👤 F Pérez-Jiménez

Fatty acids and other components of the diet may modulate, among others, mechanisms involved in homeostasis, aging, and age-related diseases. Using a proteomic approach, we have studied how dietary oil affected plasma proteins in young (6 months) or old (24 months) rats fed lifelong with two experimental diets enriched in either sunflower or virgin olive oil. After the depletion of the most abundant proteins, levels of less abundant proteins were studied using two-dimensional electrophoresis and mass spectrometry. Our results showed that compared with the sunflower oil diet, the virgin olive oil diet induced significant decreases of plasma levels of acute phase proteins such as inter-alpha inhibitor H4P heavy chain (at 6 months), hemopexin precursor (at 6 and 24 months), preprohaptoglobin precursor (at 6 and 24 months), and α-2-HS glycoprotein (at 6 and 24 months); antioxidant proteins such as type II peroxiredoxin (at 24 months); proteins related with coagulation such as fibrinogen γ-chain precursor (at 24 months), T-kininogen 1 precursor (at 6 and 24 months), and apolipoprotein H (at 6 and 24 months); or with lipid metabolism and transport such as apolipoprotein E (at 6 and 24 months) and apolipoprotein A-IV (at 24 months). The same diet increased the levels of apolipoprotein A-1 (at 6 and 24 months), diminishing in general the changes that occurred with age. Our unbiased analysis reinforces the beneficial role of a diet rich in virgin olive oil compared with a diet rich in sunflower oil, modulating inflammation, homeostasis, oxidative stress, and cardiovascular risk during aging. Show less

The S2 allele of the SstI polymorphism of the apolipoprotein (apo) C-III gene has been associated with elevated triacylglycerol concentrations, high blood pressure, and increased risk of coronary artery disease, all of which are characteristic of an insulin-resistant state. To study the effect of this mutation on carbohydrate metabolism in healthy persons, we gave 41 male subjects 3 consecutive diets. The first was rich in saturated fat [15% protein, 47% carbohydrate, 38% fat (20% saturated)], the second was a National Cholesterol Education Program Step 1 diet [15% protein, 57% carbohydrate, 28% fat (< 10% saturated)], and the last was rich in monounsaturated fat [15% protein, 47% carbohydrate, 38% fat (22% monounsaturated, < 10% saturated)]. At the end of each dietary period, subjects received an oral-glucose-tolerance test (OGTT). Apo C-III genotype significantly affected basal glucose concentrations (P < 0.045) and insulin concentrations after the OGTT (P < 0.012). APOC3*S1/APOC3*S2 subjects (n = 13) had higher insulin concentrations after the OGTT than APOC3*S1/APOC3*S1 subjects (n = 28) in the 3 periods (diet 1: P < 0.0004; diet 2: P < 0.01; diet 3: P < 0.008). Multiple regression analysis showed that this polymorphism predicted the insulin response to the OGTT (P < 0.031) and the difference between basal insulin concentrations and insulin concentrations after the OGTT (P < 0.002) with the saturated fat diet. In summary, our results suggest that the mutation in the apo C-III gene affects insulin response to an OGTT, which could result in reduced sensitivity to insulin, especially when persons consume diets rich in saturated fat. Show less

The plasma lipid response to changes in dietary fat and cholesterol can vary between individuals. The SstI polymorphism, arising from a cytosine to guanosine substitution in the 3' untranslated region of the APOC3 gene distinguishes between two alleles--S1 and S2. The S2 allele has been associated with elevated plasma triacylglycerol, cholesterol, and apolipoprotein (apo) C-III concentrations. In 90 young men we examined the effect of the same mutation on the response of low-density-lipoprotein (LDL) cholesterol to dietary monounsaturated fat. The frequency for the S2 allele was 0.14. Subjects were fed a low-fat diet for 25 d, followed by a diet rich in monounsaturated fatty acid (22% MUFA, 38% total fat) for 28 d; lipoproteins were measured at the end of each diet. There were no significant differences in initial total cholesterol between subjects with the APOC3*S1/APOC3*S1 (S1/S1) and APOC3*S1/APOC3*S2 (S1/S2) genotypes. After consumption of the diet high in MUFA, significant increases in LDL cholesterol (0.13 mmol/L, P < 0.027) were noted in the S1/S1 subjects whereas a significant decrease was observed in the S1/S2 subjects (-0.18 mmol/L, P < 0.046). Significant genotypic effects were seen for diet-induced changes in LDL cholesterol (P < 0.00034), total cholesterol (P < 0.009), and apo B (P < 0.0014). A study of the effect of the interaction between this mutation with that present in position -76 of the APOA1 gene promoter region (G/A) revealed that both mutations had an additive effect on changes in total cholesterol, LDL cholesterol, and apo B induced by diets. Plasma LDL-cholesterol responsiveness to the diet may be explained, at least in part, by variation at the APOC3 gene locus. Show less