Trine Porsgaard

Lymphatic fatty acid absorption profile during 24 hours after administration of triglycerides to rats.

In this study we determined in rats the complete 24-h lymphatic fatty acid profile after administration of either rapeseed oil (RO) or rapeseed oil interesterified with 10∶0 (RO/C10) with special emphasis on the transition from absorptive to postabsorptive phase. Rats were subjected to cannulation of the main mesenteric lymph duct and the next day oils were administered through a gastric feeding tube. Lymph was collected in 1-h fractions for the following 24 h. The time for maximum lymphatic transport of fatty acids was at 4 h with fast changes in fatty acid composition from the fatty acids of endogenous origin to those of the administered oils. Seven to eight hours after administration the transport was significantly lower than maximum, indicating the change from absorptive to postabsorptive phase. At 24 h after administration of either oil the transport of total fatty acids, palmitic acid (16∶0), and linoleic acid (18∶2n−6) together with oleic acid (18∶1n−9) after RO had not returned to the transport at baseline. In contrast, the transport of decanoic acid (10∶0) and α-linolenic acid (18∶3n−3) returned to baseline values between 12 and 15 h. This indicated that the absorption of purely exogenous fatty acids (illustrated by 10∶0 and 18∶3n−3) was complete at 15 h and that the fatty acids transported between 15 and 24 h were derived mostly from endogenous stores.

Gastric Emptying in Rats following Administration of a Range of Different Fats Measured as Acetaminophen Concentration in Plasma

Aim: To investigate the gastric emptying upon administration of ten different fats in order to determine whether major differences in fatty acid profiles resulted in differences in gastric emptying. Methods: Gastric emptying was measured as the appearance of acetaminophen in plasma which represents an indirect measure of gastric emptying. Emulsified fats with added acetaminophen were fed by gavage to rats, and the plasma concentration of acetaminophen was followed for 3 h by repeated blood sampling from the carotid artery. The fats administered included rapeseed, corn, and fish oils, lard, and cocoa butter as well as different structured lipids containing decanoic acid (10:0) and long-chain n-3 polyunsaturated fatty acids of marine origin. Overall, these fats had wide variations in fatty acid compositions and triacylglycerol structures. Results: No statistically significant differences were observed in gastric emptying between the groups fed the different fats, except for the emptying of tridecanoin (tri-10:0) that was statistically significantly slower than that of randomized oil, cocoa butter, and rapeseed oil (p < 0.05). The slower emptying of tri-10:0 could be caused by a lower caloric intake of this fat as compared with the other fats, because similar weights of fat were administered. Conclusion: The gastric emptying of fat was not influenced by fatty acid composition and triacylglycerol structure of the fats administered.

Absorption by rats of tocopherols present in edible vegetable oils.

The absorption of tocopherols (α, γ, and σ) and fatty acids from rapeseed (RO), soybean (SOO), and sunflower (SUO) oil, both from the natural oils and from the oils following moderate heating (180°C for 15 min), was measured in lymphcannulated rats. Oils were administered as emulsions through a gastrostomy tube, and lymph samples were collected for 24 h. The composition of tocopherols in oils and lymph fractions was measured by high-performance liquid chromatography, and fatty acids were measured by gas-liquid chromatography. The highest accumulated transport of α-tocopherol was observed after SUO administration, the lowest after SOO, with RO in between, corresponding to their relative contents (41.6±8.8, 32.7±5.0, and 24.9±4.3 μg at 24 h after administration of SUO, RO, and SOO, respectively). The calculated recoveries (in %) 24 h after oil administration were 21.4±4.5, 45.7±7.0, and 78.8±13.5 for SUO, RO, and SOO, respectively, suggesting that the absorption efficiency decreased when the α-tocopherol concentration increased. The recovery of α-tocopherol was higher than the recoveries of γ-and σ-tocopherol, indicating that the different tocopherols were not absorbed to the same extent or with similar rates. No differences between unheated and heated oils were observed in the absorption of tocopherols, whereas heating led to lower absorption of fatty acids, thus showing no direct association between absorption of tocopherols and fatty acids.

Size and number of lymph particles measured by a particle sizer during absorption of structured oils in rats.

Chylomicrons transport absorbed fat from the intestine to the circulation. During dietary fat absorption, the chylomicrons become larger in diameter, and in some studies an increase in chylomicron number has been observed as well. In the present study, we compared particle size and number in rat lymph following administration of four different oils. We administered fish oil, medium-chain TAG (MCT), and two structured oils differing in intramolecular structure, with either medium-chain FA in the outer positions of the TAG and long-chain n−3 PUFA in the sn-2 position (MLM oil) or with the reverse structure (LML oil), to lymph-cannulated rats and collected lymph in fractions for the following 8 h. Chylomicron size was measured by a particle size analyzer immediately after collection, and from these data the number of chylomicrons present was estimated. The number of particles in lymph increased during the absorption of oils containing long-chain PUFA (MLM, LML, and fish oil), whereas it was not affected by administration of MCT. The FA from MCT were probably absorbed via the portal vein; therefore, only a small number of particles were measured in lymph. When comparing the two structured oils, we observed a tendency toward a higher number of particles after LML administration, although the difference was not statistically significant. The highest number of particles after administration of all oils was observed in the size intervals 53–80 and 80–121 nm and probably represented small chylomicrons. Thus, the FA composition influenced the number of particles in lymph during absorption, whereas TAG structure had only a minor influence.

Absorption in rats of rapeseed, soybean, and sunflower oils before and following moderate heating

Rapeseed, soybean, and sunflower oil were heated for 15 min in a 5-mm oil layer in a pan at 180°C. The fatty acid composition was almost unaffected by heating, while the polymer content rose slightly and the tocopherol content decreased, except in soybean oil. The absorption of oils before and after heating was investigated in lymph-cannulated rats. Oils were administered as emulsions through a gastrostomy tube and lymph was collected during the next 24 h. The highest accumulated lymphatic transport of total fatty acids was observed after administration of rapeseed oil, and the lowest after heated sunflower oil. The accumulated transport was similar for all unheated oils. The transport of fatty acids was significantly lower in rats receiving heated oil compared to those receiving the corresponding unheated oil. Small increases in polymers may have contributed to the decreased lymphatic transport of oil following heating, although this probably does not fully explain the effect. The absorption of sunflower oil was more affected by heating than the absorption of soybean or rapeseed oil. Furthermore, the largest decrease in total activity of tocopherols following heating was observed in sunflower oil. Overall, these results demonstrate that the absorption of vegetable oils is affected by moderate heating.

Effect of orlistat on fat absorption in rats: A comparison of normal rats and rats with diverted bile and pancreatic juice

Orlistat is a specific inhibitor of pancreatic and gastric lipases leading to decreased absorption of fat. In the present study, we measured the effect of orlistat on lymphatic fat transport in rats following intake of oils very different in FA composition and TAG, structure, and compared this with the transport in normal rats and rats with fat malabsorption. Rats were subjected to cannulation of the main mesenteric lymph duct, and a feeding catheter was inserted into the stomach. In addition, malabsorbing rats were cannulated in the common bile and pancreatic duct. Emulsified safflower, fish, and randomized oils were administered, and lymph was collected for 24 h and analyzed for FA composition. Administration of 25 mg orlistat together with the dietary oils resulted in very small changes from baseline lymphatic transport, indicating that inhibition of the fat absorption was almost complete and furthermore that the source of fat had no influence on the inhibitory effect of orlistat. Orlistat did not interfere with the absorption of the hydrolysis products, since high absorption of sn-2 MAG and FFA (oleic acid) mixed with orlistat was observed. The baseline lymphatic transport in the orlistat group was higher than in the malabsorbing group, but this was the result of generally lower transport of endogenous FA in the malabsorbing group, presumably caused by the absence of bile FA. The transport of FA in normal rats was several-fold higher than the transport after orlistat addition and in malabsorbing rats. Thus, this study showed that orlistat inhibited fat hydrolysis, and thereby lymphatic absorption, almost completely independently of the fat administered.

Postprandial lipid responses of butter blend containing fish oil in a single-meal study in humans.

The postprandial effects of a butter product containing fish oil were investigated in a single-meal, randomized crossover study with a commercial butter product as the control. Twelve healthy males consumed two test meals with (13)C-labelled cholesterol (45 mg) and either an interesterified butter blend with fish oil (352 mg n-3 long-chain PUFA (LCPUFA)) or the commercial butter blend. Blood samples were collected after the meals and in the fasting condition on the test day and the following morning, and were analysed for cholesterol absorption, plasma lipid profile and fatty acid composition. No significant difference in the postprandial plasma fatty acid composition was observed between the groups, neither difference in cholesterol absorption, plasma cholesterol or the cholesterol contents of plasma lipoproteins. The incorporation of fish oil in the butter resulted in a significant lower concentration of triacylglycerols in the plasma 2 h after the meal in comparison with the commercial butter blend (p = 0.02); there was, however, no significant difference 24 h after the meal. In conclusion, fish oil-enriched butter blend provides a source to increase the intake of n-3 LCPUFA in the population, but has no acute effect on cholesterol absorption and plasma cholesterol concentration in human.

Lymphatic transport in rats of interesterified oils containing conjugated linoleic acids.

In this study we examined the lymphatic transport in rats of FA after administration of interesterified oils containing CLA, with emphasis on the location of CLA and octanoic acid in the TAG. The oils were produced by enzymatic interesterification. Eight oils with different structures or FA profiles were examined in this study: MCM, CMC, OCO, and COC, where M was expected to be octanoic acid and O oleic acid. In group 1, C was CLA as a mixture of the two CLA isomers c9, t11 or t10,c12, and in group 2, C was mainly the isomer t10,c12. Rats were subjected to cannulation of the mesenteric lymph duct, and the following day they were intragastrically administered one of the oils and lymph samples were collected for 24 h. The lymphatic transport of total FA from 0 to 8 h in group 1 was significantly (P<0.05) higher for the OCO-1 and the COC-1 oils than for the CMC-1 oil. Similarly, in group 2 the transport was higher for the OCO-2 oil than for the CMC-2 oil. The recovery of both of the CLA isomers examined was similar (50–70%) and independent of the isomer, oil structure, and FA profile, whereas more octanoic acid was recovered from the CMC oils than from the MCM oils. The results indicated that the FA profiles and the position of octanoic acid had only a minor influence on the absorption of CLA.

Time-related fatty acid profiles of plasma and lymph after gastric administration of fats to rats fed high-fat diets.

Abstract We examined in rats the intestinal absorption of 4 different dietary fats (rapeseed oil (RO), rapeseed oil interesterified with decanoic acid (RC10), olive oil (OO), and butter) after feeding a high-fat (30 wt-%) diet rich in trans -fatty acids (mainly trans -C18:1) for 3 weeks. The trans -fatty acids were used as markers for the contribution from the endogenous stores to the circulating pool of fatty acids during the absorption, thereby enabling us to measure differences in release of endogenous fatty acids caused by differences in the administered fats. Rats with cannulated left carotid artery were divided into 4 groups after a 24 h fast and fed intragastrically with a fat load. Blood samples were collected regularly and fatty acid compositions as well as insulin and glucagon concentrations were determined ( experiment 1 ). In 2 other groups of rats the mesenteric lymph duct was cannulated and they were fed intragastrically either RC10 or butter. Lymph was collected and analyzed for fatty acid composition ( experiment 2 ). The fatty acid composition of plasma lipids changed rapidly according to the administered fats and a biphasic response was observed for nearly all fatty acids investigated. Although decreasing during the early absorptive phase a continuous contribution of endogenous trans -C18:1 and arachidonic acid was observed in plasma. Small differences were observed between the 4 dietary fats. In lymph, the transport of trans -C18:1 rose markedly after butter administration partly caused by the content of this fatty acid in butter, while the transport of trans -C18:1 after RC10 was unchanged although still transported at a reasonable high rate. The transport of arachidonic acid increased after administration of both butter and RC10. Minor changes were observed in plasma concentrations of insulin and glucagon during the absorption.

The protease inhibitors ritonavir and saquinavir influence lipid metabolism: a pig model for the rapid evaluation of new drugs.

BACKGROUND Studies of the effects of antiretroviral drugs on lipid metabolism are limited by the availability of suitable models. We have thus developed an animal model utilising Göttingen mini-pigs. The normal lipid metabolism of mini-pigs closely reflects that of humans and they are expected to have similar reactions to antiretroviral drugs. METHODS The pigs were treated orally with high doses of the protease inhibitors ritonavir and saquinavir for 4 weeks. The model allows repeated concomitant biopsies from liver, muscle, adipose tissue and plasma samples. RESULTS The study showed a general decrease in polyunsaturated fatty acids; changes in both saturated and monounsaturated fatty acids were also apparent after antiretroviral treatment. The changes were observed after 4 weeks of treatment. At 4 weeks post-treatment, the levels of all fatty acids were lower compared with pretreatment levels, suggesting a prolonged effect of the antiretroviral drug treatment lasting beyond the 4 week post-treatment observation period. CONCLUSIONS The Göttingen mini-pig model is a promising animal model for rapid screening of the metabolic effects induced by antiretroviral drugs.