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Maternal protein restriction affects postnatal growth and the expression of key proteins involved in lifespan regulation in mice.

Chen JH, Martin-Gronert MS, Tarry-Adkins J, Ozanne SE - PLoS ONE (2009)

Bottom Line: Recuperated animals expressed decreased levels of many insulin signalling proteins including PI3 kinase subunits p85alpha (P = 0.018), p110beta (P = 0.048) and protein kinase C zeta (P = 0.006) which may predispose these animals to insulin resistance.Sirt1 protein expression was reduced in recuperated offspring.These observations suggest that maternal protein restriction can affect major metabolic pathways implicated in regulation of lifespan at a young age which may explain the impact of maternal diet on longevity.

View Article: PubMed Central - PubMed

Affiliation: University of Cambridge Metabolic Research Laboratories Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom. jhc36@cam.ac.uk

ABSTRACT
We previously reported that maternal protein restriction in rodents influenced the rate of growth in early life and ultimately affected longevity. Low birth weight caused by maternal protein restriction followed by catch-up growth (recuperated animals) was associated with shortened lifespan whereas protein restriction and slow growth during lactation (postnatal low protein: PLP animals) increased lifespan. We aim to explore the mechanistic basis by which these differences arise. Here we investigated effects of maternal diet on organ growth, metabolic parameters and the expression of insulin/IGF1 signalling proteins and Sirt1 in muscle of male mice at weaning. PLP mice which experienced protein restriction during lactation had lower fasting glucose (P = 0.038) and insulin levels (P = 0.046) suggesting improved insulin sensitivity. PLP mice had higher relative weights (adjusted by body weight) of brain (P = 0.0002) and thymus (P = 0.031) compared to controls suggesting that enhanced functional capacity of these two tissues is beneficial to longevity. They also had increased expression of insulin receptor substrate 1 (P = 0.021) and protein kinase C zeta (P = 0.046). Recuperated animals expressed decreased levels of many insulin signalling proteins including PI3 kinase subunits p85alpha (P = 0.018), p110beta (P = 0.048) and protein kinase C zeta (P = 0.006) which may predispose these animals to insulin resistance. Sirt1 protein expression was reduced in recuperated offspring. These observations suggest that maternal protein restriction can affect major metabolic pathways implicated in regulation of lifespan at a young age which may explain the impact of maternal diet on longevity.

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Effects of maternal protein restriction on organ weights.Organ weights were measured 21 days after birth. (A) Organ weights were expressed as mean±SEM (* P<0.05, ** P<0.01, *** P<0.001 compared to control; n = control (C): 10, postnatal low protein (PLP): 8, recuperated (R): 10). (B) Percentage organ weight change of PLP and R mice compared to the mean of control organ weights (mean±SEM; * P<0.05, ** P<0.01, *** P<0.001; n = C: 10, PLP: 8, R: 10). (C) Relative organ weights were expressed as percentage of body weights (mean±SEM; * P<0.05, ** P<0.01, *** P<0.001 compared to control; n = C: 10, PLP: 8, R: 10).
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pone-0004950-g002: Effects of maternal protein restriction on organ weights.Organ weights were measured 21 days after birth. (A) Organ weights were expressed as mean±SEM (* P<0.05, ** P<0.01, *** P<0.001 compared to control; n = control (C): 10, postnatal low protein (PLP): 8, recuperated (R): 10). (B) Percentage organ weight change of PLP and R mice compared to the mean of control organ weights (mean±SEM; * P<0.05, ** P<0.01, *** P<0.001; n = C: 10, PLP: 8, R: 10). (C) Relative organ weights were expressed as percentage of body weights (mean±SEM; * P<0.05, ** P<0.01, *** P<0.001 compared to control; n = C: 10, PLP: 8, R: 10).

Mentions: In general, except for the brain, lung and thymus, organ weights of PLP mice were smaller than that of control mice with vastus lateralis, pancreas, spleen, kidneys, liver and heart being significantly lighter (Figures 2A and 2B). In contrast, organs of recuperated mice were larger than that of control mice with spleen, heart and thymus being significantly heavier (Figures 2A and 2B). When expressed relative to body weight, PLP pancreas, kidneys and liver still remained significantly smaller than controls (Figure 2C). In contrast, the relative weights of brain and thymus in PLP were significantly higher than controls (Figure 2C). In recuperated animals the relative weights of pancreas, kidneys and liver were lower than controls, however the relative weights of spleen, heart, lung and thymus showed no difference as compared to controls (Figure 2C).


Maternal protein restriction affects postnatal growth and the expression of key proteins involved in lifespan regulation in mice.

Chen JH, Martin-Gronert MS, Tarry-Adkins J, Ozanne SE - PLoS ONE (2009)

Effects of maternal protein restriction on organ weights.Organ weights were measured 21 days after birth. (A) Organ weights were expressed as mean±SEM (* P<0.05, ** P<0.01, *** P<0.001 compared to control; n = control (C): 10, postnatal low protein (PLP): 8, recuperated (R): 10). (B) Percentage organ weight change of PLP and R mice compared to the mean of control organ weights (mean±SEM; * P<0.05, ** P<0.01, *** P<0.001; n = C: 10, PLP: 8, R: 10). (C) Relative organ weights were expressed as percentage of body weights (mean±SEM; * P<0.05, ** P<0.01, *** P<0.001 compared to control; n = C: 10, PLP: 8, R: 10).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2654922&req=5

pone-0004950-g002: Effects of maternal protein restriction on organ weights.Organ weights were measured 21 days after birth. (A) Organ weights were expressed as mean±SEM (* P<0.05, ** P<0.01, *** P<0.001 compared to control; n = control (C): 10, postnatal low protein (PLP): 8, recuperated (R): 10). (B) Percentage organ weight change of PLP and R mice compared to the mean of control organ weights (mean±SEM; * P<0.05, ** P<0.01, *** P<0.001; n = C: 10, PLP: 8, R: 10). (C) Relative organ weights were expressed as percentage of body weights (mean±SEM; * P<0.05, ** P<0.01, *** P<0.001 compared to control; n = C: 10, PLP: 8, R: 10).
Mentions: In general, except for the brain, lung and thymus, organ weights of PLP mice were smaller than that of control mice with vastus lateralis, pancreas, spleen, kidneys, liver and heart being significantly lighter (Figures 2A and 2B). In contrast, organs of recuperated mice were larger than that of control mice with spleen, heart and thymus being significantly heavier (Figures 2A and 2B). When expressed relative to body weight, PLP pancreas, kidneys and liver still remained significantly smaller than controls (Figure 2C). In contrast, the relative weights of brain and thymus in PLP were significantly higher than controls (Figure 2C). In recuperated animals the relative weights of pancreas, kidneys and liver were lower than controls, however the relative weights of spleen, heart, lung and thymus showed no difference as compared to controls (Figure 2C).

Bottom Line: Recuperated animals expressed decreased levels of many insulin signalling proteins including PI3 kinase subunits p85alpha (P = 0.018), p110beta (P = 0.048) and protein kinase C zeta (P = 0.006) which may predispose these animals to insulin resistance.Sirt1 protein expression was reduced in recuperated offspring.These observations suggest that maternal protein restriction can affect major metabolic pathways implicated in regulation of lifespan at a young age which may explain the impact of maternal diet on longevity.

View Article: PubMed Central - PubMed

Affiliation: University of Cambridge Metabolic Research Laboratories Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom. jhc36@cam.ac.uk

ABSTRACT
We previously reported that maternal protein restriction in rodents influenced the rate of growth in early life and ultimately affected longevity. Low birth weight caused by maternal protein restriction followed by catch-up growth (recuperated animals) was associated with shortened lifespan whereas protein restriction and slow growth during lactation (postnatal low protein: PLP animals) increased lifespan. We aim to explore the mechanistic basis by which these differences arise. Here we investigated effects of maternal diet on organ growth, metabolic parameters and the expression of insulin/IGF1 signalling proteins and Sirt1 in muscle of male mice at weaning. PLP mice which experienced protein restriction during lactation had lower fasting glucose (P = 0.038) and insulin levels (P = 0.046) suggesting improved insulin sensitivity. PLP mice had higher relative weights (adjusted by body weight) of brain (P = 0.0002) and thymus (P = 0.031) compared to controls suggesting that enhanced functional capacity of these two tissues is beneficial to longevity. They also had increased expression of insulin receptor substrate 1 (P = 0.021) and protein kinase C zeta (P = 0.046). Recuperated animals expressed decreased levels of many insulin signalling proteins including PI3 kinase subunits p85alpha (P = 0.018), p110beta (P = 0.048) and protein kinase C zeta (P = 0.006) which may predispose these animals to insulin resistance. Sirt1 protein expression was reduced in recuperated offspring. These observations suggest that maternal protein restriction can affect major metabolic pathways implicated in regulation of lifespan at a young age which may explain the impact of maternal diet on longevity.

Show MeSH
Related in: MedlinePlus