Stimulation of liver IGF-1 expression promotes peak bone mass achievement in growing rats: A study with Pomegranate seed oil

3 years ago

Stimulation of liver IGF-1 expression promotes peak bone mass achievement in growing rats: A study with Pomegranate seed oil

Peak bone mass (PBM) achieved at adulthood is a strong determinant of future onset of osteoporosis and maximizing it is one of the strategies to combat the disease. Recently, pomegranate seed oil (PSO) has been shown to have bone-sparing effect in ovariectomized mice. However, its effect on growing skeleton and its molecular mechanism remains unclear. In the present study, we evaluated the effect of PSO on PBM in growing rats and associated mechanism of action. PSO was given at various doses to 21-days old growing rats for 90 days by oral gavage. The changes in bone parameters were assessed by μ-CT and histology. ELISA was performed to analyze the levels of serum IGF-1. Western blotting from bone and liver tissues were done. CHIP assay was performed to study the histone acetylation levels at IGF-1 gene. The results of the study show that PSO treatment significantly increases bone length, bone formation rate, biomechanical parameters, BMD and bone microarchitecture along with enhanced muscle and brown fat mass. This effect was due to the increased serum levels of IGF-1 and stimulation of its signaling in the bones. Studies focusing on acetylation of histones in the liver, the major site of IGF-1 synthesis, showed enrichment of acetylated H3K9 and H3K14 at IGF-1 gene promoter and body. Further, the increased acetylation at H3K9 and H3K14 was associated with a reduced HDAC1 protein level. Together, our data suggest that PSO promotes the PBM achievement via increased IGF-1 expression in liver and IGF-1 signaling in bone.

Publisher URL: www.sciencedirect.com/science

DOI: S0955286317305247