Soybean saponin modulates nutrient sensing pathways and metabolism in zebrafish

Soybean saponin (SA) is known as a major anti-nutritional factor that causes metabolic disturbances and growth reduction in fish. However, the mechanisms underlying these effects were far from fully understood. In particular, the influences of SA on nutrient sensing and downstream metabolic pathways remain largely unexplored. Using zebrafish as an animal model, this study was conducted to examine the phenotypic and molecular responses after dietary SA treatment for 2 weeks. SA at both 5 and 10 g/kg diet levels significantly reduced growth performance and feed efficiency, and damaged the morphology of the intestinal mucosa. SA stimulated AMP-activated protein kinase but reduced target of rapamycin (TOR) activities in both feeding trial and cellular studies. Furthermore, SA increased the mRNA expressions of growth axis genes including growth hormone, insulin-like growth factor 1, growth hormone receptor A, and growth hormone receptor B, but decreased insulin-like growth factor-binding protein 2 at both mRNA and protein levels. SA also increased the expressions of key metabolic enzymes involved in glutamine synthetase, glutamate dehydrogenase and lipolysis, hormone-sensitive lipase and lipoprotein lipase. Our results demonstrated that SA modulated nutrient sensing pathways and metabolism, thus provide new aspects on the explanation of the physiological effects of SA.