Alteration of FXR phosphorylation and sumoylation in liver in the development of adult catch-up growth
Alteration of FXR phosphorylation and sumoylation in liver in the development of adult catch-up growth
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DOI：
10.1177/1535370216641788
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发表时间：
2017-02
影响因子：
3.2
通讯作者：
Xiang Hu;Qiao Zhang;Juan Zheng;W. Kong;Hao-hao Zhang;T. Zeng;Jiaoyue Zhang;Jie Min;Chaodong Wu;Lulu Chen
中科院分区：
文献类型：
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作者：
Xiang Hu;Qiao Zhang;Juan Zheng;W. Kong;Hao-hao Zhang;T. Zeng;Jiaoyue Zhang;Jie Min;Chaodong Wu;Lulu Chen
成人的追赶性生长，越来越被认为是非常普遍的胰岛素抵抗相关疾病的重要致病因素，特别是在发展中国家/地区。本研究旨在探讨成年大鼠追赶生长过程中胆汁酸水平、胆汁酸受体/法尼醇X受体及其下游信号通路的磷酸化和类小泛素化以及胰岛素敏感性和血脂水平的变化。将雄性Sprague-Dawley大鼠随机分为4组，用于两个采样点：热量限制组，正常饲料喂养的成年人和正常饲料对照组的追赶生长，持续4或8周（N4，N8单独）。我们发现血清总胆汁酸和法尼醇X受体磷酸化增加，而法尼醇X受体类小分子化及其下游小异二聚体伴侣表达无显着变化。再喂养后，血清总胆汁酸、法尼醇X受体磷酸化和类小泛素化水平以及Cyp 7a 1、SREBP-1c mRNA水平升高，与脂肪堆积相关的小分子异源二聚体伴侣表达显著降低，全身和骨骼肌胰岛素抵抗明显。我们的研究结果表明，脂肪积累和胰岛素抵抗与胆汁酸增加，法尼醇X受体磷酸化的改变，sumoylation及其下游信号通路。胆汁酸、法尼醇X受体磷酸化和类小泛素化及其下游信号通路的变化可能在成人追赶生长过程中脂肪积累和胰岛素抵抗的发病机制中起重要作用。
Catch-up growth in adult, is increasingly recognized as an important causative factor for the extremely prevalent insulin resistance-related diseases especially in developing countries/territories. We aimed to investigate the alteration of bile acids level, phosphorylation and sumoylation of its interacting protein, bile acid receptor/farnesoid X receptor and their downstream signaling pathway, as well as insulin sensitivity and lipid profile in catch-up growth in adult rats. Male Sprague-Dawley rats were randomly allocated into four groups for two sampling points: caloric restriction group, catch-up growth in adult refed with normal chow and their normal chow controls for four or eight weeks (N4, N8 individually).We found that total serum bile acids and farnesoid X receptor phosphorylation increased without significant changes in farnesoid X receptor sumoylation and its downstream small heterodimer partner expression at the end of caloric restriction stage, while the visceral fat decreased and insulin resistance never occurred in these animals; After refeeding, total serum bile acids, farnesoid X receptor phosphorylation and sumoylation, as well as Cyp7a1, SREBP-1c mRNA levels were higher with significant decrease in small heterodimer partner expression, which is associated fat accumulation, and drastic insulin resistance in whole body and skeletal muscle. Our findings demonstrated that the fat accumulation and insulin resistance are associated with increases of bile acids, alteration of farnesoid X receptor phosphorylation, and sumoylation and its downstream signaling pathway. These changes of bile acids, farnesoid X receptor phosphorylation and sumoylation, as well as their downstream signaling might be of importance in the etiology of fat accumulation and insulin resistance in catch-up growth in adult.