Figure 8. ATG7 ASO inhibits autophagy in apoB ASO–treated mice but has no effect on either TG secretion or liver TG, despite an increase in liver weight.

Increased ER stress and apoptosis were also evident. Apobec-1–KO mice were treated with apoB ASO for 6 weeks, and either control or ATG7 ASO was added for the final 3 weeks. (A) Liver homogenate was run on an SDS-PAGE and immunoblotted for ATG7, LC3, p62, and actin. N = 5–6 livers per group. (B) Triton WR1339 was injected i.v., blood samples were obtained every 30 minutes over the next 120 minutes, and plasma TG levels were measured. N = 2–3 mice per group. (C) Livers were weighed at the time of euthanization. N = 5–6 livers per group. *P < 0.05, by Student’s t test, for apoB plus ATG7 ASO versus apoB ASO control. (D) Liver lipids were extracted, and TG was measured enzymatically. N = 5–6 livers per group. (E) Primary hepatocytes were labeled with ¹⁴C OA for 2 hours, and then unlabeled chase media were added and collected every 4 hours over a 16-hour period. N = 6 wells from 2 mice per group. *P < 0.05, by Student’s t test, for apoB plus ATG7 ASO versus apoB ASO control. (F) The total amount of ¹⁴C OA oxidized over the 16-hour time points was summed for each group of mice. N = 6 wells from 2 mice per group. (G) Liver homogenate was run on a 10% SDS-PAGE and immunoblotted for the ER stress markers GRP78, p-eIF2α, and actin. N = 5–6 livers per group. (H) Liver homogenates were run on 8% or 12% SDS-PAGE and immunoblotted for various markers of apoptosis, either total or cleaved. N = 5–6 livers per group. All values represent the mean ± SD.