The Experts below are selected from a list of 10458 Experts worldwide ranked by ideXlab platform
Khosrow Adeli - One of the best experts on this subject based on the ideXlab platform.
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the glucagon like peptide 1 receptor is essential for postprandial Lipoprotein Synthesis and secretion in hamsters and mice
Diabetologia, 2010Co-Authors: Joanne Hsieh, Christine Longuet, Christopher Baker, B Qin, Lisa Federico, Daniel J Drucker, Khosrow AdeliAbstract:Aims/hypothesis Glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors attenuate postprandial lipaemia through mechanisms that remain unclear. As dyslipidaemia is a contributing risk factor for cardiovascular disease in type 2 diabetes, we examined the mechanisms linking pharmacological and physiological regulation of GLP-1 action to control of postprandial lipid metabolism.
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intracellular mechanisms mediating the inhibition of apob containing Lipoprotein Synthesis and secretion in hepg2 cells by avasimibe ci 1011 a novel acyl coenzyme a cholesterol acyltransferase acat inhibitor
Biochemical Pharmacology, 2002Co-Authors: Changiz Taghibiglou, Stephen C. Van Iderstine, Agnes Kulinski, Debbie Rudy, Khosrow AdeliAbstract:We have studied the cellular and molecular mechanisms involved in the suppression of apoB secretion from HepG2 cells following incubation with avasimibe (CI-1011), a novel inhibitor of acyl-coenzyme A: cholesterol acyltransferase (ACAT). Cellular lipid analysis revealed that avasimibe significantly decreased the Synthesis of cholesterol and cholesteryl ester, and, at higher doses, of triglyceride. Time-course trypsin protection assays revealed that avasimibe induced the accumulation of translocationally arrested apoB intracellularly. Pulse-chase studies showed that the treatment with avasimibe induced a >75% decrease in apoB secretion relative to control, but initially enhanced the protein stability and cellular accumulation of apoB. Subcellular fractionation of microsomes further confirmed the accumulation of secretion-incompetent apoB-Lipoproteins in the endoplasmic reticulum (ER) and Golgi compartments of avasimibe-treated HepG2 cells. Although incubation of drug-treated cells with carbobenzoxyl-leucinyl-leucinyl-leucinal (MG132), a potent proteasome inhibitor, increased cellular apoB (70%), it failed to increase apoB secretion. Drug treatment induced an accumulation of secretion-incompetent apoB-containing Lipoprotein particles, the majority of which demonstrated a density in a range similar to that of high-density Lipoprotein. However, studies in permeabilized cells demonstrated that, at longer chase times, intracellularly accumulated apoB was eventually degraded, indicating that the inhibition of degradation may be transient. Oleate treatment of avasimibe-treated cells partially restored apoB secretion but not to the levels seen in control cells. In summary, we hypothesize that avasimibe acutely blocks the secretion of apoB and its associated Lipoproteins from HepG2 cells, transiently enhancing its membrane association and cellular accumulation with eventual intracellular degradation of accumulated apoB.
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modulation of hepatic Lipoprotein Synthesis and secretion by taxifolin a plant flavonoid
Journal of Lipid Research, 2000Co-Authors: Andre Theriault, Qi Wang, B Chen, Adrian A. Franke, Stephen C Van Iderstine, Khosrow AdeliAbstract:In the present study, the effects of taxifolin, a plant flavonoid, on lipid, apoLipoprotein B (apoB), and apo- Lipoprotein A-I (apoA-I) Synthesis and secretion were deter- mined in HepG2 cells. Pretreatment of cells with ( 6 )-taxi- folin led to an inhibition of cholesterol Synthesis in a dose- and time-dependent manner, with an 86 6 3% inhibition at 200 m M observed within 24 h. As to the mechanism underly- ing this inhibitory effect, taxifolin was shown to inhibit the activity of HMG-CoA reductase by 47 6 7%. In addition, cellular cholesterol esterification, and triacylglycerol and phospholipid syntheses, were also significantly suppressed in the presence of taxifolin. ApoA-I and apoB Synthesis and secretion were then studied by pulse-chase experiments. ApoA-I secretion was found to increase by 36 6 10%. In contrast, an average reduction of 61 6 8% in labeled apoB in the medium was apparent with taxifolin. This effect on secretion appeared not to be exerted at the transcriptional level. Rather, the effect on apoB secretion was found to be exerted in the early stages of apoB degradation and to be sen- sitive to dithiothreitol (DTT) and insensitive to N -acetyl- leucyl-leucyl-norleucinal, suggesting a proteolytic pathway involving a DTT-sensitive protease. Fractionation of se- creted apoB revealed a slight shift in the distribution of secreted apoB-containing Lipoproteins. Cholesteryl ester, rather than triacylglycerol, was shown to be the lipid that primarily regulated apoB secretion. In summary, our data suggest that taxifolin decreases hepatic lipid Synthesis with a concomitant decrease and increase in apoB and apoA-I secretion, respectively. — Theriault, A., Q. Wang, S. C. Van Iderstine, B. Chen, A. A. Franke, and K. Adeli. Modulation of hepatic Lipoprotein Synthesis and secretion by taxifolin, a plant flavonoid. J. Lipid Res. 2000. 41: 1969-1979.
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Modulation of hepatic Lipoprotein Synthesis and secretion by taxifolin, a plant flavonoid.
Journal of lipid research, 2000Co-Authors: Andre Theriault, Qi Wang, Stephen C. Van Iderstine, B Chen, Adrian A. Franke, Khosrow AdeliAbstract:In the present study, the effects of taxifolin, a plant flavonoid, on lipid, apoLipoprotein B (apoB), and apoLipoprotein A-I (apoA-I) Synthesis and secretion were determined in HepG2 cells. Pretreatment of cells with (+/-)-taxifolin led to an inhibition of cholesterol Synthesis in a dose- and time-dependent manner, with an 86 +/- 3% inhibition at 200 microM observed within 24 h. As to the mechanism underlying this inhibitory effect, taxifolin was shown to inhibit the activity of HMG-CoA reductase by 47 +/- 7%. In addition, cellular cholesterol esterification, and triacylglycerol and phospholipid syntheses, were also significantly suppressed in the presence of taxifolin. ApoA-I and apoB Synthesis and secretion were then studied by pulse-chase experiments. ApoA-I secretion was found to increase by 36 +/- 10%. In contrast, an average reduction of 61 +/- 8% in labeled apoB in the medium was apparent with taxifolin. This effect on secretion appeared not to be exerted at the transcriptional level. Rather, the effect on apoB secretion was found to be exerted in the early stages of apoB degradation and to be sensitive to dithiothreitol (DTT) and insensitive to N-acetyl-leucyl-leucyl-norleucinal, suggesting a proteolytic pathway involving a DTT-sensitive protease. Fractionation of secreted apoB revealed a slight shift in the distribution of secreted apoB-containing Lipoproteins. Cholesteryl ester, rather than triacylglycerol, was shown to be the lipid that primarily regulated apoB secretion. In summary, our data suggest that taxifolin decreases hepatic lipid Synthesis with a concomitant decrease and increase in apoB and apoA-I secretion, respectively.
Naoto Kubota - One of the best experts on this subject based on the ideXlab platform.
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nape pld controls oea Synthesis and fat absorption by regulating Lipoprotein Synthesis in an in vitro model of intestinal epithelial cells
The FASEB Journal, 2019Co-Authors: Miki Igarashi, Kazuhide Watanabe, Tsuyoshi Tsuduki, Ikuo Kimura, Naoto KubotaAbstract:Oleoylethanolamide (OEA), a fatty acid ethanolamide (FAE), is a lipid mediator that controls food intake and lipid metabolism. Accumulating data imply the importance of intestinal OEA in controlling satiety in addition to gastrointestinal peptide hormones. Although the biochemical pathway of FAE production has been illustrated, the enzymes responsible for the cleavage of OEA from its precursor N-acyl-phosphatidylethanolamine (NAPE) must be identified among reported candidates in the gut. In this study, we assessed the involvement of NAPE-specific phospholipase D (NAPE-PLD), which can directly release FAEs from NAPE, in intestinal OEA Synthesis and lipid metabolism. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPER-associated protein 9 (Cas9)-mediated deletion of the NAPE-PLD gene in intestinal epithelial-like Caco-2 cells reduced OEA levels, regardless of their differentiation states. Transcriptome analysis revealed that deletion of NAPE-PLD activates a transcriptional program for nutrient transportation, including lipids and Lipoproteins, and inactivates cell-cycle or mitosis-related genes in Caco-2 cells. In addition, the basolateral secretion of Lipoproteins was increased in NAPE-PLD-deleted cells although Lipoprotein size was not affected. By contrast, cellular lipid levels were reduced in NAPE-PLD-deleted cells. Overall, these results indicate that NAPE-PLD plays important roles in OEA Synthesis and fat absorption by regulating Lipoprotein production in the intestinal epithelial cells.-Igarashi, M., Watanabe, K., Tsuduki, T., Kimura, I., Kubota, N. NAPE-PLD controls OEA Synthesis and fat absorption by regulating Lipoprotein Synthesis in an in vitro model of intestinal epithelial cells.
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nape pld controls oea Synthesis and fat absorption by regulating Lipoprotein Synthesis in an in vitro model of intestinal epithelial cells
The FASEB Journal, 2019Co-Authors: Miki Igarashi, Kazuhide Watanabe, Tsuyoshi Tsuduki, Ikuo Kimura, Naoto KubotaAbstract:Oleoylethanolamide (OEA), a fatty acid ethanolamide (FAE), is a lipid mediator that controls food intake and lipid metabolism. Accumulating data imply the importance of intestinal OEA in controllin...
Ernest G. Seidman - One of the best experts on this subject based on the ideXlab platform.
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caco 2 cells as a model for intestinal Lipoprotein Synthesis and secretion
The FASEB Journal, 1995Co-Authors: Emile Levy, Maalekian Mehran, Ernest G. SeidmanAbstract:Caco-2 cells, an intestinal cell line derived from a human colorectal carcinoma that spontaneously differentiates under standard culture conditions, lends itself to the in vitro study of human gut in view of its efficient intestinal transport processes. Among its multiple biological functions are those related to the absorption, transport, and metabolism of lipids and Lipoproteins. Despite their intestinal origin, confluent Caco-2 cell monolayers primarily express L-FABP for the uptake of apical dietary long chain fatty acids, incorporating them into triglycerides by the glycerol 3-phosphate pathway, and assembling very-low-density Lipoprotein, high-density Lipoprotein, and low-density Lipoprotein. The monoacyl-glycerol pathway is inactive in Caco-2 cells. Furthermore, the secretion of newly synthesized triglyceride-rich Lipoproteins is very restricted, despite abundant production of apoLipoprotein (apo) B. The regulation of apoB Synthesis and its mRNA editing at the enterocyte level has been intensively ...
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caco 2 cells as a model for intestinal Lipoprotein Synthesis and secretion
The FASEB Journal, 1995Co-Authors: Emile Levy, Mariam Mehran, Ernest G. SeidmanAbstract:Caco-2 cells, an intestinal cell line derived from a human colorectal carcinoma that spontaneously differentiates under standard culture conditions, lends itself to the in vitro study of human gut in view of its efficient intestinal transport processes. Among its multiple biological functions are those related to the absorption, transport, and metabolism of lipids and Lipoproteins. Despite their intestinal origin, confluent Caco-2 cell monolayers primarily express L-FABP for the uptake of apical dietary long chain fatty acids, incorporating them into triglycerides by the glycerol 3-phosphate pathway, and assembling very-low-density Lipoprotein, high-density Lipoprotein, and low-density Lipoprotein. The monoacyl-glycerol pathway is inactive in Caco-2 cells. Furthermore, the secretion of newly synthesized triglyceride-rich Lipoproteins is very restricted, despite abundant production of apoLipoprotein (apo) B. The regulation of apoB Synthesis and its mRNA editing at the enterocyte level has been intensively examined in Caco-2 cells. Luminal fatty acids, calcium ion, as well as vitamins and hormones are known to modulate the apoB-48/apoB-100 at the transcriptional and/or translational level. The regulation of 3-hydroxy-3-methylglutaryl-CoA reductase and acyl-CoA: (cholesterol acyltransferase), the key enzymes governing intracellular cholesterol handling, have also been extensively examined in Caco-2 cells. In many respects this cell line provides an excellent in vitro model for the investigation of intestinal Lipoprotein metabolism; however, their limited secretion capacity remains a potential drawback to comparisons with the in vivo physiological state.
Emile Levy - One of the best experts on this subject based on the ideXlab platform.
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intestinal lipid handling evidence and implication of insulin signaling abnormalities in human obese subjects
Arteriosclerosis Thrombosis and Vascular Biology, 2014Co-Authors: Alain Veilleux, Emilie Grenier, Picard Marceau, Andre C Carpentier, Denis Richard, Emile LevyAbstract:Objective— Animal models have evidenced the role of intestinal triglyceride-rich Lipoprotein overproduction in dyslipidemia. However, few studies have confronted this issue in humans and disclosed the intrinsic mechanisms. This work aimed to establish whether intestinal insulin resistance modifies lipid and Lipoprotein homeostasis in the intestine of obese subjects. Approach and Results— Duodenal specimens obtained from 20 obese subjects undergoing bariatric surgery were paired for age, sex, and body mass index with or without insulin resistance, as defined by the homeostasis model assessment of insulin resistance. Insulin signaling, biomarkers of inflammation and oxidative stress, and Lipoprotein assembly were assessed. The intestine of insulin-resistant subjects showed defects in insulin signaling as demonstrated by reduced protein kinase B phosphorylation and increased p38 mitogen-activated protein kinase phosphorylation, likely as the result of high oxidative stress (evidenced by malondialdehyde and conjugated dienes) and inflammation (highlighted by nuclear factor-κB, tumor necrosis factor-α, interleukin-6, intercellular adhesion molecule-1, and cyclooxygenase-2). Enhanced de novo lipogenesis rate and apoLipoprotein B-48 biogenesis along with exaggerated triglyceride-rich Lipoprotein production were observed, concomitantly with the high expression levels of liver and intestinal fatty acid–binding proteins and microsomal transfer protein. The presence of an aberrant intracellular cholesterol transport/metabolism was also suggested by the reduced expression of ATP-binding cassette A1 transporter and proprotein convertase subtilisin/kexin type 9. Conclusions— According to the present data, the small intestine may be classified as an insulin-sensitive tissue. Dysregulation of intestinal insulin signaling, possibly triggered by oxidative stress and inflammation, was associated with exaggerated lipogenesis and Lipoprotein Synthesis, which may represent a key mechanism for atherogenic dyslipidemia in patients with metabolic syndrome. # Significance {#article-title-60}
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caco 2 cells as a model for intestinal Lipoprotein Synthesis and secretion
The FASEB Journal, 1995Co-Authors: Emile Levy, Maalekian Mehran, Ernest G. SeidmanAbstract:Caco-2 cells, an intestinal cell line derived from a human colorectal carcinoma that spontaneously differentiates under standard culture conditions, lends itself to the in vitro study of human gut in view of its efficient intestinal transport processes. Among its multiple biological functions are those related to the absorption, transport, and metabolism of lipids and Lipoproteins. Despite their intestinal origin, confluent Caco-2 cell monolayers primarily express L-FABP for the uptake of apical dietary long chain fatty acids, incorporating them into triglycerides by the glycerol 3-phosphate pathway, and assembling very-low-density Lipoprotein, high-density Lipoprotein, and low-density Lipoprotein. The monoacyl-glycerol pathway is inactive in Caco-2 cells. Furthermore, the secretion of newly synthesized triglyceride-rich Lipoproteins is very restricted, despite abundant production of apoLipoprotein (apo) B. The regulation of apoB Synthesis and its mRNA editing at the enterocyte level has been intensively ...
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caco 2 cells as a model for intestinal Lipoprotein Synthesis and secretion
The FASEB Journal, 1995Co-Authors: Emile Levy, Mariam Mehran, Ernest G. SeidmanAbstract:Caco-2 cells, an intestinal cell line derived from a human colorectal carcinoma that spontaneously differentiates under standard culture conditions, lends itself to the in vitro study of human gut in view of its efficient intestinal transport processes. Among its multiple biological functions are those related to the absorption, transport, and metabolism of lipids and Lipoproteins. Despite their intestinal origin, confluent Caco-2 cell monolayers primarily express L-FABP for the uptake of apical dietary long chain fatty acids, incorporating them into triglycerides by the glycerol 3-phosphate pathway, and assembling very-low-density Lipoprotein, high-density Lipoprotein, and low-density Lipoprotein. The monoacyl-glycerol pathway is inactive in Caco-2 cells. Furthermore, the secretion of newly synthesized triglyceride-rich Lipoproteins is very restricted, despite abundant production of apoLipoprotein (apo) B. The regulation of apoB Synthesis and its mRNA editing at the enterocyte level has been intensively examined in Caco-2 cells. Luminal fatty acids, calcium ion, as well as vitamins and hormones are known to modulate the apoB-48/apoB-100 at the transcriptional and/or translational level. The regulation of 3-hydroxy-3-methylglutaryl-CoA reductase and acyl-CoA: (cholesterol acyltransferase), the key enzymes governing intracellular cholesterol handling, have also been extensively examined in Caco-2 cells. In many respects this cell line provides an excellent in vitro model for the investigation of intestinal Lipoprotein metabolism; however, their limited secretion capacity remains a potential drawback to comparisons with the in vivo physiological state.
Miki Igarashi - One of the best experts on this subject based on the ideXlab platform.
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nape pld controls oea Synthesis and fat absorption by regulating Lipoprotein Synthesis in an in vitro model of intestinal epithelial cells
The FASEB Journal, 2019Co-Authors: Miki Igarashi, Kazuhide Watanabe, Tsuyoshi Tsuduki, Ikuo Kimura, Naoto KubotaAbstract:Oleoylethanolamide (OEA), a fatty acid ethanolamide (FAE), is a lipid mediator that controls food intake and lipid metabolism. Accumulating data imply the importance of intestinal OEA in controlling satiety in addition to gastrointestinal peptide hormones. Although the biochemical pathway of FAE production has been illustrated, the enzymes responsible for the cleavage of OEA from its precursor N-acyl-phosphatidylethanolamine (NAPE) must be identified among reported candidates in the gut. In this study, we assessed the involvement of NAPE-specific phospholipase D (NAPE-PLD), which can directly release FAEs from NAPE, in intestinal OEA Synthesis and lipid metabolism. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPER-associated protein 9 (Cas9)-mediated deletion of the NAPE-PLD gene in intestinal epithelial-like Caco-2 cells reduced OEA levels, regardless of their differentiation states. Transcriptome analysis revealed that deletion of NAPE-PLD activates a transcriptional program for nutrient transportation, including lipids and Lipoproteins, and inactivates cell-cycle or mitosis-related genes in Caco-2 cells. In addition, the basolateral secretion of Lipoproteins was increased in NAPE-PLD-deleted cells although Lipoprotein size was not affected. By contrast, cellular lipid levels were reduced in NAPE-PLD-deleted cells. Overall, these results indicate that NAPE-PLD plays important roles in OEA Synthesis and fat absorption by regulating Lipoprotein production in the intestinal epithelial cells.-Igarashi, M., Watanabe, K., Tsuduki, T., Kimura, I., Kubota, N. NAPE-PLD controls OEA Synthesis and fat absorption by regulating Lipoprotein Synthesis in an in vitro model of intestinal epithelial cells.
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nape pld controls oea Synthesis and fat absorption by regulating Lipoprotein Synthesis in an in vitro model of intestinal epithelial cells
The FASEB Journal, 2019Co-Authors: Miki Igarashi, Kazuhide Watanabe, Tsuyoshi Tsuduki, Ikuo Kimura, Naoto KubotaAbstract:Oleoylethanolamide (OEA), a fatty acid ethanolamide (FAE), is a lipid mediator that controls food intake and lipid metabolism. Accumulating data imply the importance of intestinal OEA in controllin...