Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5857940 | Reproductive Toxicology | 2016 | 12 Pages |
â¢The potential mechanism under prenatal food restriction and adult NAFLD was explored.â¢The adverse intrauterine programming of hepatic lipid metabolism could increase the susceptibility to NAFLD.â¢The adverse intrauterine programming of glucocorticoid-IGF1 axis could accelerate the occurrence of NAFLD.
The present study aims to explore the mechanisms of fetal origin of high susceptibility to adult high-fat diet induced-nonalcoholic fatty liver disease in rat offspring undergoing intrauterine growth retardation (IUGR) induced by prenatal food restriction (FR) from gestational day 11 until full-term delivery. We observed that adult IUGR offspring rats exhibited gender-dependent catch-up growth with lower serum corticosterone (CORT) but up-regulation of the insulin-like growth factor 1 (IGF1) pathway, higher hepatic Kleiner scores and lower lipid export and oxidation. Furthermore, fetal IUGR offspring rats showed lower body weights with higher serum CORT but down-regulated IGF1 pathway, which was accompanied by enhanced lipid de novo synthetic gene expression, lower lipid output and oxidation gene expression. It is suggested that a “two-programming” mechanism, which refers to the adverse intrauterine programming of hepatic lipid de novo synthesis and glucocorticoid-IGF1 axis programming associated with postnatal catch-up growth, could explain the increased susceptibility.