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Non\u2010pregnant ewes were assigned to a control group (Con, fed 100% of NRC nutrient recommendations, <jats:italic>n<\/jats:italic>= 7) or obesogenic group (OB, fed 150% of National Research Council (NRC) recommendations, <jats:italic>n<\/jats:italic>= 7) diet from 60 days before to 75 days after conception (term 150 days) when fetal semitendinosus skeletal muscle (St) was sampled. OB mothers developed severe obesity accompanied by higher maternal and fetal plasma glucose and insulin levels. In fetal St, activity of phosphoinositide\u20103 kinase (PI3K) associated with insulin receptor substrate\u20101 (IRS\u20101) was attenuated (<jats:italic>P<\/jats:italic> &lt; 0.05), in agreement with the increased phophorylation of IRS\u20101 at serine 1011. Phosphorylation of AMP\u2010activated protein kinase (AMPK) at Thr 172, acetyl\u2010CoA carboxylase at Ser 79, tuberous sclerosis 2 at Thr 1462 and eukaryotic translation initiation factor 4E\u2010binding protein 1 at Thr 37\/46 were reduced in OB compared to Con fetal St. No difference in energy status (AMP\/ATP ratio) was observed. The expression of protein phosphatase 2C was increased in OB compared to Con fetal St. Plasma tumour necrosis factor \u03b1 (TNF\u03b1) was increased in OB fetuses indicating an increased inflammatory state. Expression of peroxisome proliferator\u2010activated receptor \u03b3 (PPAR\u03b3) was higher in OB St, indicating enhanced adipogenesis. The glutathione: glutathione disulphide ratio was also lower, showing increased oxidative stress in OB fetal St. In summary, we have demonstrated decreased signalling of the AMPK system in skeletal muscle of fetuses of OB mothers, which may play a role in altered muscle development and development of insulin resistance in the offspring.<\/jats:p>","DOI":"10.1113\/jphysiol.2007.149633","type":"journal-article","created":{"date-parts":[[2008,3,28]],"date-time":"2008-03-28T00:26:54Z","timestamp":1206664014000},"page":"2651-2664","source":"Crossref","is-referenced-by-count":135,"title":["AMP\u2010activated protein kinase signalling pathways are down regulated and skeletal muscle development impaired in fetuses of obese, over\u2010nourished sheep"],"prefix":"10.1113","volume":"586","author":[{"given":"Mei 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