Postnatal treatment with dexamethasone perturbs hepatic and cardiac energy metabolism and is associated with a sustained atherogenic plasma lipid profile in suckling rats.
Early exposure to glucocorticoids (GC) has been proposed to disturb hepatic and cardiac function in later life. In the present study, we evaluated early metabolic alterations upon GC treatment that may predispose to long-term abnormalities. Rats were injected with dexamethasone (DEX) at d 1, 2, and 3 after birth and controls received saline (SAL). Rats were killed at 2, 7, and 14 d of age. Compared with SAL, DEX induced lower plasma insulin levels, hyperglycemia, hyperketonemia, and dyslipidemia at 2 d. At the same time, DEX treatment significantly increased expression of gluconeogenic and fatty acid oxidation genes in liver and expression of genes involved fatty acid utilization in heart. At 7 d, DEX-treated rats showed insulin resistance with hyperlipidemia, whereas hepatic and cardiac gene expression patterns were largely normalized. Hyperlipidemia and a significantly increased hepatic triglyceride content in DEX-treated rats were prominent at 14 d without large differences in hepatic and cardiac gene expression patterns. Thus, neonatal DEX administration transiently affects cardiac and hepatic gene expression patterns in suckling rats associated with sustained effects on plasma glucose and lipid concentrations. Whether these early effects of DEX contribute to hepatic and cardiac abnormalities at adult age needs further evaluation.
Liu
Yan
Y
Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
Havinga
Rick
R
Bloks
Vincent W
VW
Baller
Juul F
JF
van der Leij
Feike R
FR
Reijngoud
Dirk-Jan
DJ
Sauer
Pieter J J
PJ
Kuipers
Folkert
F
D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D001786:Blood Glucose / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D007657:Ketone Bodies / Q000097:blood / Q000378:metabolism; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000494:pharmacology
D001786:Blood Glucose; D005227:Fatty Acids; D005938:Glucocorticoids; D007328:Insulin; D007657:Ketone Bodies; D008055:Lipids; D012965:Sodium Chloride; D003907:Dexamethasone