👤 Maria Isabel Queipo-Ortuño

Several epidemiological studies have related an increase of lipids in the postprandial state to an individual risk for the development of CVD, possibly due to the increased plasma levels of TAG and fatty acids (FA) through enzymes of FA metabolism. The interaction between nutrition and the human genome determines gene expression and metabolic response. The aim of the present study was to evaluate the influence of a fat overload on the gene mRNA levels of lipogenic regulators in peripheral blood mononuclear cells (PBMC) from patients with the metabolic syndrome. The study included twenty-one patients with criteria for the metabolic syndrome who underwent a fat overload. Measurements were made before and after the fat overload of anthropometric and biochemical variables and also the gene mRNA levels of lipogenic factors. The main results were that the fat overload led to an increased mRNA levels of sterol regulatory element binding protein-1 (SREBP1), retinoid X receptor α (RXRα) and liver X receptor α (LXRα) in PBMC, and this increase was associated with the FA synthase (FASN) mRNA levels. We also found that TAG levels correlated with FASN mRNA levels. In addition, there was a positive correlation of SREBP1 with RXRα and of LXRα with the plasma lipoperoxide concentration. The fat overload led to an increase in regulators of lipogenesis in PBMC from patients with the metabolic syndrome. Show less

Apolipoprotein C-III (APOC3) is a component of triglyceride rich lipoproteins, and SstI polymorphism has been associated with hypertriglyceridemia. Apolipoprotein A-I (APOA1) is the major component of HDL and MspI polymorphism has been associated with APOA1 and HDL-C levels. Thus, we study the influence of these polymorphisms in the postprandial response in metabolic syndrome (MS). 73 MS patients and 21 healthy subjects underwent a fat overload, with measurements of their fasting and postprandial lipid profile. The APOC3 SstI and the APOA1MspI polymorphisms were genotyped. No significant differences were found in the lipid profile with respect to the MspI genotype. Patients with the S2S2 APOC3 genotype had significantly higher fasting and postprandial triglyceride levels and postprandial APOC3 and chylomicron-triglyceride levels compared with the other SstI APOC3 genotypes. Homozygosity for the minor allele of the APOC3 SstI polymorphism was associated to a worse postprandial response in MS patients. Show less

Apolipoprotein A5 is a key gene controlling VLDL synthesis and hydrolysis and is the target of the main pharmacological agent to lower triglycerides (fibrates). We hypothesised that variability in the promoter of the APOA5 gene may affect the individual response to fibrate therapy, in both the fasting and postprandial states. We selected 50 subjects with the metabolic syndrome who also had important increase in fasting triglycerides. A subgroup of 36 patients underwent lipid-lowering treatment with 160 mg/day of fenofibrate (Secalip) for 3 months. The participants underwent a 60 g fat overload with a commercial preparation, after which we assessed the influence of the -1131T>C APOA5 SNP on the postprandial response. Compared with non-carriers, the C allele carriers had significantly higher triglyceride levels at baseline (54.87%), and at 3h (61.08%) and 4h (68.35%). Other lipid parameters were not affected by the APOA5 genotype. Our results indicate that carriers of the -1131C allele had a better response to fenofibrate treatment (reduction in triglyceride levels of 40.33% at baseline, P=0.018; and postprandially, 37.64% at 3h, P=0.028 and 42.58% at 4h after the high-fat meal, P=0.018) than wild-type subjects (30.91% decrease at baseline, P<0.001; and 26.61% at 3h P=0.005 and 22.95% at 4h P=0.033 after the high-fat meal). Thus, the treatment for patients with the metabolic syndrome and elevated plasma triglyceride levels may vary according to whether they carry the APOA5 -1131T>C polymorphism. Show less