Abstract
Purpose :
To investigate the role of PPAR-γ in high-fat diet induced meibomian gland inflammation in mice.
Methods :
4-week-old male C57BL/6 mice were fed with a standard diet (SD) or a high-fat diet (HFD) for different durations from 4 weeks to 16 weeks. Some HFD mice were oral administrated with rosiglitazone (HFD-rosi mice). The weight of mice was quantified. The ocular surface and eyelid were observed under slit lamp microscope. Tear samples from SD and HFD mice were examined by Raman spectroscopy. Meibomian gland tissue sections underwent H&E staining, Oil Red O staining and immuno-fluorescence staining for CD45 and CD11b. The gene expression of PPAR-γ, IL-1β, L-6, IL-8, TNF-α, IFN-γ, MMP-3, MMP-9 in meibomian gland were evaluated by qRT-PCR. Western blot was performed to detect PPAR-γ, IL-1β, IL-6, TNF-α, HO-1, 4-HNE, Nrf-2, NF-κB p65, p-NF-κB p65, p38, p-p38, JNK, p-JNK, ERK, and p-ERK.
Results :
High fat diet led to a significant increase of body weight and hyperlipidemia in mice. Oil Red O staining showed accumulation of lipid in meibomian gland acinus in HFD mice. HE staining showed an increase in periglandular cell infiltrates in HFD mice. Increased infiltrations of CD45+ and CD11b+ cells were observed in meibomian gland in HFD mice than those observed in SD mice. The Raman test results showed lipid composition of tear in HFD mice differs from that of SD mice. Meibomian glands of HFD mice exhibited decreased PPAR-γ expression, increased production of inflammatory cytokines and significant increase in phosphorylation of MAPKs and NF-κB p65 compared with SD groups. 4 weeks of HFD mice shift to SD for 4 weeks showed reversed phenotype, decreased the production of inflammatory cytokines, suppressed the activation of MAPK and NF-κB p65 pathway, with increased expression of PPAR-γ in meibomian gland compared with the HFD mice. In HFD-rosi mice, rosiglitazone treatment stimulated the expression of PPAR-γ,decreased the expression of inflammatory cytokines and inhibited the phosphorylation of MAPKs and NF-κB p65 in meibomian gland.
Conclusions :
High-fat diet induced meibomian gland inflammation by inhibiting PPAR-γ expression and activating MAPK and NF-ΚB signaling pathway in mice.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.