Metabolic changes in response to food intake in somatostatin 1.1 deficient zebrafish

Somatostatin is a multifunctional hormone with several genes in teleost fishes. A zebrafish CRISPR/Cas9 knockout of the somatostatin 1.1 (sst1.1) with persistent hyperglycaemia and hyperlipidaemia displayed reduced fecundity when fed brine shrimp ad libitum. Here, we investigated the effect of feeding brine shrimp one to three times a day on fecundity and liver transcriptomics of the sst1.1 mutant compared to their wild-type siblings to unravel molecular pathways associated with the phenotype. We find that the sst1.1 deficient zebrafish had high mortality when fed at the highest rate and that in both genotypes, growth and fecundity were proportional to food intake. Although glucose and cholesterol decreased substantially at the lowest level of feeding, they were still higher in the mutant than in the wild-type zebrafish. Furthermore, sst1.1 deficiency had a small but significant effect on the hepatic expression of protein, carbohydrate, and fatty acid biosynthesis genes, contributing to the mutant's diabetic phenotype.