Triglycerides and Cardiovascular Disease

Circulation, Journal Year: 2011, Volume and Issue: 123(20), P. 2292 - 2333

Published: April 19, 2011

Language: Английский

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Chylomicrons promote intestinal absorption of lipopolysaccharides

Journal of Lipid Research, Journal Year: 2008, Volume and Issue: 50(1), P. 90 - 97

Published: Sept. 25, 2008

Recent data suggest that dietary fat promotes intestinal absorption of lipopolysaccharides (LPS) from the gut microflora, which might contribute to various inflammatory disorders. The mechanism fat-induced LPS is unclear, however. Intestinal-epithelial cells can internalize apical surface and transport Golgi. Golgi complex also contains newly formed chylomicrons, lipoproteins long-chain through mesenteric lymph blood. Because has affinity for we hypothesized chylomicron formation absorption. In agreement with our hypothesis, found CaCo-2 released more cell-associated after incubation oleic-acid (OA), a fatty acid induces formation, than butyric (BA), short-chain does not induce formation. Moreover, effect OA was blocked by inhibitor Pluronic L-81. We observed intragastric triolein (TO) gavage followed increased plasma LPS, whereas tributyrin (TB), or TO plus L-81, not. Most intestinally absorbed present on remnants (CM-R) in Chylomicron promoted nodes (MLN) production TNFα mRNA MLN. Together, epithelial may release chylomicrons pools. Chylomicron-associated postprandial responses chronic diet-induced inflammation target tissues. A high-fat diet increases risk acute (1Alipour A. Elte J.W. van Zaanen H.C. Rietveld A.P. Cabezas M.C. Postprandial endothelial dysfunction..Biochem. Soc. Trans. 2007; 35: 466-469Crossref PubMed Scopus (94) Google Scholar, 2Burdge G.C Calder P.C. Plasma cytokine response during period: potential causal process vascular disease?.Br. J. Nutr. 2005; 93: 3-9Crossref (112) Scholar) diseases such as atherosclerosis diabetes (3Greenberg A.S Obin M.S. Obesity role adipose tissue metabolism..Am. Clin. 2006; 83: 461S-465SCrossref 4Hotamisligil G.S Inflammation metabolic disorders..Nature. 444: 860-867Crossref (6120) 5Van Gaal L.F Mertens I.L. De Block C.E. Mechanisms linking obesity cardiovascular disease..Nature. 875-880Crossref (1986) Scholar). proinflammatory diets mainly been attributed properties acids. Indeed, acids are known be able modulate immune system (6Fritsche K. Fatty modulators response..Annu. Rev. 26: 45-73Crossref (236) activate innate receptor TLR4, (7Shi H. Kokoeva M.V. Inouye Tzameli I. Yin Flier J.S. TLR4 links immunity acid-induced insulin resistance..J. Invest. 116: 3015-3025Crossref (2640) 8Suganami T. Tanimoto-Koyama Nishida Itoh M. Yuan X. Mizuarai S. Kotani Yamaoka Miyake Aoe et al.Role toll-like 4/NF-kappaB pathway saturated changes interaction between adipocytes macrophages..Arterioscler. Thromb. Vasc. Biol. 27: 84-91Crossref (615) Some susceptible oxidation before their absorption, promote relevant (9Navab Hama S.Y. Reddy S.T. Ng C.J. Van Lenten B.J. Laks Fogelman A.M. Oxidized lipids mediators coronary heart disease..Curr. Opin. Lipidol. 2002; 13: 363-372Crossref (91) other (10Navab Gharavi N. Watson A.D. disorders..Curr. Metab. Care. 2008; 11: 459-464Crossref (92) However, excess only systemic exposure potentially free derivatives, but its recently facilitate highly bacterial (11Cani P.D Amar Iglesias M.A. Poggi Knauf C. Bastelica D. Neyrinck Fava F. Tuohy K.M. Chabo al.Metabolic endotoxemia initiates resistance..Diabetes. 56: 1761-1772Crossref (4053) 12Erridge Attina Spickett C.M. Webb D.J. meal low-grade endotoxemia: evidence novel inflammation..Am. 86: 1286-1292Crossref (544) This interesting, because affect whole body interfere metabolism function system.Dietary transported absorptive enterocyte extra-intestinal incorporation triglycerides into lymph. Once circulation, these large lipoprotein particles significant amounts upon lipases tethered endothelium, this partially explain putative proatherogenic 13Fruchart J.C Nierman Stroes E.S. Kastelein J.J. Duriez P. New factors patient assessment..Circulation. 2004; 109: III15-III19Crossref 14Botham K.M Moore E.H. Pascale Bejta induction macrophage foam cell remnants..Biochem. 454-458Crossref (48) have high (15Vreugdenhil A.C Rousseau C.H. Hartung Greve 't Veer Buurman W.A Lipopolysaccharide (LPS)-binding protein mediates detoxification chylomicrons..J. Immunol. 2003; 170: 1399-1405Crossref (161) 16Read T.E Grunfeld Kumwenda Z.L. Calhoun Kane J.P. Feingold K.R. Rapp J.H. Triglyceride-rich prevent septic death rats..J. Exp. Med. 1995; 182: 267-272Crossref 17Harris H.W Read T.E. Jones A.L. Eichbaum E.B. Bland G.F. Chylomicrons alter fate endotoxin, decreasing tumor necrosis factor preventing death..J. 1993; 91: 1028-1034Crossref (181) thus fat, likely concomitantly LPS. Whereas sequestration would reduce toxicity enhance hepatic clearance (17Harris Scholar), it nevertheless possible could correlate content. dieting, lead prolonged chylomicronemia, augment extra-hepatic exposure, perhaps increasing disorders.An important question therefore how One possibility paracellular leakage across epithelium. supported recent observations intestinal-epithelial tight-junction integrity compromised obese mice (18Brun Castagliuolo Leo V.D. Buda Pinzani Palu G. Martines Increased permeability mice: new pathogenesis nonalcoholic steatohepatitis..Am. Physiol. Gastrointest. Liver 292: G518-G525Crossref (652) studies demonstrating experimental luminal oleic (OA) cause small-intestinal damage (19Kvietys P.R Specian R.D. Grisham M.B. Tso Jejunal mucosal injury restitution: hydrolytic products food digestion..Am. 1991; 261: G384-G391Crossref 20Velasquez O.R Henninger Fowler Crissinger K.D. Oleic developing piglet intestine..Am. 264: G576-G582Crossref An alternative enters proper transcellular cells. occur so called microfold (M-cells), permeable bacteria macromolecules sampling antigens underlying lymphoid (21Hathaway L.J Kraehenbuhl M immunity..Cell. Mol. Life Sci. 2000; 57: 323-332Crossref (103) Scholar).Uptake limited M-cells, however, demonstrated enterocytes (22Neal M.D Leaphart Levy R. Prince Billiar T.R. Watkins Li Cetin Ford Schreiber Enterocyte phagocytosis translocation barrier..J. 176: 3070-3079Crossref (290) where relate tolerance (23Hornef M.W Frisan Vandewalle Normark Richter-Dahlfors Toll-like 4 resides apparatus colocalizes internalized lipopolysaccharide cells..J. 195: 559-570Crossref (351) 24Lotz Gutle Walther Menard Bogdan Hornef M.W. Postnatal acquisition endotoxin 203: 973-984Crossref (337) Interestingly, compartment assembled located prior basolateral secretion (25Sabesin S.M Frase Electron microscopic assembly, intracellular transport, rat intestine..J. Lipid Res. 1977; 18: 496-511Abstract Full Text PDF Therefore, result concomitant pools.In study, explored cultured basolaterally secrete OA-induced when were incubated added together L-81 (Pl-81). Using vivo studies, significantly blood compared (TB) caused mRNA. TO-dependent completely Pl-81, even though uptake enterocytes. results strongly part enrichment LPS.MATERIALS AND METHODSCells, media, reagentsCaCo-2 cells, CMT93 T84 purchased ATCC (Manassas, VA). grown HEPES- bicarbonate-buffered DMEM/Ham's F12 medium supplemented 5% fetal calf serum (FCS) antibiotics. subcultured once week up 30 passages (final passage number ∼50). For experiments, near-confluent 75 cm2 flask trypsinized resuspended 10 ml medium; 0.1 suspension seeded per (26Luchoomun Hussain M.M. Assembly differentiated Caco-2 Nascent preformed phospholipids preferentially used assembly..J. Chem. 1999; 274: 19565-19572Abstract (155) supports (collagen coated "transwells," 12 6 wells/plate; pore size 3 μm, Corning Corp.) 21 days triweekly changes. DMEM 10% antibiotics within passages. similar inserts at densities 1 day confluency, transepithelial difference exceeded 400Ω/cm2. membrane described MEM-based enriched requiring little no ("Opti-MEM") Invitrogen, FCS Hyclone. Sodium-salts taurocholic-, butyric- (BA) oleic- acids, TO, TB Sigma Aldrich, chain (MCT) oil (consisting containing octanoic decanoic acids) Novartis. generous gift BASF corporation (Florham Park, NJ) 3% (by volume) [comparable block gavaged rats (27Xie Q-M. Shao J-S. Alpers D.H. Rat alpha 1-antitrypsin regulated triacylglycerol feeding..Am. 276: G1452-G1460Crossref Scholar)] 0.2% vitro experiments (E. coli 0114:B4) Limulus Amoebocyte Lysate assay Lonza Biosciences. [3H] Labeled molecular weight dextran 125NaI obtained Amersham, [3H]retinol American Radiolabeled Chemicals (St. Louis, MO). All reagents Aldrich.AnimalsMale C57Bl/6 Jackson Laboratory allowed acclimatize 2 weeks experiments. LDL-receptor knockout background Dr. Alan Daugherty. age onset did exceed 11 weeks. light/dark cycle 12/12 h maintained had adlib access water food. animal institutional approval.Radiolabeling LPSThe 125I-labeled kindly donated der Westhuyzen laboratory. labeled according chloramine-T protocol (28Hunter Standardization method iodination. Proceedings Society Experimental Biology Medicine..Society Medicine (New York, N.Y.). 1970; 133: 989-992Crossref (153) 29Ulevitch R.J preparation characterization radioiodinated lipopolysaccharide..Immunochemistry. 1978; 15: 157-164Crossref (63) Briefly, mg dissolved 0.05 borate buffer (pH8) 50 mM p-OH methylbenzimidate 37°C overnight. After extensive dialysis treated Na125I, unbound radiolabel removed overnight against sterile saline cold.ImmunoblottingFifteen μl media transwell cultures diluted 4× SDS sample buffer. samples boiled reduced β-mercapto-ethanol subjected SDS-PAGE 4–20% Tris-Glycine gel being transferred onto PVDF membrane. Apolipoprotein B (apoB)-48 identified polyclonal anti-human ApoB antibody (Calbiochem; cross-reacting mouse ApoB) band migrating around 250 kDa.Isolation CM-RPlasma (0.175 ml) LDL centrifuged Beckman Airfuge (15 min 110,000 RPM) order float chylomicron-remnant (30Reddy M.N Fitzsimons E.J. Clarifying lipemic an air-driven ultracentrifuge determination high-density cholesterol..Clin. Chim. Acta. 1986; 154: 141-144Crossref (6) top layer (<10% carefully isolated endotoxin-free initial volume.Detection LPSUndiluted directly manufacturer's instructions. pipette tips tubes certified free.RT-PCRRNA transcribed cDNA MMLV reverse transcriptase Biochain Optimax kit, using random hexamers. Expression quantified real-time PCR primer pairs 5′-AGC-CGA-TGG-GTT-GTA-CCT / 5′-TGA-GTT-GGT-CCC-CCT-TCT (TNFα) 5′-CGG-CTA-CCA-CAT-CCA-AGG-AA 5′-GCT-GGA-ATT-ACC-GCG-GCT (18S rRNA) annealing temperature 60°C.Statistical analysesAll represented average ± SD. Groups ANOVA Bonferroni's posthoc tests Student's t-tests. Differences groups considered statistically P < 0.05.RESULTSIngestion LCT causes increase associated (remnant) fractionTo test whether (LCT) endogenous blood, measured bioactive TB. since previously shown delayed CM-R (31Ishibashi Perrey Chen Z. Osuga Shimada Ohashi Harada Yazaki Y. Yamada Role low density (LDL) remnants. quantitative study lacking receptor, apolipoprotein E, both..J. 1996; 271: 22422-22427Abstract (109) allowing us isolate wild-type mice. fasted (4 h) then 0.2 Ninety minutes later, animals euthanatized, collected, 0.175 Bioactive total fractions same volume initially (32Levin Bang F.B. extracellular coagulation limulus blood..Bull. Johns Hopkins Hosp. 1964; 115: 265-274PubMed As expected, floated TO-gavaged (not shown), contained apoB-48 (Fig. 1B). fraction 1A). conclude endogenous, most particles.Inhibition blocks triglyceride-mediated LPSTo further involved material intestine received oral subsequently h. Thereafter, second either TB, (Pl-81) 33Pool Nutting D.F. Simmonds W.J. Effect L81, hydrophobic surfactant, cholesterol homeostasis..Am. G256-G262Crossref 34Nayak Harrison Retinyl ester cells: specific dependent assembly 2001; 42: 272-280Abstract half gavage, sacrificed collected analyzed radioactivity. Fig. 2, higher radioactivity Pl-81 TO. Thus, stimulates formation.Fig. 2Chylomicron 125I-LPS Mice phosphate-buffered 125I-LPS. another fast, Pl-81. Thirty euthanatized Fractional estimated assuming mouse. N = group, asterisk denotes statistical significance 0.01 (ANOVA).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Long-chain MLN chylomicron-dependent mannerChylomicrons entering stream cleared To determine correlated lymph, minus homogenization. Consistent hypothesis enhances decreased amount 3A). separate radiolabeled marker retinol (34Nayak 35Karpe Bell Bjorkegren Hamsten Quantification triglyceride-rich healthy men retinyl labeling simultaneous measurement apolipoproteins B-48 B-100..Arterioscler. 199-207Crossref (142) instead indeed resulted 3B, content consistent depends 3Chylomicron deposition (MLN). Fasted (A) (B) and, triglyceride homogenates combined animal. Shown n Asterisk (t-test).View (PPT)The finding deposited suggests tissue, least enriching gut-derived material. investigate possibility, μg LCT, MCT, 90 later. RT-PCR. 4, levels MCT presence Although cannot excluded contributed (see Discussion), should contributor responses.Fig. 4Dietary expression (LCT), oil, (3% volume). RNA pooled each mRNA, relative 18S rRNA, RT-PCR (B). five group; error bars indicate (P 0.05; ANOVA). Panel shows corresponding ApoB-48 mice.View (PPT)Chylomicron cellsTo ("transwells") model (36Levy E. Mehran Seidman synthesis secretion..FASEB 9: 626-635Crossref (177) unlabeled (0.1 mg/ml) t

Language: Английский

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Obesity, adiposity, and dyslipidemia: A consensus statement from the National Lipid Association

Journal of clinical lipidology, Journal Year: 2013, Volume and Issue: 7(4), P. 304 - 383

Published: May 31, 2013

Language: Английский

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The Role of Triglycerides in Atherosclerosis

Current Cardiology Reports, Journal Year: 2011, Volume and Issue: 13(6), P. 544 - 552

Published: Oct. 3, 2011

Language: Английский

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Hypertriglyceridemia and atherosclerosis

Lipids in Health and Disease, Journal Year: 2017, Volume and Issue: 16(1)

Published: Dec. 1, 2017

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and it has been confirmed that increased low density lipoprotein cholesterol (LDL-C) an independent risk factor for atherosclerosis. Recently, increasing evidence showed hypertriglyceridemia associated with incremental ASCVD risk. But proatherogenic mechanism triglyceride (TG) remains unclear. Therefore, this article focuses on clinical studies related to hypertriglyceridemia, in order provide reference prevention treatment ASCVD.

Language: Английский

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New insight into dyslipidemia‐induced cellular senescence in atherosclerosis

Biological reviews/Biological reviews of the Cambridge Philosophical Society, Journal Year: 2022, Volume and Issue: 97(5), P. 1844 - 1867

Published: May 15, 2022

Atherosclerosis, characterized by lipid-rich plaques in the arterial wall, is an age-related disorder and a leading cause of mortality worldwide. However, specific mechanisms remain complex. Recently, emerging evidence has demonstrated that senescence various types cells, such as endothelial cells (ECs), vascular smooth muscle (VSMCs), macrophages, progenitor (EPCs), adipose-derived mesenchymal stem (AMSCs) contributes to atherosclerosis. Cellular atherosclerosis share causative stimuli, which dyslipidemia attracted much attention. Dyslipidemia, mainly referred elevated plasma levels atherogenic lipids or lipoproteins, functional impairment anti-atherogenic plays pivotal role both cellular In this review, we summarize current for dyslipidemia-induced during atherosclerosis, with focus on low-density lipoprotein (LDL) its modifications, hydrolysate triglyceride-rich lipoproteins (TRLs), high-density (HDL), respectively. Furthermore, describe underlying linking Finally, discuss senescence-related therapeutic strategies special attention given anti-atherosclerotic effects promising geroprotectors well anti-senescence lipid-lowering drugs.

Language: Английский

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Comprehensive Metabolic Profiling of Inflammation Indicated Key Roles of Glycerophospholipid and Arginine Metabolism in Coronary Artery Disease

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 8, 2022

Background Systemic immune inflammation is a key mediator in the progression of coronary artery disease (CAD), concerning various metabolic and lipid changes. In this study, relationship between inflammatory index profile patients with CAD was investigated to provide deep insights into disturbances related inflammation. Methods Widely targeted plasma metabolomic lipidomic profiling performed 1,234 CAD. Laboratory circulating markers were mainly used define general systemic low-grade states. Multivariable-adjusted linear regression adopted assess associations 860 metabolites 7 markers. Least absolute shrinkage selection operator (LASSO) logistic-based classifiers multivariable logistic applied identify biomarkers states develop models for discriminating an advanced state. Results Multiple species linearly associated seven [false discovery rate (FDR) &lt;0.05]. LASSO multivariable-adjusted analysis identified significant 45 immune-inflammation index, 46 neutrophil–lymphocyte ratio states, 32 score, 26 high-sensitivity C-reactive protein ( P &lt; 0.05). Glycerophospholipid metabolism arginine proline determined as altered pathways Predictive based solely on metabolite combinations showed feasibility (area under curve: 0.81 0.88) four parameters that represent successfully validated using validation cohort. The inflammation-associated metabolite, namely, β-pseudouridine, carotid arteriosclerosis indicators Conclusions This study provides further information profiles represented by These potential pathological changes during may aid development therapeutic targets.

Language: Английский

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Impaired antioxidant activity of high-density lipoprotein in chronic kidney disease

Translational research, Journal Year: 2008, Volume and Issue: 153(2), P. 77 - 85

Published: Dec. 11, 2008

Language: Английский

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New Insights into the Regulation of Chylomicron Production

Annual Review of Nutrition, Journal Year: 2015, Volume and Issue: 35(1), P. 265 - 294

Published: May 14, 2015

Dietary lipids are efficiently absorbed by the small intestine, incorporated into triglyceride-rich lipoproteins (chylomicrons), and transported in circulation to various tissues. Intestinal lipid absorption mobilization chylomicron synthesis secretion highly regulated processes. Elevated production rate contributes dyslipidemia seen common metabolic disorders such as insulin-resistant states type 2 diabetes likely increases risk for atherosclerosis these conditions. An in-depth understanding of regulation may provide leads development drugs that could be therapeutic utility prevention atherosclerosis. Chylomicron is subject factors, including diet, body weight, genetic variants, hormones, nutraceuticals, medications, emerging interventions bariatric surgical procedures. In this review we discuss production, mechanisms underlie dysregulation, potential avenues future research.

Language: Английский

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HDL metabolism and activity in chronic kidney disease

Nature Reviews Nephrology, Journal Year: 2010, Volume and Issue: 6(5), P. 287 - 296

Published: March 23, 2010

Language: Английский

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