Journal article
Up-Regulation of Toll-Like Receptor 4/Nuclear Factor-κB Signaling Is Associated with Enhanced Adipogenesis and Insulin Resistance in Fetal Skeletal Muscle of Obese Sheep at Late Gestation
Endocrinology (Philadelphia), Vol.151(1), pp.380-387
01/01/2010
Handle:
https://hdl.handle.net/2376/106272
PMCID: PMC2803146
PMID: 19887565
Abstract
Abstract Maternal obesity is increasing at an alarming rate. We previously showed that maternal obesity induces an inflammatory response and enhances adipogenesis in fetal skeletal muscle at midgestation. The objective of this study was to evaluate effects of maternal obesity on adipogenesis, inflammatory signaling, and insulin pathways at late gestation when ovine fetal skeletal muscle matures. Nonpregnant ewes were assigned to a control diet (Con, fed 100% of National Research Council nutrient recommendations, n = 6) or obesogenic diet (OB, fed 150% of National Research Council recommendations, n = 6) from 60 d before to 135 d after conception (term 148 d) when the fetal semitendenosus skeletal muscle was sampled. Expression of the adipogenic marker, peroxisome proliferator-activated receptor-γ, was increased in OB compared with Con fetal semitendenosus muscle, indicating up-regulation of adipogenesis. More intramuscular adipocytes were observed in OB muscle. Phosphorylation of inhibitor-κB kinase-α/β and nuclear factor-κB RelA/p65 were both increased in OB fetal muscle, indicating activation of nuclear factor-κB pathway. Phosphorylation of c-Jun N-terminal kinase and c-Jun (at Ser 63 and Ser 73) was also elevated. Toll-like receptor 4 expression was higher in OB than Con fetal muscle. Moreover, despite higher insulin concentrations in OB vs. Con fetal plasma (2.89 ± 0.53 vs. 1.06 ± 0.52 ng/ml; P < 0.05), phosphorylation of protein kinase B at Ser 473 was reduced, indicating insulin resistance. In conclusion, our data show maternal obesity-induced inflammatory signaling in late gestation fetal muscle, which correlates with increased im adipogenesis and insulin resistance, which may predispose offspring to later-life obesity and diabetes.
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- Title
- Up-Regulation of Toll-Like Receptor 4/Nuclear Factor-κB Signaling Is Associated with Enhanced Adipogenesis and Insulin Resistance in Fetal Skeletal Muscle of Obese Sheep at Late Gestation
- Creators
- Xu Yan - Department of Animal Science (X.Y., M.J.Z., W.X., J.F.T., S.P.F., M.D.), Center for the Study of Fetal Programming, University of Wyoming, Laramie, Wyoming 82071Mei J Zhu - Department of Animal Science (X.Y., M.J.Z., W.X., J.F.T., S.P.F., M.D.), Center for the Study of Fetal Programming, University of Wyoming, Laramie, Wyoming 82071Wei Xu - Department of Animal Science (X.Y., M.J.Z., W.X., J.F.T., S.P.F., M.D.), Center for the Study of Fetal Programming, University of Wyoming, Laramie, Wyoming 82071Jun F Tong - Department of Animal Science (X.Y., M.J.Z., W.X., J.F.T., S.P.F., M.D.), Center for the Study of Fetal Programming, University of Wyoming, Laramie, Wyoming 82071Stephen P Ford - Department of Animal Science (X.Y., M.J.Z., W.X., J.F.T., S.P.F., M.D.), Center for the Study of Fetal Programming, University of Wyoming, Laramie, Wyoming 82071Peter W Nathanielsz - Center for Pregnancy and Newborn Research (P.W.N.), University of Texas Health Sciences Center, San Antonio, Texas 78229Min Du - Department of Animal Science (X.Y., M.J.Z., W.X., J.F.T., S.P.F., M.D.), Center for the Study of Fetal Programming, University of Wyoming, Laramie, Wyoming 82071
- Publication Details
- Endocrinology (Philadelphia), Vol.151(1), pp.380-387
- Academic Unit
- Animal Sciences, Department of
- Identifiers
- 99900546722501842
- Language
- English
- Resource Type
- Journal article