Maternal protein intake in the pregnant rat programs the insulin axis and body composition in the offspring

Evidence to support an association between early nutrition and the development of obesity in the rat is equivocal. In this study we have investigated the postnatal growth, glucose tolerance, and adipocyte function of the offspring from pregnant rats fed with diets containing either 20% or 8% protein during gestation. By 25 weeks of age, the female offspring of dams fed with the diet containing 8% protein had a significantly lower adult body weight due in part to a decrease in body fat. The peak concentration of insulin after oral administration of a glucose dose was significantly lower in both the male and female offspring of the dams fed with the diet containing 8% protein. However, the ability of insulin to stimulate lipogenesis or suppress lipolysis in fat cells isolated from the offspring was not influenced by the prenatal diet. Hepatic phosphoenolpyruvate carboxykinase activity was reduced in female offspring of dams fed with the diet containing 8% protein. These results show that adult body composition is determined during the prenatal period as a result of programming of the insulin axis. This metabolic programming influences hepatic metabolism; however, there is no evidence for a programmed change in adipocyte function.     

Effect of Ethanol on Maternal and Offspring Characteristics: Comparison of Three Liquid Diet Formulations Fed during Gestation

Maternal blood alcohol levels, weight gain during pregnancy, parturition time, perinatal mortality, and postnatal growth of offspring were compared in groups of pregnant rats fed one of three ethanol-containing liquid diets (Kahn's formula = BSA diet, Revised Wiener's = RA6 diet, and Lieber-DeCarli's high protein 82C diet = LDA diet). The three ethanol diets all contained the same amount of ethanol-derived energy (36% of total energy), but differed in the amount of energy contributed by protein (17, 30, and 25%), fat (36, 24, and 13%), and carbohydrate (12, 10, and 27%), respectively. The experimental design also included dams that were pair-fed isocaloric ethanol-free versions of the three ethanol diets (designated BSP, RP6, and LDA, respectively) and a group of dams fed a pelleted casein-based solid diet (PC diet). All experimental diets were fed ad libitum from gestational day 7 to delivery. The effect of ethanol exposure in utero was most severe in mothers and offspring fed the BSA diet. The feed efficiency ratio (maternal weight gain/total dietary energy consumed) of this low-protein ethanol diet was less than that of RA6 or LDA diets. The feed efficiency ratio calculated for RA6 and LDA diets was not different from that of PC diet. Compared with rats fed RA6 and LDA diets, the rats that were fed BSA diet exhibited deficient maternal weight gain, greater parturition delay, impaired fetal growth, and increased perinatal mortality among the offspring. BSA dams had the highest blood ethanol levels of all groups fed ethanol diets, and exhibited the least difference in blood ethanol concentrations between the day (2 PM) and night (9 PM) periods of the diurnal cycle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of protein malnutrition on glycoprotein, protein and lipid synthesis in the rat cerebellum during the period of brain growth spurt

Female Wistar rats were fed a normal-protein diet (25% casein) or a low-protein diet (8% casein) during pregnancy and lactation. The two diets were isocaloric and contained appropriate amounts of mineral salts and vitamins. Pups from dams submitted to the low-protein diet had a lower body weight than normally fed controls as early as on the day of birth, but a difference in cerebellar weight between the two groups was observed only on the 15th postnatal day. Malnutrition had no effect on cerebellar protein concentration, which increased with age in both groups. The cerebellar DNA concentration was higher at 7 and 15 days of age in normally fed rats than in malnourished rats, whereas at 21 days of age it was higher in the malnourished animals. [U-14C]Leucine and [2-3H]mannose incorporation into proteins and lipid synthesis from acetyl coenzyme A (CoA) derived from [U-14C]leucine markedly decreased with age in the cerebellum of rats fed both diets. [2-3H]Mannose incorporation into cerebellar glycoproteins was greater in malnourished rats during the period of brain growth spurt than in normally fed rats at all ages studied. Prenatal and postnatal protein malnutrition had no effect on [U-14C]leucine incorporation into cerebellar proteins or on cerebellar lipid synthesis from acetyl-CoA derived from [U-14C]leucine during the period of brain growth spurt.     

Folate supplementation during pregnancy improves offspring cardiovascular dysfunction induced by protein restriction

Dietary protein restriction in the rat compromises the maternal cardiovascular adaptations to pregnancy and leads to raised blood pressure and endothelial dysfunction in the offspring. In this study we have hypothesized that dietary folate supplementation of the low-protein diet will improve maternal vascular function and also restore offspring cardiovascular function. Pregnant Wistar rats were fed either a control (18% casein) or protein-restricted (9% casein) diet +/-5 mg/kg folate supplement. Function of isolated maternal uterine artery and small mesenteric arteries from adult male offspring was assessed, systolic blood pressure recorded, and offspring thoracic aorta levels of endothelial nitric oxide (NO) synthase mRNA measured. In the uterine artery of late pregnancy dams, vasodilatation to vascular endothelial growth factor was attenuated in the protein-restricted group but restored with folate supplementation, as was isoprenaline-induced vasodilatation (P<0.05). In male offspring, protein restriction during pregnancy led to raised systolic blood pressure (P<0.01), impaired acetylcholine-induced vasodilatation (P<0.01), and reduced levels of endothelial NO synthase mRNA (P<0.05). Maternal folate supplementation during pregnancy prevented this elevated systolic blood pressure associated with a protein restriction diet. With folate supplementation, endothelium-dependent vasodilatation and endothelial NO synthase mRNA levels were not significantly different from either the control or protein-restricted groups. Maternal folate supplementation of the control diet had no effect on blood pressure or vasodilatation. This study supports the hypothesis that folate status in pregnancy can influence fetal development and, thus, the risks of cardiovascular disease in the next generation. The concept of developmental origins of adult disease focuses predominately on fetal life but must also include a role for maternal cardiovascular function.     

Effects of nutritional quality during early development on body weight and reproductive maturation of guinea pigs (Cavia aperea f. porcellus)

In many species, somatic and reproductive maturation are sensitive to seasonally-fluctuating environmental conditions such as food quality. The protein content of the diet during early development has been considered to be particularly important, a low-protein diet during gestation and lactation typically delaying growth and reproductive onset. To investigate the effects of maternal and early postnatal diet quality on body weight and puberty of male and female domestic guinea pigs, we fed F0-mothers either a low-protein (14%, LQ-group) or a high-protein diet (23%, HQ-group) during gestation and lactation. Their male and female offspring received the same respective diets until six weeks of age; afterward they were switched to an intermediate control diet. Body weight of F1-subjects was significantly affected by the dietary treatment. Reproductive parameters were only affected in F1-females but not in F1-males. We conclude that in guinea pigs, growth is sensitive to the quality of the maternal and early postnatal diet, and that reproductive maturation is more sensitive in females.     

Maternal folic acid supplementation to dams on marginal protein level alters brain fatty acid levels of their adult offspring

Studies on fetal programming of adult diseases have highlighted the importance of maternal nutrition during pregnancy. Folic acid and long-chain essential polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth. However, folic acid effects may also involve alteration of LC-PUFA metabolism. Because marginal deficiency of LC-PUFAs during critical periods of brain growth and development is associated with risks for adult diseases, it is highly relevant to investigate how maternal supplementation of such nutrients can alter brain fatty acid levels. We examined the impact of folic acid supplementation, conventionally used in maternal intervention, on brain essential fatty acid levels and plasma corticosterone concentrations in adult offspring at 11 months of age. Pregnant female rats from 4 groups (6 in each) were fed with casein diets either with 18 g protein/100 g diet (control diet) or treatment diets that were marginal in protein (MP), such as 12 g protein/100 g diet supplemented with 8 mg folic acid (FAS/MP), 12 g protein/100 g diet without folic acid (FAD/MP), or 12 g protein/100 g diet (MP) with 2 mg folic acid. Pups were weaned to a standard laboratory diet with 18 g protein/100 g diet. All male adult offspring in the FAS/MP group showed lower docosahexaenoic acid (P<.05) as compared with control adult offspring (6.04+/-2.28 vs 10.33+/-0.86 g/100 g fatty acids) and higher n-6/n-3 ratio (P<.05). Docosahexaenoic acid levels in FAS/MP adult offspring were also lower (P<.05) when compared with the MP group. Plasma corticosterone concentrations were higher (P<.05) in male adult offspring from the FAS/MP group compared with control as well as the MP adult offspring. Results suggest that maternal folic acid supplementation at MP intake decreased brain docosahexaenoic acid levels probably involving corticosterone increase.     

Prenatal exposure to a maternal low protein diet shortens life span in rats

BACKGROUND: Postweaning diet restriction is associated with prolongation of life span, reduced age-related disease and slower ageing. The effects of diet restriction imposed prior to weaning have not been so well characterised, but studies suggest an opposite effect with increased age-related diseases occurring in offspring exposed to undernutrition in prenatal life. It remains unclear whether life span is similarly adversely affected by early diet restriction. OBJECTIVE: The present study in rats aimed to evaluate the impact of a maternal low protein diet upon the life span of the resulting offspring. METHODS: Rat dams were fed either a 180-gram casein/kg control diet or a 90-gram casein/kg low protein diet from conception until the end of pregnancy. The offspring were then maintained with minimal handling until death from natural causes or distress-necessitated euthanasia. RESULTS: The average life span of female rats exposed to low protein diets in utero was reduced by 11% (p = 0.044, Kaplan-Meier analysis). There was a similar but non- significant trend in the male offspring (control 76 +/- 3 weeks, low protein 73 +/- 3 weeks). In addition the rats exposed to a prenatal low protein diet had significantly higher systolic blood pressure at 4 weeks of age and tended to be smaller than control animals in postnatal life. CONCLUSION: The results suggest that intrauterine diet restriction reduces life span in rats and contrasts with the well-recognised increase in life span produced by postweaning diet restriction. The timing of the nutritional intervention appears to be critical and recognition of this is relevant to understanding the mechanisms underlying the effects of diet restriction on ageing and life span.     

Fetal Exposure to Ethanol Enhances Pituitary-Adrenal and Temperature Responses to Etanol in Adult Rats

Long lasting effects of perinatal ethanol exposure were studied in adult rats who were the offspring of dams fed a 5.0% w/v ethanol-containing liquid diet ad libitum or pair-fed the isocaloric control diet during gestation weeks 2 and 3 or during postnatal week 1. Fetal exposure to ethanol reduced body weight of pups at birth unless the ethanol diet was supplemented with casein; neonatal exposure to the ethanol or pair-fed diets, casein supplemented or not, reduced pup weights until day 21 postnatally when weights of all fetally or neo-natalty exposed pups were normal. Between 52 and 120 days of age females were tested for pituitary-adrenal and temperature responses to a challenge dose of ethanol. Prenatally ethanol-exposed rats showed significantly higher plasma corticosterone titers and developed a greater hypothermia in response to an intraperitoneal injection of ethanol (0.75–1.5 g/kg) than did pair-fed controls. Similar response enhancement did not occur in the postnatally ethanol-exposed rats. Temporal patterns of blood ethanol levels after an intraperitoneal injection of ethanol (1.5 g/kg) were similar in prenatally ethanol-exposed females and their pair-fed controls. The data indicate that exposure to ethanol in utero exerts persistent effects on the offspring, rendering them more responsive to the hypothermic and pituitary-adrenal activating effects of alcohol as adults.     

Ketosis resistance in the male offspring of protein-malnourished rat dams

Plasma β-hydroxybutyrate concentrations were measured in the offspring of rats that were fed either a control (20% protein) diet or low-protein (8% protein) diet during pregnancy and lactation. Low-protein offspring had significantly lower plasma β-hydroxybutyrate compared with controls in the fed state (P < .04) and after fasting for 24 hours (P < .001) and 48 hours (P < .04). There were no differences in blood glucose, acetoacetate, plasma glucagon, cholesterol, or glycerol between control and low-protein offspring. However, plasma nonesterified fatty acids (NEFAs) were significantly higher in low-protein offspring in the fed state (P < .05). In contrast, plasma triglycerides and insulin were significantly lower in low-protein offspring compared with controls when fed (P < .001) and after a 24-hour fast (P < .001). These results suggest that poor maternal and early postnatal nutrition can have long-term effects on ketone body metabolism in the offspring during adulthood. This apparent ketosis resistance is similar to that observed in some forms of human diabetes.     

Hepatic and very low-density lipoprotein fatty acids in obese offspring of overfed dams

The combined effects of developmental programming and high-fat feeding at weaning on fatty acid metabolism of the offspring are not well known. In the present study, we aim at characterizing the influence of maternal and offspring's own diets on liver and very low-density lipoprotein (VLDL) lipids; fatty acid profiles of VLDL and liver phospholipids, triglycerides, and cholesteryl esters; and hepatic enzyme activities. Twenty obese male rats born to cafeteria diet–fed dams and 20 control rats born to control diet–fed dams were selected. At weaning, 10 rats of each group were fed control or cafeteria diet. Obese rats had a significant increase in serum glucose, insulin, leptin, VLDL apolipoprotein B100 and lipid levels, and hepatic fatty acid synthase and a reduction in acyl–coenzyme A oxidase and dehydrogenase activities compared with control pups at day 21 and day 90. Hepatic steatosis was apparent only at day 90. The proportions of saturated fatty acids and monounsaturated fatty acids and the oleic to stearic acid ratio were significantly increased, whereas polyunsaturated fatty acids and the arachidonic to linoleic acid ratio were decreased, in liver and VLDL lipids of obese pups compared with controls. The cafeteria diet at weaning induced more severe abnormalities in obese rats. In conclusion, maternal cafeteria diet induced a permanent reduction in hepatic β-oxidation and an increase in hepatic lipogenesis that caused liver steatosis and VLDL and fatty acid alterations in adult offspring. These preexisting alterations in offspring were worsened under a high-fat diet from weaning to adulthood. Nutritional recommendations in obesity must then target maternal and postnatal nutrition, especially fatty acid composition.     

Altered body composition and metabolism in the male offspring of high fat-fed rats

An intrauterine environment may play a role in predisposing a developing fetus to metabolic diseases during adulthood. We investigated the hypothesis that a maternal diet high in omega-6 polyunsaturated fat can modify the programming of an offspring's glucose tolerance, insulin sensitivity, body composition, lipid metabolism, and insulin signaling. High omega-6 polyunsaturated fat diets were fed to female rats 4 weeks before mating and throughout the gestation period. The offspring were maintained on chow diet. At 3 months of age, indirect calorimetry, oral glucose tolerance tests, and dual x-ray absorptiometry measurements were performed. Triglyceride content and beta-hydroxyacyl coenzyme A dehydrogenase activity were determined in the liver and quadriceps muscle. Expression levels of key insulin signaling pathway proteins were measured in the liver and quadriceps muscle of the 3-month-old offspring. Offspring from the fat-fed dams had significantly increased proportions of both total body fat and abdominal fat. All offspring displayed normal insulin sensitivity and glucose tolerance, although the offspring from the fat-fed dams were significantly more hyperinsulinemic 15 minutes after an oral glucose challenge. Whole body fuel oxidation was not altered. The offspring of fat-fed dams had significantly elevated liver triglyceride content. Insulin signaling protein expression levels in the offspring of fat-fed dams were consistent with reduced hepatic insulin sensitivity but increased quadriceps insulin sensitivity. A maternal diet high in omega-6 polyunsaturated fat evokes programming within the metabolic processes of the offspring that may predispose the offspring to the development of metabolic diseases.     

Effects of capsaicin in combination with diets of varying protein content on the duodenal absorptive cells of the rat

The effects of capsaicin, a pungent principle of capsicum pepper, and its combination with various diets on the morphology of duodenal mucosa was studied on young rats grouped and maintained on six different diets for periods of 28 and 56 days: normal diet with and without capsaicin, high-protein diet with and without capsaicin, and low-protein diet with and without capsaicin. Goblet cells in the capsaicin-treated animals increased in number. Ultrastructural alterations occurred in absorptive cells of rats fed a low-protein diet and also in those fed diets supplemented with capsaicin for both 28 and 56 days. The most striking ultrastructural alterations developed in animals that received the low-protein diet supplemented with capsaicin. This study shows that capsaicin intensifies the morphological alterations associated with a low-protein diet.     

Modulation of susceptibility to weight gain and insulin resistance in low birthweight rats by treatment of their mothers with leptin during pregnancy and lactation

OBJECTIVES: To investigate whether administration of leptin to rats during pregnancy and lactation affects placental 11beta-hydroxysteroid dehydrogenase (11beta-HSD2) activity and the susceptibility of their offspring to weight gain and insulin resistance. DESIGN: Pregnant rats fed on a low-protein diet were administered leptin or saline by subcutaneous minipump from day 14 of gestation and throughout lactation. A further group was fed a normal diet and given saline. After weaning, the offspring of each group were fed on a normal diet until 6 weeks of age and then half of each group was transferred to a high-fat diet until 12 months of age. RESULTS: Plasma leptin levels were raised two-fold on days 16-18 of pregnancy in the leptin-treated dams, but, despite a constant rate of infusion, at parturition they dipped to control levels before rising again. The activity of placental 11beta-HSD2 was reduced by the low-protein diet; this reduction was prevented by treating the dams with leptin. The male offspring of the saline-treated dams gained more weight and had higher plasma leptin levels on the high fat than the chow diet, but the offspring of the leptin-treated dams did not. Fasting blood glucose and intraperitoneal glucose tolerance at 6 and 12 months of age was unaffected by the high-fat diet, but only the offspring of the leptin-treated dams achieved this control without raised insulin levels. CONCLUSIONS: The rate of leptin clearance appears to increase at parturition. The administration of leptin to rats during late pregnancy and lactation makes their male offspring less susceptible to high-fat-diet-induced weight gain and insulin resistance.     

Nutritional effects on the lifespan of Syrian hamsters

Syrian hamsters were fed one of nine semipurified diets composed of three casein levels (9, 18, and 36 g/385 Kcal), with each of three corn oil levels (4.5, 9.0, and 18.0 g/385 Kcal). These diets were given either for five weeks and were followed by control diet (18 g casein and 9 g corn oil/385 Kcal) or control diet was fed for the first five weeks and was followed by the nine diets. Calorie consumption, maximum body weight and length of growth period and of life are reported. Calorie consumption was directly related to dietary fat levels. Maximum body weights increased with increasing dietary fat and protein when the various diets were fed during weeks 1–5. This result was not due to a conditioning of the animals fed high-fat or high-protein levels during weeks 1–5 to consume more calories after week 5, since after this time consumption was the same in all groups fed the control diet. When diets were fed from week 6 body weight increased in both sexes with increased dietary fat; however, higher dietary protein increased female and decreased male maximum body weight. Males took longer to reach these maximum weights than females, and were not affected by receiving the various diets during weeks 1–5. However, when diets were fed from week 6 until death, the growth period increased with higher dietary fat or protein. Male hamsters survived longer than females with each experimental treatment. Animals fed low-fat, low-protein diet or high-fat, high-protein diet during the first 5 weeks of the study survived longest. When diets were fed from 6 weeks until death, survival increased as dietary fat rose for both sexes. In contrast, survival improved as dietary protein rose for females or decreased for males. These studies establish a basis for further investigations on the link between nutrition and longevity in the Syrian hamster.     

Sex-specific effects of prenatal low-protein and carbenoxolone exposure on renal angiotensin receptor expression in rats

Experimental models have shown the developing cardiovascular and renal systems to be sensitive to mild shifts in maternal nutrition, leading to altered function and risk of disease in adult life. The offspring of Wistar rats fed a low-protein diet during pregnancy exhibit a reduced nephron number and hypertension in postnatal life, providing a useful tool to examine the mechanistic basis of programming. Evidence indicates that upregulation of the renin-angiotensin system plays an important role, in particular through receptor-mediated changes in angiotensin II activity. However, although programmed hypertension has proven dependent on maternal glucocorticoids, there appear to be conflicting effects of prenatal low-protein and glucocorticoid exposure on postnatal angiotensin receptor expression. This study aimed to resolve this issue by comparing the effects of low-protein and glucocorticoid exposures on postnatal nephron number and angiotensin receptor expression. In addition, this study examined the modulation of prenatal treatment effects by postnatal inhibition of type 1 angiotensin receptor. The data demonstrates that whereas prenatal low-protein and glucocorticoid exposure have a similar effect in reducing nephron number, there are age- and gender-related differences in their effects on postnatal angiotensin receptor expression. In addition, this study provides novel evidence of a substantial upregulation of type 2 angiotensin receptor expression in low-protein- and glucocorticoid-exposed female offspring at 20 weeks of age, with implications for subsequent renal remodeling and function. Despite being targeted to the postnephrogenic period, inhibition of type 1 angiotensin receptor had an inhibitory effect on renal and somatic growth, additionally indicating its unsuitability during early life.     

Accelerated aging of reproductive capacity in male rat offspring of protein-restricted mothers is associated with increased testicular and sperm oxidative stress

Maternal protein restriction (MPR) in pregnancy causes life course organ dysfunction, but few studies link the developmental origins of disease hypothesis to early aging. Suboptimal developmental nutrition increases oxidative stress (OS) and male infertility, damaging sperm function. We hypothesized that MPR in pregnancy accelerates age-related changes in testicular and sperm function related to both maternal diet and increased testicular OS in rat offspring. We studied male rats whose pregnant mothers ate either control (C, 20 % casein) or restricted (R, 10 % casein) isocaloric diet. After birth, mothers and offspring ate C diet. Testes were retrieved at 19 days gestation and across the life course (postnatal day (PND) 21, 36, 110, and 850) to measure OS markers, antioxidant enzymes, serum FSH, LH, and testosterone, and PND 110 sperm OS and quality. Fertility rate was evaluated at PND 110, 450, and 850. Offspring showed age- and MPR-related changes in testosterone, testicular OS markers and antioxidant enzymes and fertility, and maternal diet-related OS and sperm antioxidant enzyme changes. Developmental programming is considered a key factor in predisposing to chronic disease. Our data show that programming also plays an important role in aging trajectory. This interaction is a little studied area in aging biology that merits more investigation.     

Effect of parental malnutrition on enzyme content of rat pancreas

The aim of this study was to assess in rat pups the influence of protein diets ingested by their mothers during gestation and lactation on the enzyme content of the pancreas of the offspring. Rat pups born of either well-nourished mothers or of mothers fed a diet moderately restricted in protein (9% casein w/w) were studied. After weaning, the pups were fed on one of three diets: a well-balanced diet, a 5% casein diet (protein restricted), or a well-balanced diet of a similar caloric value as the protein-restricted diet (pair-fed rat pups). The pups were sacrificed after intervals of one to 25 weeks after weaning. The results showed that the enzyme content of the pancreas increased progressively with time in pups born of malnourished mothers, particularly in pups fed the protein-restricted diet. This suggests prolonged maturation of the pancreas. Pups fed the 5% casein diet had a decreased amylase content per milligram of DNA but not of other enzymes. Malnutrition in the mother inceased the ratio of enzymes to DNA and the total pancreatic enzyme content at different times after weaning, indicating that maternal malnutrition had a prolonged effect on the pancreatic enzyme content of the pups' pancreas. This mechanism could play a role in the pathogenesis of tropical chronic calcific pancreatitis in man and explain some of the geographic differences in the incidence of the disease.     

Dietary fatty acid composition during pregnancy and lactation in the rat programs growth and glucose metabolism in the offspring

AIMS/HYPOTHESIS: We investigated of the effects of fatty acid composition of the maternal diet on fetal and postnatal growth, morphology of the pancreas and glucose metabolism and muscle hexosamine concentrations in the adult offspring of rats. METHODS: High-fat diets enriched with either saturated or unsaturated fatty acids were fed to female adult rats 2 weeks before mating until the end of the weaning period. After weaning, the offspring was maintained on a diet with a balanced fatty acid content. At 3 months of age, pancreatic Langerhans islet size and number were assessed by morphometric analysis and oral glucose tolerance tests (OGTT) were carried out. RESULTS: The unsaturated fatty acid diet showed lower birth weight and reduced postnatal weight gain. Furthermore, this group showed increased pancreatic islet numbers without affected glucose tolerance at the age of 12 weeks. The offspring of the saturated fatty acid diet group showed a reduced number of large pancreatic islets. Moreover, a faster and higher insulin response was observed after an oral glucose load in these animals. Muscle hexosamine concentrations were not different between groups. CONCLUSION/INTERPRETATION: Maternal diets enriched with either saturated fatty acids or unsaturated fatty acids had opposite effects on pancreatic islet development in rat offspring, with consequences for the insulin response at 12 weeks of age. Therefore, maternal dietary fatty acid composition plays a role in programming growth, pancreatic development and glucose metabolism in the offspring.     

Maternal high-fat diet programs Wnt genes through histone modification in the liver of neonatal rats

Maternal high-fat (HF) diets during gestation and lactation have been shown to contribute to metabolic disorders in offspring. Molecular and epigenetic mechanisms underlying this connection may be essential for the prevention and treatment of the fetal origins of metabolic diseases. The current study examined the impact of maternal HF diets on Wnt signaling and histone modification in offspring. Time-pregnant Sprague-Dawley rats were fed either control diet or HF diet during gestation and lactation and then the neonatal offspring of both groups were investigated. The neonatal offspring born to dams fed on HF diets exhibited increases in serum glucose and liver triglyceride levels. Maternal exposure to the HF diet also repressed the mRNA expression of Wnt1 and nuclear β-catenin protein in the liver of offspring. The altered Wnt1 gene expression may be due to the changes of acetylation of H4 at its promoter as well as acetylation of H4 and methylation of H3K9 at coding region. Maternal exposure to the HF diet induced suppression of the Wnt/β-catenin signaling pathway through histone modification, potentially increasing the risk of metabolic syndrome.