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A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.

Oster M, Murani E, Metges CC, Ponsuksili S, Wimmers K - PLoS ONE (2011)

Bottom Line: Depending on the gestational dietary exposure, mRNA expression levels of genes related to energy metabolism, N-metabolism, growth factor signaling pathways, lipid metabolism, nucleic acid metabolism and stress/immune response were affected either in a short-term or in a long-term manner.The effects encompassed a modulation of the genome in terms of an altered responsiveness of energy and nutrient sensing pathways.Differential expression of genes related to energy production and nutrient utilization contribute to the maintenance of development and growth performance within physiological norms, however the modulation of these pathways may be accompanied by a predisposition for metabolic disturbances up to adult stages.

View Article: PubMed Central - PubMed

Affiliation: Research Unit Molecular Biology, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany.

ABSTRACT
In rodent models and in humans the impact of gestational diets on the offspring's phenotype was shown experimentally and epidemiologically. The underlying programming of fetal development was shown to be associated with an increased risk of degenerative diseases in adulthood, including the metabolic syndrome. There are clues that diet-dependent modifications of the metabolism during fetal life can persist until adulthood. This leads to the hypothesis that the offspring's transcriptomes show short-term and long-term changes depending on the maternal diet. To this end pregnant German landrace gilts were fed either a high protein diet (HP, 30% CP) or an adequate protein diet (AP, 12% CP) throughout pregnancy. Hepatic transcriptome profiles of the offspring were analyzed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn). Depending on the gestational dietary exposure, mRNA expression levels of genes related to energy metabolism, N-metabolism, growth factor signaling pathways, lipid metabolism, nucleic acid metabolism and stress/immune response were affected either in a short-term or in a long-term manner. Gene expression profiles at fetal stage 94 dpc were almost unchanged between the diets. The gestational HP diet affected the hepatic expression profiles at prenatal and postnatal stages. The effects encompassed a modulation of the genome in terms of an altered responsiveness of energy and nutrient sensing pathways. Differential expression of genes related to energy production and nutrient utilization contribute to the maintenance of development and growth performance within physiological norms, however the modulation of these pathways may be accompanied by a predisposition for metabolic disturbances up to adult stages.

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pone-0021691-g003: Experimental design.

Mentions: Animal care and tissue collection procedures followed the guidelines of the German Law of Animal Protection and the experimental protocol was approved by the Animal Care Committee of the State Mecklenburg-Vorpommern (Landesamt für Landwirtschaft, Lebensmittelsicherheit und Fischerei, Mecklenburg - Vorpommern, Germany; LVL MV/TSD/7221.3-1.1-006/04; LALLF M-V/TSD/7221.3-1.2-05/06; LALLF M-V/TSD/7221.3-1.2-013/06). The animal experiment was performed as described [14]. A high protein diet (HP) containing 30% (w/w) crude protein or an adequate protein diet (AP) containing 12% crude protein were formulated to be isocaloric (13.6 MJ ME/kg on average). The gilts of both groups consumed 2.6 kg/d resulting in a significantly different protein intake but equal energy intake [14]. The gestation diets did not affect reproductive parameters like litter size and litter weight as well as percentage of stillborn and mummies [14]. At insemination German Landrace primiparous sows (n = 48) were randomly assigned to either the HP or the AP group (Figure 3). Tissue sampling included offspring of these sows at one prenatal (94 dies post conceptionem (dpc)) and three postnatal time points (1, 28, 188 dies post natum (dpn)). At d 94 of gestation, a subset of eight sows per dietary group was subjected to Caesarean section (EXP1). Sows were anesthetized as described [14]. This experiment was performed over 5 replicates. Eight viable foetuses per sow were collected starting at the tip of the left uterus horn and alternating between left and right horn. Fetuses were killed by i.v. injection of T61 (Intervet, Unterschleissheim, Germany) in the V. cava cranialis and liver samples were immediately collected (approximately 500 mg), frozen in liquid nitrogen, and stored at until analysis. Fetuses originated from litters of at least 11 viable piglets. Fetuses of HP fed dams showed a decreased weight compared to AP fetuses at 94 dpc (HP: 622119 g, and AP: 711118 g, respectively; ; n = 32). The smallest and the heaviest fetus were selected for transcriptome analysis. In the second experiment (EXP2) offspring selected for the postnatal time points was born to primiparous sows after prostaglandin induction of parturition as described [14] and farrowed after a mean pregnancy duration of 115 days. This experiment was conducted over 8 replicates and offspring of a subset of 4 sows (2 per diet per replicate) with a minimum of 11 live born piglets (median litter size = 13) was used. At birth 10 piglets in each litter were distributed over three time points (1, 28, 188 dpn). For the microarray analyses, 8 sib pairs, which were balanced for sex (all stages) and discordant for weight (light and heavy piglet; stages 94 dpc and 1 dpn only) were chosen per stage and diet. Thirty-six hours after birth, the lightest and the heaviest piglet within one litter were killed by i.m. injection of 1.25 mg propionyl-promazine (0.2 ml Combelen, Bayer AG, Leverkusen, Germany) and 50 mg ketamine (Ursotamin, Serumwerk Bernburg AG, Germany). Samples were immediately collected from lobus sinister hepaticus (approximately 500 mg), frozen in liquid nitrogen, and stored at until analysis. The remaining piglets were cross-fostered to non-experimental sows of 2nd to 4th parities, which were on the AP diet during gestation. All sows were fed AP lactation diets. Litter size during suckling was standardized to 11 piglets per sow. Male piglets were castrated at d 4 of age. From weaning (28 dpn) to slaughter (188 dpn), all piglets were individually reared. They had free access to standard diets formulated for post-weaning (d 29 to d 76), growing (d 77 to d 105) and finishing periods [65] and had the same feed intake. At 28 dpn and 188 dpn of age, pigs were weighed after an overnight fast and killed by electronarcosis followed by exsanguination in the experimental slaughterhouse of FBN. Liver tissue was immediately collected from lobus sinister hepaticus, frozen in liquid nitrogen, and stored at until use for RNA isolation. In our experiment piglets (1 dpn) born from HP sows had significantly lower birth weight (HP: 1.210.04 kg, and AP: 1.410.04 kg respectively, ) that mainly resulted from reduced body fat, whereas body mass index and ponderal index did not differ from the AP group [14]. Mean birth weights of animals of the HP group used for microarray analyses were numerically but not significantly lower than birth weights of AP offspring (HP: 1.310.31 kg, and AP: 1.360.31 kg, respectively; ; n = 32). At 28 dpn, the animals of the AP and HP group showed no difference in body weight (HP: 7.361.54 kg, and AP: 7.592.14 kg respectively; ; n = 32) and body composition, i.e. muscle, fat depots, bones, skin, as well as in analytical components (protein, fat, ash, moisture) or structural and biochemical properties of fat and muscle tissues [25]. Also at 188 dpn offspring of AP and HP sows did not differ significantly in body weight (HP: 131.417.11 kg, and AP: 131.5515.11 kg respectively; ; n = 32). Like at earlier ages animals of the HP group tended have lower meat but higher fat percentage, but the differences were not significant [24].


A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.

Oster M, Murani E, Metges CC, Ponsuksili S, Wimmers K - PLoS ONE (2011)

Experimental design.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3138750&req=5

pone-0021691-g003: Experimental design.
Mentions: Animal care and tissue collection procedures followed the guidelines of the German Law of Animal Protection and the experimental protocol was approved by the Animal Care Committee of the State Mecklenburg-Vorpommern (Landesamt für Landwirtschaft, Lebensmittelsicherheit und Fischerei, Mecklenburg - Vorpommern, Germany; LVL MV/TSD/7221.3-1.1-006/04; LALLF M-V/TSD/7221.3-1.2-05/06; LALLF M-V/TSD/7221.3-1.2-013/06). The animal experiment was performed as described [14]. A high protein diet (HP) containing 30% (w/w) crude protein or an adequate protein diet (AP) containing 12% crude protein were formulated to be isocaloric (13.6 MJ ME/kg on average). The gilts of both groups consumed 2.6 kg/d resulting in a significantly different protein intake but equal energy intake [14]. The gestation diets did not affect reproductive parameters like litter size and litter weight as well as percentage of stillborn and mummies [14]. At insemination German Landrace primiparous sows (n = 48) were randomly assigned to either the HP or the AP group (Figure 3). Tissue sampling included offspring of these sows at one prenatal (94 dies post conceptionem (dpc)) and three postnatal time points (1, 28, 188 dies post natum (dpn)). At d 94 of gestation, a subset of eight sows per dietary group was subjected to Caesarean section (EXP1). Sows were anesthetized as described [14]. This experiment was performed over 5 replicates. Eight viable foetuses per sow were collected starting at the tip of the left uterus horn and alternating between left and right horn. Fetuses were killed by i.v. injection of T61 (Intervet, Unterschleissheim, Germany) in the V. cava cranialis and liver samples were immediately collected (approximately 500 mg), frozen in liquid nitrogen, and stored at until analysis. Fetuses originated from litters of at least 11 viable piglets. Fetuses of HP fed dams showed a decreased weight compared to AP fetuses at 94 dpc (HP: 622119 g, and AP: 711118 g, respectively; ; n = 32). The smallest and the heaviest fetus were selected for transcriptome analysis. In the second experiment (EXP2) offspring selected for the postnatal time points was born to primiparous sows after prostaglandin induction of parturition as described [14] and farrowed after a mean pregnancy duration of 115 days. This experiment was conducted over 8 replicates and offspring of a subset of 4 sows (2 per diet per replicate) with a minimum of 11 live born piglets (median litter size = 13) was used. At birth 10 piglets in each litter were distributed over three time points (1, 28, 188 dpn). For the microarray analyses, 8 sib pairs, which were balanced for sex (all stages) and discordant for weight (light and heavy piglet; stages 94 dpc and 1 dpn only) were chosen per stage and diet. Thirty-six hours after birth, the lightest and the heaviest piglet within one litter were killed by i.m. injection of 1.25 mg propionyl-promazine (0.2 ml Combelen, Bayer AG, Leverkusen, Germany) and 50 mg ketamine (Ursotamin, Serumwerk Bernburg AG, Germany). Samples were immediately collected from lobus sinister hepaticus (approximately 500 mg), frozen in liquid nitrogen, and stored at until analysis. The remaining piglets were cross-fostered to non-experimental sows of 2nd to 4th parities, which were on the AP diet during gestation. All sows were fed AP lactation diets. Litter size during suckling was standardized to 11 piglets per sow. Male piglets were castrated at d 4 of age. From weaning (28 dpn) to slaughter (188 dpn), all piglets were individually reared. They had free access to standard diets formulated for post-weaning (d 29 to d 76), growing (d 77 to d 105) and finishing periods [65] and had the same feed intake. At 28 dpn and 188 dpn of age, pigs were weighed after an overnight fast and killed by electronarcosis followed by exsanguination in the experimental slaughterhouse of FBN. Liver tissue was immediately collected from lobus sinister hepaticus, frozen in liquid nitrogen, and stored at until use for RNA isolation. In our experiment piglets (1 dpn) born from HP sows had significantly lower birth weight (HP: 1.210.04 kg, and AP: 1.410.04 kg respectively, ) that mainly resulted from reduced body fat, whereas body mass index and ponderal index did not differ from the AP group [14]. Mean birth weights of animals of the HP group used for microarray analyses were numerically but not significantly lower than birth weights of AP offspring (HP: 1.310.31 kg, and AP: 1.360.31 kg, respectively; ; n = 32). At 28 dpn, the animals of the AP and HP group showed no difference in body weight (HP: 7.361.54 kg, and AP: 7.592.14 kg respectively; ; n = 32) and body composition, i.e. muscle, fat depots, bones, skin, as well as in analytical components (protein, fat, ash, moisture) or structural and biochemical properties of fat and muscle tissues [25]. Also at 188 dpn offspring of AP and HP sows did not differ significantly in body weight (HP: 131.417.11 kg, and AP: 131.5515.11 kg respectively; ; n = 32). Like at earlier ages animals of the HP group tended have lower meat but higher fat percentage, but the differences were not significant [24].

Bottom Line: Depending on the gestational dietary exposure, mRNA expression levels of genes related to energy metabolism, N-metabolism, growth factor signaling pathways, lipid metabolism, nucleic acid metabolism and stress/immune response were affected either in a short-term or in a long-term manner.The effects encompassed a modulation of the genome in terms of an altered responsiveness of energy and nutrient sensing pathways.Differential expression of genes related to energy production and nutrient utilization contribute to the maintenance of development and growth performance within physiological norms, however the modulation of these pathways may be accompanied by a predisposition for metabolic disturbances up to adult stages.

View Article: PubMed Central - PubMed

Affiliation: Research Unit Molecular Biology, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany.

ABSTRACT
In rodent models and in humans the impact of gestational diets on the offspring's phenotype was shown experimentally and epidemiologically. The underlying programming of fetal development was shown to be associated with an increased risk of degenerative diseases in adulthood, including the metabolic syndrome. There are clues that diet-dependent modifications of the metabolism during fetal life can persist until adulthood. This leads to the hypothesis that the offspring's transcriptomes show short-term and long-term changes depending on the maternal diet. To this end pregnant German landrace gilts were fed either a high protein diet (HP, 30% CP) or an adequate protein diet (AP, 12% CP) throughout pregnancy. Hepatic transcriptome profiles of the offspring were analyzed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn). Depending on the gestational dietary exposure, mRNA expression levels of genes related to energy metabolism, N-metabolism, growth factor signaling pathways, lipid metabolism, nucleic acid metabolism and stress/immune response were affected either in a short-term or in a long-term manner. Gene expression profiles at fetal stage 94 dpc were almost unchanged between the diets. The gestational HP diet affected the hepatic expression profiles at prenatal and postnatal stages. The effects encompassed a modulation of the genome in terms of an altered responsiveness of energy and nutrient sensing pathways. Differential expression of genes related to energy production and nutrient utilization contribute to the maintenance of development and growth performance within physiological norms, however the modulation of these pathways may be accompanied by a predisposition for metabolic disturbances up to adult stages.

Show MeSH
Related in: MedlinePlus