Maternal Obesity-Impaired Insulin Signaling in Sheep and Induced Lipid Accumulation and Fibrosis in Skeletal Muscle of Offspring1
Maternal Obesity-Impaired Insulin Signaling in Sheep and Induced Lipid Accumulation and Fibrosis in Skeletal Muscle of Offspring1
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DOI：
10.1095/biolreprod.110.089649
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发表时间：
2011-07
期刊：
影响因子：
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通讯作者：
Xu Yan;Yan Huang;Junxing Zhao;N. Long;A. B. Uthlaut;Mei J. Zhu;S. Ford;P. Nathanielsz;M. Du
中科院分区：
文献类型：
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作者：
Xu Yan;Yan Huang;Junxing Zhao;N. Long;A. B. Uthlaut;Mei J. Zhu;S. Ford;P. Nathanielsz;M. Du
近几十年来，母亲肥胖的患病率迅速增加。我们以前的研究表明，母体肥胖影响胎儿期骨骼肌的发育。本研究的目的是评估母亲肥胖对后代骨骼肌特性的影响。从怀孕前2个月到断奶，母羊饲喂对照饮食（100%能量需求，Con）或致肥胖饮食（150%能量需求，OB）。断奶后，后代羔羊饲喂维持日粮，直到19月龄，然后自由采食12周，以测量采食量。在22月龄时，对背最长肌（LD）进行活检。OB的下游胰岛素信号传导低于Con羔羊，如蛋白激酶B、雷帕霉素的哺乳动物靶蛋白和4-E结合蛋白1的磷酸化减少所示。另一方面，OB中蛋白激酶C和胰岛素受体底物1的磷酸化水平高于Con羔羊。与Con后代肌肉相比，在OB中观察到更多的肌内脂肪细胞，并且脂肪细胞标记物过氧化物酶体增殖物激活受体γ的表达也较高，这与较高的肌内甘油三酯含量一致。脂肪酸转运蛋白1和分化簇36（也称为脂肪酸移位酶）在OB组中均增加。此外，与Con后代相比，在OB中也检测到更高的胶原蛋白含量。总之，我们的数据表明，与对照羔羊相比，肥胖母亲的后代肌肉中的胰岛素信号传导受损，这与肌内甘油三酯增加和脂肪酸转运蛋白的更高表达相关。这些数据清楚地表明，母体肥胖损害了后代骨骼肌的功能，支持成人代谢疾病的胎儿编程。
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.