N-3 fatty acid deficiency in the rat pineal gland: effects on phospholipid molecular species composition and endogenous levels of melatonin and lipoxygenase products

Abstract

N-3 essential fatty acid deficiency affects a number of biological and physiological processes. In this study, we investigated the effect of n-3 essential fatty acid status on two key pineal biochemical functions, melatonin production and lipoxygenation, using pineal glands from rats given an n-3-adequate or n-3-deficient diet. The pineal total lipid profile and phospholipid molecular species distribution altered by n-3 deficiency were evaluated in parallel. In pineal glands from n-3-deficient rats, an 87% reduction of 22:6n-3 (docosahexaenoic acid) was observed, and this decrease was accompanied by increases in 22:4n-6 (docosatetraenoic acid, 3-fold), 22:5n-6 (docosapentaenoic acid, 12-fold), and 20:4n-6 (arachidonic acid, 48%). The significant decrease of 22:6n-3 containing species in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) was also evident. These decreases in 22:6n-3 containing PL species were compensated by substantial accumulations of 22:4n-6 or 22:5n-6 and slight increases in 20:4n-6 containing PL species in PC and PE. In PS, however, the accumulation of n-6 species was not adequate to compensate for the loss of 22:6n-3 species. N-3 deficiency significantly reduced non-esterified 20:4n-6 and 22:6n-3 levels in pineals (25% and 65%, respectively). Concomitantly, the endogenous 12-HETE level decreased by 35% in deficient pineals. In contrast, n-3 deficiency led to a more than 60% increase in the daytime pineal melatonin level. In conclusion, n-3 fatty acid deficiency not only has profound effects on pineal lipid profiles but also on pineal biochemical activities. These results suggest that n-3 fatty acids may play a critical role in regulating pineal function.