Effects of essential fatty acid deficiency on prostaglandin synthesis and fatty acid composition in rat renal medulla

Abstract

Studies are reported on the capacity of isolated rat renal papilla (inner medulla) to synthesize and release prostaglandin (PG) E from endogenous and exogenous precursor(s) during development of an essential fatty acid (EFA) deficiency in the rat. Weanling (21-day-old) male Sprague-Dawley rats were fed a fat-free diet supplemented with either 5% hydrogenated coconut oil (HCO) or 5% safflower oil (SO). At approximately 3, 6 and 7 weeks (6. 9 and 10 weeks of age), groups of animals fed each diet were killed for studies of PGE synthesis in the renal papillae. Differences in the fatty acid composition of the papillae lipids of the animals of each group were also determined. The in vitro production of PGE from endogenous precursor(s) was significantly reduced in the papillae from the 6-week-old rats fed the HCO diet compared to the control (SO) rats, and appeared to be near maximally depressed in the 10-week-old animals compared to that of animals fed an EFA deficient diet for over a year in an accessory experiment. Analyses of the fatty acids of the papillae lipids of the HCO groups showed that the levels of 18:2 and 20:4 were markedly reduced, and those of 16:1, 18:1 and 20:3 were elevated compared to the controls even in the 6-week-old animals, typical of an EFA deficiency. The papillae lipids of the animals fed the HCO diet were also depleted of their stores of 22:4 omega 6. A fatty acid believed to be derived by chain elongation of 20:3 omega 9, 22:3, was found in large concentrations in the papillae triglycerides of the EFA deficient rats. Incubations of exogenous arachidonic acid (20:4) in homogenates and tissue slices of the papillae of the HCO dietary groups showed that the PG synthetase was not impaired by an EFA deficiency. The rate of PGE synthesis in the papillae of the EFA deficient animals was generally enhanced when exogenous 20:4 was added, indicating that the concentration of available precursor(s) is a primary factor in the control of PGE synthesis in the papilla of the rat.

The inhibition of lung colonization of B16-F10 melanoma cells in EFA-deficient animals is related to enhanced apoptosis and reduced angiogenesis

“…The reduced expression of VEGF in metastatic colonies grown in EFAdeficient animals might reflect the reduced synthesis of PGE2 in these animals [25][26][27][28] -an observation in line with the finding that VEGF is reduced in animals fed n-3 PUFA-enriched diets [32,56], a dietary manipulation that reduces PGE2 synthesis [32].…”

“…In conclusion, the data derived from the present study suggest that the reduced pulmonary colonization of B16-F10 cells represents the final step of a series of phenomena consisting in: decreased generation of prostaglandins due to EFA deficiency [25][26][27][28] -diminution of VEGF expression -reduced microvessel density -induction of apoptotic activity. This sequence, however, does not rule out the possibility that apoptosis might be primarily induced by the deprivation of an important nutritional factor, such as linoleic acid, in EFA-deficient animals.…”

“…This possibility was suggested by the finding that arachidonic acid metabolites, whose synthesis is reduced in EFA-deficient animals [25][26][27][28], influence apoptosis [29][30][31] and angiogenesis [32][33][34]. The apoptotic activity was investigated by immunolocalization of bax and bcl-2, gene products that control apoptosis through the so-called mitochondrial pathway [21,35].…”

Spontaneously hypertensive rats: Eicosa‐8,11,14‐trienoic acid metabolism and arachidonic acid biosynthesis

“…This observation is consistent with a diminished renal PGE 2 excretion and vascular prostacyclin synthesis [6]. A primary factor in the control of prostaglandin synthesis in the renal papilla is the availability of the precursor [7]. In SHR there is a defect in the release of DGLA [8] and it was shown that dietary DGLA reverses hypertension induced in rats by diets rich in saturated fats, probably because in the microsomal fraction of the cell [10] by alternating sequences of desaturations and elongations.…”

Relation between Essential Fatty Acid Metabolism and Gastrointestinal Symptoms in Cystic Fibrosis

“…It might also be illustrated by the fact that most patients after diagnosis have several years with very mild symptoms. It is also known that EFA deficiency may down-regulate the eicosanoid synthesis (46).…”