A maternal low protein diet has pronounced effects on mitochondrial gene expression in offspring liver and skeletal muscle; protective effect of taurine.
BACKGROUND
Low birth weight is associated with an increased risk of developing impaired glucose tolerance, and eventually type 2 diabetes in adult life. Gestational protein restriction in rodents gives rise to a low birth weight phenotype in the offspring.


RESULTS
We examined gene expression changes in liver and skeletal muscle of mice subjected to gestational protein restriction (LP) or not (NP), with or without taurine supplementation in the drinking water. LP offspring had a 40% lower birth weight than NP offspring, with taurine preventing half the decrease. Microarray gene expression analysis of newborn mice revealed significant changes in 2012 genes in liver and 967 genes in skeletal muscle of LP offspring. Taurine prevented 30% and 46% of these expression changes, respectively. Mitochondrial genes, especially those involved with oxidative phosphorylation, were more abundantly changed than other genes. The mitochondrial genes were mainly upregulated in liver, but downregulated in skeletal muscle, despite no change in citrate synthase activity in either tissue. Taurine preferentially rescued genes concerned with fatty acid metabolism in liver and with oxidative phosphorylation and TCA cycle in skeletal muscle. A mitochondrial signature was seen in the liver of NP offspring with taurine supplementation, as gene sets for mitochondrial ribosome as well as lipid metabolism were over represented in 4-week-old offspring subjected to gestational taurine supplementation. Likewise, 11 mitochondrial genes were significantly upregulated by gestational taurine supplementation in 4-week-old NP offspring.


CONCLUSIONS
Gestational protein restriction resulted in lower birth weight associated with significant gene expression changes, which was different in liver and muscle of offspring. However, a major part of the birth weight decrease and the expression changes were prevented by maternal taurine supplementation, implying taurine is a key factor in determining expression patterns during development and in that respect also an important component in metabolic fetal programming.
Mortensen
Ole Hartvig
OH
Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. ole@hartvig.org
Olsen
Hanne Lodberg
HL
Frandsen
Lis
L
Nielsen
Peter Eigil
PE
Nielsen
Finn Cilius
FC
Grunnet
Niels
N
Quistorff
Bjørn
B
D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight; D001835:Body Weight / Q000502:physiology; D002950:Citrate (si)-Synthase / Q000378:metabolism; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D005260:Female; D005786:Gene Expression Regulation; D050259:Genes, Mitochondrial; D008099:Liver / Q000166:cytology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013654:Taurine / Q000008:administration & dosage*
D013654:Taurine; D002950:Citrate (si)-Synthase
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