Maternal Endotoxemia Results in Obesity and Insulin Resistance in Adult Male Offspring1

Events in utero appear to be important factors contributing to the development of somatic disorders at adult age. The aim of this study was to examine whether maternal immune challenge would be followed at adult age by metabolic and endocrine abnormalities in the offspring. Pregnant rats were given injections of either endotoxin (Escherichia coli lipopolysaccharide; 0.79 mg/kg, ip) or vehicle on days 8, 10, and 12 of gestation. Adult male offspring to lipopolysaccharide-exposed dams were heavier than controls (P < 0.05) and showed increased adipose tissue weights (P < 0.05), elevated food intake (P < 0.05), and increased circulating leptin (P < 0.01). The effect of insulin on glucose uptake was reduced, as measured by an euglycemic hyperinsulinemic clamp technique (P < 0.05). Serum levels of 17β-estradiol and progesterone were elevated (P< 0.01 and P < 0.05, respectively). Baseline levels of corticosterone were normal, but the corticosterone response to stress was attenuated (P < 0.05), and hippocampal gl...