Nuclear oxysterol receptors, LXRs, are involved in the maintenance of mouse caput epididymidis structure and functions.

In this study we looked at the epididymides and spermatozoa of mice knocked-out for nuclear oxysterol receptors (LXR). We have shown that LXR-deficient mice exhibited upon ageing a severe disruption of their caput epididymides associated with abnormal accumulation of neutral lipids. The epididymis defaults were correlated with sperm head fragility and infertility. In agreement with the observed caput defect in transgenic animals in which both LXRalpha and LXRbeta isoforms were disrupted, we have shown here that both receptors are expressed in caput and cauda epididymides regions. LXRbeta was predominantly expressed throughout the mouse epididymis while the expression of LXRalpha was weaker. In addition, the expression of selected genes that can be considered as markers of adult epididymis function was monitored via Northern blots in the different single and double LXR-deficient backgrounds. Altogether, the data presented here suggest that LXR receptors are important actors in epididymis function.

A polyunsaturated fatty acid diet lowers blood pressure and improves antioxidant status in spontaneously hypertensive rats.

gamma-Linolenic acid [GLA, 18:3(n-6)], eicosapentaenoic acid [EPA, 20:5(n-3)] and docosahexaenoic acid [DHA, 22:6(n-3)] have been reported to prevent cardiovascular diseases. However, they are highly unsaturated and therefore more sensitive to oxidation damage. We investigated the effects of a diet rich in these polyunsaturated fatty acids (PUFA) on blood pressure, plasma and lipoprotein lipid concentrations, total antioxidant status, lipid peroxidation and platelet function in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Five-week-old SHR and WKY rats were fed for 10 wk either a diet containing Isio 4 oil or a diet rich in GLA, EPA and DHA (5.65, 6.39 and 4.94 g/kg dry diet, respectively). The total antioxidant status was assayed by monitoring the rate of free radical-induced hemolysis. VLDL-LDL sensitivity to copper-induced lipid peroxidation was determined as the production of thiobarbituric acid reactive substances. After dietary PUFA supplementation, a significant decrease in blood pressure of SHR rats (-20 mm Hg) was observed and the total antioxidant status was enhanced. VLDL-LDL resistance to copper-induced peroxidation was increased in both strains. The PUFA supplementation did not change platelet maximum aggregation in SHR rats, but it decreased the aggregation speed. In hypertensive rats, GLA + EPA + DHA supplementation lowers blood pressure, enhances total anti-oxidant status and resistance to lipid peroxidation, diminishes platelet aggregation speed and lowers plasma lipid concentrations. Thus, it enhances protection against cardiovascular diseases. Therefore, nutritional recommendations for cardiovascular disease prevention should take into account the pharmacologic properties of GLA, EPA and DHA.

Fatty acid metabolism, pharmacological nutrients and hypertension.

The purpose of the present study was to investigate the effect of a concentrated preparation (EPA 30) containing eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3) on the limiting desaturation steps of the polyunsaturated fatty acid biosynthesis in spontaneously hypertensive rats (SHR). Adult SHR were divided into two groups: one group received a standard diet, and the experimental group the standard diet including 0.8% of EPA30 for 9 weeks. Blood pressure was measured at the end of the diets. The desaturase activities and fatty acid composition were determined in isolated hepatocytes. The blood pressure did not decrease in the experimental group. The desaturated products of the n-6 family (gamma-linolenic acid, 18:3 n-6 and arachidonic acid, 20:4 n-6) were lowered in the EPA30 group, when their respective substrates (18:2 n-6 and 20:3 n-6) were increased. EPA and DHA were higher in the experimental group delta 6 n-3, delta 6 n-6 and delta 5 n-6 desaturase activities were depressed approximately 20% in the EPA30 group. EPA30 being an active nutrient on the EFAs cascade, increasing the level of PG3 precursors and decreasing the level of PG2 precursors, favourable conditions have been established to reduce hypertension. The underlying mechanism related to the regulation of desaturase activities by these fatty nutrients remains to be elucidated.