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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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Number of regulated probe-sets in liver tissue.The numbers at the horizontal arrows indicate the quantity of probe-sets significantly regulated between the adjacent ontogenetic stages in either AP or HP offspring, whereas the numbers in the intersections indicate the quantity of probe-sets commonly regulated between stages in AP and HP offspring. The numbers at vertical arrows are the number of probe-sets differentially expressed between AP and HP offspring at the same ontogenetic stage (arrows between boxes show direction of the comparisons; small arrows to top = up-regulated, small arrows to bottom = down-regulated probe-sets).
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pone-0021691-g001: Number of regulated probe-sets in liver tissue.The numbers at the horizontal arrows indicate the quantity of probe-sets significantly regulated between the adjacent ontogenetic stages in either AP or HP offspring, whereas the numbers in the intersections indicate the quantity of probe-sets commonly regulated between stages in AP and HP offspring. The numbers at vertical arrows are the number of probe-sets differentially expressed between AP and HP offspring at the same ontogenetic stage (arrows between boxes show direction of the comparisons; small arrows to top = up-regulated, small arrows to bottom = down-regulated probe-sets).

Mentions: Expression of mRNA was compared in HP and AP offspring within each ontogenetic stage (Figure 1). At stage 94 dpc 7 probe-sets differed significantly between HP and AP fetuses (1 increased). It was not possible to assign those genes to significant regulated metabolic pathways. In perinatal piglets (stage 1 dpn) 878 probe-sets differed between HP offspring (503 for HPAP) and AP offspring. Ingenuity Pathway Analysis indicates enrichment of molecular routes related to energy metabolism, lipid metabolism, N-metabolism, cellular growth and immune response (Table 1). In particular, genes associated with oxidative phosphorylation (OXPHOS), biosynthesis of steroids, and valine, leucine and isoleucine degradation were found diminished in HP offspring. Furthermore, genes associated with RAN signaling as well as PPARGC1a and PRKAA2 showed an increased expression in HP offspring at stage 1 dpn. Analysis towards common regulation of genes higher expressed in HP than AP revealed 217 potential regulatory elements (RE) (177 for HPAP) that corresponded to 103 transcription factors (TF) (107 for HPAP). In juvenile piglets (stage 28 dpn) 498 probe-sets differed between HP and AP offspring. The expression of 274 probe-sets was increased in the HP offspring compared with AP offspring. At juvenile stage, pathways of lipid metabolism and N-metabolism were enriched. Genes associated with fatty acid metabolism, and valine, leucine and isoleucine degradation showed a decreased mRNA expression in HP offspring. Analysis using DiRE identified 125 RE within the genes up-regulated in HP (103 for HPAP) that were associated with 101 TF (100 for HPAP). In adult pigs (stage 188 dpn) 1,903 probe-sets were significantly different between HP and AP offspring. Of these 1,177 probe-sets showed higher expression and 726 probe-sets showed lower expression in HP than in AP. The mRNA expression levels of genes associated with glucocorticoid receptor signaling, RAN signaling, PPAR signaling and IGF-1 signaling as well as fatty acid elongation in mitochondria and mitochondrial dysfunction were increased in HP offspring. The genes up-regulated in HP compared to AP were related to 117 (118 for HPAP) TF that fitted 448 potential RE (190 for HPAP). No genes were found consistently differentially expressed between the groups along all examined stages. However, at 1 dpn and 188 dpn 142 probe-sets were differentially regulated in both stages between HP and AP.


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)

Number of regulated probe-sets in liver tissue.The numbers at the horizontal arrows indicate the quantity of probe-sets significantly regulated between the adjacent ontogenetic stages in either AP or HP offspring, whereas the numbers in the intersections indicate the quantity of probe-sets commonly regulated between stages in AP and HP offspring. The numbers at vertical arrows are the number of probe-sets differentially expressed between AP and HP offspring at the same ontogenetic stage (arrows between boxes show direction of the comparisons; small arrows to top = up-regulated, small arrows to bottom = down-regulated probe-sets).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0021691-g001: Number of regulated probe-sets in liver tissue.The numbers at the horizontal arrows indicate the quantity of probe-sets significantly regulated between the adjacent ontogenetic stages in either AP or HP offspring, whereas the numbers in the intersections indicate the quantity of probe-sets commonly regulated between stages in AP and HP offspring. The numbers at vertical arrows are the number of probe-sets differentially expressed between AP and HP offspring at the same ontogenetic stage (arrows between boxes show direction of the comparisons; small arrows to top = up-regulated, small arrows to bottom = down-regulated probe-sets).
Mentions: Expression of mRNA was compared in HP and AP offspring within each ontogenetic stage (Figure 1). At stage 94 dpc 7 probe-sets differed significantly between HP and AP fetuses (1 increased). It was not possible to assign those genes to significant regulated metabolic pathways. In perinatal piglets (stage 1 dpn) 878 probe-sets differed between HP offspring (503 for HPAP) and AP offspring. Ingenuity Pathway Analysis indicates enrichment of molecular routes related to energy metabolism, lipid metabolism, N-metabolism, cellular growth and immune response (Table 1). In particular, genes associated with oxidative phosphorylation (OXPHOS), biosynthesis of steroids, and valine, leucine and isoleucine degradation were found diminished in HP offspring. Furthermore, genes associated with RAN signaling as well as PPARGC1a and PRKAA2 showed an increased expression in HP offspring at stage 1 dpn. Analysis towards common regulation of genes higher expressed in HP than AP revealed 217 potential regulatory elements (RE) (177 for HPAP) that corresponded to 103 transcription factors (TF) (107 for HPAP). In juvenile piglets (stage 28 dpn) 498 probe-sets differed between HP and AP offspring. The expression of 274 probe-sets was increased in the HP offspring compared with AP offspring. At juvenile stage, pathways of lipid metabolism and N-metabolism were enriched. Genes associated with fatty acid metabolism, and valine, leucine and isoleucine degradation showed a decreased mRNA expression in HP offspring. Analysis using DiRE identified 125 RE within the genes up-regulated in HP (103 for HPAP) that were associated with 101 TF (100 for HPAP). In adult pigs (stage 188 dpn) 1,903 probe-sets were significantly different between HP and AP offspring. Of these 1,177 probe-sets showed higher expression and 726 probe-sets showed lower expression in HP than in AP. The mRNA expression levels of genes associated with glucocorticoid receptor signaling, RAN signaling, PPAR signaling and IGF-1 signaling as well as fatty acid elongation in mitochondria and mitochondrial dysfunction were increased in HP offspring. The genes up-regulated in HP compared to AP were related to 117 (118 for HPAP) TF that fitted 448 potential RE (190 for HPAP). No genes were found consistently differentially expressed between the groups along all examined stages. However, at 1 dpn and 188 dpn 142 probe-sets were differentially regulated in both stages between HP and AP.

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