Abstract-Maternal obesity is increasingly prevalent and may affect the long-term health of the child. We investigated the effects of maternal diet-induced obesity in mice on offspring metabolic and cardiovascular function. Female C57BL/6J mice were fed either a standard chow (3% fat, 7% sugar) or a palatable obesogenic diet (16% fat, 33% sugar) for 6 weeks before mating and throughout pregnancy and lactation. Offspring of control (OC) and obese dams (OO) were weaned onto standard chow and studied at 3 and 6 months of age. OO were hyperphagic from 4 to 6 weeks of age compared with OC and at 3 months locomotor activity was reduced and adiposity increased (abdominal fat pad mass; PϽ0.01). OO were heavier than OC at 6 months (body weight, PϽ0.05). OO abdominal obesity was associated with adipocyte hypertrophy and altered mRNA expression of ␤-adrenoceptor 2 and 3, 11␤HSD-1, and PPAR-␥ 2. OO showed resistance artery endothelial dysfunction at 3 months, and were hypertensive, as assessed by radiotelemetry (nighttime systolic blood pressure at 6 months [ Key Words: obesity Ⅲ pregnancy Ⅲ developmental programming Ⅲ metabolic syndrome Ⅲ appetite Ⅲ blood pressure Ⅲ mouse O besity among women of reproductive age is presenting a critical challenge to health care. 29% of USA women aged 20 to 39 years are reported to be clinically obese 1 and there is serious concern in many European countries over the increasing obesity among young women. 2 While obesity is associated with increased risk of almost every common complication of pregnancy, obesity in the mother may play a direct role in transmission of an obesogenic and diabetogenic trait from generation to generation. Increasing evidence suggests that children born of pregnancies complicated by either obesity or related gestational diabetes mellitus (GDM) are at increased risk of obesity, impaired glucose tolerance, and other facets of the metabolic syndrome. 3 Animal models have proven invaluable in interrogation of associations between maternal diet and body composition and offspring phenotype. 4 Those studies which have addressed effects of maternal calorific excess, including several from our laboratory, have generally fed rats diets rich in animal fat. 4 -7 Because young women of reproductive age often consume excessive amounts of sugars as well as fats, 8 the relevance of a diet rich in fat alone is limited. In this study, we induced obesity by feeding mice a highly palatable diet rich in sugars and animal fat, and addressed the hypothesis that diet-induced obesity during pregnancy can transmit a propensity for adiposity, glucose intolerance, and cardiovascular dysfunction to the offspring. Obesity was induced in female mice and offspring cardiovascular and metabolic function

The administration of a low protein (LP, 8% protein/dry matter) but isocaloric diet to gestating rats did not affect their fertility, but slightly reduced the quantity of food intake as well as body weight gain. The LP diet also did not affect the placental weight, but the weight of the offspring was decreased. Accordingly the fetal endocrine pancreas was altered by the LP diet. Two different morphometric analyses showed that in the LP neonate B-cell proliferation and islet size were reduced in the head of the pancreas. In the pancreatic tail, these parameters were also decreased but to a lesser extend. Islet vascularization in the neonates was dramatically reduced in both parts of the pancreas when the mothers were fed with the LP diet.

A low-protein diet (8 vs. 20%) administered during pregnancy affects the structure and function of the endocrine pancreas of the offspring. At 21.5 days of gestation, we reported a reduction of cell proliferation, islet size, islet vascularization, and pancreatic insulin content. In this study, we demonstrated an impairment of insulin secretion of these fetal islets when stimulated in vitro with amino acids such as arginine and leucine. If the offspring is kept on the same low-protein diet during suckling, weaning, and adulthood, fasting insulin levels remain low in the presence of normal blood glucose levels. Glucose tolerance at 70 days is impaired, with lower insulin response. In addition, permanent functional damage seems to be induced in utero by a low-protein diet, because a normal diet given from birth to adulthood does not restore normal insulin response after a glucose challenge. Our experimental results stress the impact of a balanced diet with qualitative and quantitative amino acid composition for the fetal endocrine pancreas to develop normally, without lasting functional and structural consequences in adulthood.

BackgroundChanges in imprinted gene dosage in the placenta may compromise the prenatal control of nutritional resources. Indeed monoallelic behaviour and sensitivity to changes in regional epigenetic state render imprinted genes both vulnerable and adaptable.Methods and FindingsWe investigated whether a high-fat diet (HFD) during pregnancy modified the expression of imprinted genes and local and global DNA methylation patterns in the placenta. Pregnant mice were fed a HFD or a control diet (CD) during the first 15 days of gestation. We compared gene expression patterns in total placenta homogenates, for male and female offspring, by the RT-qPCR analysis of 20 imprinted genes. Sexual dimorphism and sensitivity to diet were observed for nine genes from four clusters on chromosomes 6, 7, 12 and 17. As assessed by in situ hybridization, these changes were not due to variation in the proportions of the placental layers. Bisulphite-sequencing analysis of 30 CpGs within the differentially methylated region (DMR) of the chromosome 17 cluster revealed sex- and diet-specific differential methylation of individual CpGs in two conspicuous subregions. Bioinformatic analysis suggested that these differentially methylated CpGs might lie within recognition elements or binding sites for transcription factors or factors involved in chromatin remodelling. Placental global DNA methylation, as assessed by the LUMA technique, was also sexually dimorphic on the CD, with lower methylation levels in male than in female placentae. The HFD led to global DNA hypomethylation only in female placenta. Bisulphite pyrosequencing showed that neither B1 nor LINE repetitive elements could account for these differences in DNA methylation.ConclusionsA HFD during gestation triggers sex-specific epigenetic alterations within CpG and throughout the genome, together with the deregulation of clusters of imprinted genes important in the control of many cellular, metabolic and physiological functions potentially involved in adaptation and/or evolution. These findings highlight the importance of studying both sexes in epidemiological protocols and dietary interventions.

Taurine appears to have multiple functions and plays an important role in many physiological processes, such as osmoregulation, immunomodulation and bile salt formation. Taurine analogues/derivatives have recently been reported to have a marked activity on various disorders. Taken together, these observations actualize the old story of taurine.