Almudena Gil-Villarino

Differential effects of dietary fat on chick plasma and liver composition and HMG-CoA reductase activity

The comparative effects of diet supplementation with 10% saturated fat rich in 12:0 and 14:0 fatty acids (coconut oil), without and with 1% added cholesterol, and with 10% unsaturated fat rich in n-3 polyunsaturated fatty acids (menhaden oil) on cholesterol metabolism in neonatal chicks were examined to clarify the different mechanisms of their hyper- and hypolipidemic action. Supplementation of coconut oil produced a significant hypercholesterolemia after 7 days of treatment, with a similar increase in the amount of both free and esterified cholesterol. Supplementation of coconut oil plus cholesterol produced a higher increase of plasma cholesterol levels (approximately two to three times higher than those found with standard diet). However, supplementation of menhaden oil induced a significant decrease in total cholesterol after only 2 weeks of treatment. Levels of plasma triglycerides did not change by coconut oil addition to the diet, but a significant increase was observed after coconut oil plus cholesterol feeding. Menhaden oil produced a transient decrease in plasma triglycerides. Hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity did not change with coconut oil treatment. However, both coconut oil plus cholesterol and menhaden oil supplemented diets drastically decreased reductase activity after 1 week of dietary manipulation. These results show that different nutrients with the same inhibitory effect on reductase activity produced opposite effects on plasma cholesterol content, suggesting the existence of important differences in the regulatory mechanisms implied in cholesterol biosynthesis and its accumulation in plasma.

Production of a rapid hypercholesterolemia in young chick by feeding coconut oil from two different sources and fatty acid composition

In this work, we have studied comparatively the effects of supplementation to a standard diet with the same proportion (20%) of saturated fat (coconut oil) from two different commercial sources and with clear differences in their fatty acid composition. Both experimental diets produced a rapid (24 h) and significant hypercholesterolemia in ICday-old chicks. However, plasma cholesterol levels were higher in animals fed a diet supplemented with coconut oil for commercial cooking use (“Pastry”) than in those fed a diet with coconut oil for pharmaceutical use (“Pharmacy”). Both dietary manipulations rapidly (24 h) increased the percentages of the more hypercholesterolemic fatty acids (12:0 and 14:0) in plasma. This increase was higher after “Pastry” than after “Pharmacy” diet feeding. Likewise, the percentages of the hypocholesterolemic fatty acids (18: 1 n-9 and 18:2 n-6) were lower in plasma from treated animals than in control, especially after feeding the “Pastry” diet. Ah these differences may be implied in the high hypercholesterolemic effects showed by “Pastry” diet. The hyper-cholesterolemia was not accompanied by changes in the levels of liver cholesterol.

Hypocholesterolemic activity of dipyridamole: effects on chick plasma and lipoprotein composition and arachidonic acid levels.

We have studied the effects of dipyridamole treatment on chick plasma and lipoprotein composition in postprandial and fasting (12 h) conditions. Plasma cholesterol levels were higher in fasted than in fed chicks, whereas triglycerides declined during starvation. Dipyridamole treatment reduced plasma cholesterol content, mainly of the free cholesterol fraction. In postprandial conditions, total cholesterol content of high and low density lipoproteins decreased in a similar proportion to that observed in plasma. However, cholesterol and other chemical constituents of intermediate and very low density lipoproteins were more drastically reduced by dipyridamole than in plasma. Total amounts of these lipoprotein fractions were also reduced about 50%. The effects of dipyridamole in fasted animals were not significant. To our knowledge, this is one of the first reports about the response of lipoprotein cholesterol to dipyridamole treatment. A strong decrease was also found in the arachidonic acid content of plasma phospholipids and cholesterol esters fractions.

Differential changes in the fatty acid composition of the main lipid classes of chick plasma induced by dietary coconut oil

For a better understanding of the hyperlipidemic function of saturated fat, we have studied the comparative effects of diet supplementation with 10 and 20% coconut oil on the main lipid classes of chick plasma. Changes in fatty acid composition of free fatty acid and triglyceride fractions were parallel to that of the experimental diet. Thus, the increase in the percentages of 12:0 and 14:0 acids may contribute to the hypercholesterolemic effects of coconut oil feeding. Plasma phospholipids incorporated low levels of 12:0 and 14:0 acids whereas 18:0, the main saturated fatty acid of this fraction, also increased after coconut oil feeding. The percentage of 20:4 n-6 was higher in plasma phospholipids than in the other fractions and was significantly decreased by our dietary manipulations. Likewise, minor increases were found in the percentages of 12:0 and 14:0 acids in plasma cholesterol esters. However, the percentage of 18:2 acid significantly increased after coconut oil feeding. Our results show a relationship between fatty acid composition of diets and those of plasma free fatty acid and triglyceride fractions, whereas phospholipids and cholesterol esters are less sensitive to dietary changes.

Changes in plasma lipid composition induced by coconut oil. Effects of dipyridamole

The comparative effects of 10–20% coconut oil feeding on fatty acid composition of the main lipid classes of chick plasma have been studied with and without simultaneous treatment with dipyridamole in order to clarify the hypolipidemic role of this drug. Coconut oil drastically increased the percentages of lauric and myristic acids in free fatty acid and triacylglycerol fractions, whereas these changes were less pronounced in phospholipids and cholesterol esters. The percentage of arachidonic acid was higher in plasma phospholipids than in the other fractions and was significantly decreased by coconut oil feeding. Linoleic acid, the main fatty acid of cholesterol esters, was drastically increased by coconut oil feeding. Changes induced by the simultaneous administration of dipyridamole were more pronounced in the phospholipids and cholesterol esters than in the other fractions. The fall observed in linoleic acid levels after dipyridamole treatment may be of interest for a lower production of its derived eicosanoids, especially in plasma phospholipids and cholesterol esters.ResumenSe estudia el efecto de la suplementación de la dieta con aceite de coco al 10–20% sobre la composición en ácidos grasos de las principales fracciones lipídicas del plasma de pollo en relación con la administración conjunta de dipiramidol, a fin de comprobar la función hipolipemiante de este fármaco. El aceite de coco incrementa drásticamente los porcentajes de los ácidos laúrico y mirístico en las fracciones de ácidos grasos libres y de triglicéridos, con cambios menores en los fosfolípidos y en los ésteres de colesterol. El porcentaje de ácido araquidónico es mayor en los fosfolípidos plasmáticos que en las otras fracciones y disminuye significativamente por el consumo de aceite de coco. El ácido linoleico, el principal ácido graso de los ésteres de colesterol, se incrementa fuertemente por el aceite de coco. Los cambios inducidos por la administración conjunta de dipiridamol son más pronunciados en los fosfolípidos y en los ésteres de colesterol que en las otras fracciones. El descenso observado en los niveles de ácido linoleico tras el tratamiento con dipiridamol puede tener interés por la menor producción de sus derivados eicosanoides, especialmente en los fosfolípidos y en los ésteres de colesterol plasmáticos.

Dipyridamole prevents the coconut oil-induced hypercholesterolemia. A study on lipid plasma and lipoprotein composition.

For a better understanding of the hypolipidemic function of dipyridamole, we have studied the comparative effects of diet supplementation with 10% coconut oil with and without dipyridamole on the lipid plasma and lipoprotein composition in chicks. This study was performed under postprandial and food-deprivation (12h) conditions. Coconut oil induced a clear hypercholesterolemia under both feeding conditions. Simultaneous administration of dipyridamole maintained total and esterified cholesterol at levels similar to those observed in control animals sacrificed under postprandial conditions. Under these conditions, our results also show that dipyridamole significantly reduced cholesterol levels in all the chick plasma lipoproteins that were increased by coconut oil administration. Nevertheless, it should be emphasised that the levels of total cholesterol found in intermediate- and very-low-density lipoproteins were lower than in control. All chemical components of these fractions were significantly decreased by dipyridamole. The effects were not significant in chicks deprived of food. In conclusion, our results show that the hypercholesterolemia induced by coconut oil was prevented by dipyridamole. To our knowledge, this is one of the first reports on the antihypercholesterolemic effects of dipyridamole.

Dipyridamole reduces cholesterol and triglyceride levels in plasma and lipoproteins from young chicks fed a saturated fat-enriched diet

We have studied the value of dipyridamole for the prevention of hypercholesterolemia caused by saturated fat. This study shows that supplementation of 10-20% coconut oil to the diet induced a significant hypercholesterolemia under postprandial conditions. Simultaneous administration of dipyridamole and 10% coconut oil for 2 weeks maintained plasma cholesterol and triglycerides at levels similar to control, counteracting the increase induced by coconut oil. Dipyridamole significantly reduced cholesterol levels in all the chick plasma lipoproteins that were increased by coconut oil administration. However, it should be emphasized that cholesterol and other chemical components were more drastically reduced by dipyridamole in intermediate- and very-low-density lipoproteins than in other lipoprotein fractions.

Coconut oil induces short-term changes in lipid composition and enzyme activity of chick hepatic mitochondria

We studied the short-term effects of a 20% coconut oil supplementation to the chick diet on lipid composition of liver and hepatic mitochondria, and changes that occurred in mitochondrial-associated enzymes as a result of this diet. No significant differences were observed in the lipid contents of liver when young chicks were fed the experimental diet, whereas hepatic mitochondria rapidly changed in response to this diet. Total cholesterol significantly increased in mitochondria at 24 hours of coconut oil diet feeding and decreased when dietary treatment was prolonged for 5 to 14 days. Changes in total mitochondrial phospholipids showed an inverse profile. A significant decrease in phosphatidylethanolamine and an increase in sphingomyelin were found at 24 hours. The cholesterol/phospholipid molar ratio significantly and rapidly (24 hours) increased in mitochondria from treated animals. Cytochrome oxidase activity drastically increased after 24 hours of experimental diet feeding and lowered to the control values when dietary manipulation was prolonged for 5 to 14 days. ATPase activity showed an inverse profile. Changes in cytochrome oxidase activity were parallel to changes in the cholesterol/phospholipid molar ratio, whereas changes in ATPase activity showed an inverse correlation with changes in this molar ratio. To our knowledge, this is one of the first reports on the very rapid response (24 hours) of mitochondrial lipid composition and function to saturated fat feeding.

Influence of fasting status on the effects of coconut oil on chick plasma and lipoprotein composition

For a better understanding of the hyperlipidemic function of saturated fat, we have studied the effects of diet supplementation with 10–20% coconut oil on the chick plasma and lipoprotein composition under postprandial and starvation conditions. A significant hypercholesterolemia was found in chicks fed the standard diet after 12 h of food deprivation. In these conditions, LDL-cholesterol also increased, whereas triglyceride levels were reduced in HDL, VLDL and chylomicron fractions. Coconut oil induced a significant hypercholesterolemia under both conditions, also increasing the plasma triglyceride content under postprandial conditions, but not after starvation. Coconut oil feeding increased all the chemical components of HDL, especially under postprandial conditions, but did not affect the HDL-triglycerides under food-deprivation conditions. Total cholesterol and triglyceride levels in LDL increased after coconut oil supplementation to the diet. Differences were more pronounced under postprandial conditions. Changes in VLDL and chylomicron composition were less evident.ResumenPara profundizar en el conocimiento de la actividad hiperlipidémica de la grasa saturada, se estudia el efecto de la suplementación de la dieta con aceite de coco (10–20%) sobre la composición química del plasma y de las lipoproteínas de pollo tanto en condiciones postprandiales como de ayuno. En animales controles, se observa una significativa hipercolesterolemia tras 12 h de ayuno. En estas condiciones, el LDL-colesterol también aumenta, mientras que los niveles de triglicéridos disminuyen en las fracciones HDL, VLDL y quilomicrones. El aceite de coco produce una significativa hipercolesterolemia en ambas condiciones nutricionales, aumentando los niveles de triglicéridos sólo en condiciones postprandiales. Respecto de las lipoproteínas, el aceite de coco incrementa todos los componentes de las HDL, especialmente en condiciones postprandiales, pero no afecta a los HDL-triglicéridos en ayuno. En la fracción LDL, el colesterol total y los triglicéridos aumentan tras la suplementación de aceite de coco. Las diferencias son más acusadas en condiciones postprandiales. Los cambios en la composición de las VLDL y de los quilomicrones resultan menos evidentes.

Influence of dipyridamole on the fatty acid composition of the main lipid classes of chick serum.

We have studied the effects of dipyridamole treatment on the fatty acid composition of the main lipid classes of chick serum bearing in mind the relationship between platelet aggregation and eicosanoids production from arachidonic acid. In the free fatty acids, percentages of MUFA and n-6 PUFA fell. The effects of dipyridamole appeared to be less pronounced in triglyceride fraction, but more so in serum phospholipids and cholesterol esters. The percentage of arachidonic acid was significantly reduced by dipyridamole, as well as that of different n-3 PUFA present in phospholipid fraction. The percentage of linoleic acid in serum cholesterol esters was significantly lowered by dipyridamole, whereas that of arachidonic acid did not change significantly. Our results suggest that decreased arachidonic acid in the serum phospholipids and linoleic acid in all lipid classes may be of importance in order to dipyridamole participation in several pathologies characterized by an imbalance in the production of vasodilator and vasoconstrictor prostanoids.