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

Mischke M, Pruis MG, Boekschoten MV, Groen AK, Fitri AR, van de Heijning BJ, Verkade HJ, Müller M, Plösch T, Steegenga WT - PLoS ONE (2013)

Bottom Line: Exclusively male offspring had significantly higher body weight upon maternal WSD.Only 10% of these significantly changed genes overlapped in both sexes.We conclude that maternal WSD affects physiological parameters and induces substantial changes in the molecular profile of the liver in two-week-old pups.

View Article: PubMed Central - PubMed

Affiliation: Nutrition, Metabolism & Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.

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.

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Related in: MedlinePlus

Offspring’s body, liver, and blood parameters.(A) Body weight at postnatal day (PD) 8 and 14, (B) liver weight at PD 14, (C) liver weight/body weight ratio, and (D) plasma triglycerides (TG), plasma cholesterol (Cho), and plasma non-esterified fatty acids (NEFA) were determined in offspring of maternal LFD or maternal WSD. Light blue circle = male/maternal LFD; dark blue circle = male/maternal WSD; pink square = female/maternal LFD; red square = female/maternal WSD. *p≤0.05; **p≤0.01.
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pone-0078623-g002: Offspring’s body, liver, and blood parameters.(A) Body weight at postnatal day (PD) 8 and 14, (B) liver weight at PD 14, (C) liver weight/body weight ratio, and (D) plasma triglycerides (TG), plasma cholesterol (Cho), and plasma non-esterified fatty acids (NEFA) were determined in offspring of maternal LFD or maternal WSD. Light blue circle = male/maternal LFD; dark blue circle = male/maternal WSD; pink square = female/maternal LFD; red square = female/maternal WSD. *p≤0.05; **p≤0.01.

Mentions: The body weight of offspring from WSD and LFD dams at postnatal day (PD) 8 and PD14 (sacrifice) showed a significant increase over time that was independent from sex or diet (Figure 2A). At both time points, male offspring of WSD dams were significantly heavier than offspring of LFD dams. For female offspring, significant differences in body weight were not detected at any time (Figure 2A). In both sexes, liver weight was significantly higher at sacrifice in offspring of WSD dams, leading to a significant increased liver weight/body weight ratio in WSD females only (Figure 2B and C). For blood parameters, likewise differences between the sexes were observed: in male offspring of WSD dams, plasma TG and plasma cholesterol levels were significantly higher and lower, respectively, when compared with offspring from LFD dams (Figure 2D). In females, only NEFA plasma levels were affected by the mother’s diet, and were significantly lower in WSD offspring (Figure 2D).


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

Mischke M, Pruis MG, Boekschoten MV, Groen AK, Fitri AR, van de Heijning BJ, Verkade HJ, Müller M, Plösch T, Steegenga WT - PLoS ONE (2013)

Offspring’s body, liver, and blood parameters.(A) Body weight at postnatal day (PD) 8 and 14, (B) liver weight at PD 14, (C) liver weight/body weight ratio, and (D) plasma triglycerides (TG), plasma cholesterol (Cho), and plasma non-esterified fatty acids (NEFA) were determined in offspring of maternal LFD or maternal WSD. Light blue circle = male/maternal LFD; dark blue circle = male/maternal WSD; pink square = female/maternal LFD; red square = female/maternal WSD. *p≤0.05; **p≤0.01.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3818485&req=5

pone-0078623-g002: Offspring’s body, liver, and blood parameters.(A) Body weight at postnatal day (PD) 8 and 14, (B) liver weight at PD 14, (C) liver weight/body weight ratio, and (D) plasma triglycerides (TG), plasma cholesterol (Cho), and plasma non-esterified fatty acids (NEFA) were determined in offspring of maternal LFD or maternal WSD. Light blue circle = male/maternal LFD; dark blue circle = male/maternal WSD; pink square = female/maternal LFD; red square = female/maternal WSD. *p≤0.05; **p≤0.01.
Mentions: The body weight of offspring from WSD and LFD dams at postnatal day (PD) 8 and PD14 (sacrifice) showed a significant increase over time that was independent from sex or diet (Figure 2A). At both time points, male offspring of WSD dams were significantly heavier than offspring of LFD dams. For female offspring, significant differences in body weight were not detected at any time (Figure 2A). In both sexes, liver weight was significantly higher at sacrifice in offspring of WSD dams, leading to a significant increased liver weight/body weight ratio in WSD females only (Figure 2B and C). For blood parameters, likewise differences between the sexes were observed: in male offspring of WSD dams, plasma TG and plasma cholesterol levels were significantly higher and lower, respectively, when compared with offspring from LFD dams (Figure 2D). In females, only NEFA plasma levels were affected by the mother’s diet, and were significantly lower in WSD offspring (Figure 2D).

Bottom Line: Exclusively male offspring had significantly higher body weight upon maternal WSD.Only 10% of these significantly changed genes overlapped in both sexes.We conclude that maternal WSD affects physiological parameters and induces substantial changes in the molecular profile of the liver in two-week-old pups.

View Article: PubMed Central - PubMed

Affiliation: Nutrition, Metabolism & Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.

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.

Show MeSH
Related in: MedlinePlus