Limits...
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.

Show MeSH

Related in: MedlinePlus

Growth curves of pups of control, postnatal low protein and recuperated mice during lactation.Body weights of pups were recorded at days 3, 7, 14 and 21 of age. To maximize the effects of maternal diet, recuperated pups (R) were culled to 4 and control pups (C) were culled to 8 (if litter size was greater than 8) whereas postnatal low protein pups (PLP) were unculled. Means±SEM are shown (* P<0.05, ** P<0.01, *** P<0.001 compared to control; n = C: 13, PLP: 11, R: 16).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2654922&req=5

pone-0004950-g001: Growth curves of pups of control, postnatal low protein and recuperated mice during lactation.Body weights of pups were recorded at days 3, 7, 14 and 21 of age. To maximize the effects of maternal diet, recuperated pups (R) were culled to 4 and control pups (C) were culled to 8 (if litter size was greater than 8) whereas postnatal low protein pups (PLP) were unculled. Means±SEM are shown (* P<0.05, ** P<0.01, *** P<0.001 compared to control; n = C: 13, PLP: 11, R: 16).

Mentions: Pups of mothers fed the low protein diet during pregnancy were significantly smaller than controls (1.46±0.04 g vs 1.65±0.07 g on day 3, P = 0.006; Figure 1). Cross-fostering to mothers fed the control diet resulted in rapid catch-up growth such that by day 7 recuperated offspring had a similar body weight to controls (3.68±0.18 g vs 3.78±0.22 g; Figure 1), by day 14 they had overtaken the weight of controls and at day 21 they were significantly heavier than controls (8.92±0.52 g vs. 7.89±0.26 g, P = 0.047; Figure 1). In contrast, offspring of normally fed mothers when suckled by low protein fed dams grew slowly during lactation; by day 7 they were significantly smaller than controls (2.98±0.11 g vs. 3.78±0.22, P = 0.002; Figure 1) and this difference was further increased by day 14 and day 21 (4.96±0.23 g vs. 6.79±0.15 g, P = 0.00013 and 5.96±0.42 g vs. 7.89±0.26 g, P = 0.0002; Figure 1).


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)

Growth curves of pups of control, postnatal low protein and recuperated mice during lactation.Body weights of pups were recorded at days 3, 7, 14 and 21 of age. To maximize the effects of maternal diet, recuperated pups (R) were culled to 4 and control pups (C) were culled to 8 (if litter size was greater than 8) whereas postnatal low protein pups (PLP) were unculled. Means±SEM are shown (* P<0.05, ** P<0.01, *** P<0.001 compared to control; n = C: 13, PLP: 11, R: 16).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654922&req=5

pone-0004950-g001: Growth curves of pups of control, postnatal low protein and recuperated mice during lactation.Body weights of pups were recorded at days 3, 7, 14 and 21 of age. To maximize the effects of maternal diet, recuperated pups (R) were culled to 4 and control pups (C) were culled to 8 (if litter size was greater than 8) whereas postnatal low protein pups (PLP) were unculled. Means±SEM are shown (* P<0.05, ** P<0.01, *** P<0.001 compared to control; n = C: 13, PLP: 11, R: 16).
Mentions: Pups of mothers fed the low protein diet during pregnancy were significantly smaller than controls (1.46±0.04 g vs 1.65±0.07 g on day 3, P = 0.006; Figure 1). Cross-fostering to mothers fed the control diet resulted in rapid catch-up growth such that by day 7 recuperated offspring had a similar body weight to controls (3.68±0.18 g vs 3.78±0.22 g; Figure 1), by day 14 they had overtaken the weight of controls and at day 21 they were significantly heavier than controls (8.92±0.52 g vs. 7.89±0.26 g, P = 0.047; Figure 1). In contrast, offspring of normally fed mothers when suckled by low protein fed dams grew slowly during lactation; by day 7 they were significantly smaller than controls (2.98±0.11 g vs. 3.78±0.22, P = 0.002; Figure 1) and this difference was further increased by day 14 and day 21 (4.96±0.23 g vs. 6.79±0.15 g, P = 0.00013 and 5.96±0.42 g vs. 7.89±0.26 g, P = 0.0002; Figure 1).

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