Benny Jensen

INTAKE OF MARINE FAT, RICH IN (n-3)-POLYUNSATURATED FATTY ACIDS, MAY INCREASE BIRTHWEIGHT BY PROLONGING GESTATION

Birthweights in the Faroe Islands are among the highest in the world. Compared with Denmark, the average birthweight of liveborn singleton infants of primiparous mothers is 194 g higher, and a substantial part of this difference seems to be attributable to longer gestation. Prostaglandins play an important part in the timing of parturition in human beings. Dietary (n-3)-polyunsaturated fatty acids (PUFA) in high amounts influence endogenous prostaglandin metabolism. Owing to the large consumption of marine fat, the average intake of (n-3)-PUFA in the Faroes by far exceeds that in Denmark. The hypothesis proposed is that dietary (n-3)-PUFA in high amounts prolong gestation in human beings by interfering with uterine production of prostaglandins, possibly by inhibiting the production of dienoic prostaglandins, primarily PGF2 alpha and PGE2, which are mediators of uterine contractions and cervical ripening.

Essential function of linoleic acid esterified in acylglucosylceramide and acylceramide in maintaining the epidermal water permeability barrier. Evidence from feeding studies with oleate, linoleate, arachidonate, columbinate and α-linolenate

Essential fatty acid-deficient rats were supplemented with 300 mg per day of pure fatty acid esters: oleate (O), linoleate (L), arachidonate (A), and columbinate (C) for 10 days. During this period, the rats in groups L, A, and C all showed a decrease in their initially high trans-epidermal water loss, a classical essential fatty acid-deficiency symptom, to a level seen in non-deficient rats (group N). The trans-epidermal water loss in rats of group O was unaffected by the supplementation. Fatty acid composition of two epidermal sphingolipids, acylglucosylceramide and acylceramide, from the skin were determined. The results indicate that re-establishment of a low trans-epidermal water loss was associated with incorporation of linolenate into the two epidermal sphingolipids. Supplementation with columbinate resulted in relatively high amounts of this fatty acid in the investigated epidermal sphingolipids. Analysis of pooled skin specimens from a previous study in which weanling rats were fed a fat-free diet and supplemented orally with pure alpha-linolenate for 13 weeks (Hansen, H.S. and Jensen, B. (1983) Lipids 18, 682-690) revealed very little polyunsaturated fatty acid in the two sphingolipids. These rats showed increased evaporation which was comparable to that of essential fatty acid-deficient rats. We interpret these results as strong evidence for a very specific and essential function of linoleic acid in maintaining the integrity of the epidermal water permeability barrier. This function of linoleate is independent of its role as precursor for arachidonate and icosanoids.

Gestation length and birth weight in relation to intake of marine n -3 fatty acids

It has been hypothesized that marine n-3 fatty acids ingested during pregnancy prolong duration of pregnancy and increase fetal growth rate in humans. By a combined self-administered questionnaire and interview applied in the 30th week of gestation we assessed dietary intake of marine n-3 fatty acids and energy in a population-based sample of 965 pregnant Danish women; in a random 14% subsample we also measured marine n-3 fatty acids relative to arachidonic acid (FA-ratio) in erythrocytes. Mean intake of marine n-3 fatty acids was 0.25 (95% range 0-0.75) g/d. We could detect no association between n-3 fatty acid intake and FA-ratio on the one hand, and gestation length, birth weight and birth length on the other. The analyses were adjusted for maternal height, prepregnant weight, parity and smoking. The conclusion from the study was that within the intake range of this population, marine n-3 fatty acids ingested in the weeks prior to the 30th week of pregnancy seem not to be a predictor of gestation length or fetal growth rate.

Gestational age in relation to marine n-3 fatty acids in maternal erythrocytes: A study of women in the Faroe Islands and Denmark

Gestation is longer in Faroese than Danish women, possibly because of the high intake of marine long-chain n-3 fatty acids that down regulates formation of prostaglandins from arachidonic acid. Polyunsaturated fatty acids were quantified in erythrocytes obtained within 2 days of delivery from randomly selected groups of 62 Faroese and 37 Danish women with an assessable gestational age. Average ratio of long-chain n-3 fatty acids to arachidonic acid [(3/6) ratio] was 0.73 (SD = 0.11) in Faroese women and 0.61 (SD = 0.12) in Danish women (p less than 0.0001), corresponding to the higher intake of marine n-3 fatty acids in the Faroes. A 20% increase in the (3/6) ratio was associated with an increase in pregnancy duration of 5.7 days in Danish women (95% confidence interval, 1.4 to 10.1 days; p = 0.02) and 0.7 days in Faroese women (95% confidence interval, -2.0 to 3.3; p = 0.6). The hypothesized exposure-effect relationship may be weaker or absent at the higher level of exposure seen in the Faroese group.

Fish oil versus arachis oil food supplementation in relation to pregnancy duration in rats

Throughout pregnancy, Lewis rats were fed standard rat chow supplemented with 15% (w/w) of either MaxEPA fish oil (FO) or arachis oil (AO); a third group was fed standard rat chow only (St) (n = 15, 15, and 16 rats, respectively). Compared to AO-rats, FO-rats had substantially higher levels of n-3 fatty acids and lower levels of n-6 fatty acids in maternal and fetal tissues at delivery. FO-rats had a longer average gestational age than AO-rats (p less than 0.01), primarily due to a high proportion of AO-rats with short gestations. Birthweights of FO-rats were lower than those of AO-rats (p less than 0.05), which may be related to the lower maternal weight gain during pregnancy and the lower food consumption observed in FO-rats (p less than 0.01). Litter size and occurrence of stillborn pups were not significantly different in the groups (p greater than 0.1). The findings are compatible with the hypothesis that gestational age is positively related to a high dietary intake of n-3 fatty acids.

Urinary prostaglandin E2 and vasopressin excretion in essential fatty acid-deficient rats: effect of linolenic acid supplementation

Three groups of weanling male rats were fed on a fat-free diet for 13 weeks. One group received only the fat-free diet (FF rats), the other 2 groups received the fat-free diet and a daily supplement of 2 energy% ethyl linoleate ([n−6] rats), or 2 energy% ethyl linolenate ([n−3] rats). Urinary excretion of prostaglandin E2 (PGE2), immunoreactive arginine vasopressin (iA VP), and kallikrein were determined. PGE2 was quantitated with a radioimmunoassay having 4.9% cross-reactivity with prostaglandin E3 (PGE3). After 4 weeks on the diet, water consumption and urinary iAVP excretion increased significantly in the FF rats and the (n−3) rats compared with the (n−6) rats. Urinary PGE2 excretion was the same for all 3 groups during the first 10 weeks; thereafter it decreased in FF rats and (n−3) rats compared with the (n−6) rats. There was no difference in urinary PGE2 excretion between the FF rats and the (n−3) rats, even though large differences were found in the percentage of arachidonic acid (20∶4[n−6]), icosapentaenoic acid (20∶5[n−3]), and icosatrienoic acid (20∶3[n−9]) of total kidney fatty acids as well as of kidney phosphatidylinositol fatty acids. Fractionation of urine extracts on high performance liquid chromatography with radioimmunoassay detection indicated that (n−3) rats excreted very little PGE3, if any. Urine output followed the same pattern, as did urinary PGE2 excretion. Urinary kallikrein was estimated at week 12 only. It was found to be significantly lower in FF rats and (n−3) rats. Increased water consumption and increased urinary iAVP excretion seem to be early symptoms (after 4 weeks) of EFA deficiency, whereas decreased urine output and decreased urinary PGE2 excretion occur much later (after 10 weeks). Two energy% linolenate supplementation to a fat-free diet did not change the appearance of any of the measured EFA-deficiency symptoms except for a slightly improved growth rate. There was no evidence of a significant urinary PGE3 excretion in spite of an extreme enrichment of kidney lipids with 20∶5(n−3). It is suggested that urinary PGE2 is derived from precursors delivered from an arachidonic acid pool, which is rather resistant to restriction in dietary linoleate.

Apparent in vivo retroconversion of dietary arachidonic to linoleic acid in essential fatty acid-deficient rats

Essential fatty acid-deficient rats were fed ethyl [U-14C]arachidonate (308 dpm/nmol) and when a decrease in the transepidermal water loss was seen, the epidermal sphingolipids, acylglucosylceramide and acylceramide were isolated. [14C]Linoleic acid (approx. 130 dpm/nmol) was present in both lipid classes, while the substrate was only detected in the former. These results intimate that in vivo retroconversion of arachidonic to linoleic acid can be induced in the rat.

Extremely decreased release of prostaglandin E2-like activity from chopped lung of ethyl linolenate-supplemented rats

Three groups of weanling male rats were reared on a fat-free diet for 13 weeks. One group received only the fat-free diet (FF rats), the other 2 groups received the fat-free diet and a daily supplement of 2 energy% ethyl linoleate ([n−6] rats), or 2 energy% ethyl linolenate ([n−3] rats). The chopped lung preparation was used to illustrate an in vitro prostaglandin formation. PGE2-like activity was quantified on rat stomach strip. The release of PGE2-like activity expressed as ng PGE2-equivalent per g lung tissue (mean±SD) was 23±7, <6, and 65±20 for the FF rats, the (n−3) rats, and the (n−6) rats, respectively. PGE2 quantification by radioimmunoassay of the chopped lung effluent collected after passing over the rat stomach strip revealed the same release pattern as the bioassay. Fractionation of chopped lung effluent on HPLC with radioimmunoassay detection indicated that the lung tissue from (n−3) rats released very little PGE3, if any, in spite of a 20∶5(n−3)/20∶4(n−6) ratio of 5.2 in the lipids of the lung. It is suggested that the pool of arachidonic acid for prostaglandin production in vitro is different from the one which functions in vivo, and that these pools are differently affected by dietary EFA.

Pregnancy duration and the ratio of long-chain n-3 fatty acids to arachidonic acid in erythrocytes from Faroese women

Abstract. Dietary long‐chain n‐3 fatty acids (FA) may prolong gestation by inhibiting formation of prostaglandins from arachidonic acid. FA were quantified in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and total lipids (TL) of red cells sampled during pregnancy from 29 Faroese women. The ratio of long‐chain n‐3 FA to arachidonic acid (the (3/6) ratio) was used as the most relevant single measure of exposure. In 18 women with certain gestational age and with spontaneous onset of delivery, gestational age was significantly associated with the (3/6) ratio quantified in PC (correlation coefficient 0.50, P = 0.035), but not with the (3/6) ratio in PE (correlation coefficient 0.21, P = 0.40) or TL (correlation coefficient 0.29, P = 0.26). The association with the (3/6) ratio in PC could not be attributed to confounding by maternal age, weight, marital status or smoking.

Synergism between thapsigargin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate on the release of [14C]arachidonic acid and histamine from rat peritoneal mast cells.

Thapsigargin is a potent skin irritating sesquiterpene lactone isolated from the roots of Thapsia garganica L. (Apiaceae). In rat peritoneal mast cells thapsigargin induced a calcium-dependent non-cytotoxic [14C]arachidonic acid and histamine release. A minor amount of the released [14C]arachidonic acid was converted to [14C]prostaglandin D2. A potentiated effect was found between thapsigargin and 12-O-tetradecanoylphorbol 13-acetate, as well as between A23187 and the phorbol ester with respect to release of [14C]arachidonic acid and histamine. It is suggested that the synergistic effect is due to activation of protein kinase C by 12-O-tetradecanoylphorbol 13-acetate and to increased intracellular calcium concentration mediated by A23187 as well as thapsigargin. [14C]arachidonic acid was released mainly from phosphatidylcholine. It is suggested that this release may be due to an action of phospholipase A2, and that protein kinase C is involved in activation of phospholipase A2.