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Maternal Western-style high fat diet induces sex-specific physiological and molecular changes in two-week-old mouse offspring.

ABSTRACT: Maternal diet is associated with the development of metabolism-related and other non-communicable diseases in offspring. Underlying mechanisms, functional profiles, and molecular markers are only starting to be revealed. Here, we explored the physiological and molecular impact of maternal Western-style diet on the liver of male and female offspring. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) for six weeks before mating, as well as during gestation and lactation. Dams and offspring were sacrificed at postnatal day 14, and body, liver, and blood parameters were assessed. The impact of maternal WSD on the pups' liver gene expression was characterised by whole-transcriptome microarray analysis. Exclusively male offspring had significantly higher body weight upon maternal WSD. In offspring of both sexes of WSD dams, liver and blood parameters, as well as hepatic gene expression profiles were changed. In total, 686 and 604 genes were differentially expressed in liver (p?0.01) of males and females, respectively. Only 10% of these significantly changed genes overlapped in both sexes. In males, in particular alterations of gene expression with respect to developmental functions and processes were observed, such as Wnt/beta-catenin signalling. In females, mainly genes important for lipid metabolism, including cholesterol synthesis, were changed. We conclude that maternal WSD affects physiological parameters and induces substantial changes in the molecular profile of the liver in two-week-old pups. Remarkably, the observed biological responses of the offspring reveal pronounced sex-specificity.

SUBMITTER: Mischke M

PROVIDER: S-EPMC3818485 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Maternal Western-style high fat diet induces sex-specific physiological and molecular changes in two-week-old mouse offspring.

Mischke Mona M Pruis Maurien G M MG Boekschoten Mark V MV Groen Albert K AK Fitri Aditia R AR van de Heijning Bert J M BJ Verkade Henkjan J HJ Müller Michael M Plösch Torsten T Steegenga Wilma T WT

PloS one 20131105 11

Maternal diet is associated with the development of metabolism-related and other non-communicable diseases in offspring. Underlying mechanisms, functional profiles, and molecular markers are only starting to be revealed. Here, we explored the physiological and molecular impact of maternal Western-style diet on the liver of male and female offspring. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) for six weeks befor ...[more]

PMID: 24223833

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Project description:Maternal diet is associated with the development of metabolism-related and other non-communicable diseases in offspring. Underlying mechanisms, functional profiles, and molecular markers are only starting to be revealed. Here, we explored the physiological and molecular impact of maternal Western-style diet on the liver of male and female offspring. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) for six weeks before mating, as well as during gestation and lactation. Dams and offspring were sacrificed at postnatal day 14, and body, liver, and blood parameters were assessed. The impact of maternal WSD on the pups' liver gene expression was characterised by whole-transcriptome microarray analysis. Exclusively male offspring had significantly higher body weight upon maternal WSD. In offspring of both sexes of WSD dams, liver and blood parameters, as well as hepatic gene expression profiles were changed. In total, 686 and 604 genes were differentially expressed in liver (pM-bM-^IM-$0.01) of males and females, respectively. Only 10% of these significantly changed genes overlapped in both sexes. In males, in particular alterations of gene expression with respect to developmental functions and processes were observed, such as Wnt/beta-catenin signalling. In females, mainly genes important for lipid metabolism, including cholesterol synthesis, were changed. We conclude that maternal WSD affects physiological parameters and induces substantial changes in the molecular profile of the liver in two-week-old pups. Remarkably, the observed biological responses of the offspring reveal pronounced sex-specificity. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) as six weeks pre-treatment before mating, as well as during gestation and lactation. Offspring were sacrificed at postnatal week two, livers were removed and RNA samples were subjected to gene expression profiling.

Project description:ObjectiveIn humans, offspring of women who are overweight or obese are more likely to develop metabolic disease later in life. Studies in lower animal species reveal that a calorically-dense maternal diet is associated with alterations in islet cell mass and function. The long-term effects of maternal diet on the structure and function of offspring islets with characteristics similar to humans are unknown. We used a well-established non-human primate (NHP) model to determine the consequences of exposure to Western-Style Diet (WSD) in utero and during lactation on islet cell mass and function in the offspring.MethodsFemale Japanese Macaques (Macaca fuscata) were fed either control (CTR) or WSD before and throughout pregnancy and lactation. Offspring were weaned onto CTR or WSD to generate four different groups based on maternal/offspring diets: CTR/CTR, WSD/CTR, CTR/WSD, and WSD/WSD. Offspring were analyzed at three years of age. Pancreatic tissue sections were immunolabelled to measure α- and β-cell mass and proliferation as well as islet vascularization. Live islets were also isolated to test the effects of WSD-exposure on islet function ex vivo. Offspring glucose tolerance was correlated with various maternal characteristics.Resultsα-cell mass was reduced as a result of maternal WSD exposure. α-cell proliferation was reduced in response to offspring WSD. Islet vasculature did not differ among the diet groups. Islets from WSD/CTR offspring secreted a greater amount of insulin in response to glucose ex vivo. We also found that maternal glucose tolerance and parity correlated with offspring glucose tolerance.ConclusionsMaternal WSD exposure results in persistently decreased α-cell mass in the three-year old offspring. WSD/CTR islets secreted greater amounts of insulin ex vivo, suggesting that these islets are primed to hyper-secrete insulin under certain metabolic stressors. Although WSD did not induce overt impaired glucose tolerance in dams or offspring, offspring born to mothers with higher glucose excursions during a glucose tolerance test were more likely to also show higher glucose excursions.

Project description:Maternal diabetes-induced fetal programming predisposes offspring to type 2 diabetes, cardiovascular disease, and obesity in adulthood. However, lifelong health and disease trajectories depend on several factors and nutrition is one of the main ones. We intend to understand the role of maternal diabetes-induced fetal programming and its association with a high-fat diet during lifelong in the female F1 generation focusing on reproductive outcomes and the possible changes in physiological systems during pregnancy as well as the repercussions on the F2 generation at birth. For this, we composed four groups: F1 female pups from control (OC) or from diabetic dams (OD) and fed with standard (SD) or high-fat diet from weaning to full-term pregnancy. During pregnancy, glucose intolerance and insulin sensitivity were evaluated. In a full-term pregnancy, the maternal blood and liver were collected to evaluate redox status markers. The maternal blood, placental tissue, and fetal blood (pool) were collected to evaluate adiponectin and leptin levels. Maternal reproductive parameters were evaluated as well. Maternal diabetes and high-fat diet consumption, in isolation, were both responsible for increased infertility rates and fasting glucose levels in the F1 generation and fetal growth restriction in the F2 generation. The association of both conditions showed, in addition to those, increased lipoperoxidation in maternal erythrocytes, regardless of the increased endogenous antioxidant enzyme activities, glucose intolerance, decreased number of implantation sites and live fetuses, decreased litter, fetal and placental weight, increased preimplantation losses, and increased fetal leptin serum levels. Thus, our findings show that fetal programming caused by maternal diabetes or lifelong high-fat diet consumption leads to similar repercussions in pregnant rats. In addition, the association of both conditions was responsible for glucose intolerance and oxidative stress in the first generation and increased fetal leptin levels in the second generation. Thus, our findings show both the F1 and F2 generations harmed health after maternal hyperglycemic intrauterine environment and exposure to a high-fat diet from weaning until the end of pregnancy.

Dataset Information

Maternal Western-style high fat diet induces sex-specific physiological and molecular changes in two-week-old mouse offspring.

Publications

Maternal Western-style high fat diet induces sex-specific physiological and molecular changes in two-week-old mouse offspring.

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