Fig 2: Incremental postprandial changes in plasma sCD14 (A), LBP:sCD14 ratio (B), IL-6 (C), and glucose (D) at week 0 of the intervention and in plasma sCD14 (E), LBP:sCD14 ratio (F), IL-6 (G), and glucose (H) at week 9 of the intervention in healthy obese and nonobese premenopausal women who consumed low-fat yogurt or the control food followed by the challenge meal. Data are means ± SEMs, n = 30. The effects of obesity status (obese compared with nonobese), dietary treatment (low-fat yogurt compared with control food), and the obesity × treatment interaction on net iAUC were determined by 2-factor ANOVA (PROC GLM). A post hoc F test (sliceby) was applied when P-interaction was <0.05. *YO different from CO, P < 0.05. #YN different from CN, P < 0.05. CN, control nonobese; CO, control obese; iAUC, incremental AUC; LBP, LPS-binding protein; sCD14, soluble CD14; YN, yogurt nonobese; YO, yogurt obese; ?, difference.

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: Networks of selected measures reveal several strong associations with metabolic disease score and between measures. (A and B) Correlation subnetworks of all the non-microbe-selected measures (A) and the nearest neighbors of LBP (B). All Spearman rank correlations with an FDR P < 0.25 are shown. Subnetworks were pulled from a larger network of all VSURF selected measures (see Fig. S3 and Table S2). (C) Network of interactions between measures calculated using iRF. All edges represent an interaction (i.e., proximity in a decision tree) that occurred in 30% or more of the decision trees.