Yolanda M. Pacheco

Effects of meals rich in either monounsaturated or saturated fat on lipid concentrations and on insulin secretion and action in subjects with high fasting triglyceride concentrations

BACKGROUNDnThe nature of dietary fats and fasting concentrations of triglycerides affect postprandial hypertriglyceridemia and glucose homeostasis.nnnOBJECTIVESnThe objectives were to examine the effects of meals enriched in monounsaturated fatty acids (MUFAs) or saturated fatty acids (SFAs) on postprandial lipid, glucose, and insulin concentrations and to examine the extent of β cell function and insulin sensitivity in subjects with high fasting triglyceride concentrations.nnnDESIGNnFourteen men with fasting hypertriglyceridemia and normal glucose tolerance were given meals (≈10 kcal/kg body weight) containing MUFAs, SFAs, or no fat. Blood samples were collected at baseline and hourly over 8 h for analysis.nnnRESULTSnThe high-fat meals significantly increased postprandial concentrations of triglycerides, nonesterified fatty acids, and insulin and postprandial indexes of β cell function. However, postprandial indexes of insulin sensitivity decreased significantly. These effects were significantly attenuated with MUFAs relative to SFAs.nnnCONCLUSIONSnMUFAs postprandially buffered β cell hyperactivity and insulin intolerance relative to SFAs in subjects with high fasting triglyceride concentrations. These data suggest that, in contrast with SFAs, MUFA-based strategies may provide cardiovascular benefits to persons at risk by limiting lipid and insulin excursions and may contribute to optimal glycemic control after meal challenges.

Influence of postprandial triglyceride-rich lipoproteins on lipid-mediated gene expression in smooth muscle cells of the human coronary artery

AIMSnPostprandial triglyceride-rich lipoproteins (TRL) have a direct effect on vascular smooth muscle cells (SMC) and they increase the risk of atherogenesis. Here, we have tested the hypothesis that the different fatty acid composition of TRL is capable of differentially modifying gene expression in human coronary artery SMC (CASMC). In addition, the effect of TRL on cell proliferation and transcription factor activation was also evaluated.nnnMETHODS AND RESULTSnTRL were prepared from plasma of healthy volunteers after the ingestion of meals enriched in refined olive oil (ROO), butter or a mixture of vegetable and fish oils (VEFO). We use cDNA microarrays to determine the genes differentially expressed in TRL-treated CASMC. Correspondence cluster analysis demonstrated that TRL-butter, -ROO and -VEFO provoked different transcriptional profiles in CASMC. Sixty-six genes were regulated by TRL-butter, 55 by -ROO, and 47 by -VEFO. The data revealed that TRL-butter predominantly activated genes involved in the regulation of cell proliferation and inflammation. Likewise, TRL-VEFO induced the expression of genes implicated in inflammation, while TRL-ROO promoted a less atherogenic gene profile.nnnCONCLUSIONnThe pathophysiological contribution of TRL to the development of atherosclerosis and the stability of atherosclerotic plaques may depend on the fatty acid composition of TRL. Our findings suggest a role for macrophage-inhibiting cytokine-1 (MIC-1) in coronary artery cardiovascular events.

Oleic acid in olive oil: from a metabolic framework toward a clinical perspective.

Traditionally, nutrients such as fatty acids have been viewed as substrates for the generation of high-energy molecules and as precursors for the biosynthesis of macromolecules. However, accumulating data from multiple lines of evidence suggest that dietary fatty acids are linked not only to health promotion but also to disease pathogenesis. Metabolism in humans is regulated by complex hormonal signals and substrate interactions. For many years, the clinical focus has centered on a wide metabolic picture after an overnight fast. Nonetheless, the postprandial state (i.e., the period that comprises and follows a meal) is an important one, and silent disturbances in this period are involved in the genesis of numerous pathological conditions, including atherosclerosis. In this review article, we present an overview of the evidence demonstrating the relevance of oleic acid in olive oil on different nutrition-related issues. We also discuss the impact of oleic acid in olive oil and its clinical relevance to major risk factors for cardiovascular disease in the context of the postprandial state and with regard to other dietary fatty acids.

Severe Immune Dysregulation Affects CD4+CD25hiFoxP3+ Regulatory T Cells in HIV-Infected Patients With Low-level CD4 T-Cell Repopulation Despite Suppressive Highly Active Antiretroviral Therapy

We hypothesized that CD4(+)CD25(hi)FoxP3(+) regulatory T cells (Tregs) could be involved in the high immune activation existing in patients with low-level CD4 T-cell repopulation under suppressive high active antiretroviral therapy (hereafter, LLR patients). Sixteen LLR patients, 18 human immunodeficiency virus (HIV)-infected controls (hereafter, HIV controls), and 16 healthy subjects were included. The frequency of CD4(+)CD25(hi)FoxP3(+) and HIV-specific Treg suppressive function were assessed. Relationships between Treg and CD4/CD8 activation (HLA-DR/CD38) and the frequency of naive CD4 T-cells were assessed. Low-level patients showed a higher Treg frequency but reduced HIV-specific immunosuppressive functions than HIV controls. Whereas in healthy subjects a strong negative correlation between Tregs and activated CD8 T cells emerged (rxa0=xa0-0.75, Pxa0<xa0.001), it appeared disrupted in both HIV-infected groups (rxa0=xa0-0.06 and Pxa0=xa0.83 for LLR patients; rxa0=xa0-0.11 and Pxa0=xa0.68 for and HIV controls). Nevertheless, in LLR patients, Tregs negatively correlated with naive CD4 T cells (rxa0=xa0-0.60, Pxa0=xa0.01), whereas there was no such correlation in HIV controls (rxa0=xa0-0.19, Pxa0=xa0.46) or healthy subjects (rxa0=xa0-0.10, Pxa0=xa0.73). Remarkably, a higher ratio of Tregs to naive CD4 T cells was observed in LLR patients than in HIV controls (Pxa0=xa0.001) and healthy subjects (Pxa0<xa0.001). We conclude that LLR patients have important alterations in immunoregulation involving CD4(+)CD25(hi)FoxP3(+) Tregs. In this scenario, the role of Tregs seems to be more related to the control of the naive CD4 T-cell homeostatic proliferation, rather than to the immune activation.

Minor compounds of olive oil have postprandial anti-inflammatory effects

High postprandial levels of TAG may further induce endothelial dysfunction and inflammation in subjects with high fasting levels of TAG, an effect that seems to be related to oxidative stress. The present study investigated whether minor compounds of olive oil with antioxidant activity decrease postprandial levels of soluble isoforms of intercellular adhesion molecule 1 (sICAM-1) and vascular cell adhesion molecule 1 (sVCAM-1), as surrogate markers of vascular inflammation, after a high-fat meal. A randomized crossover and blind trial on fourteen healthy and fourteen hypertriacylglycerolaemic subjects was performed. The study involved a 1-week adaptation lead-in period on a National Cholesterol Education Program Step I diet supplemented with extra-virgin olive oil (EVOO) containing 1125 mg polyphenols/kg and 350 mg tocopherols/kg, or refined olive oil (ROO) with no polyphenols or tocopherols. After a 12 h fast, the participants ate a high-fat meal enriched in EVOO or ROO (50 g/m2 body surface area), which on average provided 3700 kJ energy with a macronutrient profile of 72% fat, 22% carbohydrate and 6% protein. Blood samples drawn hourly over the following 8 h demonstrated a similar postprandial TAG response for both EVOO and ROO meals. However, in both healthy and hypertriacylglycerolaemic subjects the net incremental area under the curve for sICAM-1 and sVCAM-1 were significantly lower after the EVOO meal. In conclusion,the consumption of EVOO with a high content of minor antioxidant compounds may have postprandial anti-inflammatory protective effects.

Long-Term Suppressive Combined Antiretroviral Treatment Does Not Normalize the Serum Level of Soluble CD14

Levels of soluble CD14 (sCD14) were longitudinally measured in 85 human immunodeficiency virus (HIV)-infected subjects during long-term receipt of suppressive combined antiretroviral therapy (cART) and compared to those in young and elderly HIV-negative control subjects. cART did not normalize sCD14 levels; rather, the HIV-infected group displayed a significantly higher sCD14 level at baseline (ie, before cART initiation), 1 year after cART initiation, and 5 years after cART initiation, compared with both control groups. Furthermore, the baseline CD4(+) T-cell count was inversely associated with the baseline sCD14 level. Our results point to the necessity of complementary therapies to treat the activated/inflamed status associated with chronic HIV infection and to the benefits of early initiation of cART.

CD4+CD25+/hiCD127lo Phenotype Does Not Accurately Identify Regulatory T Cells in All Populations of HIV-Infected Persons

The most commonly used regulatory T cell (Treg) phenotypes, CD4(+)CD25(hi)CD127(lo) and CD4(+)CD25(hi)FoxP3(+), were simultaneously used to determine the Treg frequency in 2 different groups of human immunodeficiency virus (HIV)-infected persons, one viremic and other aviremic. As expected, a strong correlation between both Treg phenotypes was observed in the aviremic group (r = 0.913; P < .001), but surprisingly, this correlation was completely absent in the viremic group (r = 0.143; P = .572). Data on T cell activation levels of both HIV groups suggest that the CD4(+)CD25(hi)CD127(lo) phenotype could just be mirroring the elevated numbers of activated non-regulatory T cells in the viremic HIV group.

A high-fat meal promotes lipid-load and apolipoprotein B-48 receptor transcriptional activity in circulating monocytes

BACKGROUNDnThe postprandial metabolism of dietary fats results in the production of apolipoprotein B-48 (apoB48)-containing triglyceride-rich lipoproteins (TRLs), which cause rapid receptor-mediated macrophage lipid engorgement via the apoB48 cell surface receptor (apoB48R). Monocytes circulate together with apoB48-containing TRLs in the postprandial bloodstream and may start accumulating lipids even before their migration to tissues and differentiation to macrophages.nnnOBJECTIVEnWe sought to determine whether circulating monocytes are equipped with apoB48R and whether, in the postprandial state, circulating monocytes accumulate lipids and modulate apoB48R transcriptional activity after intake of a high-fat meal.nnnDESIGNnIn a crossover design, we studied the effect of a high-fat meal on fasting and postprandial concentrations of triglycerides, free fatty acids, cholesterol, and insulin in 12 healthy men. TRLs and monocytes were freshly isolated at fasting, hourly until the postprandial peak, and at the late postprandial phase. TRLs were subjected to triglycerides, apoB48, and apolipoprotein B-100 analyses; and lipid accumulation and apoB48R mRNA expression levels were measured in monocytes.nnnRESULTSnMonocytes showed a time-dependent lipid accumulation in response to the high-fat meal, which was paralleled by an increase in apoB48R mRNA expression levels. These effects were coincident only with an increase in apoB48-containing TRLs in the postprandial phase and were also observed ex vivo in freshly isolated monocytes incubated with apoB48-containing TRLs.nnnCONCLUSIONnIn a setting of abundant plasma apoB48-containing TRLs, these findings highlight the role of dietary fat in inducing lipid accumulation and apoB48R gene transcription in circulating monocytes.

Different biological significance of sCD14 and LPS in HIV-infection: Importance of the immunovirology stage and association with HIV-disease progression markers

OBJECTIVESnBacterial lipopolysaccharide (LPS) and soluble CD14 (sCD14) levels have been indistinctly used to measure bacterial translocation independently of the immunovirological stage in HIV infection; however, when the association of both markers with different HIV-progression end-points has been studied, discrepant results have been reported. The aim of this study was to assess the relationship between LPS and sCD14 in different HIV-infection immune stages and to determine the relationship between these biomarkers with established HIV-disease-progression-related markers, as T-cell immune activation, high-sensitivity C-reactive protein and D-dimer.nnnMETHODSnSeventy-three chronically HIV-1-infected patients with detectable HIV-1 RNA levels were analyzed. LPS levels by use of limulus lysate assay, sCD14, intestinal fatty acid binding protein and inflammation-coagulation-associated biomarkers were assessed.nnnRESULTSnIn this study, we found that LPS and sCD14 levels were only associated when low CD4+ T-cell levels and high HIV RNA levels were present. In addition, only sCD14 levels, but not LPS, were independently associated with HIV-disease progression-related markers, supporting the clinical importance of sCD14.nnnCONCLUSIONSnThese results indicate that LPS and sCD14 have a different biological significance and should not be indistinctly used without taking the HIV immunovirological stage into account.

The TLR4 ASP299GLY polymorphism is a risk factor for active tuberculosis in Caucasian HIV-infected patients.

INTRODUCTIONnTuberculosis (TB) is a pandemic infectious disease especially frequent in HIV-infected patients. Toll-like receptor (TLR) 4 has been described to play a main role in the innate immunity against TB. In fact, single nucleotide polymorphisms (SNPs) in TLRs may influence AIDS disease progression. The association between two particular SNPs in human TLR4 (Asp299Gly and Thr399Ile) and active TB has been studied in non-HIV Africans with contradictory results. However, studies focusing on the effect of these TLR4 SNPs in active TB within a Caucasian HIV population are lacking.nnnOBJECTIVESnTo analyze the association between TLR4 Asp299Gly and Thr399Ile SNPs and active TB, in Caucasian Mediterranean HIV-infected individuals.nnnMETHODSn468 HIV-infected patients were analyzed. TLR4 genotyping was performed by real-time PCR and melting curve technology.nnnRESULTSnTB was diagnosed in 59 (12,6%) patients. In a bivariate analysis several variables resulted significantly associated with active TB; intravenous drugs use (OR= 2.2; 95% CI [1.2-3.8]), hepatitis C virus (HCV) co-infection (OR= 3.4; 95% CI [1.6-7.1]), CD4 count (p<0.001), HIV viral load (p=0.003), latent TB prophylaxis (OR= 0.3; 95% CI [0.1-0.5]), and TLR4 Asp299Gly (OR= 2.0; 95% CI [1.1-4.2]). No statistical association was found for the TLR4 Thr399Ile. After a multivariate analysis, HCV co-infection (OR= 3.8; 95% CI [2.2-6.5]), baseline CD4 count (OR= 0.996; 95% CI [0.994-0.998]), TLR4 Asp299Gly (OR= 2.57; 95% CI [1.18-5.61]) were independently associated with active TB and inversely with latent TB prophylaxis (OR= 0.24; 95% CI [0.01-0.60]).nnnCONCLUSIONSnWe describe an independent association between TLR4 Asp299Gly SNP and active TB in Caucasian Mediterranean HIV-infected patients.