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Xin He, Zhongyang Zhao, JingHua Bu, Minjie Zhang, Jie Kang, Yixuan Li, Kechun Li, Zuguo Liu, Wei Li; High fat diet induced functional and pathological changes in lacrimal gland. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1416. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the effect of high fat diet on lacrimal gland.
One-month-old male C57BL/6 mice were administered with a standard diet (SD) or a high-fat diet (HFD) for different durations from 1 month to 4 months. Some animals were shift to SD for 1 month after feeding HFD for 1 month, some HFD mice of 5-month-old were treated with fenofibrate for 1 months. Tear production was evaluated by phenol red thread. The mice were sacrificed at different time points. The lacrimal gland were harvested and processed for H&E staining, Oil red O staining, qRT-PCR, Western Blot, MDA Kit test, Cholesterol Assay Kit test, transmission electron microscope (TEM) , immumohistochemical staining (IHC staining) and immunofluorescence staining (IF staining).
After feeding with high-fat diet, tear secretion was decreased after 1 month. The acinar cells of lacrimal gland showed lipid droplets accumulation increased with time by Oil Red O staining and TEM. The content of cholesterol from lacrimal gland was gradually increased. The enzymes of fatty acid oxidation were disordered. The expression of PPAR-α gene gradually increased from one month to 3 months after HFD feeding, and obviously decreased after 4 months. Besides, the lacrimal gland showed cell infiltration around the acinus started from 1 month of HFD. IHC staining and IF staining revealed inflammatory cells infiltration increased. QRT-PCR demonstrated inflammation related factors such as IL-1β, TNF-α, TSG6, IL-10 increased significantly. In addition, the degree of lipid peroxidation was enhanced and antioxidants were increased. Furthermore, TEM showed mitochondria hypermegasoma after 4 months HFD. The apoptotic cells were increased and proliferation was decreased in lacrimal gland after HFD. After 4 months HFD, the animals were shifted to SD for 1 month, most pathologic changes could be recovered. In addition, after feeding with fenofibrate, the tear production increased, lipid droplets reduced, inflammation relieved and the oxidative stress was decreased.
Long-term high fat diet could induce lipid peroxidation, inflammatory cell infiltration, mitochondria damage, cell apoptosis increase and proliferation inhibition in lacrimal gland, resulted in aqueous tear secretion decrease, which may induce dry eye.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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