Gut-derived serotonin (GDS) promoted lipid synthesis and the inflammatory response through the HTR2A receptor in hepatocytes. (A) Relative messenger RNA (mRNA) expression of 14 HTRs on day 20 and day 30 in SD rats. (B) Relative mRNA expression of 14 HTRs in BRL-3A. (C) Relative gene expression of Htr2a, Htr2b, Htr2c in SD rats administrated TRP Free diet and LP5333401. (D) The protein level of HTR2A, HTR2B, HTR2C in SD rats fed HFSD diet for 20 or 30 days and in BRL-3A treated by free fatty acid (FFA) or 5-HT. (E) Oil red O staining and lipid content in BRL-3A (× 400). (F) The content of TG in BRL-3A. (G) The mRNA expression of genes related with lipid synthesis (Pparγ2, Srebp1c, Fas) in BRL-3A. (H) The mRNA expression of genes related with inflammation response (Tnfα, Il6, Mcp1) in BRL-3A. “C” means control group (1% BSA with FFA free), “M” means 1 mM FFA treatment; “5-HT” means 5-HT (50 μM) treatment; “5-HT + M” means 5-HT (50 μM) with FFA (1 mM) treatment; “M+T” represents FFA (1 mM) with TCB-2 (0.1 μM) treatment; “M+K” represents FFA (1 mM) and 5-HT (50 μM) with ketanserin (1 μM); All data are presented as the mean ± SEM (n = 6). #P < 0.05, ##P < 0.01, ###P < 0.001, compared with corresponding control group; *P < 0.05, **P < 0.01, and ***P < 0.001, compared with relative model group; &&P < 0.01 and &&&P < 0.001, compared with “5-HT+M” group.