Dietary cystine and liver triacylglycerols in rats: effects of dietary lysine and threonine

Addition of excess cystine to a wheat gluten diet did not alter rat liver triacylglycerols or serum cholesterol. However, if the cystine-enriched diet was supplemented with lysine and threonine, rats accumulate triacylglycerols and show increased serum cholesterol. Increases in hepatic triacylglycerols can be prevented by the further addition of methionine. This diet further increases serum cholesterol. We conclude that accumulation of triacylglycerols in the liver might be due to an increased methionine requirement, induced by the addition of excess cystine, and therefore to choline deficiency.     

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.     

Effect of ethyl choline mustard on choline dehydrogenase and other enzymes of choline metabolism

The effect of ethyl choline mustard (ECMA), and effective irreversible inhibitor of choline transport, was investigated on the enzymes of choline metabolism. ECMA at concentrations of 50 microM hardly affected choline acetyltransferase and caused only a 20% inhibition of choline kinase at a concentration of 1 mM. However, the mustard was an extremely effective inhibitor of choline dehydrogenase, producing 50% inhibition at concentrations of 6 microM. The inhibition was prevented by incubation in the presence of choline or by prior reaction of the mustard with thiosulphate. Separation of the components of the ECMA solution on TLC suggested that only the compound with an aziridine ring was an effective inhibitor of choline dehydrogenase. The inhibition was resistant to the washing out of excess unreacted mustard. The rate constant of inhibition was 395 M-1 X S-1. By the use of [3H]ECMA a single polypeptide in the enzyme preparation having a MW of 67,000 was labelled. The labelling was thiosulphate-sensitive and prevented by incubation with choline. It is concluded that ECMA is an irreversible inhibitor of choline dehydrogenase. It is at least as effective an inhibitor of choline dehydrogenase as of the choline transport system, although it does not appreciably inhibit choline acetyltransferase or choline kinase in the micromolar range.     

Specific versus non-specific effects of dietary fat on carcinogenesis

It will be apparent from this review that dietary fat can exert both specific and non-specific effects on carcinogenesis, at least in experimental animals. The non-specific effects appear to be related primarily to effects of dietary fat on energy balance. Although a positive energy balance can be achieved on a high-carbohydrate low-fat diet, it is much more likely to occur on a high-fat diet because of the high energy density of fat [101] and the fact that dietary fat is less capable of imparting a sense of satiety [102]. A continuing state of positive energy balance leads to obesity which has been associated with increased risk of cancer at a number of sites, including endometrium [103-106], postmenopausal breast cancer [107-113], renal cancer [114,115] and possibly cancers of the colorectum [116-122], pancreas [103,123] and prostate [124]. Whereas the non-specific effects of dietary fat appear to be deleterious for cancer, the specific effects in some cases can be beneficial. Examples are long-chain n-3 polyunsaturated fatty acids. CLA and tocotrienols. It is still too early to predict whether these may be of value in the prevention and/or treatment of human cancer but they seem worthy of further investigation. Knowledge of their mechanism of action may suggest novel approaches to the cancer problem and, as in the case of vitamins A and D, it may be possible to find analogues with more potent anti-cancer activity.     

The effect of dietary carbohydrate and fat on the activities of some enzymes responsible for glycerolipid synthesis in rat liver.

1. Male rats were fed for 14 days on diets containing (by wt.) 53% of starch, or on diets in which 20% of the starch was replaced by sucrose, corn oil or lard. 2. The hepatic activities of the microsomal glycerol phosphate acyltransferase, dihydroxyacetone phosphate acyltransferase, phosphatidate cytidylyltransferase, diacylglycerol acyltransferase and choline phosphotransferase, and of the soluble phosphatidate phosphohydrolase, were measured. 3. The soluble phosphatidate phosphohydrolase activity was higher in those rats fed on lard than in those fed on the starch diet. Choline phosphotransferase activity was higher in the rats fed on corn oil than in those fed on the starch diet. 4. The rate of hepatic glycerolipid synthesis was measured in vivo 1 min after injection of [1,3-3H]glycerol and [1-14C]palmitate into the portal veins. 5. The relative rate of phosphatidylcholine synthesis in vivo was increased after feeding with corn oil and the higher specific activity of choline phosphotransferase may contribute to this result. The equivalent rate of triacylglycerol synthesis was increased by feeding with lard rather than corn oil, and the increased activity of phosphatidate phosphohydrolase may partly explain this. The latter changes probably contribute to the increased concentration of triacylglycerol which other authors have observed in the livers and sera of animals fed on saturated and monounsaturated fats.     

Effect of dietary ghee--the anhydrous milk fat, on blood and liver lipids in rats

Dairy products are important sources of dietary fat in India. Anhydrous milk fat, viz., ghee, is consumed as such in the diet and also is used for frying the dishes. Ghee contains high levels of saturated fatty acids and cholesterol, which are considered risk factors for cardiovascular diseases. In the present study, ghee, at levels ranging from 0.25 to 10%, was included in a nutritionally balanced AIN-76 diet fed to Wistar rats for a period of 8 weeks. The serum lipid profiles of these animals showed a dose dependent decrease in total cholesterol, low density lipoproteins and very low density lipoproteins cholesterol, and triglyceride levels when ghee was present at levels greater than 2.5% in the diet. Liver cholesterol and triglycerides also were decreased in these animals. When ghee was included as a sole source of fat at a 10% level, polyunsaturated fatty acids in the serum and liver lipids were reduced significantly. Similar results were observed when ghee was subjected to a higher temperature (120 degrees C) to generate cholesterol oxidation products and fed to the animals. Although cholesterol oxidation products were not accumulated in serum, significant amounts were accumulated in liver only when ghee was fed as a sole source of fat at a 10% level. This study revealed that the consumption of ghee up to a 10% level in the diet altered blood lipid profiles in such a manner as not to elevate the risk factors for cardiovascular diseases.