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

Eugene A Osae,Alan R Burns,Tiffany Bullock,Susanne Brodesser,Philipp Steven,Madhavi Chintapalati,C Wayne Smith,Rachel Redfern,Samuel Hanlon,Rolando E Rumbaut

doi:10.3390/ijms21228772

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.

Highlights

Obesity has reached epidemic levels, affecting about 2 billion adults and 42 million children globally, and the associated complications, including type 2 diabetes, are on the rise [1,2,3,4,5]
The average plasma cholesteryl esters (CE), Cer and SM levels were ≈ 2 to 3-fold higher in the high-fat diet (HFD) mice compared to the ND mice, p < 0.01–
The obesogenic diet used approximates the contemporary (Western) diet compositions, and as expected, the HFD mice gained more weight, which is accompanied by significant elevations in

Summary

Introduction

Obesity has reached epidemic levels, affecting about 2 billion adults and 42 million children globally, and the associated complications, including type 2 diabetes, are on the rise [1,2,3,4,5]. 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. 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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