Comparison of the effects of dietary saturated, mono-unsaturated and polyunsaturated fatty acids on very-low-density lipoprotein secretion when delivered to hepatocytes in chylomicron remnant-like particles.

The effect of chylomicron remnant-like particles (CRLPs) enriched in saturated, mono-unsaturated or n-6 polyunsaturated fatty acids (derived from palm, olive or corn oil, respectively) on the secretion of VLDL (very-low-density lipoprotein) by rat hepatocytes in culture was investigated. CRLPs were incubated with cultured hepatocytes for 5 h. The medium was then removed and the secretion of cholesterol and triacylglycerol (TAG) into the whole medium during the following 16 h was determined. After exposure of the cells to olive oil as compared with corn and palm oil CRLPs, secretion of TAG into the medium was decreased. The TAG content of the cells was also lower in experiments with olive oil as compared with corn oil CRLPs. The levels of apoB48 (apolipoprotein B48) found in the medium remained unchanged after the exposure of the cells to the different types of remnants. These findings indicate that the type of fat in the diet directly affects VLDL lipid secretion on delivery to the liver in chylomicron remnants.

Hypercholesterolaemia alters the responses of the plasma lipid profile and inflammatory markers to supplementation of the diet with n-3 polyunsaturated fatty acids from fish oil.

BACKGROUND: The influence of supplementing the diet with long-chain n-3 polyunsaturated fatty acids (PUFA) from fish oil on plasma lipids and lipid peroxides and the production of pro-inflammatory mediators in normolipidaemic and hypercholesterolaemic rats were studied. MATERIALS AND METHODS: Rats were divided into four groups and fed one of the following diets: a control diet (containing 4% corn oil); an n-3 PUFA diet [containing 4% eicospentaenoic (EPA) + docosahexaenoic (DHA)]; a hypercholesterolaemic diet (HCH); or a HCH + n-3 PUFA diet over a 4-week period. Plasma lipids, lipid peroxides, cytokines [tumour necrosis factor (TNF)alpha, interleukin (IL)-6, interferon (IFN)gamma] and mRNA for hepatic nuclear factor-4alpha (HNF4alpha) were determined. RESULTS: Plasma triglyceride (TG), but not cholesterol, levels were decreased by the n-3 PUFA as compared with the control diet (P < 0.001), but the addition of n-3 PUFA to the HCH diet decreased both the TG (P < 0.01) and cholesterol (P < 0.05) concentrations. Plasma lipid peroxides and expression HNF4alpha mRNA were increased by n-3 PUFA in the normolipidaemic (P < 0.05), but not in the hyperlipidaemic rats. Compared with the control diet group, plasma concentrations of TNFalpha and IL-6 were increased in the n-3 PUFA (P < 0.05) and HCH diet (P < 0.05, P < 0.01, respectively) groups, but not in animals given the HCH + n-3 PUFA diet, whereas IFNgamma levels were increased in hypercholesterolaemia (P < 0.05), but were unaffected by n-3 PUFA. CONCLUSION: These results demonstrate that the major effect of fish oil n-3 PUFA is to lower the TG levels in both normo- and hyperlipidaemia. Furthermore, in the hypercholesterolaemic state, fish oil n-3 PUFA induces additional beneficial changes in the immune and peroxidation responses.

Maternal lipid metabolism and placental lipid transfer.

During early pregnancy, long-chain polyunsaturated fatty acids (LC-PUFA) may accumulate in maternal fat depots and become available for placental transfer during late pregnancy, when the fetal growth rate is maximal and fetal requirements for LC-PUFAs are greatly enhanced. During this late part of gestation, enhanced lipolytic activity in adipose tissue contributes to the development of maternal hyperlipidaemia; there is an increase in plasma triacylglycerol concentrations, with smaller rises in phospholipid and cholesterol concentrations. Besides the increase in plasma very-low-density lipoprotein, there is a proportional enrichment of triacylglycerols in both low-density lipoproteins and high-density lipoproteins. These lipoproteins transport LC-PUFA in the maternal circulation. The presence of lipoprotein receptors in the placenta allows their placental uptake, where they are hydrolysed by lipoprotein lipase, phospholipase A(2) and intracellular lipase. The fatty acids that are released can be metabolized and diffuse into the fetal plasma. Although present in smaller proportions, maternal plasma non-esterified fatty acids are also a source of LC-PUFA for the fetus, their placental transfer being facilitated by the presence of a membrane fatty acid-binding protein. There is very little placental transfer of glycerol, whereas the transfer of ketone bodies may become quantitatively important under conditions of maternal hyperketonaemia, such as during fasting, a high-fat diet or diabetes. The demands for cholesterol in the fetus are high, but whereas maternal cholesterol substantially contributes to fetal cholesterol during early pregnancy, fetal cholesterol biosynthesis rather than cholesterol transfer from maternal lipoproteins seems to be the main mechanism for satisfying fetal requirements during late pregnancy.

Lipid metabolism during the perinatal phase, and its implications on postnatal development.

During pregnancy, lipid metabolism plays a major role to warrant the availability of substrates to the foetus. By using different experimental designs in the rat we have been able to answer several questions that were open about the short- and long-term effects of alterations of lipid metabolism during the perinatal stage. The first one was to demonstrate the importance of maternal body fat depot accumulation during the first half of pregnancy. We found that conditions like undernutrition circumscribed to this specific period when foetal growth is still small, that impede such fat accumulation not only restrain intrauterine development but also have long-term consequences, as shown by an impaired glucose tolerance when adults. Secondly, undernutrition during suckling has major long-term effect decreasing body weight, even though food intake was kept normal from the weaning period. Present findings also show that a diet rich in omega-3 fatty acids during pregnancy and lactation has negative effects on offspring development, but cross fostered experiments showed that the effect was a consequence of the intake of these fatty acids during the lactation period rather than during pregnancy. Pups from dams that were fed a fish oil-rich diet during pregnancy and lactation were found to have altered glucose/insulin relationship at the age of 10 weeks. Since a omega-3 fatty acid-rich diet decreases milk yield during lactation, additional experiments were carried out to determine whether decreased food intake, altered dietary fatty acid composition, or both were responsible for the long-term effects on the glucose/insulin axis. Results show that the decreased food intake caused by a omega-3 fatty acid-rich diet rather than the change in milk composition during suckling was responsible for the reduced pancreatic glucose responsiveness to insulin release at 16 weeks of age. In conclusion, present findings indicate that impaired maternal fat accumulation during early pregnancy and food intake during lactation, rather than a difference in dietary fatty acid composition have a greater influence on postnatal development and affect glucose/insulin relationships in adult rats.

Experimental models for studying perinatal lipid metabolism. Long-term effects of perinatal undernutrition.

By using different experimental designs in the rat we have been able to answer several unanswered questions on the short- and long-term effects of alterations of lipid metabolism during the perinatal stage. The first was to demonstrate the importance of maternal body fat accumulation during the first half of pregnancy, since undernutrition in this critical period when fetal growth is slow, impedes fat depot accumulation and not only restrains intrauterine development but has long-term consequences, as shown by an impaired glucose tolerance when adults. Secondly, undernutrition during suckling has major long-term effect of decreasing body weight, even though food intake is kept normal from the weaning period. Our findings also show that a diet rich in n-3 fatty acids during pregnancy and lactation has adverse effects on offspring development, but cross fostered experiments showed that this effect was a consequence of the intake of these fatty acids during the lactation period rather than during pregnancy. Pups from dams that were fed a fish oil-rich diet during pregnancy and lactation were found to have altered glucose/insulin relationship at the age of 10 weeks. Since a n-3 fatty acid-rich diet decreases milk yield during lactation, additional experiments were carried out to determine whether decreased food intake or altered dietary fatty acid composition, or both, were responsible for the long-term effects on the glucose/insulin axis. Results show that the decreased food intake caused by a n-3 fatty acid-rich diet rather than the change in milk composition during suckling was responsible for the reduced pancreatic glucose responsiveness to insulin release at 16 weeks of age. In conclusion, present findings indicate that impaired maternal fat accumulation during early pregnancy and food intake during lactation, rather than a difference in dietary fatty acid composition, have major effects on postnatal development and affect glucose/insulin relationships in adult rats.

A sucrose-rich diet during pregnancy causes a similar response in Sprague-Dawley and Wistar rats.

BACKGROUND/AIMS: In order to determine whether the response to a sucrose-rich diet (SRD) during pregnancy in the rat varies depending on the strain, the responsiveness to a SRD (63 g sucrose/100 g) during pregnancy in Wistar and Sprague-Dawley rats was studied. METHODS: One group of rats of each strain was fed the SRD, whereas another group received the same diet except that sucrose was replaced by an equal amount of cornstarch. Half of the rats were mated, and all animals were studied 20 days later. RESULTS: Initial body weight did not differ among groups, but final body weight of pregnant Wistar rats was lower than in Sprague-Dawley, and this difference corresponded to a decrease in fetal body weight in the former. Feeding a SRD did not modify pregnancy outcome in either rat strain. Plasma triglycerides increased with a SRD, although this effect was milder in Wistar pregnant rats than in the other groups. Adipose tissue lipoprotein lipase activity was lower in pregnant than in virgin rats, but no differences were found as result of either diet or rat strain. Liver triglyceride concentration increased in virgin rats fed SRD, the effect being greater in Sprague-Dawley than in Wistar rats. CONCLUSION: Differences in the response to a SRD in pregnant and virgin rats do not depend on the strain of rats used.