Biomedical subjects

Christopher A Maloney

Publications and source records attributed to Christopher A Maloney.

4 recordsLinked to original sources

PubMed2006

Sulfur amino acid metabolism in pregnancy: the impact of methionine in the maternal diet.

Animal studies show that the balance of methionine relative to other amino acids in the maternal diet is critical, as fetal growth is not only retarded by diets that are deficient but also by those containing excess. Diets with an inappropriate balance of methionine can adversely affect both short-term reproductive function and the long-term physiology of the offspring. The catabolism of unused methionine increases the demand for glycine and may cause a deficiency. High levels of methionine may also perturb intracellular S-adenosyl methionine pools and have an effect on the methylation of DNA and proteins. Excess methionine in the diet may also indirectly influence fetal development through the production of homocysteine or by the perturbation of endocrine functions. The metabolic interactions among dietary methionine, folic acid, and choline mean that other diet components can also change the methionine requirement.

Amino Acids, Sulfur↗

PubMed2005

The expression of growth-arrest genes in the liver and kidney of the protein-restricted rat fetus.

During fetal life, there are periods of rapid cell proliferation, which are uniquely sensitive to nutritional perturbation. Feeding the pregnant rat a protein-restricted diet alters the growth trajectory of major fetal organs such as the kidney. By day 21 of gestation, the ratio of kidney weight to total body weight is reduced in the fetuses of dams fed a protein-deficient diet. In contrast, the ratio of fetal liver weight to total body weight is unchanged. To investigate the mechanisms underlying this disproportionate change in organ growth in the low-protein group, cell proliferation and differentiation have been assessed in the liver and kidney. The steady-state levels of mRNA for the growth-arrest and DNA-damage gene gadd153/CHOP-10, CCAAT enhancer-binding proteins alpha and beta were unaffected by maternal diet in both fetal liver and kidney. The mRNA for alpha-fetoprotein, albumin and hepatic glucokinase were unchanged in the liver, suggesting that maternal protein deficiency does not alter the state of differentiation. The steady-state levels of the mRNA coding for the cyclin-dependent protein kinase inhibitors (p15(INK4a), p19(INK4d), p21(CIP1), p27(KIP1) and p57(KIP2)) were unchanged in the fetal livers but were significantly increased in the kidneys of fetuses from dams fed the low-protein diet. These results show that the asymmetrical growth of the kidney is associated with increases in mRNA for the Cip/Kip cyclin-dependent kinase inhibitors and that these may reflect specific lesions in organ development.

Animals↗

PubMed2005

Gene-nutrient interactions during fetal development.

Eukaryotic cells have evolved a complex series of nutrient sensors that protect them from damage caused by acute deficiencies and also mediate adaptive responses to prolonged excess or deficiency of particular nutrients. In adults gene expression is regulated by nutrients interacting with pathways involving mammalian target of rapamycin (mTOR), CCAAT/enhancer-binding proteins (C/EBPs) and peroxisome proliferator activator proteins (PPARs). These systems are also present in key cells of the developing oocyte, embryo and fetus. In this review we will consider the role of interactions between genes and nutrients during reproduction with a particular emphasis on their possible involvement in the prenatal programming of glucose metabolism in the adult.

Animals↗

PubMed2003

Maternal protein restriction increases hepatic glycogen storage in young rats.

This study aimed to determine whether maternal protein restriction alters hepatic glycogen metabolism. Mated female rats were fed diets containing 20% protein throughout pregnancy and lactation (CONT), 8% protein throughout pregnancy and lactation (LP), or 8% protein during the last week of pregnancy only and lactation (LLP). Weights and lengths were reduced in the LLP and LP offspring compared with the CONT offspring. The LLP and LP offspring demonstrated reduced insulin concentrations at both 10 and 26 d and also failed to show the increase in insulin seen with time in the CONT offspring. Serum glucose and leptin levels increased with time but were not different among the groups; however, in relation to adiposity leptin levels were greater in the LLP and LP offspring at 26 d. The LLP and LP offspring had increased hepatic glycogen at day 10 (CONT, 75.1 +/- 9.8; LLP, 103.4 +/- 11.0; LP, 116.0 +/- 18.4 glucose residues/g tissue) and d 26 (CONT, 183.1 +/- 38.9; LLP, 395.3 +/- 16.8; LP, 396.6 +/- 15.1 glucose residues/g tissue). Glycogen synthase expression was increased in the LLP and LP offspring at 10 d but not 26 d; glucose transporter 2 and glycogen phosphorylase expressions were not different at either time. At 26 d glycogen synthase activity was not different; however, glycogen phosphorylase a activity was reduced. The enhanced capacity to store glycogen despite reductions in insulin secretion suggests increased insulin sensitivity possibly acting with an alternative non-insulin-dependent glycogen storage mechanism.

Adipose Tissue↗