Cholesterol metabolism. Its regulation at the hepatic and intestinal level

Aunque todas las células del organismo tienen capacidad para sintetizar colesterol, la mayor parte de la síntesis de éste, que da lugar a lo que se conoce como colesterol endógeno, se realiza en el hígado. El hepatocito tiene además capacidad de captar colesterol de las lipoproteínas circulantes, y a la vez de excretarlo formando parte de nuevas lipoproteínas de origen hepático o transformado en ácidos biliares. El colesterol de origen extrahepático procede principalmente de la mucosa intestinal. Aquí se realiza la absorción del colesterol de la dieta (colesterol exógeno), la biosíntesis de nuevo colesterol y la esterificación para ser almacenado en la célula o secretado a sangre en las lipoproteínas de origen intestinal. A nivel celular, la importancia del colesterol radica en que forma parte de la mayoría de las estructuras membranosas de todas las células del organismo. En este artículo se revisan algunos de estos aspectos del metabolismo del colesterol, y se analiza la influencia de la composición lipídica de un tipo de membranas celulares, las membranas microsomales, en la actividad de los enzimas reguladores del metabolismo de colesterol.Although all the cells in the body are able to form cholesterol, most part of this synthesis, leading to which is called endogenous cholesterol, occurs in the liver. Hepatocytes can also obtain cholesterol from the plasma lipoproteins. At the same time, cholesterol is either secreted from the liver in new plasma lipoproteins or transformed in bile acids. The extrahepatic cholesterol is mainly produced in the intestinal mucosa. In the site, it takes place the absorption of cholesterol from the diet (exogenous cholesterol), along with the biosynthesis of new cholesterol and the esterification of the molecule to be stored in the cell or secreted as plasma lipoproteins. At the cellular level, the importance of cholesterol comes from the fact that many of the membranous structures of all cells are partially composed of these substance. In this article some of these aspects of the colesterol metabolism are reviewed. We also describe the influence of lipid composition of microsomal membranes on the activity of colesterol metabolism regulating enzymes

Lipid Composition and Fluidity in the Jejunal Brush-Border Membrane of Spontaneously Hypertensive Rats. Effects on Activities of Membrane- Bound Proteins

The lipid compositíon and fluidity of jejunal brush-border membrane vesicles (BBMV) have been studied in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats. The activities of both Na+-dependent D-glucose cotransport and Na+-H antiport have also been determined. A significan! increase in the level of free cholesterol was observed in jejunal BBMV from SHR compared to WKY rats. Since phospholipid values did not change in either group of animals, a significan! enhancement in the free cholesterol/phospholipid ratio was observed in SHR. A decrease in the levels of phosphatidylethanolamine together with an increase in the values of phos­ phatidylserine was observed in hypertensive rats. Although the content of phosphatidylcholine (PC) and sphingomyelin (SM) was not singificantly altered in SHR, the ratio PC/SM significantly increased in these animals when compared to WKY rats. The majar fatty acids present in bursh-border membranes prepared from SHR and WKY rats were palmitic (16:0), stearic (18:0), oleic (18:1, n-9) and linoleic (18:2, n-6), and the fatty acid composition was not modified by the hypertension. A decreased fluorescence polarization, i.e., increased membrane ftuidity, was observed in SHR, which was not correlated to the increased ratio of cholesterol/phospholipid found in the brush-border membrane isolated from these animals. These structural changes found in SHR were associated to an enhancement in both Na+ -dependent D-glucose transport and Na+-H+ antiport activíty in the jejunal BBMVof SHR

Differential modulation of hepatic very low-density lipoprotein secretion by triacylglycerol-rich lipoproteins derived from different oleic-acid rich dietary oils

Minor components from dietary oils can modulate the atherogenic response of the TAG-rich lipoproteins (TRL) in which they are transported. In the present study we investigated the influence of TRL isolated from man after the intake of oleic acid-rich oils with different minor component compositions on VLDL secretion by rat primary hepatocytes. TRL were isolated from nine men after the intake of meals enriched with high-oleic sunflower oil (HOSO) or virgin olive oil (VOO) or VOO enriched with minor components (EVO). TRL were incubated with rat primary hepatocytes and the lipid accumulation was analysed in the cells and the secreted VLDL. The expression of genes for proteins related to hepatic lipid metabolism and VLDL production was also measured. Incubation of hepatocytes with TRL derived from HOSO as compared to VOO led to lower intracellular lipid accumulation and VLDL production despite higher mRNA expression for diacylglycerol-acyltransferase, microsomal TAG transfer protein, apoB and PPARα. When TRL derived from EVO were used there were no changes in VLDL secretion. These results suggest that incorporation of minor components from dietary high-oleic oils into TRL modulates the effect of these atherogenic particles on VLDL secretion. © 2007 The Authors.This work was supported by funds from Comision Interministerial de Ciencia y Tecnologia (CYCIT, AGL2005-00 572), Fondo de Investigaciones Sanitarias (FIS. Red Corporativa ISCIII G03/140-2002) and a Juan de la Cierva contract to J. S. P.Peer Reviewe

Effect of long-chain fatty alcohols from orujo olive oil on nitric oxide and eicosanoid generation

1st International Immunonutrition Workshop, Valencia, 3–5 October 2007, Valencia, SpainOlive pomace oil (‘orujo’ oil) is an olive oil product suitable for human consumption that is traditionally produced in Spain(1). The non-acylglycerol component of this oil is a good source of interesting minor components, e.g. triterpenes(2), or fatty alcohols, derived from waxy materials.This study is part of the project AGL2005–00572/ALI, financially supported by the Comision Interministerial de Ciencia y Tecnologia (CICYT).Peer reviewe

Effects of two highly monounsaturated oils on lipid composition and enzyme activities in rat jejunum

The effects of two monounsaturated fatty acid (MUFA) oils, olive oil (OO)and high-oleic sunflower oil (HOSO), with high content in oleic acid butdiffering in their non-fatty acid fraction, on brush-border membrane(BBM) lipid composition and fluidity and on mucosal enzyme activitiesof rat jejunum were studied. Animals were given semipurified diet withlinoleic acid to prevent essential fatty acid deficiency (control group)or semipurified diet containing 10% of either OO or HOSO for 12weeks. There was a significant decrease in the content of jejunalBBM phospholipids together with an increase in the level of freecholesterol in both oil-fed rats, when compared to controlgroup. Although the increase in the BBM free cholesterol levelwas not statistically significant in HOSO-fed rats, a significantdecrease in the phospholipid/free cholesterol ratio was found inboth OO and HOSO-fed animals compared to control group. Rat jejunalBBM had a high level of free fatty acids which was increased in BBMisolated from OO and HOSO-fed animals. There was no statisticalsignificant difference in the phospholipid distribution between thecontrol and the OO group. However, HOSO-fed animals showed the lowestlevel of phosphatidylethanolamine together with the highestphosphatidylcholine content and the phosphatidylcholine/sphingomyelinratio. The fatty acid pattern of jejunal BBM lipids was modifiedaccording to the major fatty acids in the oils. There was a decreasein both stearic acid (18:0) and linoleic acid (18:2 n-6), togetherwith an increase in oleic acid (18:1 n-9) in jenunal BBM isolatedfrom both oil experimental groups. All these results were accompaniedby a significant increase in the BBM fluidity (as assessed bysteady-state fluorescence polarization of diphenylhexatriene) isolatedfrom oil-fed rat, when compared to control group. OO and HOSO-fedanimals had the lowest activities of sucrase and maltase, whilealkaline phosphatase activity only was decreased in HOSO-fedanimals. The specific activity of maltase was not modified in anyexperimental rats. In summary, both MUFA oils induced similar effectson jejunal BBM lipid composition, fluidity, sucrase, maltase andlactase activities. Furthermore, HOSO intake resulted in a lowestalkaline phosphatase activity which was accompanied by changes inindividual phospholipid composition. All these results suggest thateffects of MUFA oils on jejunal BBM lipid composition and hydrolaseactivities are most likely due to the presence of high content ofoleic acid rather than other components contained in the non-fattyacid of olive oil

Potential vasorelaxant effects of oleanolic acid and erythrodiol, two triterpenoids contained in 'orujo' olive oil, on rat aorta

Orujo' olive oil is obtained by chemical processes from the waste resulting from the mechanical extraction of virgin olive oil. The aim of the present study was to evaluate a new pharmacological property of two natural triterpenoids contained in olive oil, as vasodilatory agents, and to determine their mechanism of action. The two compounds studied were oleanolic acid and erythrodiol. The vasorelaxant effect induced by these pentacyclic triterpenoids was studied in isolated thoracic rat aorta. Oleanolic acid and erythrodiol, accumulatively added, showed vasorelaxant activities in aortic rings with endothelium pre-contracted by 10-6 M-phenylephrine (maximum percentage of relaxation 86.38 (SEM 2.89) and 73.53 (SEM 6.01), respectively). They had almost no relaxant effect on depolarised or endothelium-denuded aortic segments. The relaxation was significantly attenuated by pre-treatment with the NO synthase inhibitor Nω -nitro-L-argi-nine-methylester (L-NAME; 3 × 10-4 M). To characterise the involvement of endothelial factors, in addifion to NO, arteries with endothelium were exposed to 10-5 M-indomethacin (INDO), a cyclo-oxygenase inhibitor, or INDO plus L-NAME. INDO did not have any significant effect on the relaxant response of both compounds. The combination of L-NAME plus INDO only abolished the oleanolic acid-induced relaxation. The present results suggest that the mechanism of relaxation seems to be mainly mediated by the endothelial production of NO; however, other mechanisms cannot be excluded. It can be concluded that oleanolic acid and erythrodiol may have interesting therapeutic potential as new vasodilator drugs, thus protecting the cardiovascular system. Therefore, the intake of 'orujo' olive oil, as a source of these compounds, might be beneficial in this regard.Comisión Interministerial de Ciencia y Tecnología AGL2002-00195Junta de Andalucía CAO01-00

Regional differences in transport, lipid composition, and fluidity of apical membranes of small intestine of chicken

Na+-dependent D-glucose transport was studied in brush-border membrane vesicles from duodenum, jejunum, and ileum of 5- to 6-wk-old chickens. Regional differences were found, and both initial rates and accumulation ratio of D-glucose were higher in the proximal part of the small intestine than in the ileum. To establish the mechanism(s) underlying these differences we have studied the density of Na+-dependent D-glucose cotransporter (SGLT1) as well as lipid composition and fluidity. Phlorizin-specific binding and Western blot analysis indicated a decrease in the amount of SGLT1 in the ileum when compared to the duodenum and jejunum. The distal part of the small intestine also showed a decrease in free cholesterol content and saturated-to-unsaturated fatty acid ratio together with an increase in lipid content and phosphatidylcholine-to-sphingomyelin ratio. These results were associated with a decrease in the diphenylhextriene fluorescence polarization found in brush-border membranes of the ileum. We can conclude that the decrease in the apical D-glucose transport found in the ileum is primarily due to a reduction in the amount of SGLT1 present in the brush-border membrane rather than the differences in the lipid composition and fluidity.Ministerio de Educación y Cultura de España. PB96/1255Generalitat de Catalunya.1999-SGR-0027

Effects of pomace olive oil-enriched diets on endothelial function of small mesenteric arteries from spontaneously hypertensive rats

Pomace olive oil (POM), an olive oil subproduct traditionally used in Spain, is a good source of minor components from the unsaponifiable fraction such as triterpenoids, mainly in the form of oleanolic acid, which induces vascular protection and vasodilatation. Our aim was to evaluate the effects of long-term intake of diets enriched in POM with high concentration in oleanolic acid on endothelial dysfunction associated to hypertension in small mesenteric arteries (SMA) from spontaneously hypertensive rats (SHR). During 12 weeks, rats (six rats per group) were fed either a control 2% maize oil diet (BD), or high-fat diets containing 15% refined olive oil (OL), pomace olive oil (POM), or pomace olive oil supplemented in oleanolic acid (POMO; up to 800 parts per million). Endothelial and vascular functions were assessed by relaxing or contracting responses to acetylcholine (ACh) or phenylephrine, respectively. The involvement of endothelium-derived relaxing factors in these responses was evaluated. In contrast to BD, SHR fed high-fat diets showed a biphasic response to ACh related to changes in eicosanoid metabolism. POM enhanced the endothelial function in SMA from SHR by increasing the endothelium-derived hyperpolarising factor (EDHF)-type component, whereas administration of POMO resulted in a similar contribution of NO/EDHF in the endothelial response to ACh. The present study shows that despite the lack of changes in blood pressure, consumption of POM improves endothelial function in SMA from SHR by improving the agonist-mediated EDHF/NO response. Thus, triterpenoids confer a protective role to POM against endothelial dysfunction in hypertension.Comision Interministerial de Ciencia y Tecnologia AGR163Junta de Andalucia AGL2005-00 572, AGL2008-022845/ALIFondo de Investigaciones Sanitarias ISCIII G03/140-200

Effect of long-chain fatty alcohols from orujo olive oil on nitric oxide and eicosanoid generation

Comision Interministerial de Ciencia y Tecnologia (CICYT) AGL2005–00572/AL