Alteration of FXR phosphorylation and sumoylation in liver in the development of adult catch-up growth

Abstract

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.