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

Abstract

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.

High-Fat Nutritional Challenge Reshapes Circadian Signatures in Murine Extraorbital Lacrimal Glands

“… 21 Similarly, mice fed an HFD for 10 weeks had hypertrophic meibomian glands and increased levels of lipid species in the meibum. 22 HFD feeding also leads to decreased 22 , 23 or increased tear production (∼50%) and induces dry eye-like ocular surface damage in murine models. 24 , 25 However, the effects of high fat intake on normal ocular surface homeostasis and disease in humans are not fully appreciated.…”

Association of Serum Lipid Level with Meibum Biosynthesis and Meibomian Gland Dysfunction: A Review

“…They obtained obese mice with a high-fat diet and found corneal dysfunction such as both an increase in corneal inflammatory mediators and a decrease in corneal nerve density before the development of sustained hyperglycemia [ 67 ]. Additionally, dyslipidemia in their diet-induced obesity mouse model was found to be accompanied by the alteration in both meibum composition and MG structure [ 68 ]. The level of the lipid species with saturated fatty acids was increased in meibum, and MG hypertrophy was confirmed with meibography in their animal study [ 68 ].…”

Altered Intrinsic Regional Spontaneous Brain Activity in Patients With Severe Obesity and Meibomian Gland Dysfunction: A Resting-State Functional Magnetic Resonance Imaging Study

“…SO is often coupled with hyperlipidemia ( D’Abbondanza et al, 2020 ), which is characterized by elevated blood lipid levels (causing atherosclerosis), such as cholesterol, triglycerides, and low-density lipoproteins, and decreased high-density lipoproteins ( Butovich, 2008 ; Butovich, 2010 ; Green-Church et al, 2011 ). On the one hand, an abnormality of the lipid component will affect the structure of MG and make MG hypertrophy ( Osae et al, 2020 ). On the other hand, it may lead to inflammation, which is an underlying cause of blepharitis and can eventually impact the regular excretory capabilities of the MG ( Pietiläinen et al, 2007 ).…”