Dynamic transcriptome analysis of the muscles in high-fat diet-induced obese zebrafish (Danio rerio) under 5-HT treatment

Peripheral 5-hydroxytryptamine (5-HT, also called serotonin) is reportedly a potential therapeutic target in obesity-related metabolic diseases due to its regulatory role in energy homeostasis in mammals. However, information on the detailed effect of peripheral 5-HT on the energy metabolism in fishes, especially the lipid metabolism, and the underlying mechanism remains elusive. In this study, a diet-induced obesity model was developed in the zebrafish (Danio rerio), a prototypical animal model for metabolic disorders. The zebrafish were fed a high-fat diet for 8 weeks and were simultaneously injected with PBS, 0.1 mM and 10 mM 5-HT, intraperitoneally. The body weight was significantly lower in the zebrafish injected with 0.1 mM 5-HT (P < 0.05), however, there was no change in body length (P > 0.05) at the end of the 8-week treatment. The muscle tissues from the zebrafish treated with PBS and 5-HT were collected for transcriptomic analysis and the RNA-seq revealed 1134, 3713, and 2535 genes were screened out compared to the muscular DEGs among three groups. The enrichment analysis revealed DEGs to be significantly associated with multiple metabolic pathways, including ribosome, oxidative phosphorylation, proteasome, PPAR signaling pathway, and ferroptosis. Additionally, the qRT-PCR validated 12 DEGs out of which 10 genes exhibited consistent trends. Taken together, this data provided useful information on the transcriptional characteristics of the muscle tissue in the obese zebrafish exposed to 5-HT, offering important insights into the regulatory effect of peripheral 5-HT in teleosts, as well as novel approaches for preventing and treating obesity-related metabolic dysfunction.