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

Figure 6 TM6SF2 deficiency caused the downregulation of fatty acid oxidation in liver. A: Protein levels of PPARα, CPT1A and ACOX1 was analyzed in TM6SF2-knockdown cells after palmitic acid (PA) stimulation and their response to GW7647 (10 μmol/L) treatment; B: Serum levels of β-hydroxybutyrate and acetoacetate in normal chow diet- or high-fat diet-fed AAV-shNC or AAV-shTm6sf2 mice (n = 5 mice per group); C and D: PA-dependent oxygen consumption rate in sh-Ctrl and sh-TM6SF2 L02 cells with or without etomoxir (ETO, 40 μmol/L) administration (C, n = 6). The basal respiration, maximal respiration, spare respiratory capacity, and ATP production were calculated (D); E: Protein levels of PPARα, CPT1A and ACOX1 were determined in TM6SF2-knockdown cells with or without ETO treatment under PA (150 μmol/L) stimulation; F: The hepatic mRNA levels of fatty acid oxidation-related genes in the indicated mice. ^aP < 0.05; ^bP < 0.01; ^cP < 0.001. PA: Palmitic acid; NS: Not significant; NCD: Normal chow diet; HFD: High-fat diet; OCR: Oxygen consumption rate; μM: μmol/L.