Fig 2: Result of LNP-Lbp UNA-siRNA treatment on liver lipid accumulation and lipogenesis in mice with established obesity(A–P) Effects of 8-weeks LNP-Lbp UNA-siRNA administration on Lbp mRNA levels (A and I), representative standard Masson’s trichrome staining histological liver slides (20×), LD count and area (B and J), liver triglycerides (C and K), malonyl-CoA levels (D and L), expression of lipogenic (E and M) genes, ACC protein (F and N), ACC activity (G and O), and MDA levels (H and P) in diet-induced obese male (A–H) and female (I–P) mice. *p < 0.05, **p < 0.01, and ***p < 0.001 compared with vehicle-treated obese mice.

Fig 3: Effect of LNP-Lbp UNA-siRNA treatment on insulin resistance during HFHS diet and in mice with established obesity(A–F) Effects of 6-months LNP-Lbp UNA-siRNA administration on insulin at 4, 8, and 25 weeks (A), insulin change between weeks 4 and 8 (B), and fasting glucose, HOMAIR, blood glucose during ITT, and glycemia (AUC) in ITT at the end of experiment (C–F) in HFHS-fed female and male mice. *p < 0.05, **p < 0.01, and ***p < 0.001 compared with CD; †p < 0.05 and ††p < 0.01 compared with HFHS; ‡p < 0.05, ‡‡p < 0.01, and ‡‡‡p < 0.001 compared with female mice. (G and H) Effect of 8-weeks LNP-Lbp UNA-siRNA administration on blood glucose during ITT (G) and glycemia (AUC) in ITT (H) in obese female and male mice. *p < 0.05 and **p < 0.01 compared with obese vehicle; ‡‡p < 0.01 and ‡‡‡p < 0.001 compared with female mice.

Fig 4: LNP-Lbp UNA-siRNA treatment effects on liver lipogenesis and triglycerides in mice fed with standard diet (STD) and MCD(A–I) Effects of weekly LNP-Lbp UNA-siRNA administration in STD- and MCD-fed mice on liver Lbp and lipogenesis (Fasn, Srebf1, and Scd1)-related gene expression (A and B), malonyl-CoA (C), FAS and ACC protein levels (D and E), ACC activity (F), NADPH production (Idh1, Me1)-related gene expression (G), MDA (H), and triglycerides levels (I). *p < 0.05, **p < 0.01, and ***p < 0.001 compared with vehicle; †p < 0.05, ††p < 0.01, and †††p < 0.001 compared with STD. siC, weekly LNP-non-targeting UNA-siRNA (3 mg/kg)-treated mice; siLbp, weekly LNP-Lbp UNA-siRNA (3 mg/kg)-treated mice.

Fig 5: Impact of Lbp gene knockdown in primary human hepatocytes(A–H) Effects of Lbp gene knockdown in human hepatocytes on Lbp mRNA (A), oil red O staining (B), and expression of Scd1, CPT1A, PPARA, IL6, and IL8 genes and AMPK activity (C–H). *p < 0.05, **p < 0.01, and ***p < 0.001 compared with siC. siC, control scramble siRNA.