(A) Schematic presentation of the experimental design of GalNac-conjugated ANGPTL4 ASO (ANGPTL4 ASO) treatment of CD-fed mice. (B) Angptl4 expression in eWAT and liver. (C) Plasma TAG, TC, and HDL-C from overnight-fasted 6-week Angptl4 ASO or Ctrl ASO–treated WT mice. (D) Fasting blood glucose. (E) Strategy for treatment of GalNac-conjugated ANGPTL4 ASO in fat-induced obese mice. HFD-fed mice were treated with Angptl4-ASO or Ctrl ASO for 6 weeks. (F) Body weight: number of weeks on an HFD diet is indicated (treatment was started at week 5 of HFD feeding). Inset represents fat mass measured by Echo-MRI. (G) Plasma TAG, TC, and HDL-C from overnight-fasted 6 -week ANGPTL4 ASO– or Ctrl ASO–treated HFD-fed WT mice. (H and I) Intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test in 6-week ANGPTL4 ASO– or Ctrl ASO–injected mice fed an HFD. Inset represents AUC. (J) Representative images of small intestine cross sections of HFD-fed mice from 10-week treatment of Angptl4 ASO or Ctrl ASO, stained with macrophage marker CD68 and H&E. Original magnification, ×20. (K) Activity of plasma ALT and AST after 10-week treatment of ANGPTL4 ASO or Ctrl ASO in HFD-induced obese mice. All data are represented as mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001, comparing Angptl4 ASO– with Ctrl ASO–treated mice using unpaired t test.