Maternal protein restriction induces early-onset glucose intolerance and alters hepatic genes expression in the peroxisome proliferator-activated receptor pathway in offspring

母体蛋白质限制会诱发后代早发性葡萄糖不耐受,并改变过氧化物酶体增殖激活受体途径中的肝脏基因表达

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作者:Jia Zheng, Xinhua Xiao, Qian Zhang, Miao Yu, Jianping Xu, Zhixin Wang

Conclusions

A maternal low-protein diet during pregnancy and lactation promotes early-onset glucose intolerance in the offspring mice, and the altered hepatic genes expression in peroxisome proliferator-activated receptor signaling pathway could play role in regulating this phenomenon.

Methods

To test this hypothesis, we examined the offspring of C57BL/6J mice at weaning to determine the effects of feeding their mothers a low-protein diet or normal chow diet throughout pregnancy and lactation. Gene array experiments and quantitative real-time polymerase chain reaction were utilized to explore the altered hepatic genes expression.

Results

The offspring of dams fed a low-protein diet had a lower birthweight and bodyweight, impaired glucose tolerance, decreased insulin sensitivity, and decreased serum cholesterol at weaning. Using gene array experiments, 253 differentially expressed genes were identified in the liver tissues of the offspring between the two groups. Bioinformatic analyses showed that all differentially expressed genes were mapped to 11 pathways. We focused on the 'peroxisome proliferator-activated receptor signaling pathway,' because peroxisome proliferator-activated receptors have emerged as central regulators of glucose and lipid homeostasis. Quantitative real-time polymerase chain reaction was utilized for the validation of genes in the pathway. Conclusions: A maternal low-protein diet during pregnancy and lactation promotes early-onset glucose intolerance in the offspring mice, and the altered hepatic genes expression in peroxisome proliferator-activated receptor signaling pathway could play role in regulating this phenomenon.

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