondividing cells. In parallel, systematic RNAi knockdown of lipid biosynthetic enzymes identified enzymes required for division, which highly correlated with lipids accumulated in dividing cells. We show that cells specifically regulate the localization of lipids to midbodies, membrane-based structures where cleavage occurs. We conclude that cells actively regulate and modulate their lipid composition and localization during division, with both signaling and structural roles likely. This work has broader implications for the active and sustained participation of lipids in basic biology. PMID:24462247

  17. Effect of fat type in baked bread on amylose-lipid complex formation and glycaemic response.

    PubMed

    Lau, Evelyn; Zhou, Weibiao; Henry, Christiani Jeyakumar

    2016-06-01

    The formation of amylose-lipid complexes (ALC) had been associated with reduced starch digestibility. A few studies have directly characterised the extent of ALC formation with glycaemic response. The objectives of this study were to investigate the effect of using fats with varying degree of saturation and chain length on ALC formation as well as glycaemic and insulinaemic responses after consumption of bread. Healthy men consumed five test breads in a random order: control bread without any added fats (CTR) and breads baked with butter (BTR), coconut oil (COC), grapeseed oil (GRP) or olive oil (OLV). There was a significant difference in glycaemic response between the different test breads (P=0·002), primarily due to COC having a lower response than CTR (P=0·016), but no significant differences between fat types were observed. Insulinaemic response was not altered by the addition of fats/oils. Although BTR was more insulinotropic than GRP (P<0·05), postprandial β-cell function did not differ significantly. The complexing index (CI), a measure of ALC formation, was significantly higher for COC and OLV compared with BTR and GRP (P<0·05). CI was significantly negatively correlated with incremental AUC (IAUC) of change in blood glucose concentrations over time (IAUCglucose) (r -0·365, P=0·001). Linear regression analysis showed that CI explained 13·3 % of the variance and was a significant predictor of IAUCglucose (β=-1·265, P=0·001), but IAUCinsulin did not predict IAUCglucose. Our study indicated that a simple way to modulate glycaemic response in bread could lie in the choice of fats/oils, with coconut oil showing the greatest attenuation of glycaemic response. PMID:27102847

  18. Vagal afferents are not necessary for the satiety effect of the gut lipid messenger oleoylethanolamide.

    PubMed

    Azari, Elnaz Karimian; Ramachandran, Deepti; Weibel, Sandra; Arnold, Myrtha; Romano, Adele; Gaetani, Silvana; Langhans, Wolfgang; Mansouri, Abdelhak

    2014-07-15

    The endogenous lipid messenger oleoylethanolamide (OEA) inhibits eating and modulates fat metabolism supposedly through the activation of peroxisome proliferator-activated receptor-α (PPARα) and vagal sensory fibers. We tested in adult male rats whether OEA stimulates fatty acid oxidation (FAO) and ketogenesis and whether it increases plasma levels of the satiating gut peptides glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). We also explored whether OEA still inhibits eating after subdiaphragmatic vagal deafferentation (SDA). We found that intraperitoneally injected OEA (10 mg/kg body wt) reduced (P < 0.05) food intake mainly by increasing meal latency and that this effect was stronger in rats fed a 60% high-fat diet (HFD) than in chow-fed rats. OEA increased (P < 0.05) postprandial plasma nonesterified fatty acids and β-hydroxybutyrate (BHB) in the hepatic portal vein (HPV) and vena cava (VC) 30 min after injection, which was more pronounced in HFD- than in chow-fed rats. OEA also increased the protein expression of the key ketogenetic enzyme, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, in the jejunum of HFD-fed rats, but not in the liver or duodenum of either diet group. Furthermore, OEA decreased GLP-1 and PYY concentrations (P < 0.05) in the HPV and VC 30 min after administration. Finally, OEA reduced food intake in SDA and sham-operated rats similarly. Our findings indicate that neither intact abdominal vagal afferents nor prandial increases in GLP-1 or PMID:24829501

  19. Mastication Frequency and Postprandial Blood Sugar Levels in Normoglycaemic and Dysglycaemic Individuals: A Cross- Sectional Comparative Study

    PubMed Central

    Madhu, Vinayak; Pawaskar, Priyanka Niwas; Madi, Deepak; Chowta, Nithyananda; Ramapuram, John Thomas

    2016-01-01

    Introduction Mastication has potential to affect postprandial blood glucose levels by affecting cephalic phase of insulin release. However, limited number of studies done in this regard has yielded conflicting results. Aim To evaluate effects of mastication on postprandial blood glucose levels. Materials and Methods We compared routine and thorough mastication in 2 separate groups: dysglycaemic (prediabetics and diabetics) and normoglycaemic in prospective interventional study. Blood glucose levels were measured pre-prandial and postprandial (after 2 hours) on separate days after routine and thorough mastication in both groups. Results In normoglycaemic group, thorough mastication significantly reduced postprandial blood glucose levels at 2 hours (128.25± 7.82 mg/dl on routine mastication vs 119.74±9.08 mg/dl on thorough mastication, p<0.05). Comparatively, in dysglycaemic group, thorough mastication had little effect on postprandial blood glucose levels at 2 hours (244.07±22.37 mg/dl vs. 243.55±22.87 mg/dl). Conclusion In normoglycaemic group, postprandial blood glucose concentration upon thorough mastication was significantly lower, due to early-phase insulin secretion. This simple lifestyle modification of thorough mastication can be a useful preventive measure against diabetes in people with a strong family history and other risk factors for diabetes who have not yet developed diabetes or prediabetes.

  20. Postprandial hyperoxaluria and intestinal oxalate absorption in idiopathic renal stone disease

    SciTech Connect

    Schwille, P.O.; Hanisch, E.; Scholz, D.

    1984-10-01

    Calcium and oxalate were studied in daily, fasting and postprandial urine specimens from healthy subjects and patients with idiopathic renal calcium stones in response to a test meal free of oxalate, and supplemented with calcium and 14carbon-oxalic acid. The data showed that the amount of oxalate in fasting urine of patients with stones did not differ from that in controls. Generally, patients with stones had considerable postprandial hyperoxaluria in terms of excretion and concentration, associated with a significantly higher degree of supersaturation with regard to calcium oxalate compared to controls. These findings were paralleled by decreased intestinal absorption of 14carbon-oxalate and by unchanged 24-hour urinary oxalate. Although the source of increased p

  1. Lapacho tea (Tabebuia impetiginosa) extract inhibits pancreatic lipase and delays postprandial triglyceride increase in rats.

    PubMed

    Kiage-Mokua, Beatrice Nyanchama; Roos, Nils; Schrezenmeir, Jürgen

    2012-12-01

    Earlier work in our laboratory indicated that ethanolic extracts of Tabebuia impetiginosa, Arctium lappa L., Calendula officinalis, Helianthus annuus, Linum usitatissimum and L. propolis, inhibit pancreatic lipase in vitro. In a follow-up study we assessed their effects on plasma triglycerides in rats fed on a fatty meal. Extracts, orlistat or only ethanol were given orally to the rats together with the test meal and the rate of increase of postprandial triglycerides was assessed over 4 h. Clearing of the triglycerides from the blood compartment was abolished by inhibiting lipoprotein lipase with Triton WR-1339. Our results showed that out of all the extracts, the bark of Tabebuia impetiginosa led to a significant delay in the postprandial increase of plasma triglycerides. However, lapachol, which is contained in the bark of Tabebuia impetiginosa and soluble in ethanol, had no lipase inhibitory effect in vitro and hence this substance did not seem to mediate the pertinent effect. PMID:22431070

  2. Chronic intake of fractionated yellow pea flour reduces postprandial energy expenditure and carbohydrate oxidation.

    PubMed

    Marinangeli, Christopher P F; Jones, Peter J H

    2011-12-01

    Effects of dietary fibers on human postprandial energetics remain undefined. The objective of the present study was to explore effects of whole yellow pea flour (WPF) and fractionated pea flour (FPF) on postprandial energy expenditure, substrate utilization, and hepatic triglyceride synthesis rate. Using a crossover-diet controlled design, 23 overweight men and women received muffins containing WPF, FPF, and white wheat flour (WF) for 28 days, followed by 28-day washout periods. Subjects received 50 g/day WPF and WF. Given that FPF is approximately 84% fiber, the amount of FPF administered to volunteers was equivalent to the amount of pea-derived fiber in the WPF treatment. Four weeks of FPF consumption reduced (P=.007) total postprandial energy expenditure (333.0±3.6 kcal/330 minutes) compared with WF (349.3±3.6 kcal/330 minutes). When values were normalized to the level of food energy consumed, FPF (4.6±0.3%) decreased (P=.018) the thermic effect of food (TEF) compared with WF (5.7±0.3%). Carbohydrate oxidation tended to be lower (P=.075) with FPF (44.7±2.1 g/330 minutes) versus WF (51.2±0.1.9 g/330 minutes). WPF had no effect on total energy expenditure, TEF, or carbohydrate oxidation. Only after 370 minutes was cumulative oxidation of [1-(13)C]palmitic acid higher (P=.045) in the WPF group (0.96±0.05%) compared with FPF (0.81±0.05%). Neither treatment had any effect on hepatic triglyceride synthesis rate. In conclusion, chronic ingestion of different fractions of yellow peas imposes distinctive effects on postprandial energy expenditure and substrate utilization. PMID:22145774

  3. Is Cancer Cachexia Attributed to Impairments in Basal or Postprandial Muscle Protein Metabolism?

    PubMed

    Horstman, Astrid M H; Olde Damink, Steven W; Schols, Annemie M W J; van Loon, Luc J C

    2016-01-01

    Cachexia is a significant clinical problem associated with very poor quality of life, reduced treatment tolerance and outcomes, and a high mortality rate. Mechanistically, any sizeable loss of skeletal muscle mass must be underpinned by a structural imbalance between muscle protein synthesis and breakdown rates. Recent data indicate that the loss of muscle mass with aging is, at least partly, attributed to a blunted muscle protein synthetic response to protein feeding. Whether such anabolic resistance is also evident in conditions where cachexia is present remains to be addressed. Only few data are available on muscle protein synthesis and breakdown rates in vivo in cachectic cancer patients. When calculating the theoretical changes in basal or postprandial fractional muscle protein synthesis and breakdown rates that would be required to lose 5% of body weight within a six-month period, we can define the changes that would need to occur to explain the muscle mass loss observed in cachectic patients. If changes in both post-absorptive and postprandial muscle protein synthesis and breakdown rates contribute to the loss of muscle mass, it would take alterations as small as 1%-2% to induce a more than 5% decline in body weight. Therefore, when trying to define impairments in basal and/or postprandial muscle protein synthesis or breakdown rates using contemporary stable isotope methodology in cancer cachexia, we need to select large homogenous groups of cancer patients (>40 patients) to allow us to measure physiological and clinically relevant differences in muscle protein synthesis and/or breakdown rates. Insight into impairments in basal or postprandial muscle protein synthesis and breakdown rates in cancer cachexia is needed to design more targeted nutritional, pharmaceutical and/or physical activity interventions to preserve skeletal muscle mass and, as such, to reduce the risk of complications, improve quality of life, and lower mortality rates during the various

  4. Postprandial metabolite profiles reveal differential nutrient handling after bariatric surgery compared to matched caloric restriction

    PubMed Central

    Khoo, Chin Meng; Muehlbauer, Michael J.; Stevens, Robert D.; Pamuklar, Zehra; Chen, Jiegen; Newgard, Christopher B.; Torquati, Alfonso

    2013-01-01

    Background Roux-en-Y gastric bypass (RYGB) surgery results in exaggerated postprandial insulin and incretin responses, and increased susceptibility to hypoglycemia. We examined whether these features are due to caloric restriction (CR) or altered nutrient handling. Methods We performed comprehensive analysis of postprandial metabolite responses during a 2-hour mixed-meal challenge test (MMT) in twenty morbidly obese subjects with type 2 diabetes who underwent RYGB surgery or matched CR. Acylcarnitines and amino acids was measured using targeted mass spectrometry. Linear mixed model was used to determine the main effect of interventions, and interaction term to assess the effect of interventions on postprandial kinetics. Results Two-weeks after these interventions, several gut hormones (insulin, GIP and GLP-1), glucose, and multiple amino acids, including branched-chain and aromatic species, exhibited a more rapid rate of appearance and clearance in RYGB subjects compared to CR during the MMT. In the RYGB group, changes in leucine/isoleucine, methionine, phenylalanine and GLP-1 responses were associated with changes in insulin response. Levels of alanine, pyruvate, and lactate decreased significantly at the later stages of meal challenge in RYGB subjects, but increased with CR. Conclusions RYGB surgery results in improved metabolic flexibility (i.e. greater disposal of glucose and amino acids, and more complete β-oxidation of fatty acids) compared to CR. The changes in the amino acid kinetics may augment the hormonal responses seen after RYGB surgery. The reduction in key gluconeogenic substrates in the postprandial state may contribute to increased susceptibility to hypoglycemic symptoms in RYGB subjects. PMID:23787216

  5. Is Cancer Cachexia Attributed to Impairments in Basal or Postprandial Muscle Protein Metabolism?

    PubMed Central

    Horstman, Astrid M. H.; Olde Damink, Steven W.; Schols, Annemie M. W. J.; van Loon, Luc J. C.

    2016-01-01

    Cachexia is a significant clinical problem associated with very poor quality of life, reduced treatment tolerance and outcomes, and a high mortality rate. Mechanistically, any sizeable loss of skeletal muscle mass must be underpinned by a structural imbalance between muscle protein synthesis and breakdown rates. Recent data indicate that the loss of muscle mass with aging is, at least partly, attributed to a blunted muscle protein synthetic response to protein feeding. Whether such anabolic resistance is also evident in conditions where cachexia is present remains to be addressed. Only few data are available on muscle protein synthesis and breakdown rates in vivo in cachectic cancer patients. When calculating the theoretical changes in basal or postprandial fractional muscle protein synthesis and breakdown rates that would be required to lose 5% of body weight within a six-month period, we can define the changes that would need to occur to explain the muscle mass loss observed in cachectic patients. If changes in both post-absorptive and postprandial muscle protein synthesis and breakdown rates contribute to the loss of muscle mass, it would take alterations as small as 1%–2% to induce a more than 5% decline in body weight. Therefore, when trying to define impairments in basal and/or postprandial muscle protein synthesis or breakdown rates using contemporary stable isotope methodology in cancer cachexia, we need to select large homogenous groups of cancer patients (>40 patients) to allow us to measure physiological and clinically relevant differences in muscle protein synthesis and/or breakdown rates. Insight into impairments in basal or postprandial muscle protein synthesis and breakdown rates in cancer cachexia is needed to design more targeted nutritional, pharmaceutical and/or physical activity interventions to preserve skeletal muscle mass and, as such, to reduce the risk of complications, improve quality of life, and lower mortality rates during the various

  6. Lipid structure does not modify incorporation of EPA and DHA into blood lipids in healthy adults: a randomised-controlled trial.

    PubMed

    West, Annette L; Burdge, Graham C; Calder, Philip C

    2016-09-01

    Dietary supplementation is an effective means to improve EPA and DHA status. However, it is unclear whether lipid structure affects EPA+DHA bioavailability. We determined the effect of consuming different EPA and DHA lipid structures on their concentrations in blood during the postprandial period and during dietary supplementation compared with unmodified fish oil TAG (uTAG). In a postprandial cross-over study, healthy men (n 9) consumed in random order test meals containing 1·1 g EPA+0·37 g DHA as either uTAG, re-esterified TAG, free fatty acids (FFA) or ethyl esters (EE). In a parallel design supplementation study, healthy men and women (n 10/sex per supplement) consumed one supplement type for 12 weeks. Fatty acid composition was determined by GC. EPA incorporation over 6 h into TAG or phosphatidylcholine (PC) did not differ between lipid structures. EPA enrichment in NEFA was lower from EE than from uTAG (P=0·01). Plasma TAG, PC or NEFA DHA incorporation did not differ between lipid structures. Lipid structure did not affect TAG or NEFA EPA incorporation and PC or NEFA DHA incorporation following dietary supplementation. Plasma TAG peak DHA incorporation was greater (P=0·02) and time to peak shorter (P=0·02) from FFA than from uTAG in men. In both studies, the order of EPA and DHA incorporation was PC>TAG>NEFA. In conclusion, EPA and DHA lipid structure may not be an important consideration in dietary interventions. PMID:27424661

  7. Polyopes lancifolia Extract, a Potent α-Glucosidase Inhibitor, Alleviates Postprandial Hyperglycemia in Diabetic Mice

    PubMed Central

    Min, Seong Won; Han, Ji Sook

    2014-01-01

    This study was designed to investigate the inhibitory effects of Polyopes lancifolia extract (PLE) on α-glucosidase activity, α-amylase activitiy, and postprandial hyperglycemia in streptozotocin (STZ)-induced diabetic mice. The results of this study revealed a marked inhibitory effect of PLE on α-glucosidase and α-amylase activities. The IC50s of PLE against α-glucosidase and α-amylase were 0.20 mg/mL and 0.35 mg/mL, respectively. PLE was a more effective inhibitor of α-glucosidase and α-amylase activities than acarbose, the positive control. The postprandial blood glucose levels of STZ-induced diabetic mice were significantly lower in the PLE treated group than in the control group. Moreover, PLE administration was associated with a decreased area under the curve for the glucose response in diabetic mice. These results indicate that PLE may be a potent inhibitor of α-glucosidase and α-amylase activities and may suppress postprandial hyperglycemia. PMID:24772403

  8. Association between Glucose Levels and Intraocular Pressure: Pre- and Postprandial Analysis in Diabetic and Nondiabetic Patients

    PubMed Central

    Pimentel, Luis Guilherme Milesi; Gracitelli, Carolina P. B.; da Silva, Leticia Sant'Ana Cardoso; Souza, Aline Katia Siqueira; Prata, Tiago Santos

    2015-01-01

    The aim of this study was to evaluate the relationship between glucose levels and intraocular pressure (IOP) fluctuation in diabetic and nondiabetic patients. Seventeen nondiabetic and 20 diabetic subjects underwent a complete ophthalmic examination, capillary glucose testing, and applanation tonometry in two distinct situations: first, fasting for at least 8 hours and, second, postprandial measurements. Baseline glucose levels were higher in diabetic patients (P < 0.001). Postprandial IOP was significantly higher than baseline IOP in diabetic (P < 0.001) and nondiabetic patients (P = 0.006). Postprandial glucose levels were significantly higher than baseline measurements in both diabetic (P = 0.005) and nondiabetic patients (P = 0.015). There was a significant association between glucose levels variation and IOP change in both diabetic patients (R2 = 0.540; P < 0.001) and nondiabetic individuals (R2 = 0.291; P = 0.025). There is also a significant association between the baseline glucose levels and IOP change in diabetic group (R2 = 0.445; P = 0.001). In a multivariable model, the magnitude of glucose level change remained significantly associated with IOP variation even including age, baseline IOP, ancestry, and gender as a confounding factor (P < 0.001). We concluded that there is a significant association between blood glucose levels and IOP variation, especially in diabetic patients. PMID:25642344

  9. High Amylose White Rice Reduces Post-Prandial Glycemic Response but Not Appetite in Humans

    PubMed Central

    Zenel, Alison M.; Stewart, Maria L.

    2015-01-01

    The present study compared the effects of three rice cultivars on postprandial glycemic control and appetite. A single-blind, randomized, crossover clinical trial was performed with 18 healthy subjects, nine males and nine females. Three treatments were administered at three separate study visits: commercially available conventional white rice (short grain), specialty high amylose white rice 1 (Dixiebelle), and specialty high amylose white rice 2 (Rondo). Postprandial capillary blood glucose, venous blood glucose and insulin measurements, and appetite visual analog scale (VAS) surveys were done over the course of two hours. The capillary blood glucose concentrations were significantly lower for Rondo compared to short grain rice at 30 min, and for Dixiebelle and Rondo compared to short grain rice at 45, 60, and 120 min. Capillary blood glucose area under the curve (AUC) was significantly lower for Dixiebelle and Rondo compared to short grain rice. Subjects were significantly more hungry at 30 min after Dixiebelle intake than Rondo intake, but there were no other significant effects in appetite ratings. The present study determined that intake of high amylose rice with resistant starch (RS) can attenuate postprandial blood glucose and insulin response in comparison to short grain rice. PMID:26147654

  10. Differences in postprandial inflammatory responses to a 'modern' v. traditional meat meal: a preliminary study.

    PubMed

    Arya, Fatemeh; Egger, Sam; Colquhoun, David; Sullivan, David; Pal, Sebely; Egger, Garry

    2010-09-01

    A low-grade inflammatory response ('metaflammation') has been found to be associated with certain chronic diseases. Proposed inducers of this have been aspects of the modern lifestyle, including newly introduced foods. Plasma TAG, and the inflammatory cytokines C-reactive protein (CRP), TNF-alpha and IL-6 were compared in a randomised, cross-over trial using ten healthy subjects before and after eating 100 g of kangaroo, or a 'new' form of hybridised beef (wagyu) separated by about 1 week. Postprandial levels for 1 and 2 h of TAG, IL-6 and TNF-alpha were significantly higher after eating wagyu compared with kangaroo (P = 0.002 for TAG at 1 h, P < 0.001 at 2 h; P < 0.001 for IL-6 and TNF-alpha at 1 and 2 h). CRP was significantly higher 1 h postprandially after wagyu (P = 0.011) and non-significantly higher 2 h postprandially (P = 0.090). We conclude that the metaflammatory reaction to ingestion of a 'new' form of hybridised beef (wagyu) is indicative of a low-grade, systemic, immune reaction when compared with lean game meat (kangaroo). Further studies using isoenergetic intake and isolating fatty acid components of meats are proposed. PMID:20377925

  11. Postprandial dietary fatty acids exert divergent inflammatory responses in retinal-pigmented epithelium cells.

    PubMed

    Montserrat-de la Paz, Sergio; Naranjo, M Carmen; Bermudez, Beatriz; Lopez, Sergio; Moreda, Wenceslao; Abia, Rocio; Muriana, Francisco J G

    2016-03-16

    Postprandial triglyceride-rich lipoproteins (TRLs) lead to a complex series of events that are potentially oxidative and inflammatory. The main goal of this study was to characterize the influence of postprandial TRLs with different fatty acid compositions (mainly SFAs, MUFAs or MUFAs plus omega-3 PUFAs) on oxidative and inflammatory markers in RPE cells, which play a pivotal role in age-related macular degeneration (AMD). Compared to TRL-SFAs, TRL-MUFAs and TRL-MUFAs plus omega-3 PUFAs decreased the production of ROS and nitrite, and the gene expression and secretion of IL-1β, IL-6, TNF-α, IFNγ and VEGF. For the first time we show that postprandial TRLs are metabolic entities able to induce RPE oxidative stress and inflammation in a fatty acid-dependent manner, TRL-SFAs ⋙ TRL-MUFAs = TRL-MUFAs plus omega-3 PUFAs. These exciting findings open new opportunities for developing novel nutritional strategies with olive oil as the principal dietary source of oleic acid to prevent the development and progression of AMD. PMID:26914244

  12. Intracerebroventricular injection of murine leptin enhances the postprandial metabolic rate in the rat.

    PubMed

    Ruffin, M; Nicolaidis, S

    2000-08-18

    Energy balance is achieved by means of a concomitant control of both food intake and energy expenditure. Leptin, synthesized in the adipose tissue, acts on brain structures and lowers body weight by inhibiting food intake and in parallel by enhancing energy expenditure i.e. metabolism or one of its components. Recording distinctly these components allowed us to assess the effect of an acute intracerebroventricular injection of leptin on both feeding pattern and background metabolism (i.e. energy expenditure free from the part of locomotor activity), respiratory quotient, feeding-related metabolism and locomotor activity-related metabolism. Leptin injection to Sprague-Dawley male rats induced an inhibition of feeding that began 90 min after the treatment and lasted 1 h before to return to the control feeding pattern level. Considering this late behavioral effect, it appeared that leptin may act during the postprandial period so that we recorded the different metabolic parameters following a 3 g calibrated meal itself preceded by leptin vs. artificial cerebrospinal fluid injection. Postprandial respiratory quotient was rapidly lowered in leptin-treated animals and subsequent background metabolism increased for 6 h. Thus it appeared that leptin increased the duration of the postprandial metabolic rate via the recruitment of endogenous fat stores. Enhancement in the thermic effect of food may be the reason for feeding behavior inhibition to be delayed. PMID:10936221

  13. Phlorofucofuroeckol A isolated from Ecklonia cava alleviates postprandial hyperglycemia in diabetic mice.

    PubMed

    You, Han-Nui; Lee, Hyun-Ah; Park, Mi-Hwa; Lee, Ji-Hyeok; Han, Ji-Sook

    2015-04-01

    This study was designed to investigate whether phlorofucofuroeckol A inhibited α-glucosidase and α-amylase activities and alleviated postprandial hyperglycemia in diabetic mice. Phlorofucofuroeckol A that was isolated from Ecklonia cava (brown algae) demonstrated prominent inhibitory effects against α-glucosidase and α-amylase activities. The IC50 values of phlorofucofuroeckol A against α-glucosidase and α-amylase were 19.52 and 6.34μM, respectively. These inhibitory activities of phlorofucofuroeckol A were higher than those of acarbose, which was used as a positive control. Increases in postprandial blood glucose levels were significantly more suppressed in the group administered phlorofucofuroeckol A compared to the control group in both diabetic and normal mice. Moreover, the area under the curve was significantly lower after phlorofucofuroeckol A administration (2296 versus 2690mmolmin/l) in the diabetic mice. These results suggested that phlorofucofuroeckol A is a potent α-glucosidase inhibitor and can alleviate the postprandial hyperglycemia that is caused by starch. PMID:25680946

  14. Aqueous Extract of Nypa fruticans Wurmb. Vinegar Alleviates Postprandial Hyperglycemia in Normoglycemic Rats †

    PubMed Central

    Yusoff, Nor Adlin; Ahmad, Mariam; Al-Hindi, Bassel; Widyawati, Tri; Yam, Mun Fei; Mahmud, Roziahanim; Abdul Razak, Khairul Niza; Asmawi, Mohd Zaini

    2015-01-01

    Nypa fruticans Wurmb. vinegar, commonly known as nipa palm vinegar (NPV) has been used as a folklore medicine among the Malay community to treat diabetes. Early work has shown that aqueous extract (AE) of NPV exerts a potent antihyperglycemic effect. Thus, this study is conducted to evaluate the effect of AE on postprandial hyperglycemia in an attempt to understand its mechanism of antidiabetic action. AE were tested via in vitro intestinal glucose absorption, in vivo carbohydrate tolerance tests and spectrophotometric enzyme inhibition assays. One mg/mL of AE showed a comparable outcome to the use of phloridzin (1 mM) in vitro as it delayed glucose absorption through isolated rat jejunum more effectively than acarbose (1 mg/mL). Further in vivo confirmatory tests showed AE (500 mg/kg) to cause a significant suppression in postprandial hyperglycemia 30 min following respective glucose (2 g/kg), sucrose (4 g/kg) and starch (3 g/kg) loadings in normal rats, compared to the control group. Conversely, in spectrophotometric enzymatic assays, AE showed rather a weak inhibitory activity against both α-glucosidase and α-amylase when compared with acarbose. The findings suggested that NPV exerts its anti-diabetic effect by delaying carbohydrate absorption from the small intestine through selective inhibition of intestinal glucose transporters, therefore suppressing postprandial hyperglycemia. PMID:26308046

  15. Aqueous Extract of Nypa fruticans Wurmb. Vinegar Alleviates Postprandial Hyperglycemia in Normoglycemic Rats.

    PubMed

    Yusoff, Nor Adlin; Ahmad, Mariam; Al-Hindi, Bassel; Widyawati, Tri; Yam, Mun Fei; Mahmud, Roziahanim; Razak, Khairul Niza Abdul; Asmawi, Mohd Zaini

    2015-08-01

    Nypa fruticans Wurmb. vinegar, commonly known as nipa palm vinegar (NPV) has been used as a folklore medicine among the Malay community to treat diabetes. Early work has shown that aqueous extract (AE) of NPV exerts a potent antihyperglycemic effect. Thus, this study is conducted to evaluate the effect of AE on postprandial hyperglycemia in an attempt to understand its mechanism of antidiabetic action. AE were tested via in vitro intestinal glucose absorption, in vivo carbohydrate tolerance tests and spectrophotometric enzyme inhibition assays. One mg/mL of AE showed a comparable outcome to the use of phloridzin (1 mM) in vitro as it delayed glucose absorption through isolated rat jejunum more effectively than acarbose (1 mg/mL). Further in vivo confirmatory tests showed AE (500 mg/kg) to cause a significant suppression in postprandial hyperglycemia 30 min following respective glucose (2 g/kg), sucrose (4 g/kg) and starch (3 g/kg) loadings in normal rats, compared to the control group. Conversely, in spectrophotometric enzymatic assays, AE showed rather a weak inhibitory activity against both α-glucosidase and α-amylase when compared with acarbose. The findings suggested that NPV exerts its anti-diabetic effect by delaying carbohydrate absorption from the small intestine through selective inhibition of intestinal glucose transporters, therefore suppressing postprandial hyperglycemia. PMID:26308046

  16. Avocado consumption enhances human postprandial provitamin A absorption and conversion from a novel high-β-carotene tomato sauce and from carrots.

    PubMed

    Kopec, Rachel E; Cooperstone, Jessica L; Schweiggert, Ralf M; Young, Gregory S; Harrison, Earl H; Francis, David M; Clinton, Steven K; Schwartz, Steven J

    2014-08-01

    Dietary lipids have been shown to increase bioavailability of provitamin A carotenoids from a single meal, but the effects of dietary lipids on conversion to vitamin A during absorption are essentially unknown. Based on previous animal studies, we hypothesized that the consumption of provitamin A carotenoids with dietary lipid would enhance conversion to vitamin A during absorption compared with the consumption of provitamin A carotenoids alone. Two separate sets of 12 healthy men and women were recruited for 2 randomized, 2-way crossover studies. One meal was served with fresh avocado (Persea americana Mill), cultivated variety Hass (delivering 23 g of lipid), and a second meal was served without avocado. In study 1, the source of provitamin A carotenoids was a tomato sauce made from a novel, high-β-carotene variety of tomatoes (delivering 33.7 mg of β-carotene). In study 2, the source of provitamin A carotenoids was raw carrots (delivering 27.3 mg of β-carotene and 18.7 mg of α-carotene). Postprandial blood samples were taken over 12 h, and provitamin A carotenoids and vitamin A were quantified in triglyceride-rich lipoprotein fractions to determine baseline-corrected area under the concentration-vs.-time curve. Consumption of lipid-rich avocado enhanced the absorption of β-carotene from study 1 by 2.4-fold (P < 0.0001). In study 2, the absorption of β-carotene and α-carotene increased by 6.6- and 4.8-fold, respectively (P < 0.0001 for both). Most notably, consumption of avocado enhanced the efficiency of conversion to vitamin A (as measured by retinyl esters) by 4.6-fold in study 1 (P < 0.0001) and 12.6-fold in study 2 (P = 0.0013). These observations highlight the importance of provitamin A carotenoid consumption with a lipid-rich food such as avocado for maximum absorption and conversion to vitamin A, especially in populations in which vitamin A deficiency is prevalent. This trial was registered at clinicaltrials.gov as NCT01432210. PMID:24899156

  17. Avocado Consumption Enhances Human Postprandial Provitamin A Absorption and Conversion from a Novel High–β-Carotene Tomato Sauce and from Carrots12

    PubMed Central

    Kopec, Rachel E.; Cooperstone, Jessica L.; Schweiggert, Ralf M.; Young, Gregory S.; Harrison, Earl H.; Francis, David M.; Clinton, Steven K.; Schwartz, Steven J.

    2014-01-01

    Dietary lipids have been shown to increase bioavailability of provitamin A carotenoids from a single meal, but the effects of dietary lipids on conversion to vitamin A during absorption are essentially unknown. Based on previous animal studies, we hypothesized that the consumption of provitamin A carotenoids with dietary lipid would enhance conversion to vitamin A during absorption compared with the consumption of provitamin A carotenoids alone. Two separate sets of 12 healthy men and women were recruited for 2 randomized, 2-way crossover studies. One meal was served with fresh avocado (Persea americana Mill), cultivated variety Hass (delivering 23 g of lipid), and a second meal was served without avocado. In study 1, the source of provitamin A carotenoids was a tomato sauce made from a novel, high–β-carotene variety of tomatoes (delivering 33.7 mg of β-carotene). In study 2, the source of provitamin A carotenoids was raw carrots (delivering 27.3 mg of β-carotene and 18.7 mg of α-carotene). Postprandial blood samples were taken over 12 h, and provitamin A carotenoids and vitamin A were quantified in triglyceride-rich lipoprotein fractions to determine baseline-corrected area under the concentration-vs.-time curve. Consumption of lipid-rich avocado enhanced the absorption of β-carotene from study 1 by 2.4-fold (P < 0.0001). In study 2, the absorption of β-carotene and α-carotene increased by 6.6- and 4.8-fold, respectively (P < 0.0001 for both). Most notably, consumption of avocado enhanced the efficiency of conversion to vitamin A (as measured by retinyl esters) by 4.6-fold in study 1 (P < 0.0001) and 12.6-fold in study 2 (P = 0.0013). These observations highlight the importance of provitamin A carotenoid consumption with a lipid-rich food such as avocado for maximum absorption and conversion to vitamin A, especially in populations in which vitamin A deficiency is prevalent. This trial was registered at clinicaltrials.gov as NCT01432210. PMID:24899156

  18. Ethanol impairs post-prandial hepatic protein metabolism.

    PubMed Central

    De Feo, P; Volpi, E; Lucidi, P; Cruciani, G; Monacchia, F; Reboldi, G; Santeusanio, F; Bolli, G B; Brunetti, P

    1995-01-01

    The effects of acute ethanol ingestion on whole body and hepatic protein metabolism in humans are not known. To simulate social drinking, we compared the effects of the association of a mixed meal (632 kcal, 17% amino acids, 50% glucose, 33% lipids) with a bottle of either table wine (ethanol content 71 g) or water on the estimates ([1-14C]-leucine infusion) of whole body protein breakdown, oxidation, and synthesis, and on the intravascular fractional secretory rates (FSR) of hepatically (albumin, fibrinogen) and extrahepatically (IgG) synthesized plasma proteins in two randomized groups (ethanol n = 7, water n = 7) of healthy nonalcoholic volunteers. Each study was carried out for 8 h. Protein kinetics were measured in the overnight post-absorptive state, over the first 4 h, and during a meal infusion (via a nasogastric feeding tube at constant rate) combined with the oral ingestion of wine or water, over the last 4 h. When compared with water, wine ingestion during the meal reduced (P < 0.03) by 24% the rate of leucine oxidation, did not modify the estimates of whole body protein breakdown and synthesis, reduced (P < 0.01) by approximately 30% the FSR of albumin and fibrinogen, but did not affect IgG FSR. In conclusion, 70 g of ethanol, an amount usual among social drinkers, impairs hepatic protein metabolism. The habitual consumption of such amounts by reducing t