BACKGROUND: Obesity is frequently associated with an increase in the early inflammation marker C-reactive protein (CRP), insulin resistance and changes in lipoprotein metabolism. Increased CRP is known as an independent cardiovascular risk factor. Since the apolipoproteins (apo) E and CIII components of HDL are associated with reduced cardiovascular risk and since apoE has in vitro anti-inflammatory effect, we have investigated the relationships between apoE, apoCIII (in apoB and non apoB containing lipoproteins) and CRP in obese adults. METHODS:The following parameters from 34 healthy obese fasting women (age 22 -64 y, body mass index (BMI) 28 -68 kg=m 2 ) were measured: (1) ApoE and apoCIII, in total plasma, in apoB-(E LpB, CIII LpB) and non-apoB-containing lipoproteins (E LpnonB, CIII LpnonB); (2) CRP and cytokine secreted by adipose tissue (TNF-a and its soluble receptor TNFR2); (3) triglyceride, HDL-cholesterol, systolic blood pressure, diastolic blood pressure, waist and hip circumferences, insulin, glucose. HOMA, a marker of insulin sensitivity, and the ratio E=CIII in LpB and LpnonB were calculated. RESULTS: CRP was positively correlated with BMI (P < 0.05), waist circumference (WC, P < 0.05), triglyceride (P < 0.05) and negatively correlated with apoE (P < 0.01) and E LpnonB (P < 0.05). Two multiple regression models including parameters related to CRP with a P < 0.25 were run stepwise to assess their independent contribution to CRP concentration. In the first model (including BMI, WC, HOMA, insulin, triglyceride, apoE, E LpnonB), apoE was the best predictor of CRP (P ¼ 0.01) together with triglyceride (P ¼ 0.02) and BMI (P ¼ 0.08). The second model took into account E=CIII LpnonB ratio with the parameters included in the first model. In this second model, E=CIII LpnonB was the best predictor of CRP (P ¼ 0.007), explaining 39% of CRP variance. CONCLUSION: ApoE is strongly correlated with CRP and could have an anti-inflammatory effect in vivo in obese subjects. This correlation could be limited to LpnonB lipoproteins, depending on their apoE and CIII relative content.
The aim of this study was to determine: (1) whether the Short Chain Fatty Acids (SCFA) Acetate, Propionate, and Butyrate enhance the synthesis and secretion of intestinal apolipoprotein A-IV-containing lipoproteins and (2) if so, whether these particles are able to promote cholesterol efflux in vitro. For this purpose Caco-2 cells were used for their functional properties of differentiated enterocytes. They were incubated with the three SCFA (2, 4, and 8 mM) for 48 h. Only butyrate stimulated apoA-IV gene expression and this was associated with an increase in apoA-IV secretion. A nondenaturing 2D-PAGE (agarose gel was followed by PAGE) was used to identify apoA-IV-containing lipoproteins in various media, and showed that butyrate stimulated the secretion of two small HDL sized particles. The influence of these secreted particles on cholesterol efflux was investigated using incubation of media with (3)H-cholesterol-labeled Fu5AH cells. The data indicate that conditioned media from Caco-2 cells treated with butyrate resulted in an increase of 20-30% in cholesterol efflux. We conclude that butyrate may regulate apoA-IV secretion and, therefore, modulate reverse cholesterol transport.
In isolated human platelets, exposure of subtraction 3 high-density lipoprotein (HDL,) binding sites to high concentrations of HDL, (1 mg/mL) causes rapid desensitization of HDL3 (50 jU,g/mL)-stimulated breakdown of phosphatidylcholine, as shown in approximately a 70% depression of the maximal 1,2-diacylglycerol release activity by phospholipase C. This desensitization is HDL, dose dependent (IC 50 , 150±20 ig/mL, n=6) and time dependent (t 1/2 , <30 seconds). It requires the binding of HDL,, as pretreatment of HDL, by tetranitromethane does not cause the desensitization of HDLj-induced phospholipase C activity. Permeabilization of human platelets with 10 /ig/mL digitonin, used to permit access of charged inhibitors to the cytosol, does not interfere with the pattern of HDLj (1 mg/mL) -induced desensitization of HDL, (50 /ig/mL)-stimulated phospholipase C. Inhibitors of protein kinase C (100 /umol/L H-7 and 10 /nmol/L staurosporine) markedly inhibit desensitization of HDL,-induced P revious studies have demonstrated that subtraction 3 high-density lipoprotein (HDL,) binding sites are present on platelet membranes. 13 Koller et al 3 have reported that the glycoprotein Ilb/IIIa complex, the inducible platelet fibrinogen receptor, is able to interact with lipoproteins. HDL3 was found to bind to either the 95-to 110-kD glycoprotein Ilia or to the 136-to 140-kD glycoprotein lib. Glycoprotein lib/ Ilia acts until now as a platelet HDL, binding site.Furthermore, HDL 3 binding sites are coupled to phospholipase C (PLC) through pertussis toxin-sensitive GTP binding proteins. 45 In human platelets, HDL 3 binding sites act via the PLC-mediated hydrolysis of phosphatidylcholine and the generation of 1,2-diacylglycerol, which activates the multifunctional enzyme protein kinase C (PKC). The HDL 3 -induced signaling pathway is recorded only when platelets are stimulated by low concentrations of HDL 3 (50 ixglmL). Higher HDL3 concentrations (1 mg/mL) are not able to trigger phosphatidylcholine hydrolysis, indicating a loss of responsiveness. 4 One major form of regulation of the activity of G protein-coupled receptors is desensitization, 6 -9 which is a general biological phenomenon whereby the response to a specific ligand wanes over time despite the continuous presence of the ligand. The impairment of receptor functions is linked to protein phosphorylation, which appears to be a key factor. Most often, homologous desensitization is accompanied by receptor phosphorylation, which triggers the process of functional uncoupling from G proteins. 1012 In addition, a rapid sequestration of the receptors away from the cell surface and a modulation of the expression of the receptor gene itself result in a net decrease in receptor number. 13 Whereas desensitization of the adrenergic system is rather well understood, less is known about receptors coupled to phosphatidylinositol or phosphatidylcholine turnover. 1417 Moreover, until now little has been known about HDL3 binding site regulation. Platelets therefore would seem to ...
The conversion of phosphatidylethanolamine (PE) into phosphatidylcholine (PC) by a sequence of three transmethylation reactions is shown to be stimulated by the apolipoprotein E-free subclass of high-density lipoprotein (HDL3) in isolated bovine brain capillary (BBC) membranes, HDL3-induced stimulation of BBC membranes pulsed with [methyl-14C]methionine causes a transient increase in each methylated phospholipid, i.e. phosphatidyl-N-monomethylethanolamine (PMME), phosphatidyl-NN-dimethylethanolamine (PDME) and PC. PC substrate arising from the activation of PE N-methyltransferase (PEMT) is hydrolysed by a phospholipase A2 (PLA2), as demonstrated by the accumulation of lysophosphatidylcholine (lyso-PC). When PE containing [14C]arachidonic acid in the sn-2 position ([14C]PAPE) is incorporated into BBC membranes, HDL3 stimulation induces the formation of PMME, PDME, PC and lyso-PC and the release of [14C]arachidonic acid, which correlates with the previous production of lyso-PC, suggesting that HDL3 stimulates a PLA2 that can release polyunsaturated fatty acids (PUFA). Both PEMT and PLA2 activities depend on a HDL3 concentration in the range 0-50 micrograms/ml and are strictly dependent on HDL3 binding, because HDL3 modified by tetranitromethane is no longer able to bind to specific receptors and to trigger PEMT and PLA2 activation. Moreover, HDL3 prelabelled with [14C]PAPE can stimulate PDME and lyso-PC synthesis in BBC membranes in the presence of S-adenosylmethionine, suggesting that HDL3 can supply BBC membranes in polyunsaturated PE and can activate enzymes involved in PE N-methylation and PUFA release. The results support the hypothesis of a close relationship between HDL3 binding, PE methylation and PUFA release, and suggest that the PC pool arising from PE could be used as a pathway for the supply of PUFA to the brain.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.