Fetal erythrocyte membrane lipids modification: preliminary observation of an early sign of compromised insulin sensitivity in offspring of gestational diabetic women.

AIMS: Intrauterine exposure to diabetes is a significant determinant of the development of obesity and early onset of Type 2 diabetes mellitus in the offspring. Both conditions are characterized by insulin resistance and the latter is associated with reduced membrane arachidonic and docosahexaenoic acids. Hence, we investigated if the membrane arachidonic and docosahexaenoic acids are depressed in the cord blood of babies born to women with gestational diabetes. METHODS: Cord (fetal) and maternal blood were obtained at delivery from control subjects (n = 33) and women with gestational diabetes (n = 40) and analysed for plasma triglycerides and cholinephosphoglycerides, and erythrocyte choline- and ethanolaminephosphoglycerides fatty acids. RESULTS: Babies of gestational diabetic mothers had reduced docosahexaenoic acid in the plasma (5.9 +/- 1.4 vs. 7.1 +/- 2.0, P < 0.01) and erythrocyte (4.0 +/- 2.2 vs. 5.4 +/- 2.9, P < 0.05) cholinephosphoglycerides. Moreover, the total omega-6 and omega-3 fatty acids of the erythrocyte cholinephosphoglycerides were significantly lower (P < 0.05) in these babies. A similar trend was observed in plasma triglycerides and erythrocyte ethanolaminephosphoglycerides. The maternal plasma triglycerides and erythrocyte ethanolaminephosphoglycerides fatty acids profile were not different between the two groups. However, there was a reduction in arachidonic acid and total omega-6 fatty acids in the erythrocyte cholinephosphoglycerides of the gestational diabetic women. CONCLUSION: The altered plasma and erythrocyte fatty acids in the cord blood of babies born to women with gestational diabetes suggests a perturbation in the maternal-fetal nutrient transport and/or fetal lipid metabolism.

Liver triacylglycerols and free fatty acids in streptozotocin-induced diabetic rats have atypical n-6 and n-3 pattern.

In diabetes there is a decrease in membrane arachidonic (AA) and docosahexaenoic (DHA) acids and a concomitant increase in linoleic (LA) and alpha-linolenic (ALA) acids. This metabolic perturbation is thought to be due to impaired activity of Delta(6)- and Delta(5)-desaturases. Triacylglycerols are the major lipid pool in plasma and liver tissue and have a significant influence on fatty acid composition of membrane and circulating phospholipids. Data on the distribution of n-6 and n-3 polyunsaturated fatty acids of triacylglycerols in diabetes are sparse. We investigated whether streptozotocin-induced diabetes in Sprague-Dawley rats alters fatty acid composition of triacylglycerols and free fatty acids of liver tissue. The animals were fed a breeding diet prior to mating, during pregnancy and lactation. On days 1-2 of pregnancy, diabetes was induced in 10 of the 25 rats. Liver was obtained at post partum day 16 for analysis. Relative levels of LA (P=0.03), dihomo-gamma-linolenic acid (DHGLA) (P=0.02), AA (P=0.049), total n-6 (P=0.02), ALA (P=0.013), eicosapentaenoic acid (EPA) (P=0.004), docosapentaenoic acid (22:5n-3, DPA) (P=0.013), DHA (P=0.033), n-3 metabolites (P=0.015) and total n-3 (P=0.011) were significantly higher in the triacylglycerols of the diabetics compared with the controls. Similarly, liver free fatty acids of the diabetics had higher levels of LA (P=0.0001), DHGLA (P=0.001), AA (P=0.001), n-6 metabolites (P=0.002), total n-6 (P=0.0001), ALA (P=0.003), EPA (P=0.015), docosapentaenoic (22:5n-3, P=0.003), DHA (P=0.002), n-3 metabolites (P=0.005) and total n-3 (P=0.001). We conclude that impaired activity of desaturases and/or long chain acyl-CoA synthetase could not explain the higher levels of AA, DHA and n-6 and n-3 metabolites in the diabetics. This seems to be consistent with an alteration in the regulatory mechanism, which directs incorporation of polyunsaturated fatty acids either into triacylglycerols or phospholipids.

Abnormal aortic fatty acid composition and small artery function in offspring of rats fed a high fat diet in pregnancy.

1. Disturbances of the in utero environment are associated with an increased risk of cardiovascular disease in adulthood. In this study we have determined whether abnormal vascular function in the adult offspring of rats fed a high saturated fat diet in pregnancy is associated with altered plasma lipids or vascular fatty acid content. 2. Female Sprague-Dawley rats were fed a breeding diet (4 % fat) or a diet high in saturated fat (20 % fat) for 10 days prior to and throughout pregnancy, and during weaning. Female offspring were then fed a maintenance diet (3 % fat) until 160 days of age. 3. Endothelium-dependent relaxation induced by acetylcholine was blunted in isolated branches of the femoral artery from 160-day-old female offspring of dams fed the saturated fat diet when compared with female offspring of dams fed the breeding diet. These offspring exhibited elevated plasma triglyceride and reduced plasma high density lipoprotein cholesterol concentrations. 4. The fatty acid composition of the aortas was abnormal, with a marked reduction in the content of arachidonic and docosahexaenoic acids. 5. This study demonstrates that a high fat diet in pregnant rats produces abnormal vascular function, plasma lipid disturbances and altered vascular fatty acid content in their female offspring during adulthood.

Arachidonic and docosahexaenoic acids are strongly associated in maternal and neonatal blood.

BACKGROUND: The red cell membrane fatty acid composition has frequently been used as an index of essential fatty acid (EFA) nutrition. After birth there is a decline in plasma arachidonic acid (AA) and docosahexaenoic (DHA) acids in babies fed on conventional formula which contains only the parent linoleic and alpha-linolenic acids. In human studies, the red cell phosphoglyceride composition appears to be more constant than that of plasma. In infants fed fish oil without AA, the AA proportions fall in the plasma but much less so in the red cells. This result might be considered to mean that there is no need for preformed AA. On the other hand, in a study where the levels of AA fell there was reduction of infant growth. Indeed, where cell membrane composition does change there is often an associated alteration in physiological functions of membranes. We therefore felt it worth investigating the balance between AA and DHA in a physiological situation where plasma levels are known to change, namely in pregnancy. PURPOSE: The aim of the study was to investigate a relationship between blood phosphoglyceride AA and DHA in pregnant women and neonates. SUBJECTS: Health pregnant women from London, England (n=193) and their term babies (n=45); healthy pregnant women from Seoul, South Korea (n=40) and their term babies (n=40); and preterm neonates (n=72) from London. METHOD: Blood samples were taken from British and Korean pregnant women during the third trimester, and from term and preterm babies at birth. These samples were taken for routine monitoring purposes in Korea and were a part of a study on pregnancy outcome for which ethical permission was granted from the East London and The City Health Authority and Lambeth, Southwark and Lewisham Health Authority. Approval was also obtained from the Ethical Committee of the Asan Medical Centre, Seoul, South Korea. RESULTS: AA and DHA correlated in plasma choline phosphoglycerides (CPG) of the British mothers (r=0.52 P<0.0001). The correlation coefficients and significance were much stronger in the red cell CPG and even more so in the term and preterm infant red cell CPGs ( r=0.75, 0.80 and 0.88, respectively). Similarly, AA and DHA correlated in red cell CPGs of the Korean women and their term babies. There was also a significant relationship between the two fatty acids in red cell ethanolamine phosphoglycerides in the mothers and their babies. Both linoleic (LA) and alpha-linolenic acids (ALA) were inversely associated with AA and DHA in some of the phosphoglyceride fractions of the mothers and babies. CONCLUSIONS: Although AA and DHA have different primary dietary origins, there were significant relationships between AA and DHA in the phosphoglycerides of the red cell membrane. This finding seems surprising if the red cell composition is determined by diet. These results suggest a physiological mechanism which attempts to maintain an appropriate balance between AA and DHA. It is plausible that there is an optimum balance between AA and DHA for membrane stability, deformability, enzyme and receptor function. SPONSORSHIP: The British Diabetic Association, March of Dimes Birth Defects Foundation and The Christopher H.R. Reeves Charitable Trust. European Journal of Clinical Nutrition (2000) 54, 50-56

Post-natal modulation of heart and liver phosphoglyceride fatty acids in pups.

BACKGROUND: Maternal dietary fats alter tissue fatty acids of the fetus and suckling pups. However, the possible change in tissue composition in response to the high oxygen tension extrauterine milieu independent of diet is not well understood. METHODS: We have compared the fatty acids of heart and liver choline (CPG) and ethanolamine (EPG) phosphoglycerides of rat offspring at birth and post-natal day 15. Sprague-Dawley rats were fed a breeding diet prior to mating, pregnancy and lactation. A proportion of each litter was sacrificed and the liver and heart were obtained for analysis. Changes in fatty acid composition specific to tissue (heart and liver) and phosphoglyceride (CPG and EPG) occurred post-natally. RESULTS: Relative levels of palmitate and oleate decreased and those of stearate increased in both the heart and liver phosphoglycerides of the suckling pups. There was a reduction in arachidonate/linoleate ratio primarily due to the increase in linoleic acid. With the exception in the heart EPG, the levels of arachidonic acid did not decrease concomitantly. Although the fatty acid composition of the diet did not change between pregnancy and lactation, docosahexaenoic and total n-3 increased in heart CPG and EPG and liver CPG of the suckling pups. Evidently, membrane fatty acid modulation, independent of maternal dietary fat, occurs in the extrauterine environment. It seems to favour the accretion of linoleic, arachidonic, docosahexaenoic and total n-3 fatty acids. CONCLUSION: Since there appears to be some parallel between the very preterm human neonate and rat pups with regard to nutrient store at birth and the neonatal developmental time window, our results may have relevance for the understanding of fatty acid metabolism and turnover in the human neonate.

Maternal diet high in fat reduces docosahexaenoic acid in liver lipids of newborn and sucking rat pups.

The effect of a maternal diet high in fat, similar to Western foods, and of diabetes on liver essential fatty acid composition of the mother and the newborn and sucking pups was investigated. Female Sprague-Dawley rats were fed on either a low-fat (42 g/kg) or a high-fat (329 g/kg) diet for 10 d before mating, throughout pregnancy and post-partum. On the first day of pregnancy, diabetes was induced by intravenous administration of streptozotocin in half the animals from the two diet groups. Half the pups were killed at birth, and the remaining pups and mothers at days 15 and 16 respectively. At birth, there was a significant reduction in the proportions of docosahexaenoic acid (DHA) in the liver phosphoglycerols and neutral lipids of the pups of both high-fat control and diabetic mothers compared with those of low-fat control and diabetic mothers. Diabetes decreased arachidonic (AA) and linoleic acid values in both the low- and high-fat groups at birth. The sucking pups of both the high-fat control and diabetic mothers exhibited a significant reduction in DHA and a concomitant compensatory increase in AA and a lowering in DHA-AA balance. In the mothers, the high-fat diet significantly increased the proportions of DHA in ethanolamine phosphoglycerols but had no observable effect in choline phosphoglycerols and neutral lipids. In the fetus the DHA level (g/100 g total fatty acids) was disproportionately reduced by the maternal high-fat diet. The adverse effect of the high-fat diet on the level of DHA (g/100 g total fatty acids) was greater in the neonate (and by implication the fetus) than in the sucking pups or mothers. It is concluded that a distortion of the biochemistry is induced in the offspring through a maternal high-fat diet, without genetic predisposition.