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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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Study design.C57BL/6 dams received either a low fat control diet (LFD) or a Western-style high fat diet (WSD) throughout the study. The treatment started six weeks before mating and continued during gestation and lactation. Dams and offspring were sacrificed at postnatal week two. Male and female offspring were included into further analysis: male offspring from maternal LFD (n = 6), male offspring from maternal WSD (n = 6), female offspring from maternal LFD (n = 9), female offspring from maternal WSD (n = 6).
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pone-0078623-g001: Study design.C57BL/6 dams received either a low fat control diet (LFD) or a Western-style high fat diet (WSD) throughout the study. The treatment started six weeks before mating and continued during gestation and lactation. Dams and offspring were sacrificed at postnatal week two. Male and female offspring were included into further analysis: male offspring from maternal LFD (n = 6), male offspring from maternal WSD (n = 6), female offspring from maternal LFD (n = 9), female offspring from maternal WSD (n = 6).

Mentions: Female C57BL/6 mice (five weeks of age) were purchased from Harlan (Horst, The Netherlands) and housed individually in the light- and temperature-controlled facility of the University Medical Center Groningen (lights on 7:00 am–7:00 pm, 21°C). The mice had free access to drinking water and were randomly assigned to either a semi-synthetic low fat control diet (LFD, 3.85 kcal/g; 10 E% fat, 20 E% protein, 70 E% carbohydrate; D12450B, Research Diets, New Brunswick, USA) that contained low amounts of cholesterol from lard (18.0 mg cholesterol/kg) or a semi-synthetic energy rich Western-style high fat diet (WSD, 4.73 kcal/g; 45 E% fat, 20 E% protein, 35 E% carbohydrate; D12451, Research Diets) that contained a high cholesterol content from lard (196.5 mg cholesterol/kg). After 6 weeks on their respective diets (pre-treatment period), the female mice were mated with males on control diet. In case conceiving failed, mice were allowed to re-mate. Throughout pregnancy and lactation, the dams received the same diets as during pre-treatment (Figure 1). Mice were allowed to deliver spontaneously and were left undisturbed with their litters for 24 h. Litter sizes were standardized to 5–7 pups, to ensure no litter was nutritionally biased. By natural circumstances, the litter size of some dams was reduced further, but not changing the overall male/female ratio within the diet significantly. Two weeks into lactation, dams and offspring were sacrificed by cervical dislocation under isoflurane anaesthesia. Blood was collected by cardiac puncture and livers were dissected, weighed, snap-frozen in liquid nitrogen, and stored at −80°C until further use. Both male and female offspring were included into further analysis, resulting in four experimental groups: male offspring from maternal LFD (m-LF; n = 6), male offspring from maternal WSD (m-WS; n = 6), female offspring from maternal LFD (f-LF; n = 9), female offspring from maternal WSD (f-WS; n = 6).


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)

Study design.C57BL/6 dams received either a low fat control diet (LFD) or a Western-style high fat diet (WSD) throughout the study. The treatment started six weeks before mating and continued during gestation and lactation. Dams and offspring were sacrificed at postnatal week two. Male and female offspring were included into further analysis: male offspring from maternal LFD (n = 6), male offspring from maternal WSD (n = 6), female offspring from maternal LFD (n = 9), female offspring from maternal WSD (n = 6).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0078623-g001: Study design.C57BL/6 dams received either a low fat control diet (LFD) or a Western-style high fat diet (WSD) throughout the study. The treatment started six weeks before mating and continued during gestation and lactation. Dams and offspring were sacrificed at postnatal week two. Male and female offspring were included into further analysis: male offspring from maternal LFD (n = 6), male offspring from maternal WSD (n = 6), female offspring from maternal LFD (n = 9), female offspring from maternal WSD (n = 6).
Mentions: Female C57BL/6 mice (five weeks of age) were purchased from Harlan (Horst, The Netherlands) and housed individually in the light- and temperature-controlled facility of the University Medical Center Groningen (lights on 7:00 am–7:00 pm, 21°C). The mice had free access to drinking water and were randomly assigned to either a semi-synthetic low fat control diet (LFD, 3.85 kcal/g; 10 E% fat, 20 E% protein, 70 E% carbohydrate; D12450B, Research Diets, New Brunswick, USA) that contained low amounts of cholesterol from lard (18.0 mg cholesterol/kg) or a semi-synthetic energy rich Western-style high fat diet (WSD, 4.73 kcal/g; 45 E% fat, 20 E% protein, 35 E% carbohydrate; D12451, Research Diets) that contained a high cholesterol content from lard (196.5 mg cholesterol/kg). After 6 weeks on their respective diets (pre-treatment period), the female mice were mated with males on control diet. In case conceiving failed, mice were allowed to re-mate. Throughout pregnancy and lactation, the dams received the same diets as during pre-treatment (Figure 1). Mice were allowed to deliver spontaneously and were left undisturbed with their litters for 24 h. Litter sizes were standardized to 5–7 pups, to ensure no litter was nutritionally biased. By natural circumstances, the litter size of some dams was reduced further, but not changing the overall male/female ratio within the diet significantly. Two weeks into lactation, dams and offspring were sacrificed by cervical dislocation under isoflurane anaesthesia. Blood was collected by cardiac puncture and livers were dissected, weighed, snap-frozen in liquid nitrogen, and stored at −80°C until further use. Both male and female offspring were included into further analysis, resulting in four experimental groups: male offspring from maternal LFD (m-LF; n = 6), male offspring from maternal WSD (m-WS; n = 6), female offspring from maternal LFD (f-LF; n = 9), female offspring from maternal WSD (f-WS; n = 6).

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