High-Fat Diet–Induced Functional and Pathologic Changes in Lacrimal Gland

He, Xin; Zhao, Zhongyang; Wang, Shaopan; Kang, Jie; Zhang, Minjie; Bu, Jinghua; Cai, Xiaoxin; Jia, Changkai; Li, Yixuan; Li, Kechun; Reinach, Peter S.; Quantock, Andrew J.; Liu, Zuguo; Li, Wei

doi:10.1016/j.ajpath.2020.09.002

Cited by 33 publications

(38 citation statements)

References 61 publications

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“…Our previous study also showed that a HFD could induce IL-10 expression in lacrimal gland. 44 In the current study, IL-10 was significantly increased from 4 weeks to 8 weeks; it was attenuated from 8 weeks to 16 weeks after the HFD but was still higher than that of the SD group. We hypothesized that IL-10 may have a compensatory function in suppressing the inflammation caused by a HFD in the early stages.…”

Section: Discussionsupporting

confidence: 47%

“…8 Another study from our group showed that a HFD induced abnormal lipid accumulation, inflammation, lipid peroxidation, and apoptosis in the lacrimal gland, leading to declines in aqueous tear secretion. 44 The aqueous tear secretion was reduced to about half of the normal level after 4 months on a HFD, based on our previous study. In our current study, inflammation of the MG was also evident, and there was a milky secretion on the eyelid margin after 4 months on the HFD.…”

Section: Discussionmentioning

confidence: 80%

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High-Fat Diet Induces Inflammation of Meibomian Gland

Zhang

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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To determine if a high-fat diet (HFD) induces meibomian gland (MG) inflammation in mice. METHODS.Male C57BL/6J mice were fed a standard diet (SD), HFD, or HFD supplemented with the peroxisome proliferator-activated receptor gamma (PPAR-γ ) agonist rosiglitazone for various durations. Body weight, blood lipid levels, and eyelid changes were monitored at regular intervals. MG sections were subjected to hematoxylin and eosin staining, LipidTox staining, TUNEL assay, and immunostaining. Quantitative RT-PCR and western blot analyses were performed to detect relative gene expression and signaling pathway activation in MGs. RESULTS.MG acinus accumulated more lipids in the mice fed the HFD. Periglandular CD45-positive and F4/80-positive cell infiltration were more evident in the HFD mice, and they were accompanied by upregulation of inflammation-related cytokines. PPAR-γ downregulation accompanied activation of the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways in the HFD mice. There was increased acini cell apoptosis and mitochondria damage in mice fed the HFD. MG inflammation was ameliorated following a shift to the standard diet and rosiglitazone treatment in the mice fed the HFD. CONCLUSIONS.HFD-induced declines in PPAR-γ expression and MAPK and NF-κB signaling pathway activation resulted in MG inflammation and dysfunction in mice.

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Section: Discussionsupporting

confidence: 47%

Section: Discussionmentioning

confidence: 80%

High-Fat Diet Induces Inflammation of Meibomian Gland

Zhang

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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“…This can lead to MGD and ocular surface inflammation. While there is lack of consensus on the involvement of inflammation in MGD, previous studies have reported that a high-fat diet can lead to increased oxidative stress and inflammatory cell and cytokine infiltration around the acini of the mouse lacrimal gland acini [ 50 ]. In fact, we recently published that mice fed the obesogenic also show increased levels of systemic and corneal inflammatory mediators [ 51 ], and considering the ocular surface as functional unit, it is possible that the diet-induced dyslipidemia and the alterations in meibum lipids can be pro-inflammatory, impacting the meibomian gland in a similar fashion [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Obese Mice with Dyslipidemia Exhibit Meibomian Gland Hypertrophy and Alterations in Meibum Composition and Aqueous Tear Production

Osae

Bullock

Chintapalati

et al. 2020

IJMS

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Background: Dyslipidemia may be linked to meibomian gland dysfunction (MGD) and altered meibum lipid composition. The purpose was to determine if plasma and meibum cholesteryl esters (CE), triglycerides (TG), ceramides (Cer) and sphingomyelins (SM) change in a mouse model of diet-induced obesity where mice develop dyslipidemia. Methods: Male C57/BL6 mice (8/group, age = 6 wks) were fed a normal (ND; 15% kcal fat) or an obesogenic high-fat diet (HFD; 42% kcal fat) for 10 wks. Tear production was measured and meibography was performed. Body and epididymal adipose tissue (eAT) weights were determined. Nano-ESI-MS/MS and LC-ESI-MS/MS were used to detect CE, TG, Cer and SM species. Data were analyzed by principal component analysis, Pearson’s correlation and unpaired t-tests adjusted for multiple comparisons; significance set at p ≤ 0.05. Results: Compared to ND mice, HFD mice gained more weight and showed heavier eAT and dyslipidemia with higher levels of plasma CE, TG, Cer and SM. HFD mice had hypertrophic meibomian glands, increased levels of lipid species acylated by saturated fatty acids in plasma and meibum and excessive tear production. Conclusions: The majority of meibum lipid species with saturated fatty acids increased with HFD feeding with evidence of meibomian gland hypertrophy and excessive tearing. The dyslipidemia is associated with altered meibum composition, a key feature of MGD.

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“…The amplification program follows established procedures reported elsewhere. 27 Supplementary Table S1 lists the primer sequences used. The expression of genes was assessed by the 2^ −ΔΔCt method.…”

Section: Methodsmentioning

confidence: 99%

“… 25 It secretes aqueous tears to maintain the homeostasis of the ocular surface. The lacrimal gland can be prone to pathological changes owing to abnormal glucose metabolism 26 or lipid metabolism, 27 and lesions of the lacrimal gland are often accompanied by abnormal deposition of lipids with increasing age and when sleep deprived. 28 , 29 The current study suggests that OSA is a causative factor for dry eye disease and reveals a mechanism by which OSA could lead to abnormal lacrimal gland lipid metabolism through the Hif - Pparα signaling pathway, ultimately triggering manifestations of dry eye.…”

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confidence: 99%

Obstructive Sleep Apnea Affects Lacrimal Gland Function

Wang

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose To determine the effect of obstructive sleep apnea syndrome (OSA) on lacrimal gland function and its mechanism. Methods Male mice aged seven to eight weeks were housed in cages with cyclic intermittent hypoxia to mimic OSA, and the control group was kept in a normal environment. Slit-lamp observation, fluorescein staining, and corneal sensitivity detection are used to assess cornea changes. Tear secretion was detected by phenol red cotton thread, and the pathological changes of lacrimal gland were observed by hematoxylin and eosin staining, oil red O staining, cholesterol and triglyceride kits, immunofluorescence staining, immunohistochemical staining, real-time polymerase chain reaction, transmission electron microscopy, and Western blot. Results Studies revealed a decreased tear secretion, corneal epithelial defects and corneal hypersensitivity. Myoepithelial cell damage, abnormal lipid accumulation, reduced cell proliferation, increased apoptosis and inflammatory cell infiltration in the lacrimal gland were also seen. Hif α and NF-κB signaling pathways, moreover, were activated, while Pparα was downregulated, in the lacrimal glands of OSA mice. Fenofibrate treatment significantly alleviated pathological changes of the lacrimal gland induced by OSA. Conclusion OSA disturbs the Hifα / Pparα /NF-κB signaling axis, which affects lacrimal gland structure and function and induces dry eye.

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High-Fat Diet–Induced Functional and Pathologic Changes in Lacrimal Gland

Cited by 33 publications

References 61 publications

High-Fat Diet Induces Inflammation of Meibomian Gland

High-Fat Diet Induces Inflammation of Meibomian Gland

Obese Mice with Dyslipidemia Exhibit Meibomian Gland Hypertrophy and Alterations in Meibum Composition and Aqueous Tear Production

Obstructive Sleep Apnea Affects Lacrimal Gland Function

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