Fig 1: TLR4 Suppression Leads to Beige Fat Development(A) Body weight gain of HCD mice injected daily with either 10% DMSO (HCD Vehicle) or CLI-095 (HCD CLI-095) for 5 weeks (n = 10).(B and C) OGTT (B) and normalized ITT (C) of mice as in (A) (n = 10).(D) Infrared temperature changes relative to initial values in eye, ventral, or dorsal regions, or eye during 3 hr of cold exposure of HCD mice injected daily with either 10% DMSO (HCD Vehicle) or CLI-095 (HCD CLI-095) for 5 weeks (n = 5 per group).(E) Weight of indicated organs post mortem of mice as in (A) (n = 10 per group).(F–H) Transversal [18F]FDG PET-CT images (F), standardized uptake values (SUV) of radiolabeled tracer [18F]FDG in ingSAT (G), and quantification of the total ingSAT and pgVAT volume (H) using MicroPET-CT on mice as in (A) (n = 5).(I) Representative H&E-stained histological sections from ingSAT of HCD vehicle and CLI-095 mice. Scale bar, 200 µm.(J) Relative mRNA expression of browning markers in ingSAT of HCD Vehicle and CLI-095 mice (n = 5 per group).(K) OGTT in 8-week-old wild-type (WT) and Tlr4 KO mice (n = 5–6 per group).(L) Fat/lean mass ratio in WT and Tlr4 KO mice at the indicated ages (n = 3–12 per group).(M) ITT in 8-week-old WT and Tlr4 KO mice (n = 5–6 per group).(N and O) Relative mRNA expression of browning markers in ingSAT (N) and pgVAT (O) of WT and Tlr4-/- mice (n = 6 per group).(P) Representative images of immunofluorescent staining of UCP1 in ingSAT of WT and Tlr4 KO mice. Scale bar, 200 µm.(Q) Oxygen consumption rate (OCR) in ingSAT biopsies from WT and Tlr4 KO mice detected with Seahorse analyzer. Iso, isoproterenol (n = 4 mice per group assayed in quadruplicates).(R) Relative mRNA expression of browning markers in ingSAT of AL and CR Tlr4 KO mice (n = 5 per group).(S and T) Quantification of CD11b+Siglec F+ eosinophils (S) and CD301 mean fluorescence intensity (MFI; T) in CD11b+ F4/80+ macrophages in ingSAT SVF of WT and Tlr4 KO mice (n = 5 per group).Unless otherwise indicated, error bars show mean ± SD. Significance was calculated using non-paired two-tailed Student's t test.*p = 0.05, **p = 0.01, ***p = 0.001.