Metabolic Regulation by Stress Mediators in Fetal Ovine Skeletal Muscle and Adult Bovine Myoblasts

Placental insufficiency caused by maternal stress during gestation is known to decrease birth weight and increase the risk of offspring developing metabolic deficiencies such as insulin resistance and obesity. However, the underlying mechanisms remain to be understood. Our objective was to determine if chronic maternal stress impairs subsequent glucose metabolism rates in fetal sheep near term. Pregnant ewes were treated with saline (controls) or bacterial endotoxin (LPS) every 3 day from day 100-115 of gestation (term = 150 days) to induce systemic inflammation. On gestational day 125, ewes were euthanized and fetal soleus muscle was isolated tendon-to-tendon and split longitudinally. To determine glucose uptake and glucose oxidation rates, soleus strips were incubated in KHB (Krebs Henseleit Buffer) that was un-spiked (basal) or spiked with either insulin or TNFα. In addition, Akt phosphorylation in extensor digitorum longus muscle samples was determined by western immunoblot analysis and Myosin heavy chain (MyHC) content was determined using electrophoresis. Furthermore, fiber type numbers and sizes were determined from fetal semitendinosus sections by immunohistochemistry. In primary fetal soleus muscle, glucose uptake was not different between control and maternal inflammation fetuses under basal, insulin-stimulated, or TNFα-stimulated conditions. However, insulin-stimulated glucose oxidation and TNFα-stimulated glucose oxidation were both greatly decreased (P < 0.05) in chronically stressed fetal muscle compared to controls. In addition, Akt phosphorylation was decreased (P < 0.05) after maternal inflammation when compared to controls. However, there were not differences