In utero overexposure to
glucocorticoids may explain the association between low birth weight and subsequent development of the
metabolic syndrome. We previously showed that prenatal
dexamethasone (dex) exposure in the rat lowers
birth weight and programs adult fasting and
postprandial hyperglycemia, associated with increased hepatic gluconeogenesis driven by elevated liver
glucocorticoid receptor (GR) expression. This study aimed to determine whether prenatal dex (100 microg/kg per day from embryonic d 15 to embryonic d 21) programs adult GR expression in skeletal muscle and/or adipose tissue and whether this contributes to altered peripheral
glucose uptake or metabolism. In utero dex-exposed rats remained lighter until 6 months of age, despite some early catch-up growth. Adults had smaller epididymal fat pads, with a relative increase in muscle size. Although
glycogen storage was reduced in quadriceps,
2-deoxyglucose uptake into extensor digitorum longus muscle was increased by 32% (P < 0.05), whereas uptake in other muscles and adipose beds was unaffected by prenatal dex. GR
mRNA was not different in most muscles but selectively reduced in soleus (by 23%, P < 0.05). However, GR
mRNA was markedly increased specifically in retroperitoneal fat (by 50%, P < 0.02). This was accompanied by a shift from peroxisomal proliferator-activated receptor gamma 1 to gamma 2 expression and a reduction in
lipoprotein lipase mRNA (by 28%, P < 0.02). Adipose
leptin,
uncoupling protein-3 and
resistin mRNAs, muscle GLUT-4, and circulating
lipids were not affected by prenatal dex. These data suggest that
hyperglycemia in 6-month-old rats exposed to
dexamethasone in utero is not due to attenuated peripheral
glucose disposal. However, increased GR and attenuated
fatty acid uptake specifically in visceral adipose are consistent with
insulin resistance in this crucial metabolic depot and could indirectly contribute to increased hepatic
glucose output.