Maternal endotoxemia results in obesity and insulin resistance in adult male offspring

Events in utero appear to be important factors contributing to the developm ent 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 metabo lic and endocrine abnormalities in the offspring. Pregnant rats were given injections of either endotoxin (Escherichia coil lipopolysaccharide; 0.79 m g/kg, ip) or vehicle on days 8, 10, and 12 of gestation. Adult male offspri ng to lipopolysaccharide-exposed dams were heavier than controls (P < 0.05) and showed increased adipose tissue weights (P < 0.05), elevated food inta ke (P < 0.05), and increased circulating leptin (P < 0.01). The effect of i nsulin on glucose uptake was reduced, as measured by an euglycemic hyperins ulinemic clamp technique (P < 0.05). Serum levels of 17 beta -estradiol and progesterone were elevated (P < 0.01 and P < 0.05, respectively). Baseline levels of corticosterone were normal, but the corticosterone response to s tress was attenuated (P < 0.05), and hippocampal glucocorticoid receptor pr otein was up-regulated (P < 0.05). Female offspring were uninfluenced, exce pt for increased testosterone levels (P < 0.05), increased baseline cortico sterone levels (P < 0.05), and enlargement of heart and adrenals (P < 0.05) . The results indicate that maternal endotoxemia leads to obesity, insulin resistance, and high serum levels of leptin in the adult male offspring. Th is study reports a novel animal model of obesity with features of the metab olic syndrome.