n-3 PUFA reduction caused by fabp2 deletion interferes with triacylglycerol metabolism and cholesterolhomeostasis in fish

Fatty acid-binding protein 2 (Fabp2), which is involved in the transport of long-chain fatty acids, is widely studied in mammals. Nevertheless, the role of this protein in teleost fish is mostly unknown. Here, we produced a fabp2(-/-) zebrafish (KO) animal model. Compared with wild-type zebrafish (WT), KO had a markedly decreased content of intestinal n-3 poly-unsaturated fatty acids (n-3 PUFAs) and increased levels of intestinal, hepatic, and serum triacylglycerols (TAG). The intestinal transcriptome analysis of KO and WT revealed an obviously disrupted TAG metabolism and up-regulated bile secretion in KO. Expression levels of the genes related to fatty acid transport and cholesterol (CL) absorption in the intestine of KO were significantly lower than those of WT, while the expression levels of genes related to intestinal TAG synthesis and hepatic CL synthesis were in the opposite direction. To confirm these findings, we further established fabp2 transgenic zebrafish (TG). Compared with WT, TG had a markedly increased content of intestinal n-3 PUFAs, a significantly decreased level of hepatic TAG, and significantly higher expression of genes related to fatty acid transport and CL absorption in the intestine. In conclusion, this study suggests that teleost fish fabp2 could promote intestinal n-3 PUFA absorption to mediate TAG synthesis and CL homeostasis, by regulating the genes involved in lipid metabolism.