Endocrine Abstracts (2002) 3 OC25

Programming of adult adipose tissue metabolism by prenatal glucocorticoids in the rat

ME Cleasby, BR Walker & JR Seckl

Endocrinology Unit, Department of Medical Sciences, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Edinburgh, UK

Prenatal dexamethasone (dex) administration in rats retards foetal growth, and programmes hyperinsulinaemia and glucose intolerance in adult offspring. This can be explained in part by increased hepatic gluconeogenesis, due to up-regulated glucocorticoid receptor (GR) expression, but may also involve impaired peripheral glucose disposal. In this model, we previously showed no increase in skeletal muscle GR, and have now examined GR and key metabolic genes in adipose tissue.

Pregnant rats received 100 micrograms per kilogram dex or vehicle daily subcutaneously from E15 to E21. At 6 months of age, tissues were taken from male offspring (n= 9 to 10 per group). GR mRNA was quantified in 2 adipose depots, and leptin, PPAR gamma, resistin, and lipoprotein lipase (LPL) mRNAs in retroperitoneal (RP) fat by RNAse protection assays, adjusted for beta-actin mRNA (loading control).

In prenatal dex-programmed rats, GR mRNA was increased in RP fat (0.17 plus/minus 0.02 vs 0.11 plus/minus 0.01, p=0.01), but unchanged in subcutaneous fat. In RP fat, expression of leptin and resistin were similar, but LPL mRNA was reduced in dex offspring (1.89 plus/minus 0.23 vs 2.62 plus/minus 0.17, p=0.01). Total PPAR gamma mRNA was unchanged, but there was a shift towards the PPAR gamma 2 isoform (gamma 1/total: 0.59 plus/minus 0.01 vs 0.57 plus/minus 0.01, p<0.05).

These data show programming in visceral adipose tissue of increased GR, a shift in PPAR gamma expression, consistent with that observed in other models of insulin resistance, and reduced LPL, implying a reduced capacity to import fatty acids. This suggests a role for visceral adipose tissue in the insulin resistance and glucose intolerance of dex-programmed rats.

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