Abstract
Purpose: :
The NOD mouse is an established animal model of the human disease, Sjögren’s syndrome. The lacrimal gland of male NOD mouse becomes significantly infiltrated with inflammatory cells by 12 weeks of age. Dacryadenitis is associated with massive lipid deposition in the lacrimal acinar cells, a process which starts by 6 weeks of age and is accompanied by onset of inflammatory infiltrates. The aim of this study was to identify the lipids that accumulate in lacrimal glands from NOD mice.
Methods: :
Lacrimal glands were excised from 12-week-old male NOD (n = 8) and BALB/c mice (n = 10). Lipids were extracted and lipid class distribution examined. Then the lipid classes were separated by thin layer chromatography and the fatty acid composition was determined for each of them by gas chromatography.
Results: :
Lacrimal glands were significantly heavier in NOD mouse than in BALB/c mouse (56.5 ± 6.97 mg versus 36.1 ± 5.48 mg). Lacrimal glands from NOD mouse contained twice as much lipids in quantity than those from BALB/c mouse (2.7 ± 0.45 mg versus 1.3 ± 0.26 mg per pair of gland, p<0.0001). The lipids that accumulated were mainly composed of cholesterol esters (CE): 41.5 ± 6.14 % versus 17.0 ± 3.19 % (p<0.0001), 19.7 ± 4.62 µg/mg of lacrimal gland versus 6.1 ± 1.31 (p<0.0001). Accumulation of CE was associated with an increase in palmitic acid (c16:0, 16.3 ± 1.21 % compared to 9.0 ± 1.10 % in BALB/c, p<0.0001), and monounsaturated fatty acids (mainly 18:1 n-9, 26.7 ± 1.81 % versus 13.8 ± 0.91 %, p<0.0001) and a decrease in polyunsaturated fatty acids, mainly arachidonic acid (20:4 n-6, 6.3 ± 0.33 % compared to 21.9 ± 2.37 % in BALB/c, p<0.0001) and linoleic acid (18:2 n-6, 16.4 ± 1.53 % compared to 25.7 ± 1.84 % in BALB/c, p<0.0001). Similar findings were observed in phospholipids, although changes were of a lower level of magnitude.
Conclusions: :
At 12-weeks of age, male NOD mouse lacrimal gland accumulates cholesterol esters that are mainly composed of saturated and monounsaturated fatty acids. The results altogether with other data obtained with microarray and real-time PCR suggest that fundamental changes in lipid transport in the male NOD mouse underlie the lipid accumulation. Further studies are underway to determine the extent of CE oxidation and its role in inflammation.
Keywords: lipids • lacrimal gland • metabolism