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23 February 2011 Maternal Obesity-Impaired Insulin Signaling in Sheep and Induced Lipid Accumulation and Fibrosis in Skeletal Muscle of Offspring
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The prevalence of maternal obesity is increasing rapidly in recent decades. We previously showed that maternal obesity affected skeletal muscle development during the fetal stage. The objective of this study was to evaluate the effects of maternal obesity on the skeletal muscle properties of offspring. Ewes were fed a control diet (100% energy requirement, Con) or an obesogenic diet (150% energy requirement, OB) from 2 mo before pregnancy to weaning. After weaning, the offspring lambs were fed a maintenance diet until 19 mo of age and then ad libitum for 12 wk to measure feed intake. At 22 mo old, the longissimus dorsi (LD) muscle was biopsied. The downstream insulin signaling was lower in OB than Con lambs as shown by reduction in the phosphorylation of protein kinase B, mammalian target of rapamycin, and 4-E binding protein 1. On the other hand, the phosphorylation of protein kinase C and insulin receptor substrate 1 was higher in OB compared to Con lambs. More intramuscular adipocytes were observed in OB compared to Con offspring muscle, and the expression of peroxisome proliferator-activated receptor gamma, an adipocyte marker, was also higher, which was consistent with the higher intramuscular triglyceride content. Both fatty acid transport protein 1 and cluster of differentiation 36 (also known as fatty acid translocase) were increased in the OB group. In addition, higher collagen content was also detected in OB compared to Con offspring. In conclusion, our data show that offspring from obese mothers had impaired insulin signaling in muscle compared with control lambs, which correlates with increased intramuscular triglycerides and higher expression of fatty acid transporters. These data clearly show that maternal obesity impairs the function of the skeletal muscle of offspring, supporting the fetal programming of adult metabolic diseases.

Xu Yan, Yan Huang, Jun-Xing Zhao, Nathan M. Long, Adam B. Uthlaut, Mei-Jun Zhu, Stephen P. Ford, Peter W. Nathanielsz, and Min Du "Maternal Obesity-Impaired Insulin Signaling in Sheep and Induced Lipid Accumulation and Fibrosis in Skeletal Muscle of Offspring," Biology of Reproduction 85(1), 172-178, (23 February 2011).
Received: 8 November 2010; Accepted: 1 February 2011; Published: 23 February 2011

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