| The embryo fetal stage is critical for skeletal muscle development because there is no net increase in muscle fiber number after birth. Obesity induces inflammatory responses, which might be associated with myogenesis and adipogenesis through the inhibitor of kappaB (IkappaB) kinase (IKK)/nuclear factor kappaB (NF-kappaB) signaling pathway. The objective of this study was to evaluate the effects of maternal obesity on myogenesis and adipogenesis, IKK/NF-kappaB and insulin related pathways in fetal skeletal muscle. Non-pregnant ewes were assigned to a control diet (Con, fed 100% of NRC nutrient recommendations, n = 7) or obesogenic diet (Obe, fed 150% of NRC recommendations, n = 7) from 60 days before to 135 days after conception (term 150 days) when fetal semitendenosus (St) skeletal muscle was sampled for analysis. Both mRNA and protein levels of the adipogenic marker, peroxisome proliferator-activated receptor-gamma (PPARgamma), were increased in Obe compared to Con fetal St muscle, indicating the up-regulation of adipogenesis. Phosphorylation of inhibitor kappaB kinase beta (IKKbeta) and NF-kappaB RelA/p65 were both increased in Obe fetal muscle, with a decrease in phosphorylation of IkappaB, which together indicate the activation of the IKK/NF-kappaB pathway. In addition, the mRNA levels of toll like receptor 2 (TLR2), toll like receptor 4 (TLR4) and cluster of differentiation 14 (CD14), which serve upstream of IKK/NF-kappaB pathway, were higher in Obe than in Con fetal muscle. An increase of phosphorylated c-Jun N-terminal kinase (JNK) and phophorylation of c-Jun (at Ser 63 and Ser 73) was also observed. Moreover, the protein level of insulin receptor, glucose transporter 1 (GLUT1) and glucose transporter 4 (GLUT4), phosphorylation of AMP-activated protein kinase (AMPK) at Thr 172, Acetyl-CoA carboxylase (ACC) at Ser 79, protein kinase B (PKB or Akt) at Ser 473 were all reduced in Obe compared to Con fetal St muscle, while phosphorylation of protein kinase C (PKC) was increased. In conclusion, our data showed that maternal obesity enhanced adipogenesis in fetal muscle; inflammatory IKK/NF-kappaB pathway, expression of toll like receptors and JNK pathway were up-regulated, whereas insulin related pathways involving insulin receptor, PKC, GLUT1, GLUT4, AMPK, ACC and Akt were down-regulated in fetal muscle of obese mothers. |
