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Sample records for chylomicrons

  1. Chylomicrons metabolism in patients with coronary artery disease

    International Nuclear Information System (INIS)

    Chylomicrons are the triglyceride-rich lipoproteins that carry dietary lipids absorbed in the intestine. In the bloodstream , chylomicron triglycerides are broken-down by lipoprotein lipase using apoliprotein (apo) CII as co factor. Fatty acids and glycerol resulting from the enzymatic action are absorbed and stored in the body tissues mainly adipose and muscle for subsequent utilizations energy source. The resulting triglycerides depleted remnants are taken-up by liver receptor such as the LDL receptor using mainly apo E as ligand. For methodological reasons, chylomicron metabolism has been unfrequently studied in subjects despite its pathophysiological importance, and this metabolism was not evaluated in the great clinical trials that established the link between atherosclerosis and lipids. In studies using oral fat load tests, it has been shown that in patients with coronary artery disease there is a trend to accumulation of post-prandial triglycerides, vitamin A or apo B-48 , suggesting that in those patients chylomicrons and their remnants are slowly removed from the circulation. A triglyceride-rich emulsion marked radioisotopic which mimics chylomicron metabolism when injected into the bloodstream has been described that can offer a more straight forward approach to evaluate chylomicrons. In coronary artery disease patients both lipolysis and remnant removal from the plasma of the chylomicron-like emulsions were found slowed-down compared with control subjects without the disease. The introduction of more practical techniques to assess chylomicron metabolism may be new mechanisms underlying atherogenesis. (author)

  2. Carboxylesterase1/Esterase-x regulates chylomicron production in mice.

    Directory of Open Access Journals (Sweden)

    Ariel D Quiroga

    Full Text Available Elevated postprandial plasma triacylglycerol (TG concentrations are commonly associated with obesity and the risk of cardiovascular disease. Dietary fat contributes to this condition through the production of chylomicrons. Carboxylesterases have been mainly studied for their role in drug metabolism, but recently they have been shown to participate in lipid metabolism; however, their role in intestinal lipid metabolism is unknown. Carboxylesterase1/esterase-x (Ces1/Es-x deficient mice become obese, hyperlipidemic and develop hepatic steatosis even on standard chow diet. Here, we aimed to explore the role of Ces1/Es-x in intestinal lipid metabolism. Six-month old wild-type and Ces1/Es-x deficient mice were maintained on chow diet and intestinal lipid metabolism and plasma chylomicron clearance were analyzed. Along the intestine Ces1/Es-x protein is expressed only in proximal jejunum. Ablation of Ces1/Es-x expression results in postprandial hyperlipidemia due to increased secretion of chylomicrons. The secreted chylomicrons have aberrant protein composition, which results in their reduced clearance. In conclusion, Ces1/Es-x participates in the regulation of chylomicron assembly and secretion. Ces1/Es-x might act as a lipid sensor in enterocytes regulating chylomicron secretion rate. Ces1/Es-x might represent an attractive pharmacological target for the treatment of lipid abnormalities associated with obesity, insulin resistance and fatty liver disease.

  3. Cideb facilitates the lipidation of chylomicrons in the small intestine.

    Science.gov (United States)

    Zhang, Li-Jun; Wang, Chao; Yuan, Yuan; Wang, Hui; Wu, Jie; Liu, Fang; Li, Le; Gao, Xing; Zhao, Yuan-Lin; Hu, Pei-Zhen; Li, Peng; Ye, Jing

    2014-07-01

    Cell death-inducing DFF45-like effector b (Cideb), an endoplasmic reticulum (ER)- and lipid droplet (LD)-associated protein, has been shown to play a critical role in maintaining hepatic lipid homeostasis by promoting the lipidation and maturation of VLDL particles. Here, we observed that Cideb is expressed in the jejunum and ileum sections of the small intestine, and its expression was induced by high-fat diet. Intragastric gavage with lipids resulted in the retention of lipids in the intestine in Cideb-deficient mice. In addition, we observed that mice with Cideb deficiency exhibited reduced intestinal chylomicron-TG secretion and increased lipid accumulation in the enterocytes. The sizes of chylomicrons secreted from the small intestine of Cideb-deficient mice were also smaller than those from wild-type mice. Furthermore, the overexpression of Cideb increased TG secretion and reduced lipid accumulation in the enterocyte-like Caco-2 cells. In addition, we proved that Cideb was localized to the ER and LDs and could interact with ApoB48 in Caco-2 cells. Overall, these data revealed that Cideb plays an important role in controlling intestinal chylomicron lipidation.

  4. Development of lycopene micelle and lycopene chylomicron and a comparison of bioavailability

    Science.gov (United States)

    Jyun Chen, Yi; Inbaraj, Baskaran Stephen; Shiau Pu, Yeong; Chen, Bing Huei

    2014-04-01

    The objectives of this study were to develop lycopene micelles and lycopene chylomicrons from tomato extracts for the enhancement and comparison of bioavailability. Lycopene micelles and chylomicrons were prepared by a microemulsion technique involving tomato extract, soybean oil, water, vitamin E and surfactant Tween 80 or lecithin in different proportions. The encapsulation efficiency of lycopene was 78% in micelles and 80% in chylomicrons, with shape being roughly spherical and mean particle size being 7.5 and 131.5 nm. A bioavailability study was conducted in rats by both gavage and i.v. administration, with oral bioavailability of lycopene, phytoene and phytofluene being 6.8, 4.3 and 3.1% in micelles and 9.5, 9.4 and 7.1% in chylomicrons, respectively. This outcome reveals higher lycopene bioavailability through incorporation into micelle or chylomicron systems. Both size and shape should be considered for oral bioavailability determination. For i.v. injection, lycopene micelles should be more important than lycopene chylomicrons for future clinical applications.

  5. Independent regulation of chylomicron lipolysis and particle removal rates: effects of insulin and thyroid hormones on the metabolism of artificial chylomicrons.

    Science.gov (United States)

    Zerbinatti, C V; Oliveira, H C; Wechesler, S; Quintao, E C

    1991-11-01

    The processes of chylomicron lipolysis and removal from plasma were investigated by the intra-arterial infusion of doubly labeled artificial chylomicrons in rats. The rate of lipolysis was measured as a delipidation index (DI), which is the glyceryl-tri-9,10(N)-3H oleate (3H-TO) fraction removed from the particle as fatty acids, whereas the cholesteryl(1-14C) oleate (14C-CO) plasma disappearance rate measures the splanchnic organ particle uptake. In the alloxan-diabetic rats, despite a normal DI, the 14C-CO plasma residence time (RT) was longer than in control animals and remained longer after stimulation of the lipoprotein lipase by heparin. DI and 14C-CO removal rate were not significantly altered by insulin administration to glucose-supplemented control rats. Lipolysis was remarkable in propylthiouracil (PTU)-induced hypothyroidism, and yet the 14C-CO removal rate was retarded. In hypothyroidism, heparin enhanced the 14C-CO removal more than in the control group; however, after heparin, the 14C-CO RT still remained higher in the hypothyroid animals as compared with the control group. Hyperthyroidism lowered the DI; nevertheless, the 14C-CO disappearance rate was faster than in controls. In summary, lack or excess of thyroid hormone influences both the chylomicron lipolysis and removal systems, whereas lack of insulin impairs mostly the particle removal from plasma, and excess of insulin has no effect on the chylomicron metabolism. PMID:1943739

  6. Chylomicrons metabolism in patients with coronary artery disease; Metabolismo de quilomicrons em pacientes portadores de doenca arterial coronaria

    Energy Technology Data Exchange (ETDEWEB)

    Brandizzi, Laura Ines Ventura

    2002-07-01

    Chylomicrons are the triglyceride-rich lipoproteins that carry dietary lipids absorbed in the intestine. In the bloodstream , chylomicron triglycerides are broken-down by lipoprotein lipase using apoliprotein (apo) CII as co factor. Fatty acids and glycerol resulting from the enzymatic action are absorbed and stored in the body tissues mainly adipose and muscle for subsequent utilizations energy source. The resulting triglycerides depleted remnants are taken-up by liver receptor such as the LDL receptor using mainly apo E as ligand. For methodological reasons, chylomicron metabolism has been unfrequently studied in subjects despite its pathophysiological importance, and this metabolism was not evaluated in the great clinical trials that established the link between atherosclerosis and lipids. In studies using oral fat load tests, it has been shown that in patients with coronary artery disease there is a trend to accumulation of post-prandial triglycerides, vitamin A or apo B-48 , suggesting that in those patients chylomicrons and their remnants are slowly removed from the circulation. A triglyceride-rich emulsion marked radioisotopic which mimics chylomicron metabolism when injected into the bloodstream has been described that can offer a more straight forward approach to evaluate chylomicrons. In coronary artery disease patients both lipolysis and remnant removal from the plasma of the chylomicron-like emulsions were found slowed-down compared with control subjects without the disease. The introduction of more practical techniques to assess chylomicron metabolism may be new mechanisms underlying atherogenesis. (author)

  7. Positional distribution of decanoic acid: Effect on chylomicron and VLDL TAG structures and postprandial lipemia

    DEFF Research Database (Denmark)

    Yli-Jokipii, K.M.; Schwab, U.S.; Tarvonen, R.L.;

    2004-01-01

    Although medium-chain FA (MCFA) are mainly absorbed via the portal venous system, they are also incorporated into chylomicron TAG; therefore, the positional distribution of MCFA in TAG is likely to affect their metabolic fate. We studied chylomicron and VLDL TAG structures, as well as the magnitu...... or in FFA concentrations. Thus, the positional distribution of MCFA in TAG affects their metabolic fate, but the magnitude of postprandial lipemia does not seem to be dependent on the positional distribution of MCFA in the ingested fat....

  8. Evaluation of chylomicron effect on ASP production in 3T3-L1 adipocytes

    Institute of Scientific and Technical Information of China (English)

    Ying Gao; Danny Gauvreau; Wei Cui; Marc Lapointe; Sabina Paglialunga; Katherine Cianflone

    2011-01-01

    In the past few years,there has been increasing interest in the production and physiological role of acylation-stimu-lating protein(ASP),identical to C3adesArg,a product of the alternative complement pathway generated through C3 cleavage.Recent studies in C3(-/-)mice that are ASP deficient have demonstrated a role for ASP in postprandial triglyceride clearance and fat storage.The aim of the present study was to establish a cell model and sensitive ELISA assay for the evaluation of ASP production using 3T3-L1 adipocytes.3T3-L1 preadipocytes were differentiated into adipocytes,then cultured in different media such as serum-free(SF),Dulbecco's modified Eagle's medium(DMEM)/F12+10% fetal calf serum (FBS),and at varying concentrations of chylomicrons and insulin+chylomicrons up to 48 h.ASP production in SF and DMEM/F12+10% FBS was compared.Chylomicrons stimulated ASP production in a concen-tration- and time-dependent manner.By contrast,chylo-micron treatment had no effect on the production of C3,the precursor protein of ASP,which was constant over 48 h.Addition of insulin(100 nM)to a low-dose of chylomicrons(100 μg TG/ml)significantly increased ASP production compared with chylomicrons alone at 48 h(P<0.001).Furthermore,addition of insulin significantly increased C3 secretion at both 18 and 48 h of incubation (P<0.05,P<0.001,respectively).Overall,the proportion of ASP to C3 remained constant,indicating no change in the ratio of C3 cleaved to generate ASP.This study demonstrated that 3T3-L1 adipocyte is a useful model for the evaluation of C3 secretion and ASP production by using a sensitive mouse-specific ELISA assay.The stimulation of ASP production with chylomicrons demonstrates a physiologically relevant response,and provides a strategy for further studies on ASP production and function.

  9. Prior exercise does not affect chylomicron particle number following a mixed meal of moderate fat content

    Directory of Open Access Journals (Sweden)

    Mamo John CL

    2007-03-01

    Full Text Available Abstract Background A single session of exercise has been reported to reduce fasting and postprandial triacylglycerol concentrations on the subsequent day. It is possible that exercise also reduces chylomicron particle number, which may underlie the observed reduction in postprandial triacylglycerol concentration. In the present study we aimed to determine whether a single session of exercise reduces fasting and postprandial chylomicron particle number on the subsequent day. In a randomised crossover design eight lean and healthy male and female subjects attended two postprandial testing days. On the previous day the subjects either performed 90 minutes of moderate intensity exercise or did not perform any exercise. Fasting blood samples were then collected prior to ingestion of a moderate fat mixed meal (0.44 g fat, 0.94 g carbohydrate, 0.27 g protein/kg body weight, blood was then collected after 1 h, 2 h, 4 h, 6 h, and 8 h. Results The fasting and postprandial apolipoprotein B48 concentration (marker of chylomicron particle number was not affected by prior exercise. However exercise reduced fasting triacylglycerol concentration by 16% (P P = 0.053. However when corrected for baseline concentration postprandial triacylglycerol concentration was not affected by prior exercise. Conclusion A single session of exercise of moderate intensity and 90 minutes duration reduces fasting triacylglycerol levels, however fasting and postprandial chylomicron particle number was unaffected. Furthermore it appears that previously observed reductions in postprandial triacylglycerol levels following exercise are only mediated following consumption of high, non-physiologically relevant doses of fat.

  10. Apomorphine and its esters: Differences in Caco-2 cell permeability and chylomicron affinity.

    Science.gov (United States)

    Borkar, Nrupa; Chen, Zhizhong; Saaby, Lasse; Müllertz, Anette; Håkansson, Anders E; Schönbeck, Christian; Yang, Mingshi; Holm, René; Mu, Huiling

    2016-07-25

    Oral delivery of apomorphine via prodrug principle may be a potential treatment for Parkinson's disease. The purpose of this study was to investigate the transport and stability of apomorphine and its esters across Caco-2 cell monolayer and their affinity towards chylomicrons. Apomorphine, monolauroyl apomorphine (MLA) and dilauroyl apomorphine (DLA) were subjected to apical to basolateral (A-B) and basolateral to apical (B-A) transport across Caco-2 cell monolayer. The stability of these compounds was also assessed by incubation at intestinal pH and physiological pH with and without Caco-2 cells. Molecular dynamics (MD) simulations were performed to understand the stability of the esters on a molecular level. The affinity of the compounds towards plasma derived chylomicrons was assessed. The A-B transport of intact DLA was about 150 times lower than the transport of apomorphine. In contrast, MLA was highly unstable in the aqueous media leading to apomorphine appearance basolaterally. MD simulations possibly explained the differences in hydrolysis susceptibilities of DLA and MLA. The affinity of apomorphine diesters towards plasma derived chylomicrons provided an understanding of their potential lymphatic transport. The intact DLA transport is not favorable; therefore, the conversion of DLA to MLA is an important step for intestinal apomorphine absorption. PMID:27282537

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

    Directory of Open Access Journals (Sweden)

    Slivkoff-Clark Karin M

    2012-02-01

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

  12. Effects of dietary triacylglycerol structure on triacylglycerols of resultant chylomicrons from fish oil- and seal oil-fed rats

    DEFF Research Database (Denmark)

    Høy, Carl-Erik; Christensen, Michael Søberg

    1996-01-01

    We investigated the influence of the intramolecular fatty acid distribution of dietary triacyl-sn-glycerols (TAG) rich in n-3 polyunsaturated fatty acids (PUFA) on the structure of chylomicron TAG. Fish oil and seal oil, comparable in fatty acid compositions but with different contents of major n...

  13. Chylomicrons produced by Caco‐2 cells contained ApoB‐48 with diameter of 80–200 nm

    OpenAIRE

    NAULI, ANDROMEDA M.; Sun, Yuxi; Whittimore, Judy D.; Atyia, Seif; Krishnaswamy, Guha; Nauli, Surya M.

    2014-01-01

    Abstract The small intestine generally transports dietary fats to circulation in triglyceride (TG)‐rich lipoproteins. The two main intestinal lipoproteins are chylomicron (CM) and very low‐density lipoprotein (VLDL). Unfortunately, studies on the CM biogenesis and intestinal transport of dietary fats have been hampered by the lack of an adequate in vitro model. In this study, we investigated the possible factors that might increase the efficiency of CM production by Caco‐2 cells. We utilized ...

  14. Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Chylomicron and VLDL Synthesis and Secretion in Caco-2 Cells

    OpenAIRE

    Yue Wang; Qiaowei Lin; Peipei Zheng; Lulu Li; Zhengxi Bao; Feiruo Huang

    2014-01-01

    The present research was undertaken to determine the effects of EPA (20 : 5 n-3) and DHA (22 : 6 n-3) on chylomicron and VLDL synthesis and secretion by Caco-2 cells. Cells were incubated for 12 to 36 h with 400  μ M OA, EPA, and DHA; then 36 h was chosen for further study because EPA and DHA decreased de novo triglycerides synthesis in a longer incubation compared with OA  (P 0.05). Compare...

  15. Chylomicrons produced by Caco-2 cells contained ApoB-48 with diameter of 80-200 nm.

    Science.gov (United States)

    Nauli, Andromeda M; Sun, Yuxi; Whittimore, Judy D; Atyia, Seif; Krishnaswamy, Guha; Nauli, Surya M

    2014-06-01

    The small intestine generally transports dietary fats to circulation in triglyceride (TG)-rich lipoproteins. The two main intestinal lipoproteins are chylomicron (CM) and very low-density lipoprotein (VLDL). Unfortunately, studies on the CM biogenesis and intestinal transport of dietary fats have been hampered by the lack of an adequate in vitro model. In this study, we investigated the possible factors that might increase the efficiency of CM production by Caco-2 cells. We utilized sequential NaCl gradient ultracentrifugation to isolate the CMs that were secreted by the Caco-2 cells. To confirm the successful isolation of the CMs, we performed Fat Red 7B staining, TG reading, apolipoprotein B (ApoB) measurement, and transmission electron microcopy (TEM) analysis. We then tested the effects of cell differentiation, oleic acid, mono-olein, egg lecithin, incubation time, and collagen matrix on CM secretion. We found that cell differentiation, oleic acid, and lecithin were critical for CM secretion. Using the Transwell system, we further confirmed that the CMs produced by our Caco-2 cells contained significant amount of TGs and ApoB-48 such that they could be detected without the use of isotope labeling. In conclusion, when fully differentiated Caco-2 were challenged with oleic acid, lecithin, and sodium taurocholate, 21% of their total number of lipoproteins were CMs with the diameter of 80-200 nm.

  16. Chylomicrons produced by Caco‐2 cells contained ApoB‐48 with diameter of 80–200 nm

    Science.gov (United States)

    Nauli, Andromeda M.; Sun, Yuxi; Whittimore, Judy D.; Atyia, Seif; Krishnaswamy, Guha; Nauli, Surya M.

    2014-01-01

    Abstract The small intestine generally transports dietary fats to circulation in triglyceride (TG)‐rich lipoproteins. The two main intestinal lipoproteins are chylomicron (CM) and very low‐density lipoprotein (VLDL). Unfortunately, studies on the CM biogenesis and intestinal transport of dietary fats have been hampered by the lack of an adequate in vitro model. In this study, we investigated the possible factors that might increase the efficiency of CM production by Caco‐2 cells. We utilized sequential NaCl gradient ultracentrifugation to isolate the CMs that were secreted by the Caco‐2 cells. To confirm the successful isolation of the CMs, we performed Fat Red 7B staining, TG reading, apolipoprotein B (ApoB) measurement, and transmission electron microcopy (TEM) analysis. We then tested the effects of cell differentiation, oleic acid, mono‐olein, egg lecithin, incubation time, and collagen matrix on CM secretion. We found that cell differentiation, oleic acid, and lecithin were critical for CM secretion. Using the Transwell system, we further confirmed that the CMs produced by our Caco‐2 cells contained significant amount of TGs and ApoB‐48 such that they could be detected without the use of isotope labeling. In conclusion, when fully differentiated Caco‐2 were challenged with oleic acid, lecithin, and sodium taurocholate, 21% of their total number of lipoproteins were CMs with the diameter of 80–200 nm. PMID:24907293

  17. Chylomicron and apoB48 metabolism in the JCR:LA corpulent rat, a model for the metabolic syndrome.

    Science.gov (United States)

    Mangat, R; Su, J; Scott, P G; Russell, J C; Vine, D F; Proctor, S D

    2007-06-01

    Postprandial (PP) lipaemia is a significant contributor to the development of dyslipidaemia and cardiovascular disease (CVD). It is also evident that PP lipaemia is prevalent during conditions of obesity and insulin resistance (IR) and may contribute to increased progression of CVD. Our group has assessed the potential of the obese JCR:LA-cp rat as a model of PP lipaemia in order to explore CM (chylomicron) metabolism during the onset and development of IR in the metabolic syndrome. Studies confirm that both fasting plasma and PP apoB48 (apolipoprotein B48) area under the curve are significantly elevated in the obese JCR:LA-cp phenotype as compared with lean controls. Mechanistic studies have also shown that the concentration of lymphatic CM apoB48 and CM size are significantly increased in this model. Furthermore, PP dyslipidaemia in the obese rat can be improved acutely with supplementation of n-3 polyunsaturated fatty acids. Using a different approach, we have subsequently hypothesized that the vascular remodelling that accompanies IR may explain accelerated entrapment of apoB48-containing particles. Small leucine-rich proteoglycans (including biglycan and decorin) have been observed to co-localize with apoB in human tissue. However, the potential impact of IR on vascular remodelling, particularly in the presence of obesity, remains unclear. Preliminary observations from the JCR:LA-cp model indicate that biglycan protein core content increases with age and is exacerbated by IR, suggestive of pro-atherogenic remodelling. The focus of this review is to contribute to the perspective of PP lipaemia in CVD risk associated with the metabolic syndrome through the use of animal models.

  18. Molecular analysis and intestinal expression of SAR1 genes and proteins in Anderson's disease (Chylomicron retention disease

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    Boileau Catherine

    2011-01-01

    Full Text Available Abstract Background Anderson's disease (AD or chylomicron retention disease (CMRD is a very rare hereditary lipid malabsorption syndrome. In order to discover novel mutations in the SAR1B gene and to evaluate the expression, as compared to healthy subjects, of the Sar1 gene and protein paralogues in the intestine, we investigated three previously undescribed individuals with the disease. Methods The SAR1B, SAR1A and PCSK9 genes were sequenced. The expression of the SAR1B and SAR1A genes in intestinal biopsies of both normal individuals and patients was measured by RTqPCR. Immunohistochemistry using antibodies to recombinant Sar1 protein was used to evaluate the expression and localization of the Sar1 paralogues in the duodenal biopsies. Results Two patients had a novel SAR1B mutation (p.Asp48ThrfsX17. The third patient, who had a previously described SAR1B mutation (p.Leu28ArgfsX7, also had a p.Leu21dup variant of the PCSK9 gene. The expression of the SAR1B gene in duodenal biopsies from an AD/CMRD patient was significantly decreased whereas the expression of the SAR1A gene was significantly increased, as compared to healthy individuals. The Sar1 proteins were present in decreased amounts in enterocytes in duodenal biopsies from the patients as compared to those from healthy subjects. Conclusions Although the proteins encoded by the SAR1A and SAR1B genes are 90% identical, the increased expression of the SAR1A gene in AD/CMRD does not appear to compensate for the lack of the SAR1B protein. The PCSK9 variant, although reported to be associated with low levels of cholesterol, does not appear to exert any additional effect in this patient. The results provide further insight into the tissue-specific nature of AD/CMRD.

  19. The Biogenesis of Chylomicrons

    Science.gov (United States)

    Mansbach, Charles M.; Siddiqi, Shadab A.

    2016-01-01

    The absorption of dietary fat is of increasing concern given the rise of obesity not only in the United States but throughout the developed world. This review explores what happens to dietary fat within the enterocyte. Absorbed fatty acids and monoacylglycerols are required to be bound to intracellular proteins and/or to be rapidly converted to triacylglycerols to prevent cellular membrane disruption. The triacylglycerol produced at the level of the endoplasmic reticulum (ER) is either incorporated into prechylomicrons within the ER lumen or shunted to triacylglycerol storage pools. The prechylomicrons exit the ER in a specialized transport vesicle in the rate-limiting step in the intracellular transit of triacylglycerol across the enterocyte. The prechylomicrons are further processed in the Golgi and are transported to the basolateral membrane via a separate vesicular system for exocytosis into the intestinal lamina propria. Fatty acids and monoacylglycerols entering the enterocyte via the basolateral membrane are also incorporated into triacylglycerol, but the basolaterally entering lipid is much more likely to enter the triacylglycerol storage pool than the lipid entering via the apical membrane. PMID:20148678

  20. Anderson's disease/chylomicron retention disease in a Japanese patient with uniparental disomy 7 and a normal SAR1B gene protein coding sequence

    Directory of Open Access Journals (Sweden)

    Okada Tomoo

    2011-11-01

    Full Text Available Abstract Background Anderson's Disease (AD/Chylomicron Retention Disease (CMRD is a rare hereditary hypocholesterolemic disorder characterized by a malabsorption syndrome with steatorrhea, failure to thrive and the absence of chylomicrons and apolipoprotein B48 post-prandially. All patients studied to date exhibit a mutation in the SAR1B gene, which codes for an essential component of the vesicular coat protein complex II (COPII necessary for endoplasmic reticulum to Golgi transport. We describe here a patient with AD/CMRD, a normal SAR1B gene protein coding sequence and maternal uniparental disomy of chromosome 7 (matUPD7. Methods and Results The patient, one of two siblings of a Japanese family, had diarrhea and steatorrhea beginning at five months of age. There was a white duodenal mucosa upon endoscopy. Light and electron microscopy showed that the intestinal villi were normal but that they had lipid laden enterocytes containing accumulations of lipid droplets in the cytoplasm and lipoprotein-size particles in membrane bound structures. Although there were decreased amounts in plasma of total- and low-density lipoprotein cholesterol, apolipoproteins AI and B and vitamin E levels, the triglycerides were normal, typical of AD/CMRD. The presence of low density lipoproteins and apolipoprotein B in the plasma, although in decreased amounts, ruled out abetalipoproteinemia. The parents were asymptomatic with normal plasma cholesterol levels suggesting a recessive disorder and ruling out familial hypobetalipoproteinemia. Sequencing of genomic DNA showed that the 8 exons of the SAR1B gene were normal. Whole genome SNP analysis and karyotyping revealed matUPD7 with a normal karyotype. In contrast to other cases of AD/CMRD which have shown catch-up growth following vitamin supplementation and a fat restricted diet, our patient exhibits continued growth delay and other aspects of the matUPD7 and Silver-Russell Syndrome phenotypes. Conclusions This

  1. Internal dosimetry of a chylomicron-like emulsion doubly-labeled with 3H-TG and {sup 14}C-CE in humans

    Energy Technology Data Exchange (ETDEWEB)

    Marcato, Larissa A.; Carvalho, Diego V.S.; Santos, Robinson A.; Hamada, Margarida M.; Mesquita, Carlos H. de [Energy and Nuclear Research Institute (IPEN/CNEN/SP), Sao Paulo, SP (Brazil); Vinagre, Carmen [University of Sao Paulo, SP (Brazil). The Heart Institute of the Medical School Hospital; Maranhao, Raul C. [University of Sao Paulo, SP (Brazil). Faculty of Pharmaceutical Sciences

    2010-07-01

    Full text: This paper describes a research about the calculation of the effective equivalent doses to which participants are exposed when submitted to studies that use artificial lipid emulsions doubly-labeled with radioactive tracers {sup 14}C and {sup 3}H. Several studies have used these emulsions in order to improve the knowledge of the biodistribution parameters of plasma lipoproteins. In the particular case of studies with chylomicron-like emulsion doubly- labeled with radioactive cholesteryl esters ({sup 14}C-CE) and triacylglycerols ({sup 3}H-TG) the dosimetric calculations was estimated indirectly. Initially, the LIA limits suggested by ICRP no 26 for {sup 3}H and {sup 14}C were used, however the LIA parameter is dependent on the chemical form of the labeled product and these parameters have not been scheduled yet for artificial lipoproteins. In particular for the {sup 14}C-CE, the internal dose in humans was estimated from the allometric theory using data from the biodistribution in rats with approximately 0.4 kg. The purpose of this paper is to improve the estimation of the effective equivalent dose in humans in order to contribute to future studies that will utilize artificial lipoproteins. For this study, chylomicron-like emulsion containing radioactive lipids were injected intravenously in bolus into the volunteers and aliquots of blood were collected at predetermined intervals of time. The activity of each aliquot was measured in liquid scintillator using a spectrometer. The plasmatic radioactive decay curves were determined and subsequently the kinetic parameters and effective equivalent doses were calculated using the ANACOMP software. It was proposed a kinetic model consisting of eight compartments for the biodistribution of plasma lipoproteins in humans. (author)

  2. Guidelines for the diagnosis and management of chylomicron retention disease based on a review of the literature and the experience of two centers

    Directory of Open Access Journals (Sweden)

    Castagnetti Justine

    2010-09-01

    Full Text Available Abstract Familial hypocholesterolemia, namely abetalipoproteinemia, hypobetalipoproteinemia and chylomicron retention disease (CRD, are rare genetic diseases that cause malnutrition, failure to thrive, growth failure and vitamin E deficiency, as well as other complications. Recently, the gene implicated in CRD was identified. The diagnosis is often delayed because symptoms are nonspecific. Treatment and follow-up remain poorly defined. The aim of this paper is to provide guidelines for the diagnosis, treatment and follow-up of children with CRD based on a literature overview and two pediatric centers 'experience. The diagnosis is based on a history of chronic diarrhea with fat malabsorption and abnormal lipid profile. Upper endoscopy and histology reveal fat-laden enterocytes whereas vitamin E deficiency is invariably present. Creatine kinase (CK is usually elevated and hepatic steatosis is common. Genotyping identifies the Sar1b gene mutation. Treatment should be aimed at preventing potential complications. Vomiting, diarrhea and abdominal distension improve on a low-long chain fat diet. Failure to thrive is one of the most common initial clinical findings. Neurological and ophthalmologic complications in CRD are less severe than in other types of familial hypocholesterolemia. However, the vitamin E deficiency status plays a pivotal role in preventing neurological complications. Essential fatty acid (EFA deficiency is especially severe early in life. Recently, increased CK levels and cardiomyopathy have been described in addition to muscular manifestations. Poor mineralization and delayed bone maturation do occur. A moderate degree of macrovesicular steatosis is common, but no cases of steatohepatitis cirrhosis. Besides a low-long chain fat diet made up uniquely of polyunsaturated fatty acids, treatment includes fat-soluble vitamin supplements and large amounts of vitamin E. Despite fat malabsorption and the absence of postprandial chylomicrons

  3. Carboxyl ester lipase overexpression in rat hepatoma cells and CEL deficiency in mice have no impact on hepatic uptake or metabolism of chylomicron-retinyl ester.

    Science.gov (United States)

    van Bennekum, A M; Li, L; Piantedosi, R; Shamir, R; Vogel, S; Fisher, E A; Blaner, W S; Harrison, E H

    1999-03-30

    To study the role of carboxyl ester lipase (CEL) in hepatic retinoid (vitamin A) metabolism, we investigated uptake and hydrolysis of chylomicron (CM)-retinyl esters (RE) by rat hepatoma (McArdle-RH7777) cells stably transfected with a rat CEL cDNA. We also studied tissue uptake of CM-RE in CEL-deficient mice generated by targeted disruption of the CEL gene. CEL-transfected cells secreted active enzyme into the medium. However, both control and CEL-transfected cells accumulated exogenously added CM-RE or CM remnant (CMR)-derived RE in equal amounts. Serum clearance of intravenously injected CM-RE and cholesteryl ester were not different between wild-type and CEL-deficient mice. Also, the uptake of the two compounds by the liver and other tissues did not differ. These data indicate that the lack of CEL expression does not affect the uptake of dietary CM-RE by the liver or other tissues. Moreover, the percentage of retinol formed in the liver after CM-RE uptake, the levels of retinol and retinol-binding protein in serum, and retinoid levels in various tissues did not differ, indicating that CEL deficiency does not affect hepatic retinoid metabolism and retinoid distribution throughout the body. Surprisingly, in both pancreas and liver of wild-type, heterozygous, and homozygous CEL-deficient mice, the levels of bile salt-dependent retinyl ester hydrolase (REH) activity were similar. This indicates that in the mouse pancreas and liver an REH enzyme activity, active in the presence of bile salt and distinct from CEL, is present, compatible with the results from our accompanying paper that the intestinal processing and absorption of RE were unimpaired in CEL-deficient mice.

  4. Mechanisms of microemulsion enhancing the oral bioavailability of puerarin: comparison between oil-in-water and water-in-oil microemulsions using the single-pass intestinal perfusion method and a chylomicron flow blocking approach

    Directory of Open Access Journals (Sweden)

    Tang TT

    2013-11-01

    Full Text Available Tian-Tian Tang,1,2,3 Xiong-Bin Hu,1,2,3 De-Hua Liao,1,2,3 Xin-Yi Liu,1,2,3 Da-Xiong Xiang1,2,31Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China; 2Institute of Clinical Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China; 3Key Laboratory for New Technology of Chinese Medicine Preparations of Hunan Province, Changsha, People's Republic of ChinaAbstract: The purpose of the present work was to determine the mechanisms by which microemulsions (MEs enhance the oral bioavailability of puerarin. The in situ perfusion method was used in rats to study the absorption mechanisms of an oil-in-water (O/W microemulsion (O/W-ME and a water-in-oil (W/O microemulsion (W/O-ME. The possibility of lymphatic transport of the MEs was investigated using a chylomicron flow blocking approach. The results for the absorption mechanisms in the stomach and intestines indicated that the absorption characteristics of the O/W-ME and W/O-ME depend on the segment. The W/O-ME had higher internal membrane permeability than the O/W-ME. The results of the lymphatic transport analyses showed that both the O/W-ME and W/O-ME underwent lymphatic transport and that this pathway was a major contributor to the oral bioavailability of MEs. Furthermore, the type of ME can significantly affect the absorption of puerarin through the lymphatic system due to the oil content and the form of the microemulsion after oral administration. In conclusion, these data indicate that microemulsions are an effective and promising delivery system to enhance the oral bioavailability of poorly water-soluble drugs.Keywords: microemulsion, lymphatic transport, oral bioavailability, chylomicron

  5. Postprandial chylomicron formation and fat absorption in multidrug resistance gene 2 P-glycoprotein-deficient mice

    NARCIS (Netherlands)

    Voshol, PJ; Minich, DM; Havinga, R; Elferink, RPJO; Verkade, HJJ; Groen, AK; Kuipers, F

    2000-01-01

    Background & Aims: It has been proposed that biliary phospholipids fulfill specific functions in the absorption of dietary fat from the intestine, but the physiological significance has not been established. The aim of this study was to evaluate the role of biliary phospholipids in dietary fat absor

  6. Trans-11 vaccenic acid reduces hepatic lipogenesis and chylomicron secretion in JCR:LA-cp rats.

    Science.gov (United States)

    Wang, Ye; Jacome-Sosa, M Miriam; Ruth, Megan R; Goruk, Sue D; Reaney, Martin J; Glimm, David R; Wright, David C; Vine, Donna F; Field, Catherine J; Proctor, Spencer D

    2009-11-01

    Trans-11 vaccenic acid (VA) is the predominant trans isomer in ruminant fat and a major precursor to the endogenous synthesis of cis9,trans11-conjugated linoleic acid in humans and animals. We have previously shown that 3-wk VA supplementation has a triglyceride (TG)-lowering effect in a rat model of dyslipidemia, obesity, and metabolic syndrome (JCR:LA-cp rats). The objective of this study was to assess the chronic effect (16 wk) of VA on lipid homeostasis in both the liver and intestine in obese JCR:LA-cp rats. Plasma TG (P JCR:LA-cp rats. The appreciable hypolipidemic benefits of VA may be attributed to a reduction in both intestinal CM and hepatic de novo lipogenesis pathways.

  7. Carotenoid absorption, chylomicron response curves, the influence of β-carotene supplementation on immune function and the measurement of natural killer cell function

    International Nuclear Information System (INIS)

    Absorption of β-carotene from raw, uncooked vegetables can be very low. Particle size of uncooked foods is particularly important; β-carotene absorption from pureed or finely chopped vegetables is considerably higher than from whole or sliced raw vegetables. Cooking procedures (boiling/steaming) improves the chemical extractability of carotenoids from foods and also appears to improve absorption. Dietary fat stimulates bile flow from the gall bladder which facilitates the emulsification of fat and fat soluble dietary components into lipid micelles within the small intestine. Without micelle formation carotenoids are very poorly absorbed. Several studies have shown that the absence of dietary fat or very low fat diets substantially reduces β-carotene absorption in human volunteers. Carotenoid absorption is thought to be a passive process. The assumption is that carotenoids within lipid micelles come into contact with the intestinal epithelial cell membranes and that transport from micelles to the plasma membrane and cytosol of the cell occur together with the transport of fatty acids. β-carotene appears simultaneously in lymph with newly absorbed fat from a meal and thus it is assumed that they move together across the plasma membrane and within the mucosal cell

  8. Possible mechanism for accelerated atherogenesis in male versus female rats

    International Nuclear Information System (INIS)

    Dietary fat and cholesterol enter the circulation as chylomicrons. They are removed from the circulation by attachment to lipoprotein lipase located on the endothelial surfaces. As the result of lipoprotein lipase action, chylomicrons are partially hydrolyzed and then reenter the circulation as remnants, which are rapidly cleared by the liver. We investigated the fate of 3H-retinol- and 14C-cholesterol-labeled chylomicrons injected into male and female rats. The disappearance curves of chylomicrons from the circulation were not significantly different in males and females, which suggests that translocation from plasma to endothelium is similar for both sexes. However, in male rats, the dwell time of chylomicrons on the endothelium was significantly prolonged. At 10 and 20 minutes after chylomicron injection, more label was found in the livers of female than male rats. The opposite was true for hearts. Male hearts contained significantly more endothelium-bound chylomicrons when compared with female hearts. This increase in dwell time may allow greater cholesterol deposition in the endothelium of male rats. The more rapid processing of chylomicrons was associated with a 300% greater postheparin lipoprotein lipase in female rats, which suggests a greater enzyme density at chylomicron attachment points on endothelium

  9. Vascular risk factors, vascular disease, lipids and lipid targets in patients with familial dysbetalipoproteinemia: a European cross-sectional study

    NARCIS (Netherlands)

    Koopal, C.; Retterstol, K.; Sjouke, B.; Hovingh, G.K.; Ros, E.; Graaf, J. de; Dullaart, R.P.; Bertolini, S.; Visseren, F.L.

    2015-01-01

    BACKGROUND: Familial dysbetalipoproteinemia (FD), also known as type III hyperlipoproteinemia, is a genetic dyslipidemia characterized by elevated very low density lipoprotein (VLDL) and chylomicron remnant particles that confers increased risk of cardiovascular disease (CVD). The objective of this

  10. Vascular risk factors, vascular disease, lipids and lipid targets in patients with familial dysbetalipoproteinemia : A European cross-sectional study

    NARCIS (Netherlands)

    Koopal, C.; Retterstol, K.; Sjouke, B.; Hovingh, G. K.; Ros, E.; de Graaf, J.; Dullaart, R. P. F.; Bertolini, S.; Visseren, F. L. J.

    2015-01-01

    Background: Familial dysbetalipoproteinemia (FD), also known as type III hyperlipoproteinemia, is a genetic dyslipidemia characterized by elevated very low density lipoprotein (VLDL) and chylomicron remnant particles that confers increased risk of cardiovascular disease (CVD). The objective of this

  11. Effect of dietary fatty acids on the postprandial fatty acid composition of triacylglycerol-rich lipoproteins in healthy male subjects

    DEFF Research Database (Denmark)

    Bysted, Anette; Holmer, G.; Lund, Pia;

    2005-01-01

    interesterified test fats with equal amounts of palmitic acid ( P fat), stearic acid (S fat), trans-18: 1 isomers (T fat), oleic acid (O fat), or linoleic acid (L fat) were tested. Subjects: A total of 16 healthy, normolipidaemic males ( age 23 +/- 2 y) were recruited. Interventions: The participants ingested fat......Objective: The aim of the present study was to investigate the effect of trans-18: 1 isomers compared to other fatty acids, especially saturates, on the postprandial fatty acid composition of triacylglycerols ( TAG) in chylomicrons and VLDL. Design: A randomised crossover experiment where five......-rich test meals ( 1 g fat per kg body weight) and the fatty acid profiles of chylomicron and VLDL TAG were followed for 8 h. Results: The postprandial fatty acid composition of chylomicron TAG resembled that of the ingested fats. The fatty acids in chylomicron TAG were randomly distributed among the three...

  12. A novel multiprotein complex is required to generate the prechylomicron transport vesicle from intestinal ER[S

    OpenAIRE

    Siddiqi, Shahzad; Saleem, Umair; Abumrad, Nada A.; Davidson, Nicholas O.; Storch, Judith; Siddiqi, Shadab A.; Mansbach, Charles M.

    2010-01-01

    Dietary lipid absorption is dependent on chylomicron production whose rate-limiting step across the intestinal absorptive cell is the exit of chylomicrons from the endoplasmic reticulum (ER) in its ER-to-Golgi transport vesicle, the prechylomicron transport vesicle (PCTV). This study addresses the composition of the budding complex for PCTV. Immunoprecipitation (IP) studies from rat intestinal ER solubilized in Triton X-100 suggested that vesicle-associated membrane protein 7 (VAMP7), apolipo...

  13. Different patterns of postprandial lipoprotein metabolism in normal, type IIa, type III, and type IV hyperlipoproteinemic individuals. Effects of treatment with cholestyramine and gemfibrozil.

    OpenAIRE

    Weintraub, M S; Eisenberg, S; Breslow, J L

    1987-01-01

    To study exogenous fat metabolism, we used the vitamin A-fat loading test, which specifically labels intestinally derived lipoproteins with retinyl palmitate (RP). Postprandial RP concentrations were followed in total plasma, and chylomicron (Sf greater than 1,000) and nonchylomicron (Sf less than 1,000) fractions. In normal subjects postprandial lipoproteins were present for more than 14 h, and chylomicron levels correlated inversely with lipoprotein lipase activity and fasting high density ...

  14. Methods for studying rodent intestinal lipoprotein production and metabolism

    OpenAIRE

    Kohan, Alison B.; HOWLES, PHILIP N.; Tso, Patrick

    2012-01-01

    Lipid absorption begins with the digestion of dietary triacylglycerol and ultimately results in the secretion of triacylglycerol in chylomicrons into the lymphatics. Additionally, the intestine also secretes numerous proteins and peptides involved in lipid and lipoprotein metabolism in response to food. Ultimately, chylomicrons and these proteins, peptides, and hormones are found in lymph. The lymph fistula rat model has traditionally been used to study this intestinal absorption of nutrients...

  15. Differential effects of saturated and monounsaturated fats on postprandial lipemia and glucagon-like peptide 1 responses in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Thomsen, Claus; Storm, Hanne; Holst, Jens Juul;

    2003-01-01

    butter, and the control meal plus 80 g olive oil. Triacylglycerol responses were measured in total plasma and in a chylomicron-rich and a chylomicron-poor fraction. RESULTS: No significant differences in the glucose, insulin, or fatty acid responses to the 2 fat-rich meals were seen. The plasma...... triacylglycerol and chylomicron triacylglycerol responses were highest after the butter meal. HDL-cholesterol concentrations decreased significantly after the butter meal but did not change significantly after the olive oil meal. GLP-1 responses were highest after the olive oil meal. CONCLUSIONS: Olive oil...... induced lower triacylglycerol concentrations and higher HDL-cholesterol concentrations than did butter, without eliciting significant changes in glucose, insulin, or fatty acids. Furthermore, olive oil induced higher concentrations of GLP-1, which may indicate a relation between fatty acid composition...

  16. An unusual case of familial hyperlipidaemia

    OpenAIRE

    Nagar, Renu; Arora, Uma

    2008-01-01

    A 40 days old male baby born to a consanguineous couple was found to have highly viscous and milky serum with caking of chylomicrons on refrigeration of serum. Cholesterol was 889.5 mg/dl (23.04mmol/L) and Triglycerides 12881 mg/dl (141.69mmol/L). He was active and did not have any hepatospleenomegaly, xanthomas or dysmorphic features. Thyroid functions were normal. Lipid electrophoresis showed thick chylomicron band. There was positive family history of hypertriglyceridemia in a first cousin...

  17. Emerging roles of the intestine in control of cholesterol metabolism

    NARCIS (Netherlands)

    Kruit, Janine K.; Groen, Albert K.; van Berkel, Theo J.; Kuipers, Folkert

    2006-01-01

    The liver is considered the major "control center" for maintenance of whole body cholesterol homeostasis. This organ is the main site for de novo cholesterol synthesis, clears cholesterol-containing chylomicron remnants and low density lipoprotein particles from plasma and is the major contributor t

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  19. Food matrices affect the bioavailability of (n-3) polyunsaturated fatty acids in a single meal study in humans

    DEFF Research Database (Denmark)

    Schram, Laurine B; Nielsen, Carina J.; Porsgaard, Trine;

    2007-01-01

    , a yoghurt drink, eight oil capsules, bread and butter; 4 g of fish oil was incorporated into one of the matrices. Blood samples were collected and fatty acid composition of chylomicrons was determined together with plasma levels of conjugated dienes and alpha-tocopherol. Fish oil incorporated into food...

  20. Methods to study postprandial lipemia

    DEFF Research Database (Denmark)

    Ooi, Teik Chye; Nordestgaard, Børge G

    2011-01-01

    Postprandial lipemia (PPL) refers to a dynamic sequence of plasma lipid/lipoprotein changes induced by ingestion of food. PPL results from absorption of digested dietary lipids which form chylomicrons (CM) and increased hepatic production of VLDL, stimulated by increased delivery of fats to the l...

  1. Apomorphine and its esters

    DEFF Research Database (Denmark)

    Borkar, Nrupa; Chen, Zhizhong; Saaby, Lasse;

    2016-01-01

    Oral delivery of apomorphine via prodrug principle may be a potential treatment for Parkinson's disease. The purpose of this study was to investigate the transport and stability of apomorphine and its esters across Caco-2 cell monolayer and their affinity towards chylomicrons. Apomorphine...

  2. Conséquences métaboliques des malabsorptions lipidiques : apports de l’étude des hypocholestérolémies familiales

    Directory of Open Access Journals (Sweden)

    Peretti Noël

    2012-07-01

    Full Text Available Familial hypocholesterolemia, namely abetalipoproteinemia, hypobetalipoproteinemia and chylomicron retention disease (CRD, are rare genetic diseases that cause intestinal lipid malabsorption. They provide a model to study the consequences of chronic hypocholesterolemia: protection against cardiovascular disease, increase of fatty liver disease and neurovascular complications. The understanding of their physiopathology provided new approaches to treat hypercholesterolemia.

  3. Pitavastatin versus Pravastatin in Reduction of Remnant Lipoprotein Cholesterol in Patients with Dyslipidemias.

    Science.gov (United States)

    Roever, Leonardo

    2016-05-01

    Remnant lipoproteins cholesterol are products of partially catabolized chylomicrons and very-low-density lipoprotein, from which some triglycerides have been removed. These particles are smaller and are believed to be strongly atherogenic. Elevated Remnant lipoproteins cholesterol levels were reported to be associated with endothelial dysfunction and atherosclerotic disease.

  4. Plasma apoAV levels are markedly elevated in severe hypertriglyceridemia and positively correlated with the APOA5 S19W polymorphism

    NARCIS (Netherlands)

    Henneman, P.; Schaap, F.G.; Havekes, L.M.; Rensen, P.C.N.; Frants, R.R.; Tol, A. van; Hattori, H.; Smelt, A.H.M.; Dijk, K.W. van

    2007-01-01

    Objective: The recently discovered apoAV is hypothesized to affect triglyceride metabolism by stimulating the lipolysis of triglycerides in VLDL and chylomicrons. We set out to determine the association between increased serum TG levels, plasma apoAV levels, and polymorphism of the APOA5 gene, with

  5. Lipolysis of emulsion models of triglyceride-rich lipoproteins is altered in male patients with abdominal aorta aneurysm

    Directory of Open Access Journals (Sweden)

    J.J. Hosni

    2007-03-01

    Full Text Available Disorders of the lipid metabolism may play a role in the genesis of abdominal aorta aneurysm. The present study examined the intravascular catabolism of chylomicrons, the lipoproteins that carry the dietary lipids absorbed by the intestine in the circulation in patients with abdominal aorta aneurysm. Thirteen male patients (72 ± 5 years with abdominal aorta aneurysm with normal plasma lipid profile and 13 healthy male control subjects (73 ± 5 years participated in the study. The method of chylomicron-like emulsions was used to evaluate this metabolism. The emulsion labeled with 14C-cholesteryl oleate and ³H-triolein was injected intravenously in both groups. Blood samples were taken at regular intervals over 60 min to determine the decay curves. The fractional clearance rate (FCR of the radioactive labels was calculated by compartmental analysis. The FCR of the emulsion with ³H-triolein was smaller in the aortic aneurysm patients than in controls (0.025 ± 0.017 vs 0.039 ± 0.019 min-1; P < 0.05, but the FCR of14C-cholesteryl oleate of both groups did not differ. In conclusion, as indicated by the triglyceride FCR, chylomicron lipolysis is diminished in male patients with aortic aneurysm, whereas the remnant removal which is traced by the cholesteryl oleate FCR is not altered. The results suggest that defects in the chylomicron metabolism may represent a risk factor for development of abdominal aortic aneurysm.

  6. Methods to study postprandial lipemia

    DEFF Research Database (Denmark)

    Ooi, Teik Chye; Nordestgaard, Børge G

    2011-01-01

    Postprandial lipemia (PPL) refers to a dynamic sequence of plasma lipid/lipoprotein changes induced by ingestion of food. PPL results from absorption of digested dietary lipids which form chylomicrons (CM) and increased hepatic production of VLDL, stimulated by increased delivery of fats to the...

  7. Mechanisms for oral absorption of poorly water-soluble compounds

    DEFF Research Database (Denmark)

    Lind, Marianne Ladegaard

    and 80 and soybean oil were equal, indicating that polysorbate 60 and 80 can be used as lymphotropic carriers. Furthermore, the results obtained in this chylomicron flow blocking approach by dosing halofantrine in soybean oil correlated well with previous findings in conscious, mesenteric lymph...

  8. Chyluria: a scourge of our region.

    Science.gov (United States)

    Sinha, Rajan Kumar; Ranjan, Nikhil; Singh, Neha; Amit, Keshri

    2015-01-01

    Chyluria is endemic in the Gangetic belt of India with an average of 90 cases treated annually at our institute. It is almost exclusively caused by Wuchereria bancrofti in tropical areas. Chylomicrons and triglycerides are lost in the urine from an abnormal lymphourinary fistula due to obstructive lymphatic stasis, most commonly at the renal pelvis. It is a distressingly recurrent condition with multiple exacerbations and remissions over years. Severe weakness, weight loss and haematuria occur in some patients. Diagnosis can be made by visual examination of milky urine along with the ether test of urine for chylomicrons. Intravenous urography is used to locate the site of the fistula, although the detection rate is poor. Treatment starts with conservative measures such as a high-protein low-fat diet and diethylcarbamazine therapy. In cases where conservative measures fail, endoscopic sclerotherapy (renal pelvic instillation of silver nitrate, povidone iodine or others) and surgical therapy are used. PMID:26150622

  9. Gut triglyceride production.

    Science.gov (United States)

    Pan, Xiaoyue; Hussain, M Mahmood

    2012-05-01

    Our knowledge of how the body absorbs triacylglycerols (TAG) from the diet and how this process is regulated has increased at a rapid rate in recent years. Dietary TAG are hydrolyzed in the intestinal lumen to free fatty acids (FFA) and monoacylglycerols (MAG), which are taken up by enterocytes from their apical side, transported to the endoplasmic reticulum (ER) and resynthesized into TAG. TAG are assembled into chylomicrons (CM) in the ER, transported to the Golgi via pre-chylomicron transport vesicles and secreted towards the basolateral side. In this review, we mainly focus on the roles of key proteins involved in uptake and intracellular transport of fatty acids, their conversion to TAG and packaging into CM. We will also discuss intracellular transport and secretion of CM. Moreover, we will bring to light few factors that regulate gut triglyceride production. Furthermore, we briefly summarize pathways involved in cholesterol absorption. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.

  10. Minimal contribution of severe hypertriglyceridemia in L-asparaginase-associated pancreatitis developed in a child with acute lymphocytic leukemia.

    Science.gov (United States)

    Goto, Yoshinori; Nishimura, Ryosei; Nohara, Atsushi; Mase, Shintaro; Fujiki, Toshihiro; Irabu, Hitoshi; Kuroda, Rie; Araki, Raita; Ikawa, Yasuhiro; Maeba, Hideaki; Yachie, Akihiro

    2016-08-01

    A 10-year-old girl developed L-asparaginase (ASP)-associated pancreatitis during chemotherapy for acute lymphocytic leukemia. Her symptoms showed alleviation with continuous regional arterial infusion of protease inhibitor and systemic somatostatin analog therapy. She had intermittent and marked hypertriglyceridemia, an initial trigger for pancreatitis, probably as a side effect of ASP and steroids. However, we considered the pancreatitis to have developed mainly because of factors other than hypertriglyceridemia as lipoprotein analysis confirmed chylomicron levels to be nearly undetectable. Extremely large chylomicrons contribute directly to the onset of pancreatitis by causing blockage of small vessels. Although it is necessary to examine patients for dyslipidemia developing as a side effect of ASP, therapeutic intervention for hypertriglyceridemia is not considered to prevent the onset of ASP-associated pancreatitis. PMID:27599414

  11. Intestine-Specific Mttp Deletion Decreases Mortality and Prevents Sepsis-Induced Intestinal Injury in a Murine Model of Pseudomonas aeruginosa Pneumonia

    OpenAIRE

    Dominguez, Jessica A.; Xie, Yan; Dunne, W. Michael; Yoseph, Benyam P.; Burd, Eileen M.; Coopersmith, Craig M.; Davidson, Nicholas O

    2012-01-01

    Background The small intestine plays a crucial role in the pathophysiology of sepsis and has been referred to as the “motor” of the systemic inflammatory response. One proposed mechanism is that toxic gut-derived lipid factors, transported in mesenteric lymph, induce systemic injury and distant organ failure. However, the pathways involved are yet to be defined and the role of intestinal chylomicron assembly and secretion in transporting these lipid factors is unknown. Here we studied the out...

  12. Targeting Apolipoproteins in Magnetic Resonance Imaging

    Science.gov (United States)

    Sriram, Renuka; Lagerstedt, Jens O.; Samardzic, Haris; Kreutzer, Ulrike; Petrolova, Jitka; Xie, Hongtao; Kaysen, George A.; Voss, John C.; Desreux, Jean F.; Jue, Thomas

    Maintaining normal physiological homeostasis depends upon a coordinated metabolism of both water-soluble and -insoluble substrates. In humans the body derives these molecules — such as glucose, amino acids, and fatty acids — from complex food matter. Water-soluble substrates can circulate readily in blood, while water-insoluble molecules — such as fatty acid, triacylglycerol, and cholesterol — require ampiphathic carriers to transport them from the site of biosynthesis (liver and intestine) to the target tissue. For fatty acid, albumin serves as the major transporter. For triacylglycerol and cholesterol, however, macromolecular complexes aggregate the hydrophobic molecules into the core and cover the surface with amphiphatic proteins and phospholipids to solubilize the particles in the lymphatic and circulatory systems. These macromolecules belong to a class of proteins, plasma lipoproteins, with specific functions and cellular targets. In the clinic these lipoproteins prognosticate the risk of cardiovascular disease (CVD). Lipoproteins divide usually into five major types: chylomicron, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Each lipoprotein type exhibits characteristic density, size, and composition. As implied in the name, the density varies from the low-density chylomicron (high-density HDL (1.2 g/ml). Size also varies. The chylomicron has the largest diameter (75-1,200 nm), and HDL has the smallest (5-12 nm). The physical property variation arises from each lipoprotein's distinct composition. In a chylomicron, cholesterol, triacylglycerol, and phospholipid predominate and constitute about 90% of the particle. Protein constitutes only about 10%. In contrast, the smaller HDL has less cholesterol, triacylglycerol, and phospholipid (65% of the particle) but more protein (over 30%).

  13. Formulation optimization of Docetaxel loaded self-emulsifying drug delivery system to enhance bioavailability and anti-tumor activity

    OpenAIRE

    Valicherla, Guru R.; Dave, Kandarp M.; Anees A. Syed; Mohammed Riyazuddin; Gupta, Anand P.; Akhilesh Singh; Wahajuddin,; Kalyan Mitra; Dipak Datta; Gayen, Jiaur R.

    2016-01-01

    Poor bioavailability of Docetaxel (DCT) arising due to its low aqueous solubility and permeability limits its clinical utility. The aim of the present study was to develop DCT loaded self-emulsified drug delivery systems (D-SEDDS) and evaluate its potential ability to improve the oral bioavailability and therapeutic efficacy of DCT. D-SEDDS were characterized for their in vitro antitumor activity, in situ single pass intestinal perfusion (SPIP), bioavailability, chylomicron flow blocking stud...

  14. Uptake of Dietary Retinoids at the Maternal-Fetal Barrier: IN VIVO EVIDENCE FOR THE ROLE OF LIPOPROTEIN LIPASE AND ALTERNATIVE PATHWAYS*

    OpenAIRE

    Wassef, Lesley; Quadro, Loredana

    2011-01-01

    Dietary retinoids (vitamin A and its derivatives) contribute to normal embryonic development. However, the mechanism(s) involved in the transfer of recently ingested vitamin A from mother to embryo is not fully understood. We investigated in vivo whether lipoprotein lipase (LPL) facilitates the placental uptake of dietary retinyl ester incorporated in chylomicrons and their remnants and its transfer to the embryo. We examined the effects of both genetic ablation (MCK-L0 mice) and pharmacologi...

  15. Development of alimentary cholesterol in the plasma and the plasmatic lipoproteins in man, after ingestion of a meal containing octa-deuterated cholesterol; Devenir du cholesterol alimentaire dans le plasma et les lipoproteines plasmatiques chez l`homme, apres ingestion d`un repas contenant du cholesterol octa-deutere

    Energy Technology Data Exchange (ETDEWEB)

    Becue, T.; Ferezou, J.; Simon, G. [Paris-11 Univ., 91 - Orsay (France); Bernard, P.M.; Portugal, H. [Hopital Sainte-Marguerite, 13 - Marseille (France); Dubois, C.; Lairon, D.

    1994-12-31

    Cholesterol absorbed after a test-meal has two origins with man: the biliary cholesterol and the alimentary cholesterol. In order to understand the mechanism of the modification of cholesterol intestinal absorption by oat bran, the alimentary cholesterol has been labelled with octa-deuterated cholesterol, in test-diets. The kinetics of D-cholesterol in plasma and chylomicrons is described. 1 fig., 6 refs.

  16. Enzymes involved in triglyceride hydrolysis.

    Science.gov (United States)

    Taskinen, M R; Kuusi, T

    1987-08-01

    The lipolytic enzymes LPL and HL play important roles in the metabolism of lipoproteins and participate in lipoprotein interconversions. LPL was originally recognized to be the key enzyme in the hydrolysis of chylomicrons and triglyceride, but it also turned out to be one determinant of HDL concentration in plasma. When LPL activity is high, chylomicrons and VLDL are rapidly removed from circulation and a concomitant rise of the HDL2 occurs. In contrast, low LPL activity impedes the removal of triglyceride-rich particles, resulting in the elevation of serum triglycerides and a decrease of HDL (HDL2). Concordant changes of this kind in LPL and HDL2 are induced by many physiological and pathological perturbations. Finally, the operation of LPL is also essential for the conversion of VLDL to LDL. This apparently clear-cut role of LPL in lipoprotein interconversions is contrasted with the enigmatic actions of HL. The enzyme was originally thought to participate in the catalyses of chylomicron and VLDL remnants generated in the LPL reaction. However, substantial in vitro and in vivo data indicate that HL is a key enzyme in the degradation of plasma HDL (HDL2) in a manner which opposes LPL. A scheme is presented for the complementary actions of the two enzymes in plasma HDL metabolism. In addition, recent studies have attributed a role to HL in the catabolism of triglyceride-rich lipoproteins, particularly those containing apo E. However, this function becomes clinically important only under conditions where the capacity of the LPL-mediated removal system is exceeded. Such a situation may arise when the input of triglyceride-rich particles (chylomicrons and/or VLDL) is excessive or LPL activity is decreased or absent.

  17. Intestine-Specific Mttp Deletion Increases the Severity of Experimental Colitis and Leads to Greater Tumor Burden in a Model of Colitis Associated Cancer

    OpenAIRE

    Yan Xie; Hitoshi Matsumoto; Ilke Nalbantoglu; Kerr, Thomas A.; Jianyang Luo; Rubin, Deborah C; Susan Kennedy; Davidson, Nicholas O.

    2013-01-01

    Background Gut derived lipid factors have been implicated in systemic injury and inflammation but the precise pathways involved are unknown. In addition, dietary fat intake and obesity are independent risk factors for the development of colorectal cancer. Here we studied the severity of experimental colitis and the development of colitis associated cancer (CAC) in mice with an inducible block in chylomicron secretion and fat malabsorption, following intestine-specific deletion of microsomal t...

  18. Tamoxifen-induced hypertriglyceridemia causing acute pancreatitis

    OpenAIRE

    Hemant Kumar Singh; Mahendranath S Prasad; Kandasamy, Arun K.; Kadambari Dharanipragada

    2016-01-01

    Tamoxifen has both antagonistic and agonistic tissue-specific actions. It can have a paradoxical estrogenic effect on lipid metabolism resulting in elevated triglyceride and chylomicron levels. This can cause life-threatening complications like acute pancreatitis. To our knowledge, very few cases of tamoxifen-induced pancreatitis have been reported in the literature. We report a case of severe hypertriglyceridemia and acute pancreatitis following tamoxifen use. A 50-year-old diabetic lady was...

  19. The familial hyperchylomicronemia syndrome: New insights into underlying genetic defects

    Energy Technology Data Exchange (ETDEWEB)

    Santamarina-Fojo, S.; Brewer, H.B. (National Inst. of Health, Bethesda, MD (United States))

    1991-02-20

    This case history reports the diagnosis of familial hyperchylomicronemia, a rare genetic syndrome inherited as an autosomal recessive trait. It is characterized by severe fasting hypertriglyceridemia and massive accumulations of chylomicrons in plasma. The two major molecular defects in the disease are a deficiency of lipoprotein lipase or of apo C-II. The location of the mutations in the human apolipoprotein (apo) C-II gene are identified.

  20. Serum lipoprotein lipase mass: Clinical significance of its measurement

    OpenAIRE

    Kobayashi, Junji; Nohara, Atsushi; Kawashiri, Masaaki; Inazu, Akihiro; Koizumi, Junji; Nakajima, Katsuyuki; Mabuchi, Hiroshi

    2007-01-01

    Lipoprotein lipase (LPL) is a lipolytic enzyme involved in catalyzing hydrolysis of triglycerides (TG) in chylomicrons and very low-density lipoprotein (VLDL) particles. Over the last decade, increasing attention has been paid to the clinical significance of measuring serum LPL protein mass without heparin injection to the study subjects. In earlier studies, this marker was utilized to classify LPL deficient subjects, which is an extremely rare metabolic disorder with a frequency of one in on...

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

    OpenAIRE

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

    2013-01-01

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

  2. High-resolution imaging of dietary lipids in cells and tissues by NanoSIMS analysis[S

    OpenAIRE

    Jiang, Haibo; Goulbourne, Chris N.; Tatar, Angelica; Turlo, Kirsten; Wu, Daniel; Beigneux, Anne P.; Grovenor, Chris R.M.; Fong, Loren G.; Young, Stephen G.

    2014-01-01

    Nanoscale secondary ion MS (NanoSIMS) imaging makes it possible to visualize stable isotope-labeled lipids in cells and tissues at 50 nm lateral resolution. Here we report the use of NanoSIMS imaging to visualize lipids in mouse cells and tissues. After administering stable isotope-labeled fatty acids to mice by gavage, NanoSIMS imaging allowed us to visualize neutral lipids in cytosolic lipid droplets in intestinal enterocytes, chylomicrons at the basolateral surface of enterocytes, and lipi...

  3. Amyloid-β colocalizes with apolipoprotein B in absorptive cells of the small intestine

    Directory of Open Access Journals (Sweden)

    Dhaliwal Satvinder S

    2009-10-01

    Full Text Available Abstract Background Amyloid-β is recognized as the major constituent of senile plaque found in subjects with Alzheimer's disease. However, there is increasing evidence that in a physiological context amyloid-β may serve as regulating apolipoprotein, primarily of the triglyceride enriched lipoproteins. To consider this hypothesis further, this study utilized an in vivo immunological approach to explore in lipogenic tissue whether amyloid-β colocalizes with nascent triglyceride-rich lipoproteins. Results In murine absorptive epithelial cells of the small intestine, amyloid-β had remarkable colocalization with chylomicrons (Manders overlap coefficient = 0.73 ± 0.03 (SEM, the latter identified as immunoreactive apolipoprotein B. A diet enriched in saturated fats doubled the abundance of both amyloid-β and apo B and increased the overlap coefficient of the two proteins (0.87 ± 0.02. However, there was no evidence that abundance of the two proteins was interdependent within the enterocytes (Pearson's Coefficient Conclusion The findings of this study are consistent with the possibility that amyloid-β is secreted by enterocytes as an apolipoprotein component of chylomicrons. However, secretion of amyloid-β appears to be independent of chylomicron biogenesis.

  4. Ezetimibe: Its Novel Effects on the Prevention and the Treatment of Cholesterol Gallstones and Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Ornella de Bari

    2012-01-01

    Full Text Available The cholesterol absorption inhibitor ezetimibe can significantly reduce plasma cholesterol concentrations by inhibiting the Niemann-Pick C1-like 1 protein (NPC1L1, an intestinal sterol influx transporter that can actively facilitate the uptake of cholesterol for intestinal absorption. Unexpectedly, ezetimibe treatment also induces a complete resistance to cholesterol gallstone formation and nonalcoholic fatty liver disease (NAFLD in addition to preventing hypercholesterolemia in mice on a Western diet. Because chylomicrons are the vehicles with which the enterocytes transport cholesterol and fatty acids into the body, ezetimibe could prevent these two most prevalent hepatobiliary diseases possibly through the regulation of chylomicron-derived cholesterol and fatty acid metabolism in the liver. It is highly likely that there is an intestinal and hepatic cross-talk through the chylomicron pathway. Therefore, understanding the molecular mechanisms whereby cholesterol and fatty acids are absorbed from the intestine could offer an efficacious novel approach to the prevention and the treatment of cholesterol gallstones and NAFLD.

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

    Science.gov (United States)

    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 removal of proatherogenic chylomicron remnants, we suggest that the hepatic clearance of these particles might be compromised in insulin-resistant obese subjects. Premature and accelerated atherogenesis in viscerally obese, insulin-resistant subjects may in part reflect delayed clearance of postprandial lipoprotein remnants. PMID:11500319

  6. Intestine-specific Mttp deletion decreases mortality and prevents sepsis-induced intestinal injury in a murine model of Pseudomonas aeruginosa pneumonia.

    Directory of Open Access Journals (Sweden)

    Jessica A Dominguez

    Full Text Available BACKGROUND: The small intestine plays a crucial role in the pathophysiology of sepsis and has been referred to as the "motor" of the systemic inflammatory response. One proposed mechanism is that toxic gut-derived lipid factors, transported in mesenteric lymph, induce systemic injury and distant organ failure. However, the pathways involved are yet to be defined and the role of intestinal chylomicron assembly and secretion in transporting these lipid factors is unknown. Here we studied the outcome of sepsis in mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO, which exhibit a block in chylomicron assembly together with lipid malabsorption. METHODOLOGY/PRINCIPAL FINDINGS: Mttp-IKO mice and controls underwent intratracheal injection with either Pseudomonas aeruginosa or sterile saline. Mttp-IKO mice exhibited decreased seven-day mortality, with 0/20 (0% dying compared to 5/17 (29% control mice (p<0.05. This survival advantage in Mttp-IKO mice, however, was not associated with improvements in pulmonary bacterial clearance or neutrophil infiltration. Rather, Mttp-IKO mice exhibited protection against sepsis-associated decreases in villus length and intestinal proliferation and were also protected against increased intestinal apoptosis, both central features in control septic mice. Serum IL-6 levels, a major predictor of mortality in human and mouse models of sepsis, were elevated 8-fold in septic control mice but remained unaltered in septic Mttp-IKO mice. Serum high density lipoprotein (HDL levels were reduced in septic control mice but were increased in septic Mttp-IKO mice. The decreased levels of HDL were associated with decreased hepatic expression of apolipoprotein A1 in septic control mice. CONCLUSIONS/SIGNIFICANCE: These studies suggest that strategies directed at blocking intestinal chylomicron secretion may attenuate the progression and improve the outcome of sepsis through effects

  7. Apolipoprotein AV Accelerates Plasma Hydrolysis OfTriglyceride-Rich Lipoproteins By Interaction With Proteoglycan BoundLipoprotein Lipase

    Energy Technology Data Exchange (ETDEWEB)

    Merkel, Martin; Loeffler, Britta; Kluger, Malte; Fabig, Nathalie; Geppert, Gesa; Pennacchio, Len A.; Laatsch, Alexander; Heeren, Joerg

    2005-02-22

    Apolipoprotein A5 (APOA5) is associated with differences intriglyceride levels and familial combined hyperlipidemia. In genetically engineered mice, apoAV plasma levels are inversely correlated with plasmatriglycerides. To elucidate the mechanism by which apoAV influences plasma triglycerides, metabolic studies and in vitro assays resembling physiological conditions were performed. In hAPOA5 transgenic mice(hAPOA5tr), catabolism of chylomicrons and VLDL was accelerated due to a faster plasma hydrolysis of triglycerides by lipoprotein lipase (LPL).Hepatic VLDL and intestinal chylomicron production were not affected. The functional interplay between apoAV and LPL was further investigated by crossbreeding a human LPL transgene with the apoa5 knockout, and the hAPOA5tr to an LPL deficient background. Increased LPL activity completely normalized hypertriglyceridemia of apoa5 deficient mice,however, over expression of human apoAV modulated triglyceride levels only slightly when LPL was reduced. To reflect the physiological situation in which LPL is bound to cell surface proteoglycans, we examined hydrolysis in the presence or absence of proteoglycans. Without proteoglycans, apoAV derived either from triglyceride-rich lipoproteins, hAPOA5tr HDL, or a recombinant source did not alter the LPL hydrolysis rate. In the presence of proteoglycans, however, apoAV led to a significant and dose-dependent increase in LPL mediated hydrolysis of VLDL triglycerides. These results were confirmed in cell culture using a proteoglycan-deficient cell line.A direct interaction between LPL and apoAV was found by ligand blotting.It is proposed, that apoAV reduces triglyceride levels by guiding VLDL and chylomicrons to proteoglycans bound LPL for lipolysis.

  8. Release of endothelial cell lipoprotein lipase by plasma lipoproteins and free fatty acids

    International Nuclear Information System (INIS)

    Lipoprotein lipase (LPL) bound to the lumenal surface of vascular endothelial cells is responsible for the hydrolysis of triglycerides in plasma lipoproteins. Studies were performed to investigate whether human plasma lipoproteins and/or free fatty acids would release LPL which was bound to endothelial cells. Purified bovine milk LPL was incubated with cultured porcine aortic endothelial cells resulting in the association of enzyme activity with the cells. When the cells were then incubated with media containing chylomicrons or very low density lipoproteins (VLDL), a concentration-dependent decrease in the cell-associated LPL enzymatic activity was observed. In contrast, incubation with media containing low density lipoproteins or high density lipoproteins produced a much smaller decrease in the cell-associated enzymatic activity. The addition of increasing molar ratios of oleic acid:bovine serum albumin to the media also reduced enzyme activity associated with the endothelial cells. To determine whether the decrease in LPL activity was due to release of the enzyme from the cells or inactivation of the enzyme, studies were performed utilizing radioiodinated bovine LPL. Radiolabeled LPL protein was released from endothelial cells by chylomicrons, VLDL, and by free fatty acids (i.e. oleic acid bound to bovine serum albumin). The release of radiolabeled LPL by VLDL correlated with the generation of free fatty acids from the hydrolysis of VLDL triglyceride by LPL bound to the cells. Inhibition of LPL enzymatic activity by use of a specific monoclonal antibody, reduced the extent of release of 125I-LPL from the endothelial cells by the added VLDL. These results demonstrated that LPL enzymatic activity and protein were removed from endothelial cells by triglyceride-rich lipoproteins (chylomicrons and VLDL) and oleic acid

  9. Lipidomic and spatio-temporal imaging of fat by mass spectrometry in mice duodenum during lipid digestion.

    Directory of Open Access Journals (Sweden)

    Alexandre Seyer

    Full Text Available Intestinal absorption of dietary fat is a complex process mediated by enterocytes leading to lipid assembly and secretion of circulating lipoproteins as chylomicrons, vLDL and intestinal HDL (iHDL. Understanding lipid digestion is of importance knowing the correlation between excessive fat absorption and atherosclerosis. By using time-of-flight secondary ion mass spectrometry (TOF-SIMS, we illustrated a spatio-temporal localization of fat in mice duodenum, at different times of digestion after a lipid gavage, for the first time. Fatty acids progressively increased in enterocytes as well as taurocholic acid, secreted by bile and engaged in the entero-hepatic re-absorption cycle. Cytosolic lipid droplets (CLD from enterocytes were originally purified separating chylomicron-like, intermediate droplets and smaller HDL-like. A lipidomic quantification revealed their contents in triglycerides, free and esterified cholesterol, phosphatidylcholine, sphingomyelin and ceramides but also in free fatty acids, mono- and di-acylglycerols. An acyl-transferase activity was identified and the enzyme monoacylglycerol acyl transferase 2 (MGAT2 was immunodetected in all CLD. The largest droplets was also shown to contain the microsomal triglyceride transfer protein (MTTP, the acyl-coenzyme A-cholesterol acyltransferases (ACAT 1 and 2, hormone sensitive lipase (HSL and adipose triglyceride lipase (ATGL. This highlights the fact that during the digestion of fats, enterocyte CLD contain some enzymes involved in the different stages of the metabolism of diet fatty acids and cholesterol, in anticipation of the crucial work of endoplasmic reticulum in the process. The data further underlines the dual role of chylomicrons and iHDL in fat digestion which should help to efficiently complement lipid-lowering therapy.

  10. Possible mechanisms of normal amylase activity in hyperlipemic pancreatitis.

    Science.gov (United States)

    Mishkin, S.; Bates, J.; O'Hashi, J.; Schneider, P.; Sniderman, A. D.; Wolf, R. O.

    1976-01-01

    Lipemic serum from three patients with acute pancreatitis and type IV hyperlipemia was fractionated into very-low-density lipoproteins and clear serum. Amylase activity (determined by the Phadebas method) in the component fractions did not exceed that in the original lipemic serum. Addition of these fractions or VLDL and chylomicrons from asymptomatic patients with hyperlipemia to nonlipemic serum from patients with "routine acute pancreatitis" did not inhibit amylase activity or alter the electrophoretic mobility of amylase isoenzymes. Therefore the normal amylase activity often observed in hyperlipemic pancreatitis does not result from an inhibition of amylase activity by serum lipoproteins. Images FIG. 4 FIG. 5 PMID:206333

  11. [Chylothorax in a calf].

    Science.gov (United States)

    Pusterla, N; Pusterla, J B; Thür, B; Rüsch, P

    1996-12-01

    A case of chylothorax caused by fracture of thoracal vertebrae in a two-day-old Swiss Braunvieh male calf ist described. The clinical symptoms were those of a unilateral, progressive pleural effusion. This was confirmed by radiological and ultrasonographic examinations. Thoracocentesis was performed under ultrasonographic assistance. The liquid obtained from the pleural cavity was turbid and contained chylomicrons, lymphocytes and neutrophilic granulocytes as well as a high concentration of triglycerides. These qualities go together with chylus. Immunohistological examination for BVD virus turned out to be positive. An intrauterine disturbance of osteogenesis due to BVD virus must be considered a possible cause for fracture of vertebrae during delivery.

  12. Apolipoprotein E*3-Leiden transgenic mice mode for hypolipidaemic drugs

    OpenAIRE

    Vlijmen, B.J.M. van; Pearce, N.J.; Bergö, M.; Staels, B.; Yates, J.W.; Gribble, A.D.; Bond, B.C.; Hofker, M H; Havekes, L. M.; Groot, P H E

    1998-01-01

    Apolipoprotein (APO) E*3-Leiden mice with impaired chylomicron and VLDL (very low density lipoprotein) remnant metabolism display hyperlipidaemia and atherosclerosis. In the present study, these mice were used for testing the hypolipidaemic effect of two marketed agents, lovastatin (CAS 75330-75-5) and gemfibrozil (CAS 25812-30-0) as well as a novel compound, SB 204990 (the 5- ring lactone of ±(3R*,5S*) 3-carboxy-11-(2,4-dichlorophenyl)-3,5- dihydroxyundecanoic acid, CAS 154566-12-8), a poten...

  13. Evaluation of mesenteric lymphangiography and thoracic duct ligation in cats with chylothorax: 19 cases (1987-1992)

    International Nuclear Information System (INIS)

    Mesenteric lymphangiography and thoracic duct ligation were performedon 19 cats with chylothorax between 1987 to 1992. Chylothorax was diagnosed on the basis of detection of chylomicrons in the pleural effusion or determination of a cholesterol concentration:triglyceride concentration ratio of 12 months after surgery. Four cats died between 2 and 13 days after thoracic duct ligation, but pleural effusion had resolved in 3 of these 4 cats at the time of death. Five cats were euthanatized 8 to 36 days after surgery because of persistent chylous effusion after thoracic duct ligation

  14. The origin of cholesterol in chyle demonstrated by nuclear indicator methods

    International Nuclear Information System (INIS)

    In order to obtain information about the mechanism of the intestinal absorption of cholesterol, rats having a lymphatic abdominal fistula are used. The animals receive either 4-14C- cholesterol subcutaneously or orally, or the 1-14C acetate. The study of the specific radio-activities of the cholesterol in chyle, in serum, in the lining, and in the intestinal contents makes it possible to define the roles played by the transfer cholesterol from the serum, by the cholesterol synthesised intestinally, and by the absorption cholesterol, in the formations of the lymph and of the chylomicrons. A new theory is proposed for the mechanism of cholesterol absorption. (author)

  15. [Lipoprotein receptors. Old acquaintances and newcomers].

    Science.gov (United States)

    Ducobu, J

    1997-02-01

    Lipoprotein receptors are plasma membrane proteins of high affinity which interact with circulating lipoprotein particles. The well characterized LDL receptor continues to be analysed and some new findings on its intracellular mechanisms of action have emerged. New lipoprotein receptors have recently been described: the chylomicron remnant receptor or LDL-related protein (LRP), the lipolysis stimulated receptor (LSR), the very low density lipoprotein receptor (VLDLR), the HDL receptor (HDLR) and the scavenger receptor (SR). The molecular details of the receptors will facilitate the development of new therapeutic means to improve receptor-mediated clearance of lipoproteins.

  16. Metabolism of apolipoproteins B-48 and B-100 of triglyceride-rich lipoproteins in normal and lipoprotein lipase-deficient humans.

    OpenAIRE

    Stalenhoef, A.F.; Malloy, M J; Kane, J P; Havel, R J

    1984-01-01

    The metabolism of apolipoproteins B-48 and B-100 (apo B-48 and B-100) in large triglyceride-rich lipoproteins (300 to 1500 A in diameter) has been compared in three normal subjects and two subjects with genetically determined deficiency of lipoprotein lipase. The triglyceride-rich lipoproteins were obtained from a lipoprotein lipase-deficient donor 4 hr after a fat-rich meal in order to obtain chylomicrons (containing apo B-48) and very low density lipoproteins (VLDL) (containing apo B-100), ...

  17. Formulation optimization of Docetaxel loaded self-emulsifying drug delivery system to enhance bioavailability and anti-tumor activity.

    Science.gov (United States)

    Valicherla, Guru R; Dave, Kandarp M; Syed, Anees A; Riyazuddin, Mohammed; Gupta, Anand P; Singh, Akhilesh; Wahajuddin; Mitra, Kalyan; Datta, Dipak; Gayen, Jiaur R

    2016-01-01

    Poor bioavailability of Docetaxel (DCT) arising due to its low aqueous solubility and permeability limits its clinical utility. The aim of the present study was to develop DCT loaded self-emulsified drug delivery systems (D-SEDDS) and evaluate its potential ability to improve the oral bioavailability and therapeutic efficacy of DCT. D-SEDDS were characterized for their in vitro antitumor activity, in situ single pass intestinal perfusion (SPIP), bioavailability, chylomicron flow blocking study and bio-distribution profile. The D-SEDDS were prepared using Capryol 90, Vitamin E TPGS, Gelucire 44/14 and Transcutol HP with a ratio of 32.7/29.4/8.3/29.6 using D-Optimal Mixture Design. The solubility of DCT was improved upto 50 mg/mL. The oral bioavailability of the D-SEDDS in rats (21.84 ± 3.12%) was increased by 3.19 fold than orally administered Taxotere (6.85 ± 1.82%). The enhanced bioavailability was probably due to increase in solubility and permeability. In SPIP, effective permeability of D-SEDDS was significantly higher than Taxotere. D-SEDDS showed 25 fold more in vitro cytotoxic activity compared to free DCT. Chylomicron flow blocking study and tissue distribution demonstrated the intestinal lymphatic transport of D-SEDDS and higher retention in tumor than Taxotere. The data suggests that D-SEDDS showed desired stability, enhanced oral bioavailability and in vitro antitumor efficacy. PMID:27241877

  18. Retinol and retinyl esters in parenchymal and nonparenchymal rat liver cell fractions after long-term administration of ethanol

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, M.; Blomhoff, R.; Helgerud, P.; Solberg, L.A.; Berg, T.; Norum, K.R.

    1985-09-01

    Chronic ethanol consumption reduces the liver retinoid store in man and rat. We have studied the effect of ethanol on some aspects of retinoid metabolism in parenchymal and nonparenchymal liver cells. Rats fed 36% of total energy intake as ethanol for 5-6 weeks had the liver retinoid concentration reduced to about one-third, as compared to pair-fed controls. The reduction in liver retinoid affected both the parenchymal and the nonparenchymal cell fractions. Plasma retinol level was normal. Liver uptake of injected chylomicron (3H)retinyl ester was similar in the experimental and control group. The transport of retinoid from the parenchymal to the nonparenchymal cells was not found to be significantly retarded in the ethanol-fed rats. Despite the reduction in total retinoid level in liver, the concentrations of unesterified retinol and retinyl oleate were increased in the ethanol fed rats. Hepatic retinol esterification was not significantly affected in the ethanol-fed rats. Since our study has demonstrated that liver uptake of chylomicron retinyl ester is not impaired in the ethanol-fed rat, we suggest that liver retinoid metabolism may be increased.

  19. Formulation optimization of Docetaxel loaded self-emulsifying drug delivery system to enhance bioavailability and anti-tumor activity.

    Science.gov (United States)

    Valicherla, Guru R; Dave, Kandarp M; Syed, Anees A; Riyazuddin, Mohammed; Gupta, Anand P; Singh, Akhilesh; Wahajuddin; Mitra, Kalyan; Datta, Dipak; Gayen, Jiaur R

    2016-05-31

    Poor bioavailability of Docetaxel (DCT) arising due to its low aqueous solubility and permeability limits its clinical utility. The aim of the present study was to develop DCT loaded self-emulsified drug delivery systems (D-SEDDS) and evaluate its potential ability to improve the oral bioavailability and therapeutic efficacy of DCT. D-SEDDS were characterized for their in vitro antitumor activity, in situ single pass intestinal perfusion (SPIP), bioavailability, chylomicron flow blocking study and bio-distribution profile. The D-SEDDS were prepared using Capryol 90, Vitamin E TPGS, Gelucire 44/14 and Transcutol HP with a ratio of 32.7/29.4/8.3/29.6 using D-Optimal Mixture Design. The solubility of DCT was improved upto 50 mg/mL. The oral bioavailability of the D-SEDDS in rats (21.84 ± 3.12%) was increased by 3.19 fold than orally administered Taxotere (6.85 ± 1.82%). The enhanced bioavailability was probably due to increase in solubility and permeability. In SPIP, effective permeability of D-SEDDS was significantly higher than Taxotere. D-SEDDS showed 25 fold more in vitro cytotoxic activity compared to free DCT. Chylomicron flow blocking study and tissue distribution demonstrated the intestinal lymphatic transport of D-SEDDS and higher retention in tumor than Taxotere. The data suggests that D-SEDDS showed desired stability, enhanced oral bioavailability and in vitro antitumor efficacy.

  20. Dyslipidaemia of diabetes and the intestine

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Atherosclerosis is the major complication of diabetes andhas become a major issue in the provision of medicalcare. In particular the economic burden is growing atan alarming rate in parallel with the increasing worldwideprevalence of diabetes. The major disturbanceof lipid metabolism in diabetes relates to the effect ofinsulin on fat metabolism. Raised triglycerides being thehallmark of uncontrolled diabetes, i.e. , in the presenceof hyperglycaemia. The explosion of type 2 diabeteshas generated increasing interest on the aetiology ofatherosclerosis in diabetic patients. The importanceof the atherogenic properties of triglyceride richlipoproteins has only recently been recognised by themajority of diabetologists and cardiologists even thoughexperimental evidence has been strong for many years.In the post-prandial phase 50% of triglyceride richlipoproteins come from chylomicrons produced in theintestine. Recent evidence has secured the chylomicronas a major player in the atherogenic process. In diabeteschylomicron production is increased through disturbancein cholesterol absorption, in particular Neimann PickC1-like1 activity is increased as is intestinal synthesisof cholesterol through 3-hydroxy-3-methyl glutaryl coenzyme A reductase. ATP binding cassette proteins G5and G8 which regulate cholesterol in the intestine isreduced leading to chylomicronaemia. The chylomicronparticle itself is atherogenic but the increase in thetriglyceride-rich lipoproteins lead to an atherogenic lowdensity lipoprotein and low high density lipoprotein.The various steps in the absorption process and thedisturbance in chylomicron synthesis are discussed.

  1. Enhanced incorporation of dietary DHA into lymph phospholipids by altering its molecular carrier.

    Science.gov (United States)

    Subbaiah, Papasani V; Dammanahalli, Karigowda J; Yang, Peng; Bi, Jian; O'Donnell, J Michael

    2016-08-01

    Several previous studies indicated that for optimal uptake by the brain, docosahexaenoic acid (DHA) should be present as phospholipid in the plasma. However most of dietary DHA is absorbed as triacylglycerol (TAG) because it is released as free fatty acid during digestion of either TAG-DHA (fish oil) or sn-2-DHA phospholipid (krill oil), and subsequently incorporated into TAG of chylomicrons. We tested the hypothesis that the absorption of DHA as phospholipid can be increased if it is present in the sn-1 position of dietary phospholipid or in lysophosphatidylcholine (LPC), because it would escape the hydrolysis by pancreatic phospholipase A2. We infused micelle containing the DHA either as LPC or as free acid, into the duodenum of lymph cannulated rats, and analyzed the chylomicrons and HDL of the lymph for the DHA-containing lipids. The results show that while the total amount of DHA absorbed was comparable from the two types of micelle, the percentage of DHA recovered in lymph phospholipids was 5 times greater with LPC-DHA, compared to free DHA. Furthermore, the amount of DHA recovered in lymph HDL was increased by 2-fold when LPC-DHA micelle was infused. These results could potentially lead to a novel strategy to increase brain DHA levels through the diet. PMID:27178174

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

    Science.gov (United States)

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

    1969-01-01

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

  3. New and emerging regulators of intestinal lipoprotein secretion.

    Science.gov (United States)

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

    2014-04-01

    Overproduction of hepatic apoB100-containing VLDL particles has been well documented in animal models and in humans with insulin resistance such as the metabolic syndrome and type 2 diabetes, and contributes to the typical dyslipidemia of these conditions. In addition, postprandial hyperlipidemia and elevated plasma concentrations of intestinal apoB48-containing chylomicron and chylomicron remnant particles have been demonstrated in insulin resistant states. Intestinal lipoprotein production is primarily determined by the amount of fat ingested and absorbed. Until approximately 10 years ago, however, relatively little attention was paid to the role of the intestine itself in regulating the production of triglyceride-rich lipoproteins (TRL) and its dysregulation in pathological states such as insulin resistance. We and others have shown that insulin resistant animal models and humans are characterized by overproduction of intestinal apoB48-containing lipoproteins. Whereas various factors are known to regulate hepatic lipoprotein particle production, less is known about factors that regulate the production of intestinal lipoprotein particles. Monosacharides, plasma free fatty acids (FFA), resveratrol, intestinal peptides (e.g. GLP-1 and GLP-2), and pancreatic hormones (e.g. insulin) have recently been shown to be important regulators of intestinal lipoprotein secretion. Available evidence in humans and animal models strongly supports the concept that the small intestine is not merely an absorptive organ but rather plays an active role in regulating the rate of production of chylomicrons in fed and fasting states. Metabolic signals in insulin resistance and type 2 diabetes and in some cases an aberrant intestinal response to these factors contribute to the enhanced formation and secretion of TRL. Understanding the regulation of intestinal lipoprotein production is imperative for the development of new therapeutic strategies for the prevention and treatment of

  4. Apical secretion of apolipoproteins from enterocytes

    DEFF Research Database (Denmark)

    Danielsen, E M; Hansen, Gert Helge; Poulsen, Mona Dam

    1993-01-01

    Synthesis and secretion of apolipoproteins in pig small intestine was studied by pulse-chase labeling of jejunal segments, kept in organ culture. Apo A-1 and apo B-48 were the two major proteins released, constituting 25 and 10%, respectively, of the total amount of labeled protein in the mucosal...... that enterocytes release most of their newly made free apo A-1 and a significant portion of apo B-48 by exocytosis via the brush border membrane into the intestinal lumen. Fat absorption reduced apolipoprotein secretion to the medium and induced the formation of chylomicrons, containing apo A-1 at their surface......-side medium where they appeared with a t1/2 of 50-60 min. Using tissue from fasting animals, > 85% of newly synthesized apo A-1 and about one third of apo B-48 was released to the mucosal-side medium. Newly synthesized apolipoprotein that remained associated with the intestinal segment accumulated...

  5. [Trans-intestinal cholesterol excretion (TICE): a new route for cholesterol excretion].

    Science.gov (United States)

    Blanchard, Claire; Moreau, François; Cariou, Bertrand; Le May, Cédric

    2014-10-01

    The small intestine plays a crucial role in dietary and biliary cholesterol absorption, as well as its lymphatic secretion as chylomicrons (lipoprotein exogenous way). Recently, a new metabolic pathway called TICE (trans-intestinal excretion of cholesterol) that plays a central role in cholesterol metabolism has emerged. TICE is an inducible way, complementary to the hepatobiliary pathway, allowing the elimination of the plasma cholesterol directly into the intestine lumen through the enterocytes. This pathway is poorly characterized but several molecular actors of TICE have been recently identified. Although it is a matter of debate, two independent studies suggest that TICE is involved in the anti-atherogenic reverse cholesterol transport pathway. Thus, TICE is an innovative drug target to reduce -cardiovascular diseases.

  6. Delivery of lipophilic bioactives: assembly, disassembly, and reassembly of lipid nanoparticles.

    Science.gov (United States)

    Yao, Mingfei; Xiao, Hang; McClements, David Julian

    2014-01-01

    The oral bioavailability of lipophilic bioactive molecules can be greatly increased by encapsulating them within engineered lipid nanoparticles (ELNs), such as micelles, microemulsions, nanoemulsions, or solid lipid nanoparticles (SLNs). After ingestion, these ELNs are disassembled in the gastrointestinal tract (GIT) and then reassembled into biological lipid nanoparticles (mixed micelles) in the small intestine. These mixed micelles solubilize and transport lipophilic bioactive components to the epithelial cells. The mixed micelles are then disassembled and reassembled into yet another form of biological lipid nanoparticle [chylomicrons (CMs)] within the enterocyte cells. The CMs carry the bioactive components into the systemic (blood) circulation via the lymphatic system, thereby avoiding first-pass metabolism. This article provides an overview of the various physicochemical and physiological processes responsible for the assembly and disassembly of lipid nanoparticles outside and inside the GIT. This knowledge can be used to design food-grade delivery systems to improve the oral bioavailability of encapsulated lipophilic bioactive components. PMID:24328432

  7. Chylous effusions

    Directory of Open Access Journals (Sweden)

    Tomić Ilija

    2003-01-01

    Full Text Available This paper presents 4 patients with chylothorax, and one patient with bilateral chylothorax and chyloperitoneum. The chylous effusions were of benign etiology, developed as a complication of miliary tuberculosis (1 patient, after L-2 vertebral body fracture (1 patient, and idiopathic (2 patients. The diagnosis was confirmed by the presence of chylomicrons and high content of triglycerides in the effusion, ranged 11,9-29,1 mmol/l. Lymphangiography showed multiple abnormalites of lymphatic system, the obstruction of ductus thoracicus, dilatation and convulsion of lymphatic channels, but the site of lymphatic leak was not detected. The treatment included an extended period of pleural and peritoneal drainage with total parenteral nutrition (1 patient, pleurodesis using Corynebacterium parvum (2 patients, and surgical partial parietal pleurectomy with continous drainage (1 patient. The treatment was successful in all patients.

  8. [Chylous effusions].

    Science.gov (United States)

    Tomić, Ilija; Plavec, Goran; Karlicić, Vukojica; Spasić, Vulèta; Rusović, Sinisa; Stanić, Vojkan; Cvijanović, Vlado; Ristanović, Aleksandar

    2003-01-01

    This paper presents 4 patients with chylothorax, and one patient with bilateral chylothorax and chyloperitoneum. The chylous effusions were of benign etiology, developed as a complication of miliary tuberculosis (1 patient), after L-2 vertebral body fracture (1 patient), and idiopathic (2 patients). The diagnosis was confirmed by the presence of chylomicrons and high content of triglycerides in the effusion, ranged 11.9-29.1 mmol/l. Lymphangiography showed multiple abnormalities of lymphatic system, the obstruction of ductus thoracicus, dilatation and convulsion of lymphatic channels, but the site of lymphatic leak was not detected. The treatment included an extended period of pleural and peritoneal drainage with total parenteral nutrition (1 patient), pleurodesis using Corynebacterium parvum (2 patients), and surgical partial parietal pleurectomy with continuous drainage (1 patient). The treatment was successful in all patients. PMID:14608841

  9. Papain-hydrolyzed pork meat reduces serum cholesterol level and premature atherosclerosis in dietary-induced hypercholesterolemic rabbits.

    Science.gov (United States)

    Katsuda, S; Ito, M; Waseda, Y; Morimatsu, F; Taguichi, Y; Hasegawa, M; Takaichi, S; Yamada, R; Furukawa, Y; Shimizu, T

    2000-08-01

    The effects of the low-molecular-weight fraction of papain-hydrolyzed pork meat (LMF) on the plasma cholesterol level and the generation of atherosclerosis were studied in rabbits fed a cholesterol-enriched diet. In LMF-fed rabbits, the plasma and liver cholesterol concentrations were both significantly lower (pmeat (PM). Similarly, the cholesterol concentrations of the chylomicron and VLDL fractions were significantly lower in LMF-fed rabbits than in rabbits fed PM. Deposition of lipid in transverse sections of the aortic arch was significantly less in rabbits fed LMF than in those fed PM. Electron microscopic studies revealed preventive effects against premature atherosclerotic lesions in the aorta of rabbits fed LME These results indicate that LMF has a hypocholesterolemic action and preventive effects against premature atherosclerosis. PMID:11185655

  10. [Lipoprotein metabolic characteristics in the liver and intestinal wall of rabbits after a single exposure to sunflower oil and cholesterol].

    Science.gov (United States)

    Leskova, G F

    1982-04-01

    Lipoprotein metabolism in the rabbit liver and intestinal wall was studied by an alimentary action on the cholesterol blood content. The data obtained indicated that the diet including cholesterol intensifies the release of chylomicrons into the lymph of the intestinal lymphatic trunk. Single addition of sunflower-seed oil to the diet leads to the increased deposition of high, low and very low density lipoproteins in the intestinal wall. Upon adding cholesterol to the rabbit diet the retention of low and very low density lipids in the intestine is followed by the increased release of high density lipoproteins into the blood of the portal vein. Single addition of sunflower-seed oil stimulates the synthesis of high density lipoproteins by the rabbit liver.

  11. Effect of different surfactants in biorelevant medium on the secretion of a lipophilic compound in lipoproteins using Caco-2 cell culture

    DEFF Research Database (Denmark)

    Karpf, Ditte M; Holm, René; Garafalo, Carole;

    2006-01-01

    The impact of a pharmaceutical relevant metabolizable, ionic surfactant or two synthetic, nonionic surfactants on the absorption and lipoprotein incorporation of a lipophilic drug, retinol, was studied in the Caco-2 cell culture. Filter-grown monolayers of Caco-2 cells were incubated for 20 h...... with (3)H-retinol and (14)C-oleic acid and with increasing concentrations of lyso-phosphatidylcholine (lyso-PC), Cremophor RH40, or Tween 80. The concentration of (3)H-retinol and (14)C-lipid was measured in the apical, intracellular, and basolateral compartments. The basolateral medium...... was ultracentrifugated into different lipoprotein classes and their (3)H-retinol and (14)C-lipid concentrations were determined. The cells incubated with lyso-PC and Tween 80 increased the incorporation of (3)H-retinol and (14)C-lipid into chylomicrons and very low density lipoproteins (VLDL). The explored surfactants...

  12. 微粒体甘油三脂转运蛋白MTP的结构和功能研究概况%Recent advance on microsomal triglyceride transfer protein

    Institute of Scientific and Technical Information of China (English)

    叶健强; 蒋立; 王继文

    2005-01-01

    微粒体甘油三酯转运蛋白MTP(microsomal triglyceride transfer protein,MTP)首先是从牛的肝细胞微粒体碎片中分离获得的,其作用是加速甘油三脂(triglyceride,TG)、胆固醇(cholesteryl ester,CE)和磷脂酰胆碱(phosphatidylcholine,PC)的转运和细胞或亚细胞膜的生物合成.它后来在肝细胞和小肠的微粒体膜中发现[1],由于它的位置及其转运TG可以推测与血浆脂蛋白中极低密度脂蛋白(very low densiry lipoprotein,VLDL)和乳糜微粒(chylomicrons,CM)的组装过程有关.

  13. 微粒体甘油三脂转运蛋白MTP的研究进展%Recent Advance On Microsomal Triglyceride Transfer Protein

    Institute of Scientific and Technical Information of China (English)

    叶健强; 王继文

    2005-01-01

    微粒体甘油三酯转运蛋白MTP(microsomal triglyceride transfer protein,MTP)首先是从牛的肝细胞微粒体碎片中分离获得的,其作用是加速甘油三脂(triglyceride,TG)、胆固醇(cholesteryl ester,CE)和磷脂酰胆碱(phosphatidylcholine,PC)的转运和细胞或亚细胞膜的生物合成.它后来在肝细胞和小肠的微粒体膜中发现[1],由于它的位置及其转运TG可以推测与血浆脂蛋白中极低密度脂蛋白(very low density lipoprotein,VLDL)和乳糜微粒(chylomicrons,CM)的组装过程有关.

  14. Differential effects of protein quality on postprandial lipemia in response to a fat-rich meal in type 2 diabetes: comparison of whey, casein, gluten, and cod protein

    DEFF Research Database (Denmark)

    Mortensen, Lene S; Hartvigsen, Merete L; Brader, Lea J;

    2009-01-01

    BACKGROUND: Enhanced and prolonged postprandial triglyceride responses involve increased cardiovascular disease risk in type 2 diabetes. Dietary fat and carbohydrates profoundly influence postprandial hypertriglyceridemia, whereas little information exists on the effect of proteins. OBJECTIVE......: The objective was to compare the effects of the proteins casein, whey, cod, and gluten on postprandial lipid and incretin responses to a high-fat meal in persons with type 2 diabetes. DESIGN: A crossover study was conducted in 12 patients with type 2 diabetes. Blood samples were collected over 8 h after...... and higher after the Whe-meal than after Cod- and Glu-meals in the chylomicron-poor fraction. Free fatty acids were most pronouncedly suppressed after the Whe-meal. The glucose response was lower after the Whe-meal than after the other meals, whereas no significant differences were found in insulin, glucagon...

  15. Contribution of plasma protein and lipoproteins to intestinal lymph: Comparison of long-chain with medium-chain triglyceride duodenal infusion

    Energy Technology Data Exchange (ETDEWEB)

    Sipahi, A.M.; Oliveira, H.C.; Vasconcelos, K.S.; Castilho, L.N.; Bettarello, A.; Quintao, E.C.

    1989-03-01

    In rats with intestinal lymph-fistula and electrolyte and protein losses continuously replaced by I.V. infusion, the plasma to lymph filtration of total protein, albumin, and cholesterol was similar after duodenal infusion of either long-chain (LCT) or medium-chain (MCT) triglyceride. Filtration of cholesterol into intestinal lacteals was also measured after pulsed I.V. administration of /sup 14/C-beta-sitosterol as an indirect marker for passage of lipoproteins into the lymph system. During intraduodenal administration of LCT and constant I.V. infusion of /sup 125/I-apo high density lipoprotein (HDL), intact plasma HDL appeared in lymph and contributed apo-LP to chylomicron formation. Nevertheless, most lymph apo-LP originated from local mucosal synthesis.

  16. The Physiological Regulation of Skeletal Muscle Fatty Acid Supply and Oxidation During Moderate-Intensity Exercise

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2015-01-01

    Energy substrates that are important to the working muscle at moderate intensities are the non-esterified fatty acids (NEFAs) taken up from the circulation and NEFAs originating from lipolysis of the intramuscular triacylglycerol (IMTAG). Moreover, NEFA from lipolysis via lipoprotein lipase (LPL......) in the muscle of the very-low-density lipoproteins and in the (semi) post-prandial state chylomicrons may also contribute. In this review, the NEFA fluxes and oxidation by skeletal muscle during prolonged moderate-intensity exercise are described in terms of the integration of physiological systems. Steps...... demand of the exercising muscle is the main driving force for all physiological regulatory processes. It elicits functional hyperemia, increasing the recruitment of capillaries and muscle blood flow resulting in increased NEFA delivery and accessibility to NEFA transporters and LPL. It also releases...

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

    Science.gov (United States)

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

    2016-08-01

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

  18. Activation of intestinal peroxisome proliferator-activated receptor-α increases high-density lipoprotein production

    Science.gov (United States)

    Colin, Sophie; Briand, Olivier; Touche, Véronique; Wouters, Kristiaan; Baron, Morgane; Pattou, François; Hanf, Rémy; Tailleux, Anne; Chinetti, Giulia; Staels, Bart; Lestavel, Sophie

    2013-01-01

    Aims Peroxisome Proliferator-Activated Receptor (PPAR) α is a transcription factor controlling lipid metabolism in liver, heart, muscle and macrophages. PPARα-activation increases plasma HDL-cholesterol and exerts hypotriglyceridemic actions via the liver. However, the intestine expresses PPARα, produces HDL and chylomicrons and is exposed to diet-derived PPARα ligands. Therefore, we examined the effects of PPARα-activation on intestinal lipid and lipoprotein metabolism. Methods and Results The impact of PPARα-activation was evaluated in term of HDL-related gene expression in mice, ex-vivo in human jejunal biopsies and in Caco-2/TC7 cells. ApoAI/HDL secretion, cholesterol esterification and trafficking were also studied in-vitro. In parallel to improving plasma lipid profiles and increasing liver and intestinal expression of fatty-acid-oxidation genes, treatment with the dual PPARα/δ-ligand GFT505 resulted in a more pronounced increase of plasma HDL compared to fenofibrate in mice. GFT505, but not fenofibrate, increased the expression of HDL-production genes such as apolipoprotein-AI and ATP-Binding-Cassette-A1 transporter in murine intestines. A similar increase was observed upon PPARα-activation of human biopsies and Caco-2/TC7 cells. Additionally, HDL secretion by Caco-2/TC7 cells increased. Moreover, PPARα-activation decreased the cholesterol-esterification capacity of Caco-2/TC7 cells, modified cholesterol trafficking and reduced apolipoprotein-B secretion. Conclusions PPARα-activation reduces cholesterol esterification, suppresses chylomicron- and increases HDL-secretion by enterocytes. These results identify the intestine as a target organ of PPARα-ligands with entero-hepatic tropism to reduce atherogenic dyslipidemia. PMID:22843443

  19. Impaired postprandial lipemic response in chronic kidney disease.

    Science.gov (United States)

    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. Intestine-specific deletion of microsomal triglyceride transfer protein increases mortality in aged mice.

    Directory of Open Access Journals (Sweden)

    Zhe Liang

    Full Text Available BACKGROUND: Mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO exhibit a complete block in chylomicron assembly together with lipid malabsorption. Young (8-10 week Mttp-IKO mice have improved survival when subjected to a murine model of Pseudomonas aeruginosa-induced sepsis. However, 80% of deaths in sepsis occur in patients over age 65. The purpose of this study was to determine whether age impacts outcome in Mttp-IKO mice subjected to sepsis. METHODS: Aged (20-24 months Mttp-IKO mice and WT mice underwent intratracheal injection with P. aeruginosa. Mice were either sacrificed 24 hours post-operatively for mechanistic studies or followed seven days for survival. RESULTS: In contrast to young septic Mttp-IKO mice, aged septic Mttp-IKO mice had a significantly higher mortality than aged septic WT mice (80% vs. 39%, p = 0.005. Aged septic Mttp-IKO mice exhibited increased gut epithelial apoptosis, increased jejunal Bax/Bcl-2 and Bax/Bcl-XL ratios yet simultaneously demonstrated increased crypt proliferation and villus length. Aged septic Mttp-IKO mice also manifested increased pulmonary myeloperoxidase levels, suggesting increased neutrophil infiltration, as well as decreased systemic TNFα compared to aged septic WT mice. CONCLUSIONS: Blocking intestinal chylomicron secretion alters mortality following sepsis in an age-dependent manner. Increases in gut apoptosis and pulmonary neutrophil infiltration, and decreased systemic TNFα represent potential mechanisms for why intestine-specific Mttp deletion is beneficial in young septic mice but harmful in aged mice as each of these parameters are altered differently in young and aged septic WT and Mttp-IKO mice.

  1. Solvent-free lipase catalysed synthesis of diacylgycerols as low-calorie food ingredients

    Directory of Open Access Journals (Sweden)

    Luis eVazquez

    2016-02-01

    Full Text Available Problems derived from obesity and overweight have recently promoted the development of fat substitutes and other low-calorie foods. On the one hand, fats with short and medium chain fatty acids are a source of quick energy, easily hydrolyzable and hardly stored as fat. Furthermore, 1,3-diacylglycerols are not hydrolyzed to 2-monoacylglycerols in the gastrointestinal tract, reducing the formation of chylomicron and lowers the serum level of triacylglycerols by decreasing its re-synthesis in the enterocyte and its metabolism and absorption by the enterocyte are limited in comparison with the TAG, reducing chylomicron formation. In this work these two effects were combined to synthesize short and medium chain 1,3 diacylglycerols, leading to a product with great potential as for their low-calorie properties. Lipase catalysed transesterification reactions were performed between short and medium chain fatty acid ethyl esters and glycerol. Different variables were investigated such as the type of biocatalyst, the molar ratio FAEE:glycerol, the adsorption of glycerol on silica gel or the addition of lecithin. Best reaction conditions were evaluated considering the conversion intopercentage of 1,3-DAG produced and the reaction rate. Except Novozym 435 (Candida antarctica, other lipases required the adsorption of glycerol on silica gel to form acylglycerols. Lipases that gave the best results with adsorption were Novozym 435 and Lipozyme RM IM (Rhizomucor miehei with 52% and 60.7% of DAG at 32 h, respectively. Because of its specificity for sn-1 and sn-3 positions, lipases leading to a higher proportion of 1,3-DAG vs 1,2-DAG were Lipozyme RM IM (39.8% and 20.9%, respectively and Lipase PLG (Alcaligenes sp. (35.9% and 19.3%, respectively. By adding 1% (w/w of lecithin to the reaction with Novozym 435 and raw glycerol the reaction rate was considerably increased from 41.7% to 52.8% DAG at 24 h.

  2. Enhanced oral absorption and therapeutic effect of acetylpuerarin based on D-α-tocopheryl polyethylene glycol 1000 succinate nanoemulsions

    Directory of Open Access Journals (Sweden)

    Sun DQ

    2014-07-01

    Full Text Available Deqing Sun,1,2 Xinbing Wei,1 Xia Xue,2 Zengjun Fang,3 Manru Ren,1 Haiyan Lou,1 Xiumei Zhang11Department of Pharmacology, School of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Pharmacy, 3Department of Clinical Pharmacology, Second Hospital of Shandong University, Jinan, People’s Republic of ChinaBackground: Acetylpuerarin (AP, because of its lower water solubility, shows poor absorption that hinders its therapeutic application. Thus, the aim of this study was to prepare nanoemulsions for AP, enhance its oral bioavailability, and thus improve the therapeutic effect.Methods: The nanoemulsions stabilized by D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS were prepared by high-pressure homogenization and characterized in terms of particle size, drug loading, morphology, and in vitro drug release. A lipid digestion model was used to predict in vivo drug solubilization in the gastrointestinal environment. The pharmacokinetics of AP formulations were performed in rats; meanwhile, a chylomicron flow-blocking rat model was used to evaluate the lymphatic drug transport. Moreover, the therapeutic effects of AP nanoemulsions on the model of focal cerebral ischemia-reperfusion for brain injury were also assessed.Results: The nanoemulsions with a droplet size of 150 nm were well stabilized by TPGS and showed a high loading capacity for AP. In the digestion model, the distribution of AP in aqueous phase/pellet phase was about 90%/10% for nanoemulsions and 5%/95% for oil solution, indicating that the drug encapsulated in nanoemulsions would present in solubilized form after transportation into the gastrointestinal tract, whereas drug precipitation would occur as the oil solution was orally administered. The area under the curve value of AP nanoemulsions was 5.76±0.56 µg·hour·mL-1, or was about 2.6 and 1.7 times as great as that of suspension and oil solution, respectively, indicating enhanced drug

  3. Update on the molecular biology of dyslipidemias.

    Science.gov (United States)

    Ramasamy, I

    2016-02-15

    Dyslipidemia is a commonly encountered clinical condition and is an important determinant of cardiovascular disease. Although secondary factors play a role in clinical expression, dyslipidemias have a strong genetic component. Familial hypercholesterolemia is usually due to loss-of-function mutations in LDLR, the gene coding for low density lipoprotein receptor and genes encoding for proteins that interact with the receptor: APOB, PCSK9 and LDLRAP1. Monogenic hypertriglyceridemia is the result of mutations in genes that regulate the metabolism of triglyceride rich lipoproteins (eg LPL, APOC2, APOA5, LMF1, GPIHBP1). Conversely familial hypobetalipoproteinemia is caused by inactivation of the PCSK9 gene which increases the number of LDL receptors and decreases plasma cholesterol. Mutations in the genes APOB, and ANGPTL3 and ANGPTL4 (that encode angiopoietin-like proteins which inhibit lipoprotein lipase activity) can further cause low levels of apoB containing lipoproteins. Abetalipoproteinemia and chylomicron retention disease are due to mutations in the microsomal transfer protein and Sar1b-GTPase genes, which affect the secretion of apoB containing lipoproteins. Dysbetalipoproteinemia stems from dysfunctional apoE and is characterized by the accumulation of remnants of chylomicrons and very low density lipoproteins. ApoE deficiency can cause a similar phenotype or rarely mutations in apoE can be associated with lipoprotein glomerulopathy. Low HDL can result from mutations in a number of genes regulating HDL production or catabolism; apoAI, lecithin: cholesterol acyltransferase and the ATP-binding cassette transporter ABCA1. Patients with cholesteryl ester transfer protein deficiency have markedly increased HDL cholesterol. Both common and rare genetic variants contribute to susceptibility to dyslipidemias. In contrast to rare familial syndromes, in most patients, dyslipidemias have a complex genetic etiology consisting of multiple genetic variants as established

  4. Combination of niacin extended-release and simvastatin results in a less atherogenic lipid profile than atorvastatin monotherapy

    Directory of Open Access Journals (Sweden)

    William Insull Jr

    2010-11-01

    Full Text Available William Insull Jr1, Peter P Toth2, H Robert Superko3, Roopal B Thakkar4, Scott Krause4, Ping Jiang4, Rhea A Parreno4, Robert J Padley41Baylor College of Medicine and Methodist Hospital, Houston, Texas; 2University of Illinois College of Medicine, Peoria, Illinois; 3Celera, Alameda, California, Mercer University, Atlanta, Georgia; 4Abbott, Abbott Park, Illinois, USAObjective: To compare the effects of combination niacin extended-release + simvastatin (NER/S versus atorvastatin alone on apolipoproteins and lipid fractions in a post hoc analysis from SUPREME, a study which compared the lipid effects of niacin extended-release + simvastatin and atorvastatin in patients with hyperlipidemia or mixed dyslipidemia.Patients and methods: Patients (n = 137 with dyslipidemia (not previously receiving statin therapy or having discontinued any lipid-altering treatment 4–5 weeks prior to the study received NER/S (1000/40 mg/day for four weeks, then 2000/40 mg/day for eight weeks or atorvastatin 40 mg/day for 12 weeks. Median percent changes in apolipoprotein (apo A-1, apo B, and the apo B:A-I ratio, and nuclear magnetic resonance lipoprotein subclasses from baseline to week 12 were compared using the Wilcoxon rank-sum test and Fisher’s exact test.Results: NER/S treatment produced significantly greater percent changes in apo A-I and apo B:A-I, and, at the final visit, apo B <80 mg/dL was attained by 59% versus 33% of patients, compared with atorvastatin treatment (P = 0.003. NER/S treatment resulted in greater percent reductions in calculated particle numbers for low-density lipoprotein (LDL, 52% versus 43%; P = 0.022, small LDL (55% versus 45%; P = 0.011, very low-density lipoprotein (VLDL and total chylomicrons (63% versus 39%; P < 0.001, and greater increases in particle size for LDL (2.7% versus 1.0%; P = 0.007 and VLDL (9.3% versus 0.1%; P < 0.001, compared with atorvastatin.Conclusion: NER/S treatment significantly improved apo A-I levels and the apo

  5. 脂蛋白酯酶研究进展及对动脉粥样硬化的影响%Current Progress in Lipoprotein Lipase and Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    田国平; 陈五军; 何平平; 尹卫东; 唐朝克

    2012-01-01

    Lipoprotein lipase ( LPL) which is the rate-limiting enzyme for the hydrolysis of the triglycer-ide (TG) core of circulating TG-rich lipoproteins, chylomicrons, low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL) play an important role in reducing TG deposition in vivo. Recent advances indicate that LPL gene structure, synthesis, secretion and degradation had complexity, and it is regulated by many transcription factors, miRNA, interactive proteins and hormonal. Its role in atherosclerosis in the current studies is still controversial. So we focus the LPL on the structure, synthesis and degradation, function, regulation and contribution to atherosclerosis to clarify its role in cardiovascular disease (CVD).%脂蛋白脂酶(lipoprotein lipase,LPL)主要在脏器实质细胞合成和分泌,可以水解乳糜微粒(chylomicron,CM)、低密度脂蛋白(low-density lipoproteins,LDL)及极低密度脂蛋白(very low-density lipoproteins,VLDL)中的甘油三酯(triglyceride,TG),对清除体内过多的TG至关重要.新近研究发现LPL的基因结构、合成、分泌及降解具有复杂性,生物功能的发挥和基因的表达也受到多种转录因子、微小RNA(microRNA,miRNA)、相关蛋白及营养激素的调控,其在动脉硬化性疾病中的作用也存在较大的争议.因此,本文主要针对LPL 基因的结构、合成与降解、生物功能、表达调控及与动脉硬化性心血管疾病关系的研究进展做一综述,以期进一步明确LPL在心血管疾病中的作用和意义.

  6. Gut microbiota-derived lipopolysaccharide uptake and trafficking to adipose tissue: implications for inflammation and obesity.

    Science.gov (United States)

    Hersoug, L-G; Møller, P; Loft, S

    2016-04-01

    The composition of the gut microbiota and excessive ingestion of high-fat diets (HFD) are considered to be important factors for development of obesity. In this review we describe a coherent mechanism of action for the development of obesity, which involves the composition of gut microbiota, HFD, low-grade inflammation, expression of fat translocase and scavenger receptor CD36, and the scavenger receptor class B type 1 (SR-BI). SR-BI binds to both lipids and lipopolysaccharide (LPS) from Gram-negative bacteria, which may promote incorporation of LPS in chylomicrons (CMs). These CMs are transported via lymph to the circulation, where LPS is transferred to other lipoproteins by translocases, preferentially to HDL. LPS increases the SR-BI binding, transcytosis of lipoproteins over the endothelial barrier,and endocytosis in adipocytes. Especially large size adipocytes with high metabolic activity absorb LPS-rich lipoproteins. In addition, macrophages in adipose tissue internalize LPS-lipoproteins. This may contribute to the polarization from M2 to M1 phenotype, which is a consequence of increased LPS delivery into the tissue during hypertrophy. In conclusion, evidence suggests that LPS is involved in the development of obesity as a direct targeting molecule for lipid delivery and storage in adipose tissue. PMID:26712364

  7. Transport of C-13-labelled linoleic and C-13-labelled caprylic acid in rat plasma after administration of specific structured triacylglycerols

    DEFF Research Database (Denmark)

    Vistisen, Bodil; Høy, Carl-Erik

    2004-01-01

    the transport of dietary C-13-labelled fatty acids in rat plasma to compare the chylomicron fatty acid metabolism after administration of specific structured, long chain and medium chain triacylglycerols. Rats were fed ML*M, M*LM*, L*L*L* or M*M*M* (L=linoleic acid, 18:2n-6, M=caprylic acid, 8:0, * = C-13......-labelled fatty acid) by gavage. A maximum transport of 0.5% of the administered C-13-labelled 18:2n-6 was observed in 1mL rat plasma both after administration of L*L*L* and ML*M, while approximately 0.04% of the administered C-13-labelled 8:0 was detected in 1mL plasma following administration of M......*M*M* or M*LM*. After L*L*L* administration C-13-labelled 20:4n-6 was observed in plasma, probably formed by elongation and desaturation of 18:2n-6 in the enterocyte or liver cells. Furthermore, C-13-labelled 16:0, 48:0, 18: 1n-9 and 20:4n-6 were observed in plasma of rats fed M*M*M* and M*LM* due...

  8. Korean pine nut oil replacement decreases intestinal lipid uptake while improves hepatic lipid metabolism in mice

    Science.gov (United States)

    Zhu, Shuang; Park, Soyoung; Lim, Yeseo; Shin, Sunhye

    2016-01-01

    BACKGROUND/OBJECTIVES Consumption of pine nut oil (PNO) was shown to reduce weight gain and attenuate hepatic steatosis in mice fed a high-fat diet (HFD). The aim of this study was to examine the effects of PNO on both intestinal and hepatic lipid metabolism in mice fed control or HFD. MATERIALS/METHODS Five-week-old C57BL/6 mice were fed control diets containing 10% energy fat from either Soybean Oil (SBO) or PNO, or HFD containing 15% energy fat from lard and 30% energy fat from SBO or PNO for 12 weeks. Expression of genes related to intestinal fatty acid (FA) uptake and channeling (Cd36, Fatp4, Acsl5, Acbp), intestinal chylomicron synthesis (Mtp, ApoB48, ApoA4), hepatic lipid uptake and channeling (Lrp1, Fatp5, Acsl1, Acbp), hepatic triacylglycerol (TAG) lipolysis and FA oxidation (Atgl, Cpt1a, Acadl, Ehhadh, Acaa1), as well as very low-density lipoprotein (VLDL) assembly (ApoB100) were determined by real-time PCR. RESULTS In intestine, significantly lower Cd36 mRNA expression (P metabolism; mitochondrial fatty acid oxidation and VLDL assembly. CONCLUSIONS PNO replacement in the diet might function in prevention of excessive lipid uptake by intestine and improve hepatic lipid metabolism in both control diet and HFD fed mice.

  9. Emerging roles of the intestine in control of cholesterol metabolism

    Institute of Scientific and Technical Information of China (English)

    Janine K Kruit; Albert K Groen; Theo J van Berkel; Folkert Kuipers

    2006-01-01

    The liver is considered the major "control center" for maintenance of whole body cholesterol homeostasis. This organ is the main site for de novo cholesterol synthesis,clears cholesterol-containing chylomicron remnants and low density lipoprotein particles from plasma and is the major contributor to high density lipoprotein (HDL; good cholesterol) formation. The liver has a central position in the classical definition of the reverse cholesterol transport pathway by taking up peripheryderived cholesterol from lipoprotein particles followed by conversion into bile acids or its direct secretion into bile for eventual removal via the feces. During the past couple of years, however, an additional important role of the intestine in maintenance of cholesterol homeostasis and regulation of plasma cholesterol levels has become apparent. Firstly, molecular mechanisms of cholesterol absorption have been elucidated and novel pharmacological compounds have been identified that interfere with the process and positively impact plasma cholesterol levels. Secondly, it is now evident that the intestine itself contributes to fecal neutral sterol loss as a cholesterol-secreting organ. Finally, very recent work has unequivocally demonstrated that the intestine contributes significantly to plasma HDL cholesterol levels.Thus, the intestine is a potential target for novel antiatherosclerotic treatment strategies that, in addition to interference with cholesterol absorption, modulate direct cholesterol excretion and plasma HDL cholesterol levels.

  10. Novel role of a triglyceride-synthesizing enzyme: DGAT1 at the crossroad between triglyceride and cholesterol metabolism

    Science.gov (United States)

    Sachdev, Vinay; Leopold, Christina; Bauer, Raimund; Patankar, Jay V.; Iqbal, Jahangir; Obrowsky, Sascha; Boverhof, Renze; Doktorova, Marcela; Scheicher, Bernhard; Goeritzer, Madeleine; Kolb, Dagmar; Turnbull, Andrew V.; Zimmer, Andreas; Hoefler, Gerald; Hussain, M. Mahmood; Groen, Albert K.; Kratky, Dagmar

    2016-01-01

    Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) is a key enzyme in triacylglycerol (TG) biosynthesis. Here we show that genetic deficiency and pharmacological inhibition of DGAT1 in mice alters cholesterol metabolism. Cholesterol absorption, as assessed by acute cholesterol uptake, was significantly decreased in the small intestine and liver upon DGAT1 deficiency/inhibition. Ablation of DGAT1 in the intestine (I-DGAT1−/−) alone is sufficient to cause these effects. Consequences of I-DGAT1 deficiency phenocopy findings in whole-body DGAT1−/− and DGAT1 inhibitor-treated mice. We show that deficiency/inhibition of DGAT1 affects cholesterol metabolism via reduced chylomicron size and increased trans-intestinal cholesterol excretion. These effects are independent of cholesterol uptake at the apical surface of enterocytes but mediated through altered dietary fatty acid metabolism. Our findings provide insight into a novel role of DGAT1 and identify a pathway by which intestinal DGAT1 deficiency affects whole-body cholesterol homeostasis in mice. Targeting intestinal DGAT1 may represent a novel approach for treating hypercholesterolemia. PMID:27344248

  11. [Primary and secondary hypocholesterolemia].

    Science.gov (United States)

    Song, Jun-xian; Ren, Jing-yi; Chen, Hong

    2010-10-18

    Hypocholesterolemia is characterized by serum total cholesterol that is lower than the 5th percentile for age and sex, or the cut-off value which predicts the adverse prognosis by epidemiological study. Unlike hypercholesterolemia, physicians pay less attention to the morbidity, causes and consequences of hypocholesterolemia in clinical practice. In fact, hypocholesterolemia is a common dislipidemia, and mainly results from secondary factors. The causes of primary hypocholesterolemia are some disorders owing to genetic mutation in the pathway of cholesterol absorption, biosynthesis or metabolism, including abetalipoproteinemia, hypobetalipoproteinemia, Tangier disease, chylomicron retention disease and inherited disorders of cholesterol biosynthesis. The causes of secondary hypocholesterolemia comprise anemia, hyperthyroidism, malignancy, live disease, critical illness, serious stress, malabsorption or malnutrition, acute or chronic infection, chronic inflammation, and use of some drugs. In addition, what's more important is that hypocholesterolemia can result in some adverse events, such as increased mortality, intracerebral hemorrhage, cancer, infection, adrenal failure, suicide and mental disorder. Therefore, with the practice of intensive lipid-lowering treatment and the tendency to the increased indications of statins, it's high time that physicians attached more importance to hypocholesterolemia. PMID:20957025

  12. The expression of apoB mRNA editing factors is not the sole determinant for the induction of editing in differentiating Caco-2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Galloway, Chad A. [Department of Biochemistry and Biophysics, University of Rochester School of Medicine, 601 Elmwood Ave., Rochester, NY 14642 (United States); Smith, Harold C., E-mail: harold.smith@rochester.edu [Department of Biochemistry and Biophysics, University of Rochester School of Medicine, 601 Elmwood Ave., Rochester, NY 14642 (United States)

    2010-01-01

    Apolipoprotein B mRNA is edited at cytidine 6666 in the enterocytes lining the small intestine of all mammals; converting a CAA codon to a UAA stop codon. The conversion is {approx}80% efficient in this tissue and leads to the expression of the truncated protein, ApoB48, essential for secretion of dietary lipid as chylomicrons. Caco-2 cell raft cultures have been used as an in vitro model for the induction of editing activity during human small intestinal cell differentiation. This induction of apoB mRNA editing has been ascribed to the expression of APOBEC-1. In agreement our data demonstrated differentiation-dependent induction of expression of the editing enzyme APOBEC-1 and in addition we show alternative splicing of the essential auxiliary factor ACF. However, transfection of these editing factors in undifferentiated proliferating Caco-2 cells was not sufficient to induce robust apoB mRNA editing activity. Only differentiation of Caco-2 cells could induce more physiological like levels of apoB mRNA editing. The data suggested that additional regulatory mechanism(s) were induced by differentiation that controlled the functional activity of editing factors.

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

  14. The expression of apoB mRNA editing factors is not the sole determinant for the induction of editing in differentiating Caco-2 cells

    International Nuclear Information System (INIS)

    Apolipoprotein B mRNA is edited at cytidine 6666 in the enterocytes lining the small intestine of all mammals; converting a CAA codon to a UAA stop codon. The conversion is ∼80% efficient in this tissue and leads to the expression of the truncated protein, ApoB48, essential for secretion of dietary lipid as chylomicrons. Caco-2 cell raft cultures have been used as an in vitro model for the induction of editing activity during human small intestinal cell differentiation. This induction of apoB mRNA editing has been ascribed to the expression of APOBEC-1. In agreement our data demonstrated differentiation-dependent induction of expression of the editing enzyme APOBEC-1 and in addition we show alternative splicing of the essential auxiliary factor ACF. However, transfection of these editing factors in undifferentiated proliferating Caco-2 cells was not sufficient to induce robust apoB mRNA editing activity. Only differentiation of Caco-2 cells could induce more physiological like levels of apoB mRNA editing. The data suggested that additional regulatory mechanism(s) were induced by differentiation that controlled the functional activity of editing factors.

  15. Intestinal triacylglycerol synthesis in fat absorption and systemic energy metabolism.

    Science.gov (United States)

    Yen, Chi-Liang Eric; Nelson, David W; Yen, Mei-I

    2015-03-01

    The intestine plays a prominent role in the biosynthesis of triacylglycerol (triglyceride; TAG). Digested dietary TAG is repackaged in the intestine to form the hydrophobic core of chylomicrons, which deliver metabolic fuels, essential fatty acids, and other lipid-soluble nutrients to the peripheral tissues. By controlling the flux of dietary fat into the circulation, intestinal TAG synthesis can greatly impact systemic metabolism. Genes encoding many of the enzymes involved in TAG synthesis have been identified. Among TAG synthesis enzymes, acyl-CoA:monoacylglycerol acyltransferase 2 and acyl-CoA:diacylglycerol acyltransferase (DGAT)1 are highly expressed in the intestine. Their physiological functions have been examined in the context of whole organisms using genetically engineered mice and, in the case of DGAT1, specific inhibitors. An emerging theme from recent findings is that limiting the rate of TAG synthesis in the intestine can modulate gut hormone secretion, lipid metabolism, and systemic energy balance. The underlying mechanisms and their implications for humans are yet to be explored. Pharmacological inhibition of TAG hydrolysis in the intestinal lumen has been employed to combat obesity and associated disorders with modest efficacy and unwanted side effects. The therapeutic potential of inhibiting specific enzymes involved in intestinal TAG synthesis warrants further investigation.

  16. Impact of Chronic Hepatitis C Virus Genotype 1b Infection on Triglyceride Concentration in Serum Lipoprotein Fractions

    Directory of Open Access Journals (Sweden)

    Tomohisa Nagano

    2015-08-01

    Full Text Available Reduced low-density lipoprotein (LDL cholesterol level is a characteristic feature of dyslipidemia in chronic hepatitis C virus (HCV infection. However, abnormality in serum triglyceride (TG has not been fully investigated. To clarify the impact of HCV genotype 1b (G1b infection and advanced fibrosis on serum TG profiles, TG concentrations in lipoprotein fractions were examined in fasting sera from 185 subjects with active or cleared HCV infection by high-performance liquid chromatography. Serum lipoproteins were fractionated into four classes: chylomicron, very low-density lipoprotein (VLDL, LDL, and high-density lipoprotein (HDL. Then, the significance of HCV G1b infection on TG levels in each lipoprotein fraction was determined using multiple regression models. We found that active HCV G1b infection was positively associated with high HDL-TG levels and low VLDL-TG levels, independent of other factors included in the regression model. In VLDL sub-fractions, active HCV infection was only found to be associated with low levels of large VLDL-TG. Similarly, advanced liver fibrosis in chronic HCV G1b infection was associated with high levels of LDL-TG, HDL-TG, and small VLDL-TG, independent of other clinical factors. These findings indicate that active HCV G1b infection and advanced fibrosis are closely associated with abnormal serum TG profiles.

  17. Hypolipidemic effect of young persimmon fruit in C57BL/6.KOR-ApoEshl mice.

    Science.gov (United States)

    Matsumoto, Kenji; Yokoyama, Shin-ichiro; Gato, Nobuki

    2008-10-01

    We investigated the hypolipidemic effects of young persimmon fruit (YP) on apolipoprotein E-deficient C57BL/6.KOR-ApoEshl mice. These mice exhibited higher plasma cholesterols, except for high-density lipoprotein (HDL), and lower plasma HDL cholesterol than C57BL/6.Cr mice that had the same genetic background as the C57BL/6.KOR-ApoEshl mice. Male C57BL/6.KOR-ApoEshl mice (n=5) were fed a diet supplemented with dry YP, Hachiya-kaki, at a concentration of 5% (w/w) for 10 weeks. YP treatment significantly lowered plasma chylomicron, very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterols, and triglyceride, and this response was accompanied by an elevation of fecal bile acid excretion. In the liver, sterol regulatory element binding protein-2 gene expression was significantly higher in mice fed YP, while the mRNA and protein levels of the LDL receptor did not change. These results indicate that acceleration of fecal bile acid excretion is a major mechanism of the hypolipidemic effect induced by YP in C57BL/6.KOR-ApoEshl mice. PMID:18838807

  18. Apolipoprotein A-V Deficiency Results in MarkedHypertriglyceridemia Attributable to Decreased Lipolysis ofTriglyceride-Rich Lipoproteins and Removal of Their Remnants

    Energy Technology Data Exchange (ETDEWEB)

    Grosskopf, Itamar; Baroukh, Nadine; Lee, Sung-Joon; Kamari,Yehuda; Harats, Dror; Rubin, Edward M.; Pennacchio, Len A.; Cooper, AllenD.

    2005-09-01

    Objective--ApoAV, a newly discovered apoprotein, affectsplasma triglyceride level. To determine how this occurs, we studiedtriglyceride-rich lipoprotein (TRL) metabolism in mice deficient inapoAV. Methods and Results No significant difference in triglycerideproduction rate was found between apoa5_/_ mice and controls. Thepresence or absence of apoAV affected TRL catabolism. After the injectionof 14C-palmitate and 3H-cholesterol labeled chylomicrons and 125I-labeledchylomicron remnants, the disappearance of 14C, 3H, and 125I wassignificantly slower in apoa5_/_ mice relative to controls. This wasbecause of diminished lipolysis of TRL and the reduced rate of uptake oftheir remnants in apoa5_/_ mice. Observed elevated cholesterol level wascaused by increased high-density lipoprotein (HDL) cholesterol inapoa5_/_ mice. VLDL from apoa5_/_ mice were poor substrate forlipoprotein lipase, and did not bind to the low-density lipoprotein (LDL)receptor as well as normal very-low-density lipoprotein (VLDL). LDLreceptor levels were slightly elevated in apoa5_/_ mice consistent withlower remnant uptake rates. These alterations may be the result of thelower apoE-to-apoC ratio found in VLDL isolated from apoa5_/_mice.Conclusions These results support the hypothesis that the absence ofapoAV slows lipolysis of TRL and the removal of their remnants byregulating their apoproteins content after secretion.

  19. Enhanced Bioavailability of EPA From Emulsified Fish Oil Preparations Versus Capsular Triacylglycerol.

    Science.gov (United States)

    Raatz, Susan K; Johnson, LuAnn K; Bukowski, Michael R

    2016-05-01

    For those individuals who are unable to consume adequate long chain omega-3 fatty acids (LCn3) from dietary sources, fish oil supplementation is an attractive alternative Pre-emulsified fish oil supplements, an alternative to capsular triacylglycerol, may enhance the uptake of LCn3 fatty acids it contains. A randomized, Latin-square crossover design was used to compare the effects of four fish oil supplement preparations (Emulsions S, B and N) on phospholipid fatty acid (PLFA) concentrations in ten healthy volunteers compared to oil capsules over 48 h after a single dose and chylomicron fatty acid (CMFA) was evaluated over 8 h. Blood samples were collected at 0, 2, 4, 8, 24 and 48 h and fatty acid concentrations of PLFA and CMFA were determined by gas chromatography and the integrated area under the curve over 40 h (iAUC0-48) was determined. Emulsion S and Emulsion N promoted increased uptake of EPA into PLFA over 48 h when evaluating by iAUC0-48 or individual time points of assessment. No differences were observed between supplements in the CMFA concentrations.

  20. Dyslipidaemia--hepatic and intestinal cross-talk.

    LENUS (Irish Health Repository)

    Tomkin, Gerald H

    2010-06-01

    Cholesterol metabolism is tightly regulated with the majority of de novo cholesterol synthesis occurring in the liver and intestine. 3 Hydroxy-3-methylglutaryl coenzyme A reductase, a major enzyme involved in cholesterol synthesis, is raised in both liver and intestine in diabetic animals. Niemann PickC1-like1 protein regulates cholesterol absorption in the intestine and facilitates cholesterol transport through the liver. There is evidence to suggest that the effect of inhibition of Niemann PickC1-like1 lowers cholesterol through its effect not only in the intestine but also in the liver. ATP binding cassette proteins G5\\/G8 regulate cholesterol re-excretion in the intestine and in the liver, cholesterol excretion into the bile. Diabetes is associated with reduced ATP binding cassette protein G5\\/G8 expression in both the liver and intestine in animal models. Microsomal triglyceride transfer protein is central to the formation of the chylomicron in the intestine and VLDL in the liver. Microsomal triglyceride transfer protein mRNA is increased in diabetes in both the intestine and liver. Cross-talk between the intestine and liver is poorly documented in humans due to the difficulty in obtaining liver biopsies but animal studies are fairly consistent in showing relationships that explain in part mechanisms involved in cholesterol homeostasis.

  1. Postprandial triglyceride metabolism in elderly men with subnormal testosterone levels

    Institute of Scientific and Technical Information of China (English)

    Ingvild Agledahl; John-Bjarne Hansen; Johan Svartberg

    2008-01-01

    Aim: To investigate the level of postprandial triglycerides (TG)s in elderly men with subnormal testosterone level (≤ 11.0 nmol/L) compared to men with normal testosterone level (> 11.0 nmol/L). Methods: Thirthy-seven men with subnormal and 41 men with normal testosterone aged 60-80 years underwent an oral fat load and TG levels were measured fasting and 2, 4, 6 and 8 h afterwards. Results: Men with subnormal testosterone had significantly higher body mass index (BMI) and waist circumference (P < 0.001) than men with normal testosterone. They had signifi- cantly higher area under curve (AUC, P = 0.037), incremental area under curve (AUCi, P = 0.035) and TG response (TGR, P = 0.014) for serum-TG and significantly higher AUC (P=0.023), AUCi (P=0.023) and TGR (P = 0.014) for chylomicron-TG compared to men with normal testosterone level. Adjusting for waist circumference erased the significant differences between the groups in postprandial triglyceridemia. Conclusion: Men with subnormal test- osterone have increased postprandial TG levels indicating an impaired metabolism of postprandial TG-rich lipoproteins (TRL), which may add to an unfavourable lipid profile and promote development of atherosclerosis. (Asian JAndrol 2008 Jul; 10: 542-549)

  2. New micromethod for measuring cholesterol in plasma lipoprotein fractions.

    Science.gov (United States)

    Bronzert, T J; Brewer, H B

    1977-11-01

    A method is described for the reliable, fast, and relatively inexpensive fractionation of plasma lipoproteins and quantitation of their cholesterol content. This procedure requires 350 microliter of plasma and can be completed within 3 h. Plasma lipoproteins (175 microliter of plasma) were prestained with Fat Red 7B and centrifuged (Beckman Airfuge) at plasma density (d = 1.006 kg/liter) and at a solvent density of 1.060 kg/liter, adjusted by adding solid KBr. Prestained centrifuged samples demonstrated the characteristic elevation of chylomicrons in phenotypes I and V, low-density lipoproteins of phenotype II, very-low-density lipoproteins in phenotype IV and V, and continuum of pink color throughout the centrifuge tube, diagnostic of the floating beta lipoprotein of type III. Centrifuged samples were separated into top and bottom fractions by aspiration. Cholesterol was quantitated with an enzymic oxygen-electrode analyzer (Beckman Cholesterol Analyzer). Correlation coefficients between cholesterol values for plasma from normal hyperlipidemic individuals obtained with the Beckman Analyzer vs. the Technicon AutoAnalyzer II and SMAC systems were 0.977 and 0.973, respectively.

  3. Lipases in Medicine: An Overview.

    Science.gov (United States)

    Loli, Heni; Narwal, Sunil Kumar; Saun, Nitin Kumar; Gupta, Reena

    2015-01-01

    Lipases are part of the family of hydrolases that act on carboxylic ester bonds. They are involved in catalyzing the hydrolysis of triglycerides (TG) into chylomicrons and very low density lipoprotein (VLDL) particles. Uses of lipases are evolving rapidly and currently they are reported to show high potential in medicine. Intensive study and investigations have led researchers to explore lipases for their use in substitution therapy, where in enzyme deficiency during diseased conditions is compensated by their external administration. In our body, they are used to break down fats present in food so that they can be absorbed in the intestine and deficiency of lipases leads to malabsorption of fats and fat-soluble vitamins. Lipases help a person who has cystic fibrosis, Alzheimer's disease, atherosclerosis and act as a candidate target for cancer prevention and therapy. They act as diagnostic tool and their presence or increasing levels can indicate certain infection or disease. Obesity causes metabolic disease and is a serious health problem around the world. Thus inhibiting digestive lipase to reduce fat absorption has become the main pharmacological approach to the treatment of obesity in recent years. PMID:26156413

  4. Intestinal triacylglycerol synthesis in fat absorption and systemic energy metabolism.

    Science.gov (United States)

    Yen, Chi-Liang Eric; Nelson, David W; Yen, Mei-I

    2015-03-01

    The intestine plays a prominent role in the biosynthesis of triacylglycerol (triglyceride; TAG). Digested dietary TAG is repackaged in the intestine to form the hydrophobic core of chylomicrons, which deliver metabolic fuels, essential fatty acids, and other lipid-soluble nutrients to the peripheral tissues. By controlling the flux of dietary fat into the circulation, intestinal TAG synthesis can greatly impact systemic metabolism. Genes encoding many of the enzymes involved in TAG synthesis have been identified. Among TAG synthesis enzymes, acyl-CoA:monoacylglycerol acyltransferase 2 and acyl-CoA:diacylglycerol acyltransferase (DGAT)1 are highly expressed in the intestine. Their physiological functions have been examined in the context of whole organisms using genetically engineered mice and, in the case of DGAT1, specific inhibitors. An emerging theme from recent findings is that limiting the rate of TAG synthesis in the intestine can modulate gut hormone secretion, lipid metabolism, and systemic energy balance. The underlying mechanisms and their implications for humans are yet to be explored. Pharmacological inhibition of TAG hydrolysis in the intestinal lumen has been employed to combat obesity and associated disorders with modest efficacy and unwanted side effects. The therapeutic potential of inhibiting specific enzymes involved in intestinal TAG synthesis warrants further investigation. PMID:25231105

  5. [Residual risk: The roles of triglycerides and high density lipoproteins].

    Science.gov (United States)

    Grammer, Tanja; Kleber, Marcus; Silbernagel, Günther; Scharnagl, Hubert; März, Winfried

    2016-06-01

    In clinical trials, the reduction of LDL-cholesterol (LDL-C) with statins reduces the incidence rate of cardiovascular events by approximately one third. This means, that a sizeable "residual risk" remains. Besides high lipoprotein (a), disorders in the metabolism of triglyceride-rich lipoproteins and high density liproteins have been implicated as effectors of the residual risk. Both lipoprotein parameters correlate inversely with each other. Therefore, the etiological contributions of triglycerides and / or of HDL for developing cardiovascular disease can hardly be estimated from either observational studies or from intervention studies. The largely disappointing results of intervention studies with inhibitors of the cholesteryl ester transfer protein and in particular the available set of genetically-epidemiological studies suggest that in the last decade, the importance of HDL cholesterol has been overvalued, while the importance of triglycerides has been underestimated. High triglycerides not always atherogenic, but only if they are associated with the accumulation relatively cholesterol-enriched, incompletely catabolized remnants of chylomicrons and very low density lipoproteins (familial type III hyperlipidemia, metabolic syndrome, diabetes mellitus). The normalization of the concentration of triglycerides and remnants by inhibiting the expression of apolipoprotein C3 is hence a new, promising therapeutic target. PMID:27305303

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

    Science.gov (United States)

    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

  7. Novel role of a triglyceride-synthesizing enzyme: DGAT1 at the crossroad between triglyceride and cholesterol metabolism.

    Science.gov (United States)

    Sachdev, Vinay; Leopold, Christina; Bauer, Raimund; Patankar, Jay V; Iqbal, Jahangir; Obrowsky, Sascha; Boverhof, Renze; Doktorova, Marcela; Scheicher, Bernhard; Goeritzer, Madeleine; Kolb, Dagmar; Turnbull, Andrew V; Zimmer, Andreas; Hoefler, Gerald; Hussain, M Mahmood; Groen, Albert K; Kratky, Dagmar

    2016-09-01

    Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) is a key enzyme in triacylglycerol (TG) biosynthesis. Here we show that genetic deficiency and pharmacological inhibition of DGAT1 in mice alters cholesterol metabolism. Cholesterol absorption, as assessed by acute cholesterol uptake, was significantly decreased in the small intestine and liver upon DGAT1 deficiency/inhibition. Ablation of DGAT1 in the intestine (I-DGAT1(-/-)) alone is sufficient to cause these effects. Consequences of I-DGAT1 deficiency phenocopy findings in whole-body DGAT1(-/-) and DGAT1 inhibitor-treated mice. We show that deficiency/inhibition of DGAT1 affects cholesterol metabolism via reduced chylomicron size and increased trans-intestinal cholesterol excretion. These effects are independent of cholesterol uptake at the apical surface of enterocytes but mediated through altered dietary fatty acid metabolism. Our findings provide insight into a novel role of DGAT1 and identify a pathway by which intestinal DGAT1 deficiency affects whole-body cholesterol homeostasis in mice. Targeting intestinal DGAT1 may represent a novel approach for treating hypercholesterolemia. PMID:27344248

  8. Genetic variation in SULF2 is associated with postprandial clearance of triglyceride-rich remnant particles and triglyceride levels in healthy subjects.

    Directory of Open Access Journals (Sweden)

    Niina Matikainen

    Full Text Available CONTEXT: Nonfasting (postprandial triglyceride concentrations have emerged as a clinically significant cardiovascular disease risk factor that results from accumulation of remnant triglyceride-rich lipoproteins (TRLs in the circulation. The remnant TRLs are cleared from the circulation by hepatic uptake, but the specific mechanisms involved are unclear. The syndecan-1 heparan sulfate proteoglycan (HSPG pathway is important for the hepatic clearance of remnant TRLs in mice, but its relevance in humans is unclear. OBJECTIVE: We sought to determine whether polymorphisms of the genes responsible for HSPG assembly and disassembly contribute to atherogenic dyslipoproteinemias in humans. PATIENTS AND DESIGN: We performed an oral fat load in 68 healthy subjects. Lipoproteins (chylomicrons and very low density lipoproteins 1 and 2 were isolated from blood, and the area under curve and incremental area under curve for postprandial variables were calculated. Single nucleotide polymorphisms in genes encoding syndecan-1 and enzymes involved in the synthesis or degradation of HSPG were genotyped in the study subjects. RESULTS: Our results indicate that the genetic variation rs2281279 in SULF2 associates with postprandial clearance of remnant TRLs and triglyceride levels in healthy subjects. Furthermore, the SNP rs2281279 in SULF2 associates with hepatic SULF2 mRNA levels. CONCLUSIONS: In humans, mild but clinically relevant postprandial hyperlipidemia due to reduced hepatic clearance of remnant TRLs may result from genetic polymorphisms that affect hepatic HSPG.

  9. Apolipoproteins C-I and C-III Inhibit Lipoprotein Lipase Activity by Displacement of the Enzyme from Lipid Droplets*

    Science.gov (United States)

    Larsson, Mikael; Vorrsjö, Evelina; Talmud, Philippa; Lookene, Aivar; Olivecrona, Gunilla

    2013-01-01

    Apolipoproteins (apo) C-I and C-III are known to inhibit lipoprotein lipase (LPL) activity, but the molecular mechanisms for this remain obscure. We present evidence that either apoC-I or apoC-III, when bound to triglyceride-rich lipoproteins, prevent binding of LPL to the lipid/water interface. This results in decreased lipolytic activity of the enzyme. Site-directed mutagenesis revealed that hydrophobic amino acid residues centrally located in the apoC-III molecule are critical for attachment to lipid emulsion particles and consequently inhibition of LPL activity. Triglyceride-rich lipoproteins stabilize LPL and protect the enzyme from inactivating factors such as angiopoietin-like protein 4 (angptl4). The addition of either apoC-I or apoC-III to triglyceride-rich particles severely diminished their protective effect on LPL and rendered the enzyme more susceptible to inactivation by angptl4. These observations were seen using chylomicrons as well as the synthetic lipid emulsion Intralipid. In the presence of the LPL activator protein apoC-II, more of apoC-I or apoC-III was needed for displacement of LPL from the lipid/water interface. In conclusion, we show that apoC-I and apoC-III inhibit lipolysis by displacing LPL from lipid emulsion particles. We also propose a role for these apolipoproteins in the irreversible inactivation of LPL by factors such as angptl4. PMID:24121499

  10. Apolipoproteins C-I and C-III inhibit lipoprotein lipase activity by displacement of the enzyme from lipid droplets.

    Science.gov (United States)

    Larsson, Mikael; Vorrsjö, Evelina; Talmud, Philippa; Lookene, Aivar; Olivecrona, Gunilla

    2013-11-22

    Apolipoproteins (apo) C-I and C-III are known to inhibit lipoprotein lipase (LPL) activity, but the molecular mechanisms for this remain obscure. We present evidence that either apoC-I or apoC-III, when bound to triglyceride-rich lipoproteins, prevent binding of LPL to the lipid/water interface. This results in decreased lipolytic activity of the enzyme. Site-directed mutagenesis revealed that hydrophobic amino acid residues centrally located in the apoC-III molecule are critical for attachment to lipid emulsion particles and consequently inhibition of LPL activity. Triglyceride-rich lipoproteins stabilize LPL and protect the enzyme from inactivating factors such as angiopoietin-like protein 4 (angptl4). The addition of either apoC-I or apoC-III to triglyceride-rich particles severely diminished their protective effect on LPL and rendered the enzyme more susceptible to inactivation by angptl4. These observations were seen using chylomicrons as well as the synthetic lipid emulsion Intralipid. In the presence of the LPL activator protein apoC-II, more of apoC-I or apoC-III was needed for displacement of LPL from the lipid/water interface. In conclusion, we show that apoC-I and apoC-III inhibit lipolysis by displacing LPL from lipid emulsion particles. We also propose a role for these apolipoproteins in the irreversible inactivation of LPL by factors such as angptl4. PMID:24121499

  11. Mfge8 regulates enterocyte lipid storage by promoting enterocyte triglyceride hydrolase activity

    Science.gov (United States)

    Khalifeh-Soltani, Amin; Gupta, Deepti; Ha, Arnold; Iqbal, Jahangir; Hussain, Mahmood; Podolsky, Michael J.

    2016-01-01

    The small intestine has an underappreciated role as a lipid storage organ. Under conditions of high dietary fat intake, enterocytes can minimize the extent of postprandial lipemia by storing newly absorbed dietary fat in cytoplasmic lipid droplets. Lipid droplets can be subsequently mobilized for the production of chylomicrons. The mechanisms that regulate this process are poorly understood. We report here that the milk protein Mfge8 regulates hydrolysis of cytoplasmic lipid droplets in enterocytes after interacting with the αvβ3 and αvβ5 integrins. Mice deficient in Mfge8 or the αvβ3 and αvβ5 integrins accumulate excess cytoplasmic lipid droplets after a fat challenge. Mechanistically, interruption of the Mfge8-integrin axis leads to impaired enterocyte intracellular triglyceride hydrolase activity in vitro and in vivo. Furthermore, Mfge8 increases triglyceride hydrolase activity through a PI3 kinase/mTORC2–dependent signaling pathway. These data identify a key role for Mfge8 and the αvβ3 and αvβ5 integrins in regulating enterocyte lipid processing.

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

    Science.gov (United States)

    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

  13. Mechanisms for exporting large-sized cargoes from the endoplasmic reticulum.

    Science.gov (United States)

    Saito, Kota; Katada, Toshiaki

    2015-10-01

    Cargo proteins exported from the endoplasmic reticulum to the Golgi apparatus are typically transported in coat protein complex II (COPII)-coated vesicles of 60-90 nm diameter. Several cargo molecules including collagens and chylomicrons form structures that are too large to be accommodated by these vesicles, but their secretion still requires COPII proteins. Here, we first review recent progress on large cargo secretions derived especially from animal models and human diseases, which indicate the importance of COPII proteins. We then discuss the recent isolation of specialized factors that modulate the process of COPII-dependent cargo formation to facilitate the exit of large-sized cargoes from the endoplasmic reticulum. Based on these findings, we propose a model that describes the importance of the GTPase cycle for secretion of oversized cargoes. Next, we summarize reports that describe the structures of COPII proteins and how these results provide insight into the mechanism of assembly of the large cargo carriers. Finally, we discuss what issues remain to be solved in the future.

  14. The multiligand α2-macroglobulin receptor/low density lipoprotein receptor-related protein

    DEFF Research Database (Denmark)

    Gliemann, Jørgen; Nykjær, Anders; Petersen, Claus Munck;

    1994-01-01

    The fusion of separate lines of research has greatly helped in elucidating the function of the giant members of the low density lipoprotein (LDL) receptor (LDLR) supergene family. The cDNA encoding a large protein structurally closely related to LDLR, and hence named LDLR-related protein (LRP), was...... cloned by Herz et al. in 1988.'Evidence was provided demonstrating that LRP can function as a receptor for chylomicron remnants@-migrating very low density lipoproteins (P-VLDL) rich in apolipoprotein E (apoE)?' The a2-macroglobulin (a2M) receptor (a2MR) was purified from rat livep and human p l a~e n t...... from the observation that affinity-purified a2MR/LRP contains a 40-kDa5.8 or 39-kDa6.' protein, designated a2MRAP, in addition to the a2MFULRP a- and P-chains. cDNA cloning" disclosed the 323-residue protein as both the human homologue of mouse heparin binding protein 44 (see reference 11) and...

  15. Uptake of [3H]vitamin D3 from low and high density lipoproteins by cultured human fibroblasts

    International Nuclear Information System (INIS)

    The plasma distribution and cellular uptake of [3H]vitamin D3 was studied in vitro using cultured human fibroblasts. Incubation of [3H]vitamin D3 (cholecalciferol) with plasma followed by sequential ultracentrifugal fractionation of the lipoproteins indicated that 2-4% of the radioactivity associated with the very low density lipoprotein (VLDL), 12% with low density lipoprotein (LDL), and approximately 60% with the high density lipoprotein (HDL). The remaining radioactivity, 25%, was associated with the sedimented plasma fractions. By comparison, an average of 86% of the radioactivity from [3H] 1,25-dihydroxycholecalciferol associated with the sedimented plasma fractions. The uptake of [3H]vitamin D3 from plasma, LDL, or HDL was studied in cultured human cells; uptake by normal fibroblasts was greatest from LDL and least from plasma. The cellular association of vitamin D3 was time, concentration, and temperature dependent. At a concentration of 50 μg LDL/ml of medium, the uptake of [3H]vitamin D3 from LDL at 370C was rapid and reached a maximum at approximately 4 hr; it was slower from HDL but continued to increase slowly up to 24 hr. The significance of these in vitro findings is uncertain since much of the vitamin D3 absorbed from the intestine reportedly associates with chylomicrons and is rapidly taken up by the liver

  16. Sustained and selective suppression of intestinal cholesterol synthesis by Ro 48-8071, an inhibitor of 2,3-oxidosqualene:lanosterol cyclase, in the BALB/c mouse.

    Science.gov (United States)

    Chuang, Jen-Chieh; Valasek, Mark A; Lopez, Adam M; Posey, Kenneth S; Repa, Joyce J; Turley, Stephen D

    2014-04-01

    The small intestine plays a fundamentally important role in regulating whole body cholesterol balance and plasma lipoprotein composition. This is articulated through the interplay of a constellation of genes that ultimately determines the net amount of chylomicron cholesterol delivered to the liver. Major advances in our insights into regulation of the cholesterol absorption pathway have been made using genetically manipulated mouse models and agents such as ezetimibe. One unresolved question is how a sustained pharmacological inhibition of intestinal cholesterol synthesis in vivo may affect cholesterol handling by the absorptive cells. Here we show that the lanosterol cyclase inhibitor, Ro 48-8071, when fed to BALB/c mice in a chow diet (20 mg/day/kg body weight), leads to a rapid and sustained inhibition (>50%) of cholesterol synthesis in the whole small intestine. Sterol synthesis was also reduced in the large intestine and stomach. In contrast, hepatic cholesterol synthesis, while markedly suppressed initially, rebounded to higher than baseline rates within 7 days. Whole body cholesterol synthesis, fractional cholesterol absorption, and fecal neutral and acidic sterol excretion were not consistently changed with Ro 48-8071 treatment. There were no discernible effects of this agent on intestinal histology as determined by H&E staining and the level of Ki67, an index of proliferation. The mRNA expression for multiple genes involved in intestinal cholesterol regulation including NPC1L1 was mostly unchanged although there was a marked rise in the mRNA level for the PXR target genes CYP3A11 and CES2A.

  17. Cholesterol improves the utilization of parenteral lipid emulsions.

    Science.gov (United States)

    Druml, Wilfred; Fischer, Margot

    2003-11-28

    Lipid emulsions have become an indispensable component of parenteral nutrition. Commercially available emulsions mostly have an identical composition of triglycerides (from plant oils) and egg-yolk phospholipids as emulsifier. Previous attempts to improve the composition of lipid emulsions have focused mainly on the triglyceride moiety. In the first fundamental modification of a lipid emulsion since their broader introduction into clinical medicine, we included free cholesterol in a lipid emulsion. We evaluated elimination and hydrolysis of triglycerides and lipid oxidation (by indirect calorimetry) in 10 healthy male normolipemic volunteers, comparing a conventional lipid emulsion (20% triglycerides) with an otherwise identical emulsion with the addition of 4 g/l free cholesterol. The rise in plasma triglycerides was mitigated during infusion of the cholesterol-enriched solution (323.8 +/- 27.5 vs. 202.0 +/- 18.9 mg.dL-1, p free fatty acids (400.7 +/- 39.0 vs. 532.2 +/- 64.0 mumol.L-1; p bodies (beta-hydroxybutyrate) (151.6 +/- 37.0 vs. 226.3 +/- 33.01 mumol.L-1; p fall in respiratory quotient was greater and the fraction of lipid oxidation as a percentage of total energy expenditure was increased (66.2% +/- 6.0 vs. 70.9% +/- 6.3, p < 0.05) during infusion of the modified solution. No impairment of gas exchange or other side effects were observed. Taken together these results indicate that the elimination of a cholesterol-supplemented lipid emulsion is accelerated, triglyceride hydrolysis is enhanced, and lipid oxidation is augmented. Thus, addition of cholesterol to a lipid emulsion might not only present a means of providing cholesterol in parenteral nutrition but also help to reshape artificial lipid particles to a more chylomicron-resembling composition and improve lipid utilization. PMID:14743580

  18. Alimentary lipemia: plasma high-density lipoproteins and apolipoproteins CII and CIII in healthy subjects.

    Science.gov (United States)

    Kashyap, M L; Barnhart, R L; Srivastava, L S; Perisutti, G; Allen, C; Hogg, E; Glueck, C J; Jackson, R L

    1983-02-01

    Three healthy male and three female inpatient volunteers consumed isocaloric diets for 4 wk. At weekly intervals, a fatty meal (100 g fat) was consumed by each fasting subject and blood drawn at 2 h intervals for 12 h. Of the four oral fat loads, two contained saturated fat (polyunsaturated/saturated fat ratio = 0.34) and two contained unsaturated fat (polyunsaturated/saturated fat = 2.21). The magnitude of alimentary lipemia, expressed as area under the plasma triglyceride curve, was 3- to 4-fold higher in males than females. Alimentary lipemia was inversely related to the subjects' fasting plasma high-density lipoprotein (HDL)-cholesterol, HDL apolipoprotein (apo) CIII and directly related to plasma triglycerides. The P/S ratios of the daily diet or the fat meal did not significantly influence the plasma triglyceride curve. After fat intake, mean (+/- SEM) plasma total apoCII and CIII fell to 54 +/- 20% and 73 +/- 5% of base-line, respectively, at 12 h in five of six subjects. After oral fat, an initial fall and a subsequent rise in apoCII and CIII in HDL was associated with reciprocal changes in apoC concentrations in very low-density lipoproteins. We speculate from the data that 1) plasma HDL and their apoC concentrations are important determinants of chylomicron clearance and 2) transfer of apoCs from HDL to triglyceride-rich lipoproteins in the early phase of fat absorption does not result in the total recycling of apoCs from these lipoproteins to HDL during the late phase of alimentary lipemia.

  19. High-fat meal effect on LDL, HDL, and VLDL particle size and number in the Genetics of Lipid-Lowering drugs and diet network (GOLDN: an interventional study

    Directory of Open Access Journals (Sweden)

    Straka Robert J

    2011-10-01

    Full Text Available Abstract Background Postprandial lipemia (PPL is likely a risk factor for cardiovascular disease but these changes have not been well described and characterized in a large cohort. We assessed acute changes in the size and concentration of total and subclasses of LDL, HDL, and VLDL particles in response to a high-fat meal. Participants (n = 1048 from the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN Study who ingested a high-fat meal were included in this analysis. Lipids were measured at 0 hr (fasting, 3.5 hr, and 6 hr after a standardized fat meal. Particle size distributions were determined using nuclear magnetic resonance spectroscopy. Analyses were stratified by baseline triglycerides (normal vs. elevated and gender. The effect of PPL on changes in lipoprotein subclasses was assessed using repeated measures ANOVA. Results Postprandially, LDL-C, HDL-C, VLDL-C, and triglycerides increased regardless of baseline triglyceride status, with the largest increases in VLDL-C and TG; however, those with elevated triglycerides demonstrated larger magnitude of response. Total LDL particle number decreased over the 6-hour time interval, mostly from a decrease in the number of small LDL particles. Similarly, total VLDL particle number decreased due to reductions in medium and small VLDL particles. Large VLDL particles and chylomicrons demonstrated the largest increase in concentration. HDL particles demonstrated minimal overall changes in total particle number. Conclusions We have characterized the changes in LDL and VLDL particle number, and their subclass patterns following a high-fat meal.

  20. Ultrastructure of the anterior intestinal epithelia of the orange-spotted grouper Epinephelus coioides larvae under different feeding regimes.

    Science.gov (United States)

    Primavera-Tirol, Y H; Coloso, R M; Quinitio, G F; Ordonio-Aguilar, R; Laureta, L V

    2014-04-01

    Enterocytes of the anterior to midsection of the intestine in grouper Epinephelus coioides larvae were compared among different treatments: unfed to the point-of-no-return (PNR), fed natural food only, and co-fed natural food and artificial diet. On day 3, the nutritional condition of unfed grouper larvae regressed with its reduced enterocyte heights which were further degraded on day 4, the PNR, when all the enterocytes were in advanced stages of apoptosis. The apoptosis appeared to be internally directed via the mitochondria. Among day 3 fed larvae, enterocyte heights of those fed artificial diet did not differ from those fed natural food only. Dietary phospholipid deficiency was indicated in larvae co-fed artificial diet on day 3 with an unusually large chylomicron opening into the inter-enterocyte space, and on days 6 and 33 by intestinal steatosis. On day 19, scant to absent lipid droplets in enterocytes of larvae disclosed heightened nutritional requirement preparatory to metamorphosis. As observed in unfed day 3 and premetamorphic day 19 E. coioides, larvae undergoing critical periods and starvation during development employ apoptosis to dispose of degenerated enterocytes that are phagocytosed by adjacent healthy enterocytes without causing inflammatory distress. Upon metamorphosis, grouper larval gut develops better immunity fitness with eosinophilic granule cells observed in the intestinal epithelia of day 33 larvae. Future studies on grouper larval nutrition may consider the appropriate dietary phospholipid levels and larval competence to biosynthesize highly unsaturated fatty acid from linoleic acid vis-à-vis the use of plant ingredients in artificial diet formulations. In vivo challenge tests may validate appropriate dietary nutrient supplementation and lead to better feed formulation, matching the varying energetic demands and digestive capacities of developing E. coioides larvae.

  1. Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose.

    Science.gov (United States)

    Goossens, Gijs H; Moors, Chantalle C M; Jocken, Johan W E; van der Zijl, Nynke J; Jans, Anneke; Konings, Ellen; Diamant, Michaela; Blaak, Ellen E

    2016-03-01

    Altered skeletal muscle fatty acid (FA) metabolism contributes to insulin resistance. Here, we compared skeletal muscle FA handling between subjects with impaired fasting glucose (IFG; n = 12 (7 males)) and impaired glucose tolerance (IGT; n = 14 (7 males)) by measuring arterio-venous concentration differences across forearm muscle. [²H₂]-palmitate was infused intravenously, labeling circulating endogenous triacylglycerol (TAG) and free fatty acids (FFA), whereas [U-(13)C]-palmitate was incorporated in a high-fat mixed-meal, labeling chylomicron-TAG. Skeletal muscle biopsies were taken to determine muscle TAG, diacylglycerol (DAG), FFA, and phospholipid content, their fractional synthetic rate (FSR) and degree of saturation, and gene expression. Insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp. Net skeletal muscle glucose uptake was lower (p = 0.018) and peripheral insulin sensitivity tended to be reduced (p = 0.064) in IGT as compared to IFG subjects. Furthermore, IGT showed higher skeletal muscle extraction of VLDL-TAG (p = 0.043), higher muscle TAG content (p = 0.025), higher saturation of FFA (p = 0.004), lower saturation of TAG (p = 0.017) and a tendency towards a lower TAG FSR (p = 0.073) and a lower saturation of DAG (p = 0.059) versus IFG individuals. Muscle oxidative gene expression was lower in IGT subjects. In conclusion, increased liver-derived TAG extraction and reduced lipid turnover of saturated FA, rather than DAG content, in skeletal muscle accompany the more pronounced insulin resistance in IGT versus IFG subjects. PMID:26985905

  2. Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose

    Directory of Open Access Journals (Sweden)

    Gijs H. Goossens

    2016-03-01

    Full Text Available Altered skeletal muscle fatty acid (FA metabolism contributes to insulin resistance. Here, we compared skeletal muscle FA handling between subjects with impaired fasting glucose (IFG; n = 12 (7 males and impaired glucose tolerance (IGT; n = 14 (7 males by measuring arterio-venous concentration differences across forearm muscle. [2H2]-palmitate was infused intravenously, labeling circulating endogenous triacylglycerol (TAG and free fatty acids (FFA, whereas [U-13C]-palmitate was incorporated in a high-fat mixed-meal, labeling chylomicron-TAG. Skeletal muscle biopsies were taken to determine muscle TAG, diacylglycerol (DAG, FFA, and phospholipid content, their fractional synthetic rate (FSR and degree of saturation, and gene expression. Insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp. Net skeletal muscle glucose uptake was lower (p = 0.018 and peripheral insulin sensitivity tended to be reduced (p = 0.064 in IGT as compared to IFG subjects. Furthermore, IGT showed higher skeletal muscle extraction of VLDL-TAG (p = 0.043, higher muscle TAG content (p = 0.025, higher saturation of FFA (p = 0.004, lower saturation of TAG (p = 0.017 and a tendency towards a lower TAG FSR (p = 0.073 and a lower saturation of DAG (p = 0.059 versus IFG individuals. Muscle oxidative gene expression was lower in IGT subjects. In conclusion, increased liver-derived TAG extraction and reduced lipid turnover of saturated FA, rather than DAG content, in skeletal muscle accompany the more pronounced insulin resistance in IGT versus IFG subjects.

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

    Science.gov (United States)

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

    2016-02-01

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

  4. Reduced triglyceride secretion in response to an acute dietary fat challenge in obese compared to lean mice.

    Directory of Open Access Journals (Sweden)

    Aki eUchida

    2012-02-01

    Full Text Available Obesity results in abnormally high levels of triglyceride (TG storage in tissues such as liver, heart and muscle, which disrupts their normal functions. Recently, we found that lean mice challenged with high levels of dietary fat store TGs in cytoplasmic lipid droplets in the absorptive cells of the intestine, enterocytes, and that this storage increases and then decreases over time after an acute dietary fat challenge. The goal of this study was to investigate the effects of obesity on intestinal TG metabolism. More specifically we asked whether TG storage in and secretion from the intestine are altered in obesity. We investigated these questions in diet-induced obese (DIO and leptin-deficient (ob/ob mice. We found greater levels of TG storage in the intestine of DIO mice compared to lean mice in the fed state, but similar levels of TG storage after fasting. In addition, we found similar TG storage in the intestine of lean and DIO mice at multiple time points after an acute dietary fat challenge. Surprisingly, we found remarkably lower TG secretion from both DIO and ob/ob mice compared to lean controls in response to an acute dietary fat challenge. Furthermore, we found altered mRNA levels for genes involved in regulation of intestinal TG metabolism in lean and DIO mice at fasting and in response to an acute dietary fat challenge. More specifically, we found that many of the genes related to TG synthesis, chylomicron synthesis, TG storage and lipolysis were induced in response to an acute dietary fat challenge in lean mice, but this induction was not observed in DIO mice. In fact, we found a significant decrease in intestinal mRNA levels of genes related to lipolysis and fatty acid oxidation in DIO mice in response to an acute dietary fat challenge. Our findings demonstrate altered TG handling by the small intestine of obese compared to lean mice.

  5. Revisiting the metabolism and physiological functions of caprylic acid (C8:0) with special focus on ghrelin octanoylation.

    Science.gov (United States)

    Lemarié, Fanny; Beauchamp, Erwan; Legrand, Philippe; Rioux, Vincent

    2016-01-01

    Caprylic acid (octanoic acid, C8:0) belongs to the class of medium-chain saturated fatty acids (MCFAs). Dairy products and specific oils like coconut oil are natural sources of dietary C8:0 but higher intakes of this fatty acid can be provided with MCT (Medium-Chain Triglycerides) oil that consists in 75% of C8:0. MCFAs have physical and metabolic properties that are distinct from those of long-chain saturated fatty acids (LCFAs ≥ 12 carbons). Beneficial physiological effects of dietary C8:0 have been studied for a long time and MCT oil has been used as a special energy source for patients suffering from pancreatic insufficiency, impaired lymphatic chylomicron transport and fat malabsorption. More recently, caprylic acid was also shown to acylate ghrelin, the only known peptide hormone with an orexigenic effect. Through its covalent binding to the ghrelin peptide, caprylic acid exhibits an emerging and specific role in modulating physiological functions themselves regulated by octanoylated ghrelin. Dietary caprylic acid is therefore now suspected to provide the ghrelin O-acyltransferase (GOAT) enzyme with octanoyl-CoA co-substrates necessary for the acyl modification of ghrelin. This review tries to highlight the discrepancy between the formerly described beneficial effects of dietary MCFAs on body weight loss and the C8:0 newly reported effect on appetite stimulation via ghrelin octanoylation. The subsequent aim of this review is to demonstrate the relevance of carrying out further studies to better understand the physiological functions of this particular fatty acid.

  6. [Carotenoids: 1. Metabolism and physiology].

    Science.gov (United States)

    Faure, H; Fayol, V; Galabert, C; Grolier, P; Le Moël, G; Steghens, J P; Van Kappel, A; Nabet, F

    1999-01-01

    Carotenoids are a family of pigments with at least 600 members. They derive from lycopene after steps of cyclisation, dehydrogenation and oxidation. It is their chemical structure that determines their physiochemical properties and, in part, their biological activities. About 50 carotenoids can be found in human diet and about 20 of them have been found in plasma and tissues. There is no RDA (Recommended Daily Allowance) for carotenoids. Quantities of carotenoids in diet are difficult to estimate, partly because methods used for the establishment of food composition tables were not specific and sensitive enough. Also, given values do not always take into account variations due to season and region of culture. Absorption of beta-carotene in humans has been the subject of numerous studies but only very little is known about other carotenoids. In general, absorption depends on bioavailability from the food matrix and solubility in micelles. After absorption through passive diffusion, carotenoids follow the chylomicrons metabolism. They are taken up by the liver and released in the blood stream in lipoproteins (VLDL). Carotenoids with no-substituted beta-ionone cycles (alpha and beta-carotene and beta-cryptoxanthin) have provitamin A activity. Highest activity has been found for all-trans beta-carotene. Not all steps of vitamin A biosynthesis and metabolism of other carotenoids have been clarified yet. Besides their provitamin A activity, carotenoids have numerous biological functions. They are efficient scavengers of free radicals, particularly of 1O2. In vitro they have been shown to protect LDL. However, results in vivo are inconsistent. Other functions include enhancement of gap junctions, immunomodulation and regulation of enzyme activity involved in carcinogenesis. PMID:10210743

  7. Physiological Study of Lipoprotein Lipase Gene Pvu II Polymorphism in Cases of Obesity in Egypt

    Directory of Open Access Journals (Sweden)

    Ghada El-Kannishy

    2012-01-01

    Full Text Available Genetic predisposition has been implicated in obesity. Lipoprotein lipase (LPL gene, the main lipase of chylomicrons and Low Density Lipoproteins (LDL, has a fundamental role in the transport and metabolism of plasma cholesterol. The present study was undertaken to test for the association of the LPL gene Pvu II polymorphism with obesity with or without hypertension and diabetes and dyslipidemia among affected Egyptian cases. This study has included 120 subjects affected with obesity; 57 of them were affected with metabolic syndrome (with diabetes, dyslipidemia and hypertension while the other 63 cases were not complicated and were termed simple obesity. These cases were compared to 83 healthy non-obese controls. Body Mass Index (BMI, Waist Hip Ration (WHR and serum lipid levels were measured. The LPL gene polymorphic alleles were determined by PCR-RFLP that includes polymerase chain reaction for gene amplification followed by digestion with Pvu II enzyme and analysis according to the size of digested amplified DNA. Obesity cases had a significantly higher frequency of the homozygous mutated LPL Pvu II (+/+ genotype and also of the (+ allele particularly among metabolic syndrome cases compared to controls. Cases with the (+/+ homozygous genotype showed significantly higher frequency of diabetes, lower frequency of positive family history and lower values for waist hip ratio than those with the (+/- and (-/- genotypes. These cases have showed also higher levels of total cholesterol and LDL-C, yet not reaching statistical significance. This study showed a significant association between the LPL Pvu II gene polymorphism and obesity among Egyptian cases particularly when complicated with the metabolic syndrome.

  8. Solvent-Free Lipase-Catalyzed Synthesis of Diacylgycerols as Low-Calorie Food Ingredients

    Science.gov (United States)

    Vázquez, Luis; González, Noemí; Reglero, Guillermo; Torres, Carlos

    2016-01-01

    Problems derived from obesity and overweight have recently promoted the development of fat substitutes and other low-calorie foods. On the one hand, fats with short- and medium-chain fatty acids are a source of quick energy, easily hydrolyzable and hardly stored as fat. Furthermore, 1,3-diacylglycerols are not hydrolyzed to 2-monoacylglycerols in the gastrointestinal tract, reducing the formation of chylomicron and lowers the serum level of triacylglycerols by decreasing its resynthesis in the enterocyte. In this work, these two effects were combined to synthesize short- and medium-chain 1,3-diacylglycerols, leading to a product with great potential as for their low-calorie properties. Lipase-catalyzed transesterification reactions were performed between short- and medium-chain fatty acid ethyl esters and glycerol. Different variables were investigated, such as the type of biocatalyst, the molar ratio FAEE:glycerol, the adsorption of glycerol on silica gel, or the addition of lecithin. Best reaction conditions were evaluated considering the percentage of 1,3-DAG produced and the reaction rate. Except Novozym 435 (Candida antarctica), other lipases required the adsorption of glycerol on silica gel to form acylglycerols. Lipases that gave the best results with adsorption were Novozym 435 and Lipozyme RM IM (Rhizomucor miehei) with 52 and 60.7% DAG at 32 h, respectively. Because of its specificity for sn-1 and sn-3 positions, lipases leading to a higher proportion of 1,3-DAG vs. 1,2-DAG were Lipozyme RM IM (39.8 and 20.9%, respectively) and Lipase PLG (Alcaligenes sp.) (35.9 and 19.3%, respectively). By adding 1% (w/w) of lecithin to the reaction with Novozym 435 and raw glycerol, the reaction rate was considerably increased from 41.7 to 52.8% DAG at 24 h. PMID:26904539

  9. Mitochondrial triglyceride transfer protein inhibition: new achievements in the treatment of dyslipidemias.

    Science.gov (United States)

    Kostapanos, Michael S; Rizos, Evangelos C; Papanas, Nikolaos; Maltezos, Efstratios; Elisaf, Moses S

    2013-01-01

    Current lipid-lowering drugs are often unable to achieve low density lipoprotein cholesterol (LDL-C) goals. Moreover, despite LDL-C lowering mostly by statins, a considerable residual vascular risk remains. This is partly associated with atherogenic dyslipidemia where apolipoprotein (apo) B-containing lipoproteins predominate. Mitochondrial Triglyceride (TG) transfer protein (MTP) is a key enzyme for apoB-containing lipoprotein assembly and secretion. This is mostly attributed to its capacity to transfer lipid components (TGs, cholesterol esters and phospholipids) to the endoplasmic reticulum lumen, where these lipoproteins are assembled. Several agents were developed to inhibit MTP wherever it is expressed, namely the liver and/or the intestine. Liver-specific MTP inhibitors reduce secretion of very low density lipoproteins (VLDL) mostly containing apoB100, while the intestine-specific ones reduce secretion of chylomicrons containing apoB48. These drugs can significantly reduce total cholesterol, LDL-C, TGs, VLDL cholesterol, as well as apoB levels in vivo. They may also exert anti-atherosclerotic and insulin-sensitizing effects. Limited clinical data suggest that these compounds can also improve the serum lipid profile in patients with homozygous familial hypercholesterolemia (HoFH). The accumulation of unsecreted fat in the liver and intestinal lumen is associated with elevation of aminotransferases and steatorrhea. Liver steatosis can be avoided by the use of intestine-specific MTP inhibitors, while steatorrhea by low-fat diet. Future indications for these developing drugs may include dyslipidemia associated with insulin resistant states, familial combined hyperlipidemia and HoFH. Future clinical trials are warranted to assess the efficacy and safety of MTP inhibitors in various clinical states.

  10. Intestine-Specific Mttp Deletion Increases the Severity of Experimental Colitis and Leads to Greater Tumor Burden in a Model of Colitis Associated Cancer.

    Directory of Open Access Journals (Sweden)

    Yan Xie

    Full Text Available Gut derived lipid factors have been implicated in systemic injury and inflammation but the precise pathways involved are unknown. In addition, dietary fat intake and obesity are independent risk factors for the development of colorectal cancer. Here we studied the severity of experimental colitis and the development of colitis associated cancer (CAC in mice with an inducible block in chylomicron secretion and fat malabsorption, following intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO.Mttp-IKO mice exhibited more severe injury with ∼90% mortality following dextran sodium sulfate (DSS induced colitis, compared to <20% in controls. Intestinal permeability was increased in Mttp-IKO mice compared to controls, both at baseline and after DSS administration, in association with increased circulating levels of TNFα. DSS treatment increased colonic mRNA expression of IL-1β and IL-17A as well as inflammasome expression in both genotypes, but the abundance of TNFα was selectively increased in DSS treated Mttp-IKO mice. There was a 2-fold increase in colonic tumor burden in Mttp-IKO mice following azoxymethane/DSS treatment, which was associated with increased colonic inflammation as well as alterations in cytokine expression. To examine the pathways by which alterations in fatty acid abundance might interact with cytokine signaling to regulate colonic epithelial growth, we used primary murine myofibroblasts to demonstrate that palmitate induced expression of amphiregulin and epiregulin and augmented the increase in both of these growth mediators when added to IL-1βor to TNFα.These studies demonstrate that Mttp-IKO mice, despite absorbing virtually no dietary fat, exhibit augmented fatty acid dependent signaling that in turn exacerbates colonic injury and increases tumor formation.

  11. Isolation and characterization of a mucosal triacylglycerol pool undergoing hydrolysis

    International Nuclear Information System (INIS)

    Absorbed and processed mucosal neutral lipid has been shown to be composed of at least two pools of triacylglycerol. One is likely to subserve chylomicron formation, and the other appears to be transported from the intestine via a nonlymphatic route. In the present study, 50 +/- 5% of the mucosal lipid pellets was centrifuged at 75,000 g.min [low-speed pellet (LSP)]. Discontinuous sucrose density gradient centrifugation of LSP showed that 61 +/- 7% of the lipid banded at the 0.25-0.86 M sucrose interface. Neutral lipid analysis showed that this subfraction was only 58% triacylglycerol, suggesting it was undergoing hydrolysis. Active lipolytic activity in vitro was found on incubation. The lipase had an alkaline pH optimum (pH 8.5) and persisted despite pancreatic ductular diversion. Lipolysis in vivo in a LSP fraction was shown by infusing [14C]glyceryltrioleate for 3.5 h followed by [3H]glyceryltrioleate for 30 min. Discontinuous sucrose density centrifugation of the LSP followed by an analysis of the lipids at the 0.25-0.86 M sucrose interface showed that 14C-neutral lipids were only 70 +/- 6% triacylglycerol, whereas 3H-neutral lipids were 88 +/- 2% triacylglycerol. 3H entered LSP slowly compared with the floating lipid in the same centrifuge tube. These studies suggest both in vivo and in vitro mucosal lipolysis by a specific, alkaline-active lipase. The turnover rate of LSP is likely to be slow by comparison with neutral lipid floating to the top of the centrifuge tube

  12. Esterification and hydrolysis of vitamin A in the liver of brook trout (Salvelinus fontinalis) and the influence of a coplanar polychlorinated biphenyl

    Energy Technology Data Exchange (ETDEWEB)

    Ndayibagira, A.; Spear, P.A. [Centre de Recherche TOXEN and Departement des Sciences Biologiques, Universite du Quebec a Montreal, C.P. 8888, succursale Centre Ville Montreal (Canada)

    1999-03-01

    Recent reports of extremely low retinoid stores in fish living in contaminated river systems prompted an initial investigation of the mechanisms of hepatic storage and mobilization in brook trout. Enzyme characterization in microsomes revealed a lecithin:retinol acyltransferase activity (LRAT) optimum in the alkaline range (pH 9.0; V{sub max}=0.6 nmol per mg prot. h{sup -1}; K{sub m}=10.2 {mu}M) which is not known to occur in mammals, in addition to a secondary optimum at pH 6.5 typical of mammals. Acyl CoA:retinol acyltransferase (ARAT) kinetic parameters were quite different to those of mammals. The substrate affinity of trout ARAT (K{sub m}=1.6 {mu}M) was approximately 22-fold greater than that of the rat while maximal velocity (V{sub max}=0.2 nmol per mg prot. h{sup -1}) was 18-fold less. Retinyl ester hydrolase activity (REH) was optimal under acid conditions (pH 4.2; V{sub max}=6.6 nmol per mg prot. h{sup -1}; K{sub m}=0.6 mM), was inhibited by a bile salt analogue and was greater in males than females. This REH was tentatively categorized as a bile salt-independent, acid retinyl ester hydrolase (BSI-AREH). REH was inhibited in a dose-dependent manner following in vivo exposure to a representative environmental contaminant the coplanar polychlorinated biphenyl (PCB), 3,3minutes or feet,4,4minutes or feet-tetrachlorobiphenyl (TCBP). Inhibition may be an indirect effect because enzyme activity was not affected by in vitro exposure of control microsomes. REH inhibition in the brook trout may affect the uptake of retinyl esters (REs) from chylomicron remnants as well as the mobilization of stored REs. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  13. Metabolism and fatty acid profile in fat and lean rainbow trout lines fed with vegetable oil: effect of carbohydrates.

    Directory of Open Access Journals (Sweden)

    Biju Sam Kamalam

    Full Text Available The present study investigated the effect of dietary carbohydrates on metabolism, with special focus on fatty acid bioconversion and flesh lipid composition in two rainbow trout lines divergently selected for muscle lipid content and fed with vegetable oils. These lines were chosen based on previously demonstrated potential differences in LC-PUFA synthesis and carbohydrate utilization. Applying a factorial study design, juvenile trout from the lean (L and the fat (F line were fed vegetable oil based diets with or without gelatinised starch (17.1% for 12 weeks. Blood, liver, muscle, intestine and adipose tissue were sampled after the last meal. Feed intake and growth was higher in the L line than the F line, irrespective of the diet. Moderate postprandial hyperglycemia, strong induction of hepatic glucokinase and repressed glucose-6-phosphatase transcripts confirmed the metabolic response of both lines to carbohydrate intake. Further at the transcriptional level, dietary carbohydrate in the presence of n-3 LC-PUFA deficient vegetable oils enhanced intestinal chylomicron assembly, disturbed hepatic lipid metabolism and importantly elicited a higher response of key desaturase and elongase enzymes in the liver and intestine that endorsed our hypothesis. PPARγ was identified as the factor mediating this dietary regulation of fatty acid bioconversion enzymes in the liver. However, these molecular changes were not sufficient to modify the fatty acid composition of muscle or liver. Concerning the genotype effect, there was no evidence of substantial genotypic difference in lipid metabolism, LC-PUFA synthesis and flesh fatty acid profile when fed with vegetable oils. The minor reduction in plasma glucose and triglyceride levels in the F line was linked to potentially higher glucose and lipid uptake in the muscle. Overall, these data emphasize the importance of dietary macro-nutrient interface in evolving fish nutrition strategies.

  14. 脂蛋白脂酶与代谢综合征%Lipoprotein lipase and metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    陈灶萍; 刘军; 查兵兵; 盛励; 徐炯

    2011-01-01

    Lipoprotein lipase (LPL) is the key enzyme in metabolism of lipids,which mainly hydrolyzes triglyceride (TG) and plays an important role in the metabolism of chylomicrons (CM)and very low density lipoprotein(VLDL).The defect of LPL or its abnormal activity can induce dyslipidemia and glucose metabolism disorder.Metabolic syndrome (MS) is a clinical syndrome which characterized by the cluster of cardiovascular risk factors,such as abdominal obesity,hypertension and glycolipids metabolism disorders.LPL is now considered to play an important role in the occurrence and development of MS by more and more animal and cilinical evidences,and the research of LPL will help to explore new therapeutic direction for MS.%脂蛋白脂酶是脂质代谢的关键酶,主要水解甘油三酯,在乳糜微粒及极低密度脂蛋白的代谢中发挥重要作用.该酶的缺乏或活力异常,将导致糖、脂代谢紊乱.代谢综合征(MS)是以腹型肥胖,高血压,糖、脂代谢异常等多重心血管危险因素聚集为特征的临床综合征.越来越多的动物及临床证据表明,脂蛋白脂酶参与了 MS的发生、发展,故脂蛋白脂酶的研究将有助于探索MS治疗的新方向.

  15. Traumatic chylothorax: A case report and review

    Directory of Open Access Journals (Sweden)

    Wezi Sendama

    2015-01-01

    Full Text Available Chylothorax is a rare entity characterised by leakage of lymphatic fluid into the pleural cavity from the thoracic duct. We present a case of traumatic chylothorax following a traumatic fracture of the L1 vertebra. An 84-year-old lady presented to the emergency department after being found collapsed at home. She gave a preceding history of one day of diarrhoea. Chest X-ray showed a rightsided effusion. Drainage of the effusion yielded a cloudy, off-white fluid that settled in layers in the drainage container. Pleural fluid examination revealed a lymphocyte-rich transudate with high levels of cholesterol and triglycerides. CT imaging of the chest, abdomen and pelvis revealed an acute left sided pulmonary embolus, and a multisegment burst fracture of the L1 vertebra. The patient was anticoagulated for the pulmonary embolus. Conservative fracture management was advised. Chylous drainage of 1l/24hr was observed. Due to ongoing chylous leak the patient was commenced on a medium-chain fatty acid diet and octreotide. Whilst chylous drainage ceased the patient died from infected pressure sores, malnutrition and acute kidney injury. Spinal trauma can rarely cause disruption of the thoracic duct and chylothorax. Diagnosis of chylothorax hinges on the typically high triglyceride content of chylous fluid and the detection of chylomicrons where the triglyceride concentration is equivocal. Management options for persistently draining chylothorax are varied and range from non-invasive medical measures to radiological and surgical interventions (although the patient in the case we present was an unsuitable candidate for surgery. We discuss pertinent diagnostic testing and put forward possible medical management strategies for chylothorax.

  16. [Possibility of New Circulating Atherosclerosis-Related Lipid Markers Measurement in Medical and Complete Medical Checkups: Small Dense Low-Density Lipoprotein Cholesterol and Lipoprotein Lipase].

    Science.gov (United States)

    Sumino, Hiroyuki; Nakajima, Katsuyuki; Murakami, Masami

    2016-03-01

    Small dense low-density lipoprotein cholesterol (sdLDL-C) concentrations correlate more strongly with cardiovascular disease (CVD) than other LDL-C and large LDL particle concentrations. Lipoprotein lipase (LPL) plays a central role in triglyceride-rich lipoprotein metabolism by catalyzing the hydrolysis of triglycerides in chylomicrons and very low-density lipoprotein particles and is a useful biomarker in diagnosing Type I, Type IV, and Type V hyperlipidemia. Therefore, the measurement of circulating sdLDL-C and LPL concentrations contributes to the assessment of circulating atherosclerosis-related lipid markers. However, the measurement of these lipids has not been fully adopted in medical and complete medical checkups. Recently, novel automated homogenous assay for measuring sdLDL-C and latex particle-enhanced turbidimetric immunoassay (LTIA) for measuring LPL have been developed, respectively. Using these new assays, sdLDL-C values showed excellent agreement with those obtained by isolation of the d = 1.044 - 1.063 g/mL plasma fraction by sequential ultracentrifugation, and LPL values measured with and without heparin injection were highly correlated with the values measured by the LPL-enzyme-linked immunosorbent assay (ELISA). These assays may be superior to the previous assays for the measurement of sdLDL-C and LPL concentrations due their simplicity and reproducibility. The measurements of sdLDL-C and LPL concentrations may be useful as lipid markers in the assessment of the development and progression of atherosclerosis and the detection of pathological conditions and diseases if these markers are measured in medical and complete medical checkups. We have introduced the possibility of the novel measurement of circulating atherosclerosis-related lipid markers such as sdLDL-C and LPL in medical and complete medical checkups. Further studies are needed to clarify whether sdLDL-C and LPL concentrations are related to the development and progression of

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

    Science.gov (United States)

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

    2016-02-01

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

  18. Origin of intestinal lymph cholesterol in rats: Contribution from luminal absorption, mucosal synthesis and filtration from plasma

    Energy Technology Data Exchange (ETDEWEB)

    Vasconcelos, K.S.; Sipahi, A.M.; Oliveira, H.C.; Castilho, L.N.; De Luccia, N.; Quintao, E.C.

    1989-03-01

    Measurement of cholesterol transport from plasma to intestinal lymph based on i.v. labeling with radioactive beta-sitosterol was validated by the simultaneous i.v. administration of 4-/sup 14/C-beta-sitosterol and of 1,2-/sup 3/H-cholesterol to two rats with bile duct, intestinal lymph, duodenum and jugular vein cannulations. In 11 other rats undergoing intestinal lymph duct cannulation, each potential source of lymph cholesterol was determined 2-3 weeks after i.v. pulse administration of 1,2-/sup 3/H-beta-sitosterol and 4-/sup 14/C-cholesterol. For this purpose, lymph fat, after an intragastric infusion of cottonseed oil (1900mg), was used as a marker for total cholesterol mass transported into intestinal lymph. In these two experimental groups of rats, namely, in the absence and in the presence of supplemental dietary cholesterol, filtration of cholesterol from plasma to lymph and absorption of cholesterol derived from bile did not change in the presence of exogenous cholesterol. In other words, absorption of cholesterol based on the amount of cholesterol in intestinal lymph by direct measurement was comparable to the level obtained by the isotopic procedure based upon lowering of the lymph/plasma ratio of 4-/sup 14/C-cholesterol specific activity (d.p.m./mg of cholesterol). Plasma cholesterol appearing in intestinal lymph was transported mainly in lymph lipoproteins at a density below 1.006 (i.e., chylomicrons). Esterification was not necessary for luminal cholesterol absorption under these experimental conditions.

  19. Membrane topology of human monoacylglycerol acyltransferase-2 and identification of regions important for its localization to the endoplasmic reticulum.

    Science.gov (United States)

    McFie, Pamela J; Izzard, Sabrina; Vu, Huyen; Jin, Youzhi; Beauchamp, Erwan; Berthiaume, Luc G; Stone, Scot J

    2016-09-01

    Acyl CoA:2-monoacylglycerol acyltransferase (MGAT)-2 has an important role in dietary fat absorption in the intestine. MGAT2 resides in the endoplasmic reticulum and catalyzes the synthesis of diacylglycerol which is then utilized as a substrate for triacylglycerol synthesis. This triacylglycerol is then incorporated into chylomicrons which are released into the circulation. In this study, we determined the membrane topology of human MGAT2. Protease protection experiments showed that the C-terminus is exposed to the cytosol, while the N-terminus is partially buried in the ER membrane. MGAT2, like murine DGAT2, was found to have two transmembrane domains. We also identified a region of MGAT2 associated with the ER membrane that contains the histidine-proline-histidine-glycine sequence present in all DGAT2 family members that is thought to comprise the active site. Proteolysis experiments demonstrated that digestion of total cellular membranes from cells expressing MGAT2 with trypsin abolished MGAT activity, indicating that domains that are important for catalysis face the cytosol. We also explored the role that the five cysteines residues present in MGAT2 have in catalysis. MGAT activity was sensitive to two thiol modifiers, N-ethylmaleimide and 5,5'-dithiobis-(2-nitrobenzoic acid). Furthermore, mutation of four cysteines resulted in a reduction in MGAT activity. However, when the C-terminal cysteine (C334) was mutated, MGAT activity was actually higher than that of wild-type FL-MGAT2. Lastly, we determined that both transmembrane domains of MGAT2 are important for its ER localization, and that MGAT2 is present in mitochondrial-associated membranes.

  20. 代谢综合征与脂蛋白脂酶的关系研究进展%Research on Relationship between Lipoprotein Lipase and Metabolic Syndrone

    Institute of Scientific and Technical Information of China (English)

    刘婧

    2011-01-01

    Metaholic syndrome is a complex metabolic disorder syndrome , including obesity, high blood sugar , blood pressure , blood lipid disorders. Lipoprotein lipase ( LPL ) is one of the key enzymes in lipid metabolism,the main catalyze of chylomicrons and verv low-density lipoprotein hydrolysis into triglycerides. Research showed that LPL deficiency and gene mutations cause lipodystrophy. Dfferent gene polymorphisms have a different impact on lipid metabolism.Hind Ⅲ and Pvu Ⅱ mutations cause lipid metabolism,and the S447X polymorphism may have a beneficial lipid changes. LPL is associated with the incidence of metabolic syndrome including obesity , insulin resistance , type 2 diabetes etc.%代谢综合征是一组复杂的代谢紊乱症候群,包括肥胖、高血糖、高血压、血脂紊乱等.脂蛋白脂酶(LPL)是脂代谢关键酶之一,主要催化乳糜微粒和极低密度脂蛋白中的三酰甘油水解.研究显示LPL缺乏和基因突变会导致脂肪代谢障碍,不同的基因多态性对脂代谢有着不同的影响,HindⅢ和PvuⅡ突变会导致脂代谢紊乱,而S447X多态性可能产生有益的血脂改变.LPL与肥胖、胰岛素抵抗和2型糖尿病等代谢综合征的发病有着密切的关系.

  1. Membrane topology of human monoacylglycerol acyltransferase-2 and identification of regions important for its localization to the endoplasmic reticulum.

    Science.gov (United States)

    McFie, Pamela J; Izzard, Sabrina; Vu, Huyen; Jin, Youzhi; Beauchamp, Erwan; Berthiaume, Luc G; Stone, Scot J

    2016-09-01

    Acyl CoA:2-monoacylglycerol acyltransferase (MGAT)-2 has an important role in dietary fat absorption in the intestine. MGAT2 resides in the endoplasmic reticulum and catalyzes the synthesis of diacylglycerol which is then utilized as a substrate for triacylglycerol synthesis. This triacylglycerol is then incorporated into chylomicrons which are released into the circulation. In this study, we determined the membrane topology of human MGAT2. Protease protection experiments showed that the C-terminus is exposed to the cytosol, while the N-terminus is partially buried in the ER membrane. MGAT2, like murine DGAT2, was found to have two transmembrane domains. We also identified a region of MGAT2 associated with the ER membrane that contains the histidine-proline-histidine-glycine sequence present in all DGAT2 family members that is thought to comprise the active site. Proteolysis experiments demonstrated that digestion of total cellular membranes from cells expressing MGAT2 with trypsin abolished MGAT activity, indicating that domains that are important for catalysis face the cytosol. We also explored the role that the five cysteines residues present in MGAT2 have in catalysis. MGAT activity was sensitive to two thiol modifiers, N-ethylmaleimide and 5,5'-dithiobis-(2-nitrobenzoic acid). Furthermore, mutation of four cysteines resulted in a reduction in MGAT activity. However, when the C-terminal cysteine (C334) was mutated, MGAT activity was actually higher than that of wild-type FL-MGAT2. Lastly, we determined that both transmembrane domains of MGAT2 are important for its ER localization, and that MGAT2 is present in mitochondrial-associated membranes. PMID:27373844

  2. Techniques for measuring vitamin A activity from β-carotene.

    Science.gov (United States)

    Tang, Guangwen

    2012-11-01

    Dietary β-carotene is the most important precursor of vitamin A. However, the determination of the efficiency of in vivo conversion of β-carotene to vitamin A requires sensitive and safe techniques. It presents the following challenges: 1) circulating β-carotene concentration cannot be altered by eating a meal containing ≤6 mg β-carotene; 2) because retinol concentrations are homeostatically controlled, the conversion of β-carotene into vitamin A cannot be estimated accurately in well-nourished humans by assessing changes in serum retinol after supplementation with β-carotene. In the past half-century, techniques using radioisotopes of β-carotene and vitamin A, depletion-repletion with vitamin A and β-carotene supplements, measurement of postprandial chylomicron fractions after consumption of a β-carotene dose, and finally, stable isotopes as tracers to follow the absorption and conversion of β-carotene in humans have been developed. The reported values for β-carotene to vitamin A conversion showed a wide variation from 2 μg β-carotene to 1 μg retinol (for synthetic pure β-carotene in oil) and 28 μg β-carotene to 1 μg retinol (for β-carotene from vegetables). In recent years, a stable isotope reference method (IRM) was developed that used labeled synthetic β-carotene. The IRM method provided evidence that the conversion of β-carotene to vitamin A is likely dose dependent. With the development of intrinsically labeled plant foods harvested from a hydroponic system with heavy water, vitamin A activity of stable isotope-labeled biosynthetic β-carotene from various foods consumed by humans was studied. The efficacy of plant foods rich in β-carotene, such as natural (spinach, carrots, spirulina), hybrid (high-β-carotene yellow maize), and bioengineered (Golden Rice) foods, to provide vitamin A has shown promising results. The results from these studies will be of practical importance in recommendations for the use of pure β-carotene and foods

  3. Increased palmitoyl-myristoyl-phosphatidylcholine in neonatal rat surfactant is lung specific and correlates with oral myristic acid supply.

    Science.gov (United States)

    Bernhard, Wolfgang; Raith, Marco; Pynn, Christopher J; Gille, Christian; Stichtenoth, Guido; Stoll, Dieter; Schleicher, Erwin; Poets, Christian F

    2011-08-01

    Surfactant predominantly comprises phosphatidylcholine (PC) species, together with phosphatidylglycerols, phosphatidylinositols, neutral lipids, and surfactant proteins-A to -D. Together, dipalmitoyl-PC (PC16:0/16:0), palmitoyl-myristoyl-PC (PC16:0/14:0), and palmitoyl-palmitoleoyl-PC (PC16:0/16:1) make up 75-80% of mammalian surfactant PC, the proportions of which vary during development and in chronic lung diseases. PC16:0/14:0, which exerts specific effects on macrophage differentiation in vitro, increases in surfactant during alveolarization (at the expense of PC16:0/16:0), a prenatal event in humans but postnatal in rats. The mechanisms responsible and the significance of this reversible increase are, however, not understood. We hypothesized that, in rats, myristic acid (C14:0) enriched milk is key to lung-specific PC16:0/14:0 increases in surfactant. We found that surfactant PC16:0/14:0 in suckling rats correlates with C14:0 concentration in plasma chylomicrons and lung tissue triglycerides, and that PC16:0/14:0 fractions reflect exogenous C14:0 supply. Significantly, C14:0 was increased neither in plasma PC, nor in liver triglycerides, free fatty acids, or PC. Lauric acid was also abundant in triglycerides, but was not incorporated into surfactant PC. Comparing a C14:0-rich milk diet with a C14:0-poor carbohydrate diet revealed increased C14:0 and decreased C16:0 in plasma and lung triglycerides, respectively. PC16:0/14:0 enrichment at the expense of PC16:0/16:0 did not impair surfactant surface tension function. However, the PC profile of the alveolar macrophages from the milk-fed animals changed from PC16:0/16:0 rich to PC16:0/14:0 rich. This was accompanied by reduced reactive oxygen species production. We propose that nutritional supply with C14:0 and its lung-specific enrichment may contribute to decreased reactive oxygen species production during alveolarization. PMID:21636561

  4. Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor.

    Science.gov (United States)

    Tenenbaum, Alexander; Klempfner, Robert; Fisman, Enrique Z

    2014-01-01

    The existence of an independent association between elevated triglyceride (TG) levels, cardiovascular (CV) risk and mortality has been largely controversial. The main difficulty in isolating the effect of hypertriglyceridemia on CV risk is the fact that elevated triglyceride levels are commonly associated with concomitant changes in high density lipoprotein (HDL), low density lipoprotein (LDL) and other lipoproteins. As a result of this problem and in disregard of the real biological role of TG, its significance as a plausible therapeutic target was unfoundedly underestimated for many years. However, taking epidemiological data together, both moderate and severe hypertriglyceridaemia are associated with a substantially increased long term total mortality and CV risk. Plasma TG levels partially reflect the concentration of the triglyceride-carrying lipoproteins (TRL): very low density lipoprotein (VLDL), chylomicrons and their remnants. Furthermore, hypertriglyceridemia commonly leads to reduction in HDL and increase in atherogenic small dense LDL levels. TG may also stimulate atherogenesis by mechanisms, such excessive free fatty acids (FFA) release, production of proinflammatory cytokines, fibrinogen, coagulation factors and impairment of fibrinolysis. Genetic studies strongly support hypertriglyceridemia and high concentrations of TRL as causal risk factors for CV disease. The most common forms of hypertriglyceridemia are related to overweight and sedentary life style, which in turn lead to insulin resistance, metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Intensive lifestyle therapy is the main initial treatment of hypertriglyceridemia. Statins are a cornerstone of the modern lipids-modifying therapy. If the primary goal is to lower TG levels, fibrates (bezafibrate and fenofibrate for monotherapy, and in combination with statin; gemfibrozil only for monotherapy) could be the preferable drugs. Also ezetimibe has mild positive effects in lowering TG

  5. 脂肪酸碳链长度对甘三酯体外模拟消化的影响%Effect of carbon chain length of fatty acids on simulated digestion in vitro of triglyceride

    Institute of Scientific and Technical Information of China (English)

    徐俊杰; 黄健花; 宋志华; 王兴国

    2014-01-01

    The digestions in vitro of triglycerides with different carbon chain length of fatty acids in human body were simulated by pH-stat method. From the perspective of the particle size of emulsion, the effect of different carbon chain length of fatty acids on the rate of digestion in vitro of triglyceride was studied. The results showed that after emulsification, the average particle size of tricaprylin (C8) was minimum;with the increase of carbon number differences between the other triglycerides and C8 , the particle size increased . Tricaprylin ( C8 ) had the highest rate of digestion in the process of the overall digestion;with the increase of carbon number differences between the other triglycerides and C8 , the rate of digestion re-duced. A negative correlation between particle size of chylomicron and digestion rate of triglyceride was found. The rate of digestion of tricaprylin ( C8 ) was the highest, followed by laurin ( C12 ) , triacetin (C2) and tristearin(C18).%用pH-stat法模拟不同脂肪酸链长甘三酯的人体体外消化过程,从乳化粒径的角度研究脂肪酸碳链长度对甘三酯体外消化速率的影响。结果表明:三辛酸甘油酯( C8)乳化后,平均粒径最小,其他与之碳数相差越多则粒径越大;整体消化过程中三辛酸甘油酯( C8)的消化速率最高,其他与之碳数相差越多则消化速率越小。乳糜微粒的粒径大小与甘三酯的消化速率呈负相关的关系。消化速率的大小顺序为三辛酸甘油酯(C8)>三月桂酸甘油酯(C12)>三乙酸甘油酯(C2)>三硬脂酸甘油酯( C18)。

  6. Polarized secretion of newly synthesized lipoproteins by the Caco-2 human intestinal cell line.

    Science.gov (United States)

    Traber, M G; Kayden, H J; Rindler, M J

    1987-11-01

    Lipoprotein secretion by Caco-2 cells, a human intestinal cell line, was studied in cells grown on inserts containing a Millipore filter (0.45 micron), separating secretory products from the apical and basolateral membranes into separate chambers. Under these conditions, as observed by electron microscopy, the cells formed a monolayer of columnar epithelial cells with microvilli on the apical surface and tight junctions between cells. The electrical resistances of the cell monolayers were 250-500 ohms/cm2. Both 14C-labeled lipids and 35S-labeled proteins were used to assess lipoprotein secretion. After a 24-hr incubation with [14C]oleic acid, 60-80% of the secreted triglyceride (TG) was in the basolateral chamber; 40% of the TG was present in the d less than 1.006 g/ml (chylomicron + VLDL) fraction and 50% in the 1.006 less than d less than 1.063 g/ml (LDL) fraction. After a 4-hr incubation with [35S]methionine, apolipoproteins were found to be major secretory products with 75-100% secreted to the basolateral chamber. Apolipoproteins B-100, B-48, E, A-I, A-IV, and C-III were identified by immunoprecipitation. The d less than 1.006 g/ml fraction was found to contain all of the major apolipoproteins, while the LDL fraction contained primarily apoB-100 and apoE; the HDL (1.063 less than d less than 1.21 g/ml) fraction principally contained apoA-I and apoA-IV. Mn-heparin precipitated all of the [35S]methionine-labeled apoB-100 and B-48 and a majority of the other apolipoproteins, and 80% of the [14C]oleic acid-labeled triglyceride, but only 15% of the phospholipid, demonstrating that Caco-2 cells secrete triglyceride-rich lipoproteins containing apoB. Secretion of lipoproteins was dependent on the lipid content of the medium; prior incubation with lipoprotein-depleted serum specifically reduced the secretion of lipoproteins, while addition of both LDL and oleic acid to the medium maintained the level of apoB-100, B-48, and A-IV secretion to that observed in the control

  7. 运动和饮食对脂蛋白酯酶的影响及机制研究进展%Research Advances in the Effects of Excise and Dite onL PL and Its Mechanism

    Institute of Scientific and Technical Information of China (English)

    刘桂; 王晓慧

    2014-01-01

    脂蛋白酯酶( lipoprotein lipase , LPL)主要由脂肪细胞、心肌细胞、骨骼肌细胞等实质细胞合成和分泌,可以水解乳糜微粒和极低密度脂蛋白中的甘油三酯(triglyceride,TG),对清除体内过多的TG至关重要。激素、营养、运动、过氧化物增殖因子活化受体γ( peroxisome proliferative activated receptors γ,PPARγ)、载脂蛋白、糖基化磷脂酰肌醇锱定高密度脂蛋白结合蛋白1( glycosylphosphati-dylinositol-anchored high-density lipoprotein-binding protein 1, GPIHBP1)、血管生成素样蛋白3和4(angiopoietin-like protein 3 and 4,ANGPTL3和ANGPTL4)等都可调控LPL的表达和活性。本文在介绍LPL结构、功能和调控的基础上,综述运动和饮食干预对LPL表达和活性的影响及其可能机制。%Lipoprotein lipase ( LPL) plays a major role in the metabolism and transport of lipids by hy-drolyzing core triglycerides ( TG) in chylomicrons and very low density lipoprotein .LPL is mainly synthe-sized and secreted by fat cells , myocardial cells and skeletal muscle cells .The expression and activity of LPL are regulated by multiple factors , such as hormones ,nutrition , exercise , PPARγ, apolipoproteins , glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 ( GPIHBP1 ) and angio-poietin-like proteins ( ANGPTL) .After introducing advance in LPL structure and regulation , we review the effects of exercise and diet intervention on the expression and activity of LPL and its possible mecha -nism .

  8. Pancreatitis aguda secundaria a hipertrigliceridemia: presentación de dos casos clínicos Acute pancreatitis secondary to hypertriglyceridemia: A report of two cases

    Directory of Open Access Journals (Sweden)

    S. J. Jiménez Forero

    2008-06-01

    Full Text Available La pancreatitis aguda es un proceso inflamatorio reversible. La hipertrigliceridemia como etiología de la pancreatitis aguda varía entre un 1,3 y un 11%, de acuerdo a la literatura, cuando los niveles de triglicéridos alcanzan valores por encima de 1.000 mg/dl; sin embargo, la hipertrigliceridemia se observa en un 12 a un 39% de las pancreatitis agudas como factor asociado. El objetivo del tratamiento médico es aumentar la actividad de la lipoproteinlipasa y aumentar la degradación de los quilomicrones; disminuyendo así los valores plasmáticos de triglicéridos a niveles menores de 500 mg/dl, incluso a menos de 200 mg/dl si es posible con diferentes estrategias, entre ellas la insulina. En el presente artículo, presentamos dos casos clínicos de pancreatitis severas inducidas por hipertrigliceridemia, manejadas con terapia de infusión de insulina con adecuada respuesta clínica y paraclínica con disminución significativa de los niveles de triglicéridos, 48 horas postratamiento.Acute pancreatitis is a reversible inflammatory process. Hypertriglyceridemia as a cause of acute pancreatitis reaches frequencies of 1.3-11% according to the literature when triglyceride levels reach values over 1,000 mg/dl; nevertheless hypertriglyceridemia is observed in 12-39% of acute pancreatitis cases as an associated factor. The objective of medical treatment is to increase lipoprotein-lipase activity, and to increase chylomicron breakdown thus diminishing serum triglycerides to levels smaller than 500 or even 200 mg/dl (when possible using a variety of strategies including insulin administration. In the present article, we report two cases of severe pancreatitis induced by hypertriglyceridemia that were managed with insulin infusion; both responded adequately, as measured by a significant reduction of triglyceride levels at 48 hours post-treatment.

  9. Systematic development of solid self-nanoemulsifying oily formulations (S-SNEOFs) for enhancing the oral bioavailability and intestinal lymphatic uptake of lopinavir.

    Science.gov (United States)

    Garg, Babita; Katare, O P; Beg, Sarwar; Lohan, Shikha; Singh, Bhupinder

    2016-05-01

    The present studies entail the development of the systematically optimized solid self-nanoemulsifying oily formulations (S-SNEOFs) for enhancing the systemic bioavailability of lopinavir and targeting the same to the sanctuary site, i.e., lymphatic system for complete HIV inhibition. The patient-centric quality target product profile (QTPP) was defined and critical quality attributes (CQAs) earmarked. Risk assessment studies, carried out through failure mode and effect critically analysis (FMECA), helped in identifying the plausible risks or failure modes affecting the quality attributes of the drug product. As per the preliminary studies, viz solubility and phase titration studies, and factor screening studies, Maisine (i.e., lipid), Tween 80 (emulgent), Transcutol HP (i.e., cosolvent) were selected as the critical material attributes (CMAs) of the liquid SNEOFs (L-SNEOFs). D-optimal mixture design was employed for the optimization of aforesaid CMAs and evaluated for in vitro dissolution, globule size, ex vivo permeation studies as the critical quality attributes (CQAs). Optimal composition of CMAs, was embarked through numerical optimization and desirability function, exhibited excellent permeation and drug release characteristics besides possessing globule size in nano range, i.e., 53.16 nm. Further to increase the stability and drug loading, the OPT-L-SNEOFs were then adsorbed onto the porous carrier, i.e., Aeroperl, to prepare the OPT-SNEOF tablets which were finally compressed into the tablet employing MCC as the filler. The performance evaluation through in situ SPIP studies ascribed the significant enhancement in absorptivity parameters of both the SNEOFs vis-à-vis the pure drug. Also, chylomicron flow block SPIP studies revealed lymphatic uptake of lopinavir from the SNEOFs. Overall, in vivo pharmacokinetic studies in rats revealed significant improvement in the rate and extent of oral bioavailability of the SNEOFs compared to the pure drug. These studies

  10. 民猪脂蛋白脂酶基因在冷诱导后表达变化的研究%Study on Expression of Lipoprotein Lipase Gene in Min Pig during Cold Induced

    Institute of Scientific and Technical Information of China (English)

    张冬杰; 刘娣; 汪亮; 别墅; 孙洪涛; 杨国伟; 张海波

    2011-01-01

    脂蛋白脂酶(lipoprotein lipase,LPL)是动物分解代谢的限速酶,是影响脂肪代谢通路中的一个重要基因.本研究将LPL基因作为影响民猪抗寒特性的候选基因,对其在心脏、肝脏、胃、脾脏、肾脏、肺脏、大肠、小肠、子宫、卵巢、背肌、腿肌、脂肪共计13个组织内的表达情况和低温冷诱导后在民猪肌肉组织内的表达变化情况进行了分析.结果表明,LPL基因在所检测的13个组织中均有表达,但表达量存在差异,心脏、背肌、腿肌、脂肪组织中的表达量较高,子宫和卵巢组织的表达量较低;LPL基因在民猪被冷诱导后表达水平无显著变化.%Lipoprotein lipase (LPL) plays a central role in normal lipid metabolism as the key enzyme involved in the hydrolysis of triglycerides present in chylomicrons and very low density lipoproteins.In this research, LPL was seen as a candidate gene for cold resistance, analysis the expression of LPL in heart, liver, stomach, spleen, kidney, lung, large intestine,small intestin, uterus, ovary, muscles of back, leg muscle, fat tissues and during cold induced.The results showed that LPL was an abroad expression gene, but the level was different.It was higher expressed in heart, muscles of back, leg muscle and fat, but lower expressed in uterus, ovary.The expression level of LPL was not different after cold induced.

  11. New physiological effects of the incretin hormones GLP-1 and GIP.

    Science.gov (United States)

    Asmar, Meena

    2011-02-01

    mixed meal or infusion of Intralipid and insulin. Under these experimental conditions, we were not able to demonstrate any effects of GIP on the removal rate of either chylomicron-TAG or Intralipid-derived TAG concentrations. However, we found evidence for enhanced FFA re-esterification under conditions with combined high GIP and insulin concentrations. Based on findings from this study, the third study was designed to evaluate the direct effects of GIP on regional adipose tissue and splanchnic metabolism. Regional net substrate fluxes across the subcutaneous, abdominal adipose tissue and the splanchnic tissues were examined by direct measurements of arterio-venous concentration differences of various metabolites in combination with regional blood flow measurements (Fick's principle). GIP in combination with hyperinsulinemia and hyperglycemia increased blood flow, glucose uptake, and FFA re-esterification, resulting in increased TAG deposition in abdominal, subcutaneous adipose tissue. Finally, it was not possible to demonstrate any effect of GIP per se on net lipid metabolism in the splanchnic area either during fasting conditions or in combination with hyperinsulinemia and hyperglycemia. PMID:21299928

  12. The Impact of Polymeric Nanoencapsulation on the Bioavailability of Lutein

    Science.gov (United States)

    Kamil, Alison

    lutein loaded in a water soluble NP. The findings of the rat study indicated that, compared to free lutein, PLGA-NP improved the pharmacokinetics (Cmax and AUC) of lutein in the plasma of rats and in general promoted lutein accumulation in mesenteric adipose tissue and spleen but not liver. Yet, compared to micellized lutein, although NP improved the maximal concentration of lutein in the plasma of rats as well as in selected tissues it decreased the cell uptake and secretion of lutein in Caco-2 cells. The negative effect of the NP on cell uptake and secretion was partially remedied by the addition of micelle components. These findings suggest that the delivery of lutein within polymeric NP appears to be a promising approach to improving the bioavailability of lutein in rats. The inconsistent results between the rat and cell culture models warrant further investigations to determine which approach better predicts responses in humans. Further, bile salts and phospholipids, which are necessary to stimulate synthesis and secretion of chylomicrons, appear to facilitate more effective intestinal secretion of PLGA-NP lutein. In summary, with Caco-2 cells cultured in the PS system reliably grown to display phenotypes and functions of enterocytes in the small intestine, this in vitro platform enables the generation of information that is closer to the physiology of the absorptive enterocytes. However, although the CONV system has the physiological attributes of colonic tissue, it appeared to display a greater efficacy of lutein uptake by Caco-2 cells which can provide a rapid preliminary tool for methodology development for nutrient absorption studies. Further, the delivery of lutein in polymeric NP appears to be a promising approach to improve the bioavailability of lutein in vivo but raises issues with regard to the comparability and the predictive value of in vitro models to in vivo responses.

  13. 胸导管结扎对食管癌患者术后脂类代谢的影响%Influence of thoracic duct ligation on lipid metabolism after esophagectomy

    Institute of Scientific and Technical Information of China (English)

    张永恒; 杨波; 袁真真; 陈权

    2009-01-01

    Objective To explore influence of thoracic duct ligation on lipid metabolism after esophagectomy. Methods Seventy-four patients with esophageal cancer received esophagectomy were divided into two groups by their thoracic duct ligation, 39 in ligation group and 35 in non-ligation group. All the patients were fed with nutrients through nasal-duodenal tube placed during operation from the 1 st day to the 8th day after surgery, and started taking liquid diet on the 6th day. Blood specimens were collected from the patients on the 1st day after admission, the 9th day, one month and three months after surgery,respectively for biochemical analysis,including determinations of total cholesterol(TC),triglyeeride(TG),high-density lipoprotein-cholesterol ( HDL-C) and low-density lipoprotein-cholesterol ( LDL-C) . Databetween the two groups were compared with statistical analysis. Results No significant difference in plasma levels of TC, TG and HDI.-C was found between the two groups at varied time points. Plasma level of LDL-C in the ligation group significantly decreased on the 9th day after surgery, as compared with that in the nonligation group ( P < 0. 05), and went down to the lowest level one month after surgery. Conclusions Chylomicron was blocked to enter blood stream and production of LDL-C decreased by thoracic duct ligation,which affect lipid absorption and metabolism leading to poor early nutrition in patients with esophagealsurgery due to slower establishment of collateral circulation.%目的 探讨胸导管结扎对食管癌患者术后脂类代谢的影响.方法 将74例食管癌手术患者分成胸导管结扎组(39例)和胸导管不结扎组(35例).两组均在术中置入鼻十二指肠管,从术后第1天开始肠内营养直到术后第8天.所有病例均从术后第6天经口进食流质饮食.入院第2天、手术后第9天、术后1个月、术后3个月采晨空腹静脉血,检测血浆胆固醇、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL

  14. Congenital idiopathic chylopericardium-a case report and review Of the literature%先天性乳糜性心包积液1例报告并文献复习

    Institute of Scientific and Technical Information of China (English)

    李敏; 孙正芸; 于永慧; 杨波; 林霞; 汪翼

    2011-01-01

    demonstration of chylomicrons and high levels of triglycerides at puncture pricardiocentesis.After pericardial drainage by pricardiocentesis for three times failed, a catheter was left in the pericardium for drainage.Two days later the patient was cured. At 1 week and 1 month after operation he was doing well and echocardiography did not reveal any signs of recurrence. Conclusion Primary idiopathic chylopericardium is a rare clinical entity with obscure etiology. In most cases chylopericardium is only confirmed by pericardiocentesis. Pericardiocentesis and pericardial drainage are effective conservative treatment options. Surgery should be considered for the patients with recurring chylopericardium.

  15. LPL基因突变与高甘油三酯血症相关性研究进展%The research progress of the association between the mutations in the LPL gene and hypertriglyceridemia

    Institute of Scientific and Technical Information of China (English)

    李研研; 王洪云; 马龙乐; 韩发彬

    2014-01-01

    Hypertriglyceridemia (HTG) is the one of risk factors for the development of atherosclerosis and coronary artery disease (CAD). Recent studies have shown that genetic defects of genes are playing important roles in the pathogenesis of the hypertriglyceridemia, atherosclerosis and CAD in addition to the diets and environmental factors. Lipoprotein lipase (LPL) is the rate-limiting enzyme to metabolize the triglyceride (TG) in very low density lipoprotein (VLDL) and Chylomicrons (CM) to generate the free fatty acids for the human body. A large number of different mutations in the LPL gene have been found to be associated with the hypertriglyceridemia, diabetes and CAD. The common mutations of the LPL gene identified in patients with hypertriglyceridemia are Asp9Asn, Asn291Ser, Trp86Arg, Gly188Glu, Pro207Leu, Asp250Asn,Asn318Ser and Ser474X. Experimental studies have shown that the genetic defects of the LPL gene affected its mass and the enzyme activity to hydrolyze the TG and increased the risk to develop the hypertriglyceridemia, diabetes, pancreatisis and CAD. This review summarized the research progress in the structure, function, enzyme activity and the association between the mutations in the LPL gene and the hypertriglyceridemia, diabetes and CAD.%高甘油三酯血症是导致动脉硬化和冠心病的主要危险因素之一。近年来研究发现除了环境饮食因素外,遗传因素在高甘油三酯血症、动脉硬化和冠心病的发生过程中起重要作用。脂蛋白脂酶(LPL)作为脂质代谢的关键酶,主要催化乳糜微粒和极低密度脂蛋白中的甘油三酯水解,释放游离脂肪酸供机体利用。大量研究表明高甘油三酯血症、糖尿病和冠心病患者都存在LPL基因突变。在高甘油三酯血症患者中 LPL 常见的基因突变主要是 Asp9Asn、Asn291Ser、Trp86Arg、Gly188Glu、Pro207Leu、Asp250Asn、Asn318Ser和Ser474X等。实验研究表明LPL发生基因突变后影响其蛋白的

  16. 脂蛋白脂酶缺失症基因治疗载体的构建及功能验证%Construction and Verification of Gene Therapy Vector for Lipoprotein Lipase Deficiency Disease

    Institute of Scientific and Technical Information of China (English)

    王恺龙; 郑李彬; 张帆; 沈良才; Libby Andrew; 李旭丽; 张瑾

    2013-01-01

    脂蛋白脂酶(lipoprotein lipase,LPL)是甘油三酯分解的限速酶,LPL基因缺失会引起高血脂症,虽然发病率低,但到目前为止,尚无有效治疗手段.该文构建了用于纠正LPL缺失基因型的逆转录病毒载体MSCV-hLPL,结果表明,MSCV-hLPL可以高效侵染体外培养的细胞系C2C12、HEK293和3T3-L1,并且都可以产生具有活性的脂蛋白脂酶.利用MSCV-hLPL侵染后的C2C12、HEK293和3T3-L1,分别注射到裸鼠皮下组织,发现C2C12和3T3-L1可以分泌脂蛋白脂酶到临近的肌肉组织中,显著提高LPL活性.以上工作证明,基因治疗载体可以纠正脂蛋白脂酶缺失的基因型,而脂肪细胞和肌肉细胞移植入裸鼠体内后,均可以作为生物反应器产生具有活性的LPL.这是该领域中的一次开拓性尝试,为脂蛋白脂酶缺失症治疗方法的开发打下了坚实的基础.%Lipoprotein lipase (LPL) is the rate limiting enzyme for triglycerides hydrolysis,which catalyses the hydrolysis of the triacylglycerol component of chylomicrons and very low density lipoproteins,thereby providing fatty acids and monoacylglycerol for tissue utilization.LPL gene mutation or deletion may affect the activity of LPL,and result in lipid metabolism disorder.Although the LPL deficiency disease is rare,no cure method is developed till now.In this study,the gene therapy construct MSCV-hLPL was made,which could infect muscle cell line (C2C12),kidney cell line (HEK293T) and pre-adipocyte cell line (3T3-L1) with over 80% efficiency.Nevertheless,active LPL could be detected at the surface of all these three kinds of cells.Then,three types of cells were injected into nude mice,LPL activity increased significantly in the muscle tissues under the injection sites of the 3T3-L1 line.Our results show that MSCV-hLPL could correct the LPL-/-genotype and the adipose tissue may be the best tissue for transplantation in the future.This is a ground-breaking test in LPL deficiency treatment field

  17. Utilidad y controversias del consumo de ácidos grasos de cadena media sobre el metabolismo lipoproteico y obesidad Usefulness and controversial issues of middle-chain fatty acids consumption on lipid-protein metabolism and obesity

    Directory of Open Access Journals (Sweden)

    S. G. Sáyago-Ayerdi

    2008-06-01

    because of their good absorption, and in premature-feeding milk-based formulas in order to improve calcium absorption. MCFA have become particularly important because of their possible role in treating and preventing obesity. Since they are more water soluble, they are taken-up by chylomicrons, and it is believed that they do not directly participate in lipogenesis. They are able to increase the thermogenic effect of foods, and its metabolism increases the production of ketonic agents with the subsequent anorexigenic effect. However, high doses of MCFA are required to obtain significant effects on weight reduction. The effects on lipid-protein metabolism are controversial. So, although they seem to reduce the post-prandial triglyceridemic response, the results their effects are not uniform regarding triglyceridemia and cholesterolemia. In spite of this, more and more products are being designed incorporating MCFA to treat obesity and overweight, having been considered as "GRAS" (Generally Recommended as Safe" components by the ADA. Further long-term studies are needed to warrant the usefulness of consumption of these compounds, particularly in the treatment and prevention of obesity.

  18. Metabolismo de los lípidos en los rumiantes - Lipid metabolism in ruminants

    Directory of Open Access Journals (Sweden)

    Andrés L. Martínez Marín

    2010-08-01

    dieta consumida por los rumiantes a los lípidos de sus productos ofrece la posibilidad de modificar el contenido de los ácidos grasos de la carne y, sobre todo, la leche en un sentido favorable para la salud de los consumidores.SummaryIn this paper, key aspects of lipid metabolism and characteristics ofruminants’ meat and milk fat were reviewed. Fatty acids available forabsorption in the small intestine of ruminants are from dietary andmicrobial origin and, because of microbial digestion in the rumen, aremainly nonsterified saturated fatty acids. Short chain fatty acids (less than 12 carbon atoms are absorbed into the bloodstream, bound to serum albumin and transported to the liver through the portal vein. Medium and long chain fatty acids are esterified upon their absorption and transported via lymph to the bloodstream as chylomicrons and very low density lipoproteins, to be used by the different tissues. In ruminants, the liver has a minor role in lipid metabolism compared with monogastrics, but it is especially relevant in situations of intense negative energy balance when the hepatic metabolism of lipids may be altered causing severe pathologies. Fat depots other than intramuscular depots are composed mainly of triglycerides and are the major energy reserve of the body.However, the proportion of phospholipids and triglycerides in theintramuscular fat depends on the degree of fatness. The cell membranephospholipids are the preferred site of deposition of availablepolyunsaturated fatty acids. Milk fat composition depends on the origin of the fatty acids: long chain fatty acids from dietary origin or mobilized from adipose tissue, or medium and short chain fatty acids synthesized in situ from acetate and betahydroxybutyrate. Most fatty acids incorporated into milk triglycerides are taken from the blood. The major contribution of dietary fatty acids to meat and, specially, milk fatty acids offers the possibility of changing the fatty acid profile of ruminant

  19. RECHERCHES Distribution anormale des apolipoprotéines CIII et diminution de la capacité d’efflux de cholestérol du plasma de sujets normolipidémiques présentant une maladie coronarienne précoce

    Directory of Open Access Journals (Sweden)

    Delplanque Bernadette

    2002-07-01

    Full Text Available Il est maintenant bien établi que les triglycérides plasmatiques représentent un facteur de risque indépendant d’athérosclérose et des maladies cardiovasculaires qui en découlent [1]. L’hypertriglycéridémie est connue pour être associée à une surexpression des apolipoprotéines CIII (apoCIII. Les quantités et la distribution de ces apoCIII dans le plasma sont essentielles dans le métabolisme des triglycérides, et il existe de nombreuses études épidémiologiques mettant en évidence leur association avec le développement et la progression des lésions d’athérosclérose dans les maladies cardio-vasculaires (MCV. Les apoCIII et plus particulièrement les apoCIII liées aux particules riches en triglycérides sont considérées comme de nouveaux marqueurs/facteurs de risque des MCV associés aux triglycérides comme cela a été étudié et rapporté par P. Alaupovic dans l’article précédent [2]. En outre, un certain nombre de sujets jeunes ayant fait un accident ischémique grave, présentent un bilan lipidique considéré comme normal et qui ne permet pas de les identifier. Mais on sait aussi que des sujets coronariens, normolipidémiques à jeun, peuvent présenter un retard d’épuration postprandiale des triglycérides, détectable seulement après un repas test riche en graisses [3-5]. Les retards d’épuration postprandiaux et leur toxicité sont imputés aux chylomicrons remnants qui persistent trop longtemps dans la circulation et sont considérés comme très athérogènes [6]. Dans un travail préliminaire [7], nous avions comparé un petit groupe de sujets normolipidémiques à jeun (n = 10 mais présentant une maladie coronarienne précoce (groupe CAD et montré l’existence d’anomalies du métabolisme lipidique postprandial par comparaison à un groupe de sujets contrôles. Quatre à six heures après un repas gras (1 000 kcal et 60% de lipides, la réponse de la triglycéridémie