Ana I. Perez-Caballero

Metabolic phenotypes of obesity influence triglyceride and inflammation homoeostasis

We examined the degree of postprandial triglyceride (TG) response over the day, representing a highly dynamic state, with continuous metabolic adaptations, among normal‐weight, overweight and obese patients, according to their metabolically healthy or abnormal status.

Effects of rs7903146 variation in the Tcf7l2 gene in the lipid metabolism of three different populations.

Background TCF7L2 rs7903146 is an important genetic factor predicting type 2 diabetes (T2DM) which has also been linked to higher cardiovascular risk. To date, there is little information about the additional impact of this single nucleotide polymorphism (SNP) beyond glucose metabolism. Methodology/Principal Findings We studied whether rs7903146 influenced postprandial lipid metabolism in three different populations (healthy young men, metabolic syndrome (MetS) patients and elderly persons). Eighty-eight healthy males were submitted to a single saturated fatty acid-rich test meal. Additionally, 110 middle-aged MetS patients and 20 healthy elderly persons (≥65 years) were submitted to three different dietary models followed by test meals. Minor allele homozygotes for rs7903146 showed a worse postprandial lipemia profile in young males, as seen by a lower HDL-cholesterol and Apo A1 concentration during the postprandial lipemia and a trend towards higher triglycerides (TG), than the other genotypes. In healthy elderly persons, carriers of the minor allele showed higher total cholesterol, LDL-cholesterol, Apo B and TG in the fasting state, and a higher postprandial area under the curve for total cholesterol, Apo B, small-triglyceride rich lipoprotein (TRL) cholesterol and small-(TRL) triglycerides. These results were accompanied by differential changes in adipokines. We did not observe any influence of rs7903146 on the postprandium of MetS patients. Conclusions/Significance Healthy young males and elderly persons who are carriers of the mutant allele for rs7903146 have an impaired postprandial lipid metabolism that may be mediated by an alteration in adipokine regulation, and may be related to the higher cardiovascular risk observed in these persons. Trial Registration ClinicalTrials.gov NCT00429195

Mediterranean Diet and Cardiovascular Risk: Beyond Traditional Risk Factors

A strict adherence to the Mediterranean Diet (MedDiet) has repeatedly been linked to a low risk of cardiovascular disease in several situations. Initially, the mechanisms considered as possible causes of this were based on the effects of this dietary pattern on the so-called traditional risk factors (especially lipids and blood pressure). However, the high relative reduction in the prevalence of cardiovascular morbidity and mortality were not proportional to the limited findings about regulation of those traditional risk factors. In addition to several studies confirming the above effects, current research on the MedDiet is being focused on defining its effects on non-traditional risk factors, such as endothelial function, inflammation, oxidative stress, or on controlling the conditions which predispose people to cardiovascular events, such as obesity, metabolic syndrome or type 2 diabetes mellitus. In the current article, after briefly reviewing the known effects of the MedDiet on the traditional risk factors, we will mainly focus on reviewing the current evidence about the effects that this dietary pattern exerts on alternative factors, including postprandial lipemia or coagulation, among others, as well as providing a short review on future directions.

Top Single Nucleotide Polymorphisms Affecting Carbohydrate Metabolism in Metabolic Syndrome: From the LIPGENE Study

RATIONALE Metabolic syndrome (MetS) is a high-prevalence condition characterized by altered energy metabolism, insulin resistance, and elevated cardiovascular risk. OBJECTIVES Although many individual single nucleotide polymorphisms (SNPs) have been linked to certain MetS features, there are few studies analyzing the influence of SNPs on carbohydrate metabolism in MetS. METHODS A total of 904 SNPs (tag SNPs and functional SNPs) were tested for influence on 8 fasting and dynamic markers of carbohydrate metabolism, by performance of an intravenous glucose tolerance test in 450 participants in the LIPGENE study. FINDINGS From 382 initial gene-phenotype associations between SNPs and any phenotypic variables, 61 (16% of the preselected variables) remained significant after bootstrapping. Top SNPs affecting glucose metabolism variables were as follows: fasting glucose, rs26125 (PPARGC1B); fasting insulin, rs4759277 (LRP1); C-peptide, rs4759277 (LRP1); homeostasis assessment of insulin resistance, rs4759277 (LRP1); quantitative insulin sensitivity check index, rs184003 (AGER); sensitivity index, rs7301876 (ABCC9), acute insulin response to glucose, rs290481 (TCF7L2); and disposition index, rs12691 (CEBPA). CONCLUSIONS We describe here the top SNPs linked to phenotypic features in carbohydrate metabolism among approximately 1000 candidate gene variations in fasting and postprandial samples of 450 patients with MetS from the LIPGENE study.

Influence of Obesity and Metabolic Disease on Carotid Atherosclerosis in Patients with Coronary Artery Disease (CordioPrev Study)

Background Recent data suggest that the presence of associated metabolic abnormalities may be important modifiers of the association of obesity with a poorer prognosis in coronary heart disease. We determined the influence of isolated overweight and obesity on carotid intima media thickness (IMT-CC), and also assessed whether this influence was determined by the presence of metabolic abnormalities. Methods 1002 participants from the CordioPrev study were studied at entry. We determined their metabolic phenotypes and performed carotid ultrasound assessment. We evaluated the influence of obesity, overweight and metabolic phenotypes on the IMT-CC. Results Metabolically sick participants (defined by the presence of two or more metabolic abnormalities) showed a greater IMT-CC than metabolically healthy individuals (p = 4 * 10−6). Overweight and normal weight patients who were metabolically healthy showed a lower IMT-CC than the metabolically abnormal groups (all p<0.05). When we evaluated only body weight (without considering metabolic phenotypes), overweight or obese patients did not differ significantly from normal-weight patients in their IMT-CC (p = 0.077). However, obesity was a determinant of IMT-CC when compared to the composite group of normal weight and overweight patients (all not obese). Conclusions In coronary patients, a metabolically abnormal phenotype is associated with a greater IMT-CC, and may be linked to a higher risk of suffering new cardiovascular events. The protection conferred in the IMT-CC by the absence of metabolic abnormality may be blunted by the presence of obesity. Trial Registration ClinicalTrials.gov NCT00924937