Leptin plays an indispensable role in energy homeostasis, and its involvement in metabolic activities has been extensively explored in fish. We generated mutant lines of leptina (-5 bp) and leptinb (+8 bp) in zebrafish using CRISPR/Cas9 technology to explore the metabolic characteristics of lepa and lepb mutant zebrafish in response to high glucose nutritional stress induced by high levels of carbohydrates. The results were as follows: the body weight and food intake of adult zebrafish of the two mutant species were increased; the visceral fat accumulation, whole-body crude lipid, and crude protein contents of lepb-/- were increased; and the visceral fat accumulation and crude lipid in lepa-/- zebrafish were decreased. The blood glucose levels of the two mutant zebrafish were increased, the mRNA expression levels of glycolytic genes pk and gck were decreased in the two mutant zebrafish, and there were differences between lepa-/- and lepb-/- zebrafish. The expressions of glycogen synthesis and decomposition genes were inhibited and promoted, respectively. The expression of adipose synthesis genes in the liver and muscle was stimulated in lepb-/- zebrafish but suppressed in lepa-/- zebrafish. Lipolysis and oxidation genes were also stimulated in lepa-/- zebrafish livers, while the livers of lepb-/- zebrafish were stimulated but muscle was inhibited. In conclusion, the results indicate that lepa plays a major role in glucose metabolism, which is conducive to promoting glucose utilization and lipogenesis, while lepb mainly promotes lipolysis and oxidation, regulates protein generation, and plays a minor role in glucose metabolism.
Keywords: glycometabolism; leptin; lipid metabolism; zebrafish.