A variant (rs3812316, C771G, and Gln241His) in the MLXIPL (Max-like protein X interacting protein-like) gene encoding the carbohydrate response element binding protein has been associated with lower t Show more
A variant (rs3812316, C771G, and Gln241His) in the MLXIPL (Max-like protein X interacting protein-like) gene encoding the carbohydrate response element binding protein has been associated with lower triglycerides. However, its association with cardiovascular diseases and gene-diet interactions modulating these traits are unknown. We studied 7166 participants in the PREvención with DIeta MEDiterránea trial testing a Mediterranean diet (MedDiet) intervention versus a control diet for cardiovascular prevention, with a median follow-up of 4.8 years. Diet, lipids, MLXIPL polymorphisms, and cardiovascular events were assessed. Data were analyzed at baseline and longitudinally. We used multivariable-adjusted Cox regression to estimate hazard ratios for cardiovascular outcomes. The MLXIPL-rs3812316 was associated with lower baseline triglycerides (P=5.5×10(-5)) and lower hypertriglyceridemia (odds ratio, 0.73; 95% confidence interval [CI], 0.63-0.85; P=1.4×10(-6) in G-carriers versus CC). This association was modulated by baseline adherence to MedDiet. When adherence to MedDiet was high, the protection was stronger (odds ratio, 0.63; 95% CI, 0.51-0.77; P=8.6×10(-6)) than when adherence to MedDiet was low (odds ratio, 0.88; 95% CI, 0.70-1.09; P=0.219). Throughout the follow-up, both the MLXIPL-rs3812316 (P=3.8×10(-6)) and the MedDiet intervention (P=0.030) were significantly associated with decreased triglycerides. Likewise in G-carriers MedDiet intervention was associated with greater total cardiovascular risk reduction and specifically for myocardial infarction. In the MedDiet, but not in the control group, we observed lower myocardial infarction incidence in G-carriers versus CC (hazard ratios, 0.34; 95% CI, 0.12-0.93; P=0.036 and 0.90; 95% CI, 0.35-2.33; P=0.830, respectively). Our novel results suggest that MedDiet enhances the triglyceride-lowering effect of the MLXIPL-rs3812316 variant and strengthens its protective effect on myocardial infarction incidence. URL: www.controlled-trials.com. Unique Identifier: ISRCTN35739639. Show less
Squalene is an intermediate of cholesterol biosynthesis which can be obtained from the diet where it is abundant, for example, in olive oil. The effect of this isoprenoid on the development of atheros Show more
Squalene is an intermediate of cholesterol biosynthesis which can be obtained from the diet where it is abundant, for example, in olive oil. The effect of this isoprenoid on the development of atherosclerosis was investigated on apoE-knockout mice. Two groups of animals, separated according to sex, were fed on standard chow diet: the control group receiving only vehicle and the second group an aqueous solution of squalene to provide a dose of 1g/kg/day in male and female mice. This treatment was maintained for 10 weeks. At the end of this period, plasma lipid parameters, oxidative stress markers and hepatic fat were measured as well as cross-sectional lesion area of aortic root in both groups. Data showed that in males squalene feeding reduced atherosclerotic lesion area independently of plasma lipids and activation of circulating monocytes. In contrast, squalene intake did not decrease lesion area in females, despite reducing plasma cholesterol and triglycerides, isoprostane and percentage of Mac-1 expressing white cells. In males, atherosclerotic lesion area was positively and significantly associated with hepatic fat content and the plasma triglycerides were also strongly associated with liver weight. These results indicate that administration of squalene modulates lesion development in a gender specific manner, and that accumulation of hepatic fat by liver is highly correlated with lesion progression in males. Hence, squalene administration could be used as a safe alternative to correct hepatic steatosis and atherosclerosis particularly in males. Show less