母代高脂饮食诱导子代在小鼠生命早期出现糖脂代谢紊乱且具有雄性易感性

目的：探讨孕期和哺乳期的高脂饮食能否导致子代在生命早期出现糖脂代谢紊乱。方法成年雌性C57BL/6J小鼠与正常饮食雄性小鼠进行交配,孕鼠随机分为高脂饮食组和正常饮食组,在孕期和哺乳期喂养高脂饲料或正常饲料,至交配后第一代鼠断乳时（3周龄）观察其糖脂代谢相关性指标以及肝脏病理表现。结果较正常饮食组子鼠相比,高脂饮食子鼠出生体重更低（ P＜0.05）。在断乳时,高脂饮食组雄性子鼠体重较重（ P ＝0.038）,腹腔糖耐量实验30 min和60 min血糖明显升高（P值分别为＜0.001和＜0.01）,糖耐量曲线下面积较大（P＝0.0016）,HOMA-IR值较大（P＜0.05）,雌性子鼠腹腔糖耐量实验在30 min血糖高于正常组（P＜0.01）,而糖耐量曲线下面积和HOMA-IR值在两组之间无明显统计学意义。雄性和雌性子代小鼠空腹胆固醇水平高脂饮食组均高于正常饮食组（ P值分别为＜0.0001和0.0004）,而两组雄性和雌性子代小鼠空腹胰岛素和甘油三酯水平差异均无显著性（ P均＞0.05）。另外,在断乳时高脂饮食子鼠出现肝脏脂肪变性,雌性和雄性子鼠无明显差异。结论母鼠孕期和哺乳期高脂饮食能够诱导子代在生命早期就能出现糖脂代谢紊乱并且雄性子鼠更易出现肥胖、糖耐量异常、胰岛素抵抗。     

Perinatal salt restriction: a new pathway to programming adiposity indices in adult female Wistar rats

Low birth weight has been associated with increased obesity in adulthood. It has been shown that dietary salt restriction during intrauterine life induces low birth weight and insulin resistance in adult Wistar rats. The present study had a two-fold objective: to evaluate the effects that low salt intake during pregnancy and lactation has on the amount and distribution of adipose tissue; and to determine whether the phenotypic changes in fat mass in this model are associated with alterations in the activity of the renin-angiotensin system. Maternal salt restriction was found to reduce birth weight in male and female offspring. In adulthood, the female offspring of dams fed the low-salt diet presented higher adiposity indices than those seen in the offspring of dams fed a normal-salt diet. This was attributed to the fact that adipose tissue mass (retroperitoneal but not gonadal, mesenteric or inguinal) was greater in those rats than in the offspring of dams fed a normal diet. The adult offspring of dams fed the low-salt diet, compared to those dams fed a normal-salt diet, presented the following: plasma leptin levels higher in males and lower in females; plasma renin activity higher in males but not in females; and no differences in body weight, mean arterial blood pressure or serum angiotensin-converting enzyme activity. Therefore, low salt intake during pregnancy might lead to the programming of obesity in adult female offspring.     

Exposure to maternal overnutrition and a high-fat diet during early postnatal development increases susceptibility to renal and metabolic injury later in life

Overnutrition during pre- and postnatal development both confer increased susceptibility to renal and metabolic risks later in life; however, whether they have an additive effect on the severity of renal and metabolic injury remains unknown. The present study tested the hypothesis that a combination of a pre- and postnatal diet high in fat/fructose would exacerbate renal and metabolic injury in male offspring later in life. Male offspring born to high fat/high-fructose-fed mothers and fed a high-fat/high-fructose diet postnatally (HF-HF) had increased urine albumin excretion (450%), glomerulosclerosis (190%), and tubulointerstitial fibrosis (101%) compared with offspring born to mothers fed a standard diet and fed a standard diet postnatally (NF-NF). No changes in blood pressure or glomerular filtration were observed between any of the treatment groups. The HF-HF offspring weighed ～23% more than offspring born to mothers fed a high-fat/high-fructose diet and fed a normal diet postnatally (HF-NF), as well as offspring born to mothers fed a standard diet regardless of their postnatal diet. The HF-HF rats also had increased (and more variable) blood glucose levels over 12 wk of being fed a high-fat/high-fructose diet. A combination of exposure to a high-fat/high-fructose diet in utero and postnatally increased plasma insulin levels by 140% compared with NF-NF offspring. Our data suggest that the combined exposure to overnutrition during fetal development and early postnatal development potentiate the susceptibility to renal and metabolic disturbances later in life.     

Both high and low maternal salt intake in pregnancy alter kidney development in the offspring

In humans, low glomerular numbers are related to hypertension, cardiovascular, and renal disease in adult life. The present study was designed 1) to explore whether above- or below-normal dietary salt intake during pregnancy influences nephron number and blood pressure in the offspring and 2) to identify potential mechanisms in kidney development modified by maternal sodium intake. Sprague-Dawley rats were fed low (0.07%)-, intermediate (0.51%)-, or high (3.0%)-sodium diets during pregnancy and lactation. The offspring were weaned at 4 wk and subsequently kept on a 0.51% sodium diet. The kidney structure was assessed at postnatal weeks 1 and 12 and the expression of proteins of interest at term and at week 1. Blood pressure was measured in male offspring by telemetry from postnatal month 2 to postnatal month 9. The numbers of glomeruli at weeks 1 and 12 were significantly lower and, in males, telemetrically measured mean arterial blood pressure after month 5 was higher in offspring of dams on a high- or low- compared with intermediate-sodium diet. A high-salt diet was paralleled by higher concentrations of marinobufagenin in the amniotic fluid and an increase in the expression of both sprouty-1 and glial cell-derived neutrophic factor in the offspring's kidney. The expression of FGF-10 was lower in offspring of dams on a low-sodium diet, and the expression of Pax-2 and FGF-2 was lower in offspring of dams on a high-sodium diet. Both excessively high and excessively low sodium intakes during pregnancy modify protein expression in offspring kidneys and reduce the final number of glomeruli, predisposing the risk of hypertension later in life.     

Increased maternal fat consumption during pregnancy alters body composition in neonatal mice

Maternal overnutrition prior to and during gestation causes pronounced metabolic dysfunction in the adult offspring. However, less is known about metabolic adaptations in the offspring that occur independently of postnatal growth and nutrition. Therefore, we evaluated the impact of excess maternal dietary lipid intake on the in utero programming of body composition, hepatic function, and hypothalamic development in newborn (P0) offspring. Female mice were fed a low-fat (LF) or high-fat (HF) diet and were mated after 4, 12, and 23 wk. A subset of the obese HF dams was switched to the LF diet during the second (DR2) or third (DR3) pregnancies. The HF offspring accrued more fat mass than the LF pups, regardless of duration of maternal HF diet consumption or prepregnancy maternal adiposity. Increased neonatal adiposity was not observed in the DR3 pups. Liver weights were reduced in the HF offspring but not in the DR2 or DR3 pups. Offspring hepatic triglyceride content was reduced in the HF pups, but hepatic inflammation and expression of lipid metabolism genes were largely unaffected by maternal diet. Maternal diet did not alter the hypothalamic expression of orexigenic and anorexigenic neuropeptides in the offspring. Thus, the intrauterine programming of increased neonatal adiposity and reduced liver size by maternal overnutrition is evident in mice at birth and occurs prior to the development of maternal obesity. These observations demonstrate that dietary intervention during pregnancy minimizes the deleterious effects of maternal obesity on offspring body composition, potentially reducing the offsprings' risk of developing obesity and related diseases later in life.     

Mild prenatal protein malnutrition increases alpha2C-adrenoceptor density in the cerebral cortex during postnatal life and impairs neocortical long-term potentiation and visuo-spatial performance in rats

Mild reduction in the protein content of the mother's diet from 25 to 8% casein, calorically compensated by carbohydrates, does not alter body and brain weights of rat pups at birth, but leads to significant enhancements in the concentration and release of cortical noradrenaline during early postnatal life. Since central noradrenaline and some of its receptors are critically involved in long-term potentiation (LTP) and memory formation, this study evaluated the effect of mild prenatal protein malnutrition on the alpha2C-adrenoceptor density in the frontal and occipital cortices, induction of LTP in the same cortical regions and the visuo-spatial memory. Pups born from rats fed a 25% casein diet throughout pregnancy served as controls. At day 8 of postnatal age, prenatally malnourished rats showed a threefold increase in neocortical alpha2C-adrenoceptor density. At 60 days-of-age, alpha2C-adrenoceptor density was still elevated in the neocortex, and the animals were unable to maintain neocortical LTP and presented lower visuo-spatial memory performance. Results suggest that overexpression of neocortical alpha2C-adrenoceptors during postnatal life, subsequent to mild prenatal protein malnutrition, could functionally affect the synaptic networks subserving neocortical LTP and visuo-spatial memory formation.     

Developmental aluminum toxicity in mice can be modulated by low concentrations of minerals (Fe,Zn, P,Ca, Mg) in the diet

Female Swiss Webster mice were fed diets containing 7 (control) or 1000 μg Al/g diet from conception to weaning. Pregnancy weight gain, brith weight, litter size, postnatal mortality, and weaning weight were measured. In different groups, diets low in Fe, Zn, P, or Ca and Mg (CaMg) were used as basal diets, to which Al was added. Relative to controls, who received NRC recommended levels of these nutrients, all diets with marginal essential trace elements impacted development, as demonstrated by effects on birth weight (CaMg, Fe) or weaning weight (Fe, Zn, P). Compared to diets low in Al, the 1000-mg Al/g diet led to reduced weaning weight regardless of the essential element content of the diet. Other end points were influenced by Al only within the basaldiet group; pregnancy weight gain with the low-P diet, litter size with the low-Fe diet, pregnancy completion with the low-Zn diet, and postnatal mortality with the low-CaMg or low-Zn diet. Thus, diets marginal in selected minerals can differentially alter the toxicological profile of developmental Al exposures. A basal diet was also used in which the NRC diet was supplemented with ascorbic acid, which promotes Al absorption. No modification of Al toxicity was seen with ascorbic acid supplementation.     

Folic acid content of diet during pregnancy determines post-birth re-set of metabolism in Wistar rat dams

Maternal metabolism begins to return to homeostasis (re-set) following birth and is accelerated by lactation. Delay in metabolic re-set may contribute to postpartum weight retention and later-life metabolic consequences. Folic acid (FA) is essential during pregnancy but inadequate intakes may alter 1-carbon metabolism, consequently affecting energy homeostatic systems. Our objectives were to examine the effects of FA content 1)below and 2)above requirements during pregnancy on the re-set of body weight, markers of hepatic 1-carbon metabolism and central and peripheral energy metabolic pathways in Wistar rat mothers early post-weaning (PW) compared to pregnant controls. Pregnant Wistar rats were fed an AIN-93G diet with FA at 0X, 1X (control, 2 mg FA/kg) or a range above requirements at 2.5X, 5X or 10X recommended levels then the control diet during lactation up to 1 week PW. Dams fed below (0X) or above (5X and 10X) FA requirements had delayed weight-loss from weaning up to 1 week PW, higher plasma insulin and HOMA-IR and changes in glucose and lipid metabolism-regulating genes in muscle, but not liver or adipose tissue compared to controls. Expression of folate-related genes in liver were lower in high FA fed dams. Central food intake neurons were not affected by FA diets. In conclusion, intakes of FA below (0X) or above (5X, 10X) requirements during pregnancy delayed weight-loss, dysregulated 1-carbon pathways in the liver and peripheral energy metabolic pathways in the Wistar rat mother up to 4 weeks after dietary exposure; potentially programming long-term negative metabolic effects and that of her future offspring.     

Maternal obesity reverses the resistance to LPS-induced adverse pregnancy outcome and increases female offspring metabolic alterations in cannabinoid receptor 1 knockout mice

Maternal overnutrition negatively impacts the offspring's health leading to an increased risk of developing chronic diseases or metabolic syndrome in adulthood. What we eat affects the endocannabinoid system (eCS) activity, which in turn modulates lipogenesis and fatty acids utilization in hepatic, muscle, and adipose tissues. This study aimed to evaluate the transgenerational effect of maternal obesity on cannabinoid receptor 1 knock-out (CB1 KO) animals in combination with a postnatal obesogenic diet on the development of metabolic disturbances on their offspring. CB1 KO mice were fed a control diet (CD) or a high-fat diet (HFD; 33% more energy from fat) for 3 months. Offspring born to control and obese mothers were also fed with CD or HFD. We observed that pups born to an HFD-fed mother presented higher postnatal weight, lower hepatic fatty acid amide hydrolase activity, and increased blood cholesterol levels when compared to the offspring born to CD-fed mothers. When female mice born to HFD-fed CB1 KO mothers were exposed to an HFD, they gained more weight, presented elevated blood cholesterol levels, and more abdominal adipose tissue accumulation than control-fed adult offspring. The eCS is involved in several reproductive physiological processes. Interestingly, we showed that CB1 KO mice in gestational day 15 presented resistance to LPS-induced deleterious effects on pregnancy outcome, which was overcome when these mice were obese. Our results suggest that an HFD in CB1 receptor-deficient mice contributes to a “nutritional programming” of the offspring resulting in increased susceptibility to metabolic challenges both perinatally and during adulthood.     

High-protein nutrition during pregnancy and lactation programs blood pressure, food efficiency, and body weight of the offspring in a sex-dependent manner

Maternal low-protein diet during pregnancy is a risk factor for cardiovascular disease of the offspring in later life. The impact of high-protein diet during pregnancy on the cardiovascular phenotype of the offspring, however, is still unknown. We examined the influence of a high-protein diet during pregnancy and lactation on the renal, hemodynamic, and metabolic phenotype of the F1 generation. Female Wistar rats were either fed a normal protein diet (20% protein: NP) or an isocaloric high-protein diet (40% protein: HP) throughout pregnancy and lactation. At weaning, the offspring were fed with standard diet, and they were allocated according to sex and maternal diet to four groups: normal-protein male (NPm, n = 25), normal-protein female (NPf, n = 19), high-protein male (HPm, n = 24), high-protein female (HPf, n = 29). During the experiment (22 wk), the animals were characterized by repeated measurement of body weight, food intake, blood pressure, glucose tolerance, energy expenditure, and kidney function. At the end of the study period histomorphological analyses of the kidneys and weight measurement of reproductive fat pads were conducted. There were no differences in birth weight between the study groups. No influence of maternal diet on energy expenditure, glucose tolerance, and plasma lipid levels was detected. Blood pressure and glomerulosclerosis were elevated in male offspring only, whereas female offspring were characterized by an increased food efficiency, higher body weight, and increased fat pads. Our study demonstrates that a high-protein diet during pregnancy and lactation in rats programs blood pressure, food efficiency, and body weight of the offspring in a sex-dependent manner.     

High-protein diet during gestation and lactation affects mammary gland mRNA abundance, milk composition and pre-weaning litter growth in mice

We evaluated the effect of a high-protein diet (HP) on pregnancy, lactational and rearing success in mice. At the time of mating, females were randomly assigned to isoenergetic diets with HP (40% w/w) or control protein levels (C; 20%). After parturition, half of the dams were fed the other diet throughout lactation resulting in four dietary groups: CC (C diet during gestation and lactation), CHP (C diet during gestation and HP diet during lactation), HPC (HP diet during gestation and C diet during lactation) and HPHP (HP diet during gestation and lactation). Maternal and offspring body mass was monitored. Measurements of maternal mammary gland (MG), kidney and abdominal fat pad masses, MG histology and MG mRNA abundance, as well as milk composition were taken at selected time points. HP diet decreased abdominal fat and increased kidney mass of lactating dams. Litter mass at birth was lower in HP than in C dams (14.8 v. 16.8 g). Dams fed an HP diet during lactation showed 5% less food intake (10.4 v. 10.9 g/day) and lower body and MG mass. On day 14 of lactation, the proportion of MG parenchyma was lower in dams fed an HP diet during gestation as compared to dams fed a C diet (64.8% v. 75.8%). Abundance of MG α-lactalbumin, β-casein, whey acidic protein, xanthine oxidoreductase mRNA at mid-lactation was decreased in all groups receiving an HP diet either during gestation and/or lactation. Milk lactose content was lower in dams fed an HP diet during lactation compared to dams fed a C diet (1.6% v. 2.0%). On days 14, 18 and 21 of lactation total litter mass was lower in litters of dams fed an HP diet during lactation, and the pups' relative kidney mass was greater than in litters suckled by dams receiving a C diet. These findings indicate that excess protein intake in reproducing mice has adverse effects on offspring early in their postnatal growth as a consequence of impaired lactational function.     

Folic Acid and Protein Content in Maternal Diet and Postnatal High-Fat Feeding Affect the Tissue Levels of Iron, Zinc, and Copper in the Rat

Although maternal, fetal, and placental mechanisms compensate for disturbances in the fetal environment, any nutritional inadequacies present during pregnancy may affect fetal metabolism, and their consequences may appear in later life. The aim of the present study is to investigate the influence of maternal diet during gestation on Fe, Zn, and Cu levels in the livers and kidneys of adult rats. The study was carried out on the offspring (n?=?48) of mothers fed either a protein-balanced or a protein-restricted diet (18% vs. 9% casein) during pregnancy, with or without folic acid supplementation (0.005- vs. 0.002-g folic acid/kg diet). At 10?weeks of age, the offspring of each maternal group were randomly assigned to groups fed either the AIN-93G diet or a high-fat diet for 6?weeks, until the end of the experiment. The levels of Fe, Zn, and Cu in the livers and kidneys were determined by the F-AAS method. It was found that postnatal exposure to the high-fat diet was associated with increased hepatic Fe levels (p?相似文献   

Postnatal essential fatty acid deficiency in mice affects lipoproteins, hepatic lipids, fatty acids and mRNA expression

We have previously reported that essential fatty acid deficiency (EFAD) during suckling in mice resulted in an adult lean phenotype and a resistance to diet-induced obesity. We now hypothesized that postnatal EFAD would cause long-term effects on lipid metabolism. C57BL/6 mice were fed an EFAD or a control diet from the 16th day of gestation and throughout lactation. The pups were weaned to standard diet (STD) and at 15 weeks of age given either high fat diet (HFD) or STD. Lipoprotein profiles, hepatic lipids, fatty acids and mRNA expression were analyzed in 3-week-old and 25-week-old offspring. At weaning, the EFAD pups had higher cholesterol levels in both plasma and liver and 6-fold higher concentrations of hepatic cholesterol esters than control pups. Adult EFAD offspring had higher levels of hepatic cholesterol and linoleic acid, but lower levels of dihomo-γ-linolenic acid and Pparg mRNA expression in the liver. In addition, HFD fed EFAD offspring had lower plasma total cholesterol, lower hepatic triglycerides and lower liver weight compared to controls fed HFD. In conclusion, early postnatal EFAD resulted in short-term alterations with increased hepatic cholesterol accumulation and long-term protection against diet-induced liver steatosis and hypercholesterolemia.     

Early Life Exposure to Fructose Alters Maternal,Fetal and Neonatal Hepatic Gene Expression and Leads to Sex-Dependent Changes in Lipid Metabolism in Rat Offspring

Aim

Fructose consumption is associated with altered hepatic function and metabolic compromise and not surprisingly has become a focus for perinatal studies. We have previously shown that maternal fructose intake results in sex specific changes in fetal, placental and neonatal outcomes. In this follow-up study we investigated effects on maternal, fetal and neonatal hepatic fatty acid metabolism and immune modulation.

Methods

Pregnant rats were randomised to either control (CON) or high-fructose (FR) diets. Fructose was given in solution and comprised 20% of total caloric intake. Blood and liver samples were collected at embryonic day 21 (E21) and postnatal day (P)10. Maternal liver samples were also collected at E21 and P10. Liver triglyceride and glycogen content was measured with standard assays. Hepatic gene expression was measured with qPCR.

Results

Maternal fructose intake during pregnancy resulted in maternal hepatic ER stress, hepatocellular injury and increased levels of genes that favour lipogenesis. These changes were associated with a reduction in the NLRP3 inflammasome. Fetuses of mothers fed a high fructose diet displayed increased hepatic fructose transporter and reduced fructokinase mRNA levels and by 10 days of postnatal age, also have hepatic ER stress, and elevated IL1β mRNA levels. At P10, FR neonates demonstrated increased hepatic triglyceride content and particularly in males, associated changes in the expression of genes regulating beta oxidation and the NLRP3 inflammasome. Further, prenatal fructose results in sex-dependant changes in levels of key clock genes.

Conclusions

Maternal fructose intake results in age and sex-specific alterations in maternal fetal and neonatal free fatty acid metabolism, which may be associated in disruptions in core clock gene machinery. How these changes are associated with hepatic inflammatory processes is still unclear, although suppression of the hepatic inflammasome, as least in mothers and male neonates may point to impaired immune sensing.     

The effect of dietary protein on the amino acid supply and threonine metabolism in the pregnant rat

To characterise the effects of dietary protein content on threonine metabolism during pregnancy, rats were fed diets containing 18% or 9% protein and then killed at different stages of gestation. Serum threonine concentrations fell significantly faster in the animals fed the diet containing 9% protein when compared to those fed the diet containing 18% protein. On day 4 of gestation the rate of threonine oxidation was higher in maternal liver homogenates prepared from the animals fed the diet containing 18% protein. The rate of threonine oxidation by liver homogenates fell as gestation proceeded in both diet groups. The activity of threonine dehydrogenase in the maternal liver was unaffected by dietary protein content at all stages of gestation. Serine-threonine dehydratase activity in homogenates of the maternal liver was transiently increased during the early stages of gestation in the animals fed high protein diets but was unchanged in the low protein groups. There was an increase in serine-threonine dehydratase activity in the kidney during the later stages of gestation but this was unaffected by the protein content of the maternal diet. These data show that the changes in free threonine concentrations cannot be accounted for through changes in the oxidation rate and suggest that some other factor influences the unusual metabolism of this amino acid during gestation.     

Fat and Carbohydrate Intake over Three Generations Modify Growth,Metabolism and Cardiovascular Phenotype in Female Mice in an Age-Related Manner

Environmental challenges such as a high fat diet during pregnancy can induce changes in offspring growth, metabolism and cardiovascular function. However, challenges that are sustained over several generations can induce progressive compensatory metabolic adjustments in young adults. It is not known if such effects persist during ageing. We investigated whether diets with different fat and carbohydrate contents over three generations modifies markers of ageing. Female C57BL/6 F0 mice were fed diets containing 5% or 21% fat (w/w) throughout pregnancy and lactation. Female offspring were fed the same diet as their dams until the F3 generation. In each generation, body weight, 24-hour food intake were recorded weekly, and plasma metabolites were measured by colorimetric assays, blood pressure by tail cuff plethysmography and vasoconstriction by myography on postnatal day 90 or 456. There was little effect of diet or generation on phenotypic markers in day 90 adults. There was a significant increase in whole body, liver and heart weight with ageing (d456) in the F3 21% fat group compared to the F1 and F3 5% groups. Fasting plasma glucose concentration was significantly increased with ageing in the 5% group in the F3 generation and in the 21% group in both generations. There was a significant effect of diet and generation on ex-vivo vasoconstriction in ageing females. Differences in dietary fat may induce metabolic compensation in young adults that persist over three generations. However, such compensatory effects decline during ageing.     

Dietary beta- and gamma-cyclodextrins stimulation of hepatic metallothionein gene expression in rats

This study investigated whether hepatic metallothionein gene expression is affected by dietary cyclodextrins. Young male Wistar rats were fed a basal diet or cyclodextrin-supplemented (50 g of cyclodextrin per kg diet) diets for 7 d. Copper content in the liver did not show any significant changes among rats fed the basal, beta- and gamma-cyclodextrin diets. There were no differences in liver or serum zinc among groups. Copper content in serum was markedly decreased in rats fed the gamma-cyclodextrin-supplemented diet. Liver metallothionein mRNA levels were significantly elevated in both beta- and gamma-cyclodextrins-fed rats, but not in alpha-cyclodextrin-fed rats. Thus, the increase in hepatic metallothionein mRNA levels might be due to this mechanism except for the contents of copper and zinc in the liver.     

Serum lipoprotein composition, lecithin cholesterol acyltransferase and tissue lipase activities in pregnant diabetic rats and their offspring receiving enriched n-3 PUFA diet

The effects of dietary n-3 polyunsaturated fatty acids on lipoprotein concentrations and on lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL) and lecithin cholesterol acyltransferase (LCAT) activities were studied in streptozotocin-induced diabetic rats during pregnancy and in their macrosomic offspring from birth to adulthood. Pregnant diabetic and control rats were fed Isio-4 diet (vegetable oil) or EPAX diet (concentrated marine omega-3 EPA/DHA oil), the same diets were consumed by pups at weaning. Compared with control rats, diabetic rats showed, during pregnancy, a significant elevation in very low density lipoprotein (VLDL) and low and high density lipoprotein (LDL-HDL(1))-triglyceride, cholesterol and apoprotein B100 concentrations and a reduction in apoprotein A-I levels. HTGL activity was high while LPL and LCAT activities were low in these rats. The macrosomic pups of Isio-4-fed diabetic rats showed a significant enhancement in triglyceride and cholesterol levels at birth and during adulthood with a concomitant increase in lipase and LCAT activities. EPAX diet induces a significant diminution of VLDL and LDL-HDL(1) in mothers and in their macrosomic pups, accompanied by an increase in cholesterol and apoprotein A-I levels in HDL(2-3) fraction. It also restores LPL, HTGL and LCAT activities to normal range. EPAX diet ameliorates considerably lipoprotein disorders in diabetic mothers and in their macrosomic offspring.