Limits...
Transcriptional profiling of rats subjected to gestational undernourishment: implications for the developmental variations in metabolic traits.

Morris TJ, Vickers M, Gluckman P, Gilmour S, Affara N - PLoS ONE (2009)

Bottom Line: No significant changes in expression were identified for skeletal muscle or white adipose tissue.Although the animals at day 55 have yet to develop obesity they already show biochemical abnormalities and by day 110 express a phenotype characterized by increased adiposity and altered insulin sensitivity.An analysis of pathways affected suggests that intrauterine programming of UN animals to favor fat as an energy source results in mitochondrial dysfunction which initially affects the postnatal hepatic function and subsequently, via the resultant metabolic changes in other organs leads to the evolution of a phenotype similar to that of the metabolic syndrome.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Cambridge, Cambridge, England. tjm42@cam.ac.uk

ABSTRACT
A link has been established between prenatal nutrition and the development of metabolic and cardiovascular diseases later in life, a process referred to as developmental programming. It has been suggested that the trajectory of development is shifted by alterations in the maternal nutritional state leading to changes in developmental plasticity, in part underpinned by epigenetic changes in gene regulation. However, to date, only candidate gene approaches have been used to assess expression and molecular changes in the offspring of maternally undernourished animals. Furthermore, most work has focused on animals at an age where the programmed phenotype is already manifest and little is known about changes in gene expression in the offspring prior to development of obesity and related metabolic disorders. Gene expression profiles of liver, retroperitoneal white adipose fat, and biceps femoris skeletal muscle tissue from young adult male rats (55 days old) in which nutritional status had been manipulated in utero by maternal undernutrition (UN) were compared to the profiles of offspring of ad libitum fed mothers serving as the control group (AD) (8 offspring/group). The expression profiles were determined using the Illumina RatRef-12 BeadChip. No significant changes in expression were identified for skeletal muscle or white adipose tissue. However, studies of liver tissue showed 249 differentially expressed genes (143 up regulated, 106 down regulated). Although the animals at day 55 have yet to develop obesity they already show biochemical abnormalities and by day 110 express a phenotype characterized by increased adiposity and altered insulin sensitivity. An analysis of pathways affected suggests that intrauterine programming of UN animals to favor fat as an energy source results in mitochondrial dysfunction which initially affects the postnatal hepatic function and subsequently, via the resultant metabolic changes in other organs leads to the evolution of a phenotype similar to that of the metabolic syndrome.

Show MeSH

Related in: MedlinePlus

Genes that Influence Glucose, Fat, and Energy Metabolism Pathways and IGF-1 and PI3K Signaling Pathways.(A) Summarizes the interrelationships between pathways involved in glucose, fat, and energy metabolism and highlights differentially regulated genes that influence these pathways. (B) A summary of the genes that are altered in signaling through the IGF-1 and PI3K signaling pathways and their relevance to glucose and fat metabolism. Normal arrows indicate no change in gene expression; dashed arrows indicate down regulation; bold arrows indicate up-regulation.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2749934&req=5

pone-0007271-g002: Genes that Influence Glucose, Fat, and Energy Metabolism Pathways and IGF-1 and PI3K Signaling Pathways.(A) Summarizes the interrelationships between pathways involved in glucose, fat, and energy metabolism and highlights differentially regulated genes that influence these pathways. (B) A summary of the genes that are altered in signaling through the IGF-1 and PI3K signaling pathways and their relevance to glucose and fat metabolism. Normal arrows indicate no change in gene expression; dashed arrows indicate down regulation; bold arrows indicate up-regulation.

Mentions: Analysis of the gene categories and associated pathways associated with differentially expressed genes (Table S3) has revealed some relevant changes that potentially impact on the metabolic phenotype. Table 4 summarizes the relevant categories to emerge from analysis of gene functions (some of which emerged from DAVID and Ingenuity analyses) associated with the list of differentially expressed genes. Figure 2A and 2B summarize the interrelationships between pathways involved in glucose, fat, and energy metabolism and highlight differentially regulated genes that influence these pathways.


Transcriptional profiling of rats subjected to gestational undernourishment: implications for the developmental variations in metabolic traits.

Morris TJ, Vickers M, Gluckman P, Gilmour S, Affara N - PLoS ONE (2009)

Genes that Influence Glucose, Fat, and Energy Metabolism Pathways and IGF-1 and PI3K Signaling Pathways.(A) Summarizes the interrelationships between pathways involved in glucose, fat, and energy metabolism and highlights differentially regulated genes that influence these pathways. (B) A summary of the genes that are altered in signaling through the IGF-1 and PI3K signaling pathways and their relevance to glucose and fat metabolism. Normal arrows indicate no change in gene expression; dashed arrows indicate down regulation; bold arrows indicate up-regulation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2749934&req=5

pone-0007271-g002: Genes that Influence Glucose, Fat, and Energy Metabolism Pathways and IGF-1 and PI3K Signaling Pathways.(A) Summarizes the interrelationships between pathways involved in glucose, fat, and energy metabolism and highlights differentially regulated genes that influence these pathways. (B) A summary of the genes that are altered in signaling through the IGF-1 and PI3K signaling pathways and their relevance to glucose and fat metabolism. Normal arrows indicate no change in gene expression; dashed arrows indicate down regulation; bold arrows indicate up-regulation.
Mentions: Analysis of the gene categories and associated pathways associated with differentially expressed genes (Table S3) has revealed some relevant changes that potentially impact on the metabolic phenotype. Table 4 summarizes the relevant categories to emerge from analysis of gene functions (some of which emerged from DAVID and Ingenuity analyses) associated with the list of differentially expressed genes. Figure 2A and 2B summarize the interrelationships between pathways involved in glucose, fat, and energy metabolism and highlight differentially regulated genes that influence these pathways.

Bottom Line: No significant changes in expression were identified for skeletal muscle or white adipose tissue.Although the animals at day 55 have yet to develop obesity they already show biochemical abnormalities and by day 110 express a phenotype characterized by increased adiposity and altered insulin sensitivity.An analysis of pathways affected suggests that intrauterine programming of UN animals to favor fat as an energy source results in mitochondrial dysfunction which initially affects the postnatal hepatic function and subsequently, via the resultant metabolic changes in other organs leads to the evolution of a phenotype similar to that of the metabolic syndrome.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Cambridge, Cambridge, England. tjm42@cam.ac.uk

ABSTRACT
A link has been established between prenatal nutrition and the development of metabolic and cardiovascular diseases later in life, a process referred to as developmental programming. It has been suggested that the trajectory of development is shifted by alterations in the maternal nutritional state leading to changes in developmental plasticity, in part underpinned by epigenetic changes in gene regulation. However, to date, only candidate gene approaches have been used to assess expression and molecular changes in the offspring of maternally undernourished animals. Furthermore, most work has focused on animals at an age where the programmed phenotype is already manifest and little is known about changes in gene expression in the offspring prior to development of obesity and related metabolic disorders. Gene expression profiles of liver, retroperitoneal white adipose fat, and biceps femoris skeletal muscle tissue from young adult male rats (55 days old) in which nutritional status had been manipulated in utero by maternal undernutrition (UN) were compared to the profiles of offspring of ad libitum fed mothers serving as the control group (AD) (8 offspring/group). The expression profiles were determined using the Illumina RatRef-12 BeadChip. No significant changes in expression were identified for skeletal muscle or white adipose tissue. However, studies of liver tissue showed 249 differentially expressed genes (143 up regulated, 106 down regulated). Although the animals at day 55 have yet to develop obesity they already show biochemical abnormalities and by day 110 express a phenotype characterized by increased adiposity and altered insulin sensitivity. An analysis of pathways affected suggests that intrauterine programming of UN animals to favor fat as an energy source results in mitochondrial dysfunction which initially affects the postnatal hepatic function and subsequently, via the resultant metabolic changes in other organs leads to the evolution of a phenotype similar to that of the metabolic syndrome.

Show MeSH
Related in: MedlinePlus