Obese mice show dyslipidemia and a changed meibum profile

Abstract

Purpose : Several anecdotal reports suggest abnormal lipid profiles (dyslipidemia) as occurs in obesity can contribute to meibomian gland dysfunction (MGD) by altering meibum lipid composition. The purpose was to determine if plasma and meibum cholesterol esters (CE), triglycerides(TG), ceramides (CM) and sphingomyelins (SM) change together in a mouse model of diet-induced obesity.

Methods : Male C57/BL6 mice (8/group; 5 wks old) were fed a normal (ND;15%kcal fat) or high-fat diet (HFD;42%kcal fat) for 10 wks. Blood was collected by exsanguination after a 5h fast, body and epididymal adipose tissue (eAT) were weighed, and meibum collected by manual expression from eyelids. Plasma and meibum samples were analyzed using mass spectrometry (Nano-ESI MS/MS-QTRAP 6500 SCIEX) to detect CE, TG, CM and SM species including those with long (C14 to C21) and very long (C22 to C26) acyl chains. Data were analyzed using unpaired t-tests and multiple comparisons with a Sidak-Bonferroni correction. Fold-changes were computed followed by principal component analysis (PCA). Data are expressed as means ± SEM, significance was set at p≤0.05.

Results : Compared to mice fed a ND, mice fed a HFD weighed more after 10 weeks (43.5±0.75g vs 33.6±1.4g) and showed greater eAT mass (2.7±0.1g vs 1.4±0.2g), p<0.05. Total fasting blood CE level was elevated in mice fed a HFD compared to a ND (13.0μmol±1.4 vs7.6±1.0g, p<0.05), indicating dyslipidemia. Mice fed a HFD also showed significant elevations (2 to 9 fold) in various plasma CE species while meibum CE, depending on the species, showed fold-changes ranging from -2 to +5. Plasma TG species decreased (4 to 6 fold ) in HFD mice but meibum TG species were elevated (4 to16 fold). Plasma CM species were also elevated (1.5 to 6 fold) but meibum CM did not change after HFD feeding. Both plasma and meibum SM species were significantly elevated (1.5 to 22 fold) after HFD feeding. PCA analysis revealed long saturated lipids and long monounsaturated lipids accounted for most of the overall variance in plasma (53.9% and 25.7%, respecitively) and in meibum (37.6% and 31.4%, respectively).

Conclusions : The majority of lipid species increased with HFD feeding, with long saturated and long monounsaturated lipid species accounting for most of the variance in plasma and meibum profiles. The evidence adds support to the suggestion that an obesogenic diet can result not only in dyslipidemia but also alterations in meibum composition.

This is a 2020 ARVO Annual Meeting abstract.