Prenatal dexamethasone programs expression of genes in liver and adipose tissue and increased hepatic lipid accumulation but not obesity on a high-fat diet.
The association between low birth weight and cardiovascular disease is amplified by the development of obesity. We explored the effects of postnatal high-fat (HF) feeding in dexamethasone (Dex)-programmed rats, in which prenatal glucocorticoid overexposure is associated with reduced birth weight and adult glucose intolerance. Male Wistar rats exposed to Dex or vehicle (Veh) during the last week of gestation were weaned onto HF or control diets for 6 months. Dex-exposed animals were of lower birth weight and showed catch-up growth by 7 wk. There were no differences in obesity or hyperinsulinaemia between Dex-HF and Veh-HF animals. However, Dex-HF animals had increased hepatic triglyceride content compared with Veh-HF animals. mRNA transcript profiles in adipose tissue revealed depot-specific changes in the expression of genes involved in fatty acid esterification and triglyceride synthesis and storage with prenatal Dex exposure. Thus, antenatal glucocorticoid overexposure in rats does not confer increased sensitivity to HF diet-induced obesity, but increases susceptibility to fatty liver. This may be due to depot-specific-programmed alterations in fat metabolism in adipose tissue.
Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom. mandy.drake@ed.ac.uk
Amanda J
AJ
Drake
Peter J
PJ
Raubenheimer
David
D
Kerrigan
Kerry J
KJ
McInnes
Jonathan R
JR
Seckl
Brian R
BR
Walker
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight / Q000187:drug effects / Q000235:genetics; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D003907:Dexamethasone / Q000008:administration & dosage*; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D005938:Glucocorticoids / Q000008:administration & dosage; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects / Q000235:genetics; D010766:Phosphorylation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism*
D001786:Blood Glucose; D005938:Glucocorticoids; D007328:Insulin; D014280:Triglycerides; D003907:Dexamethasone; D055372:AMP-Activated Protein Kinases