Mechanism and therapeutic strategy of hepatic TM6SF2-deficient non-alcoholic fatty liver diseases via in vivo and in vitro experiments

Figure 9 MK-4074 can improve intracellular lipid accumulation, lipid overload-induced cell death, and fatty acids β-oxidation. A: Intracellular triglyceride levels (n = 3) in TM6SF2-knockdown cells with palmitic acid (PA) (150 μmol/L) stimulation were examined after MK-4074 (10 nM) treatment for 24 h; B: Representative nile red staining images (left) and lipid droplet quantification (right) of sh-Ctrl or sh-TM6SF2 L02 cells after PA stimulation in response to MK-4074 (10 nM) treatment (10 fields of each sample were examined). Scale bars: 50 μm; C: The cellular viability was examined in TM6SF2-knockdown cells with or without MK-4074 treatment in response to PA-induced cell death (n = 5); D: The sh-Ctrl and sh-TM6SF2 cells were cultured with PA (150 μmol/L) for 24 h. Cells were then treated with MK-4074 (10 nM) for 12 h. The expression of fatty acid oxidation-related proteins was determined; E: Serum levels of β-hydroxybutyrate and acetoacetate in the indicated mice with or without MK-4074 treatment. ^aP < 0.05; ^bP < 0.01; ^cP < 0.001. NS: Not significant; HFD: High-fat diet; TG: Triglyceride; PA: Palmitic acid; μM: μmol/L.