Phosphorus nutritional requirements for fish skeletal development. New insights from zebrafish

Abstract

Nowadays the main concern in fish farming is improvement of the foods used and the reduction of nutrients excreted in the water. In fish, the only route for inorganic phosphate entry is the diet. However, any excess of this nutrient in the diet above the optimal requirement for fish will be excreted. The excess of unused/excreted inorganic phosphate is the origin of most dissolved inorganic waste resulting from intensive fish farming. As consequence, high level of Pi in the effluents of aquaculture systems leads to eutrophication of the aquatic ecosystems. Phosphorus, in the form of inorganic phosphate is involved in multitude of physiological processes and its deficiency has been shown to be responsible of defective mineralization of bones as well as disturbances of intermediary metabolism especially energy metabolism, leading to impairment of growth. It is therefore critical to know precisely the dietary requirement of inorganic phosphate in order to minimize excess phosphorus in diet without risking phosphorus deficiency in cultured fish. In order to understand animal requirements and establish new feed formulations under changing environments it is essential to characterize the regulation of phosphate homeostasis in fish. We have isolated and characterized a new parathyroid hormone (PTH) family member, named PTH4, that it is involved in bone mineral homeostasis in zebrafish. We have found that this new neuropeptide is synthesized by two clusters of neurons specifically located in lateral hypothalamus as shown by whole mount in situ hybridization. Functional studies using a stable transgenic zebrafish lines and MOs knockdown have revealed PTH4 as a powerful regulator of bone mass accrual acting on phosphate homeostasis. Our results, therefore, define a new neural brain-to-bone pathway involving signals from hypothalamus to receptors on bone cells controlling phosphate homeostasis.