Site-specific changes in the expression of fat-partitioning genes in weanling rats exposed to a low-protein diet in utero.
OBJECTIVE
Intrauterine growth restriction is associated with increased prevalence of the metabolic syndrome in adult life, including increased adiposity. The aim of this study was to investigate if maternal protein energy malnutrition is associated with changes in expression of genes involved in fat partitioning in weanling rats.


METHODS
Time-mated mothers were placed on one of two isocaloric diets, low protein [(LP), 8% protein] or control (20% protein). All mothers remained on the diet throughout pregnancy and lactation. A third group received control for 2 weeks and was switched to LP for the last week of pregnancy and lactation [late low protein (LLP) group]. Offspring were analyzed at weaning for serum glucose, nonesterified fatty acids, triglyceride, and insulin. Expression of the genes acetyl-coenzyme A carboxylase, fatty acid synthase, and carnitine palmitoyl transferase 1 were measured in liver, quadriceps muscle, and subcutaneous white adipose tissue using semiquantitative reverse transcription-polymerase chain reaction.


RESULTS
LLP and LP offspring were shorter, weighed less, had reduced serum insulin and nonesterified fatty acids, and had increased serum glucose, serum triglycerides, and hepatic triglycerides. Hepatic gene expression of acetyl-coenzyme A carboxylase and fatty acid synthase was increased 2-fold in LLP and LP offspring (p < 0.001). These changes were not seen in muscle or subcutaneous white adipose tissue. CPT-1 gene expression was unaltered in all tissues examined.


CONCLUSIONS
Maternal protein energy malnutrition programs gene expression of lipogenic enzymes in the liver of weanling offspring in a manner favoring fat synthesis that may predispose these offspring to fat accumulation and insulin resistance later in life.
Maloney
Chris A
CA
Human Nutrition Unit, School of Molecular and Microbial Biosciences, University of Sydney, Sydney, New South Wales, Australia. cmaloney@mmb.usyd.edu.au
Gosby
Alison K
AK
Phuyal
Jenny L
JL
Denyer
Gareth S
GS
Bryson
Janet M
JM
Caterson
Ian D
ID
D000103:Acetyl-CoA Carboxylase / Q000235:genetics; D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition / Q000235:genetics*; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D018753:Diet, Protein-Restricted; D064429:Fatty Acid Synthases / Q000235:genetics; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015870:Gene Expression; D007328:Insulin / Q000097:blood; D007774:Lactation; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D018482:Muscle, Skeletal / Q000201:enzymology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011502:Protein-Energy Malnutrition / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000032:analysis / Q000097:blood; D014886:Weaning
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D002334:Carnitine O-Palmitoyltransferase; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase