Influence of medium-chain triglycerides on lipid metabolism in the chick

The effect of corn oil, coconut oil, and medium-chain triglyceride (MCT, a glyceride mixture consisting almost exclusively of fatty acids of 8 and 10 carbons in length) ingestion on lipid metabolism was studied in chicks. In chicks fed cholesterol-free diets, MCT ingestion elevated plasma total lipids and cholesterol and depressed liver total lipids and cholesterol when compared to chicks receiving the corn oil diet. As a consequence of the opposite effects of MCT ingestion on plasma and liver cholesterol and total lipids, the plasma-liver cholesterol pool was not altered. When cholesterol was included in the diets, dietary MCT depressed liver and plasma total lipids and cholesterol as compared with corn oil, consequently also lowered the plasmaliver cholesterol pool. The in vitro cholesterol and fatty acid synthesis from acetate-1-¹⁴C was higher in liver slices from chicks fed MCT than in those from chicks fed corn oil. The percentage of radioactivity from acetate-1-¹⁴C incorporated into the carboxyl carbon of fatty acids by liver slices was not altered by MCT feeding, indicating that the increased acetate incorporation represented de novo fatty acid synthesis. The conversion of palmitate-1-¹⁴C to C₁₈ acids was increased in liver of chicks fed MCT, implying that fatty acid chain elongating activity was also increased. Studies on the conversion of stearate-2-¹⁴C to mono- and di-unsaturated C₁₈ acids showed that hepatic fatty acid desaturation activity was enhanced by MCT feeding. Data are presented on the plasma and liver fatty acid composition of chicks fed MCT-, corn oil-, or coconut oil-supplemented diets. The principles of laboratory animal care, as promulgated by the National Society for Medical Research, were observed.     

Nutritional evaluation of medium-chain triglycerides in the rat

Nutritional evaluation of a medium-chain triglyceride (MCT) preparation, containing about 75% octanoic acid and 25% decanoic acid, was carried out in short- and long-term experiments in rats. A casein diet containing 19.6% MCT and 2.5% safflower oil, the latter to supply essential fatty acids, was compared with similar diets containing conventional dietary fats. Data obtained in a 47-week study showed that the MCT diet supported normal growth and development. At autopsy, carcass protein and ash levels, vital organ weights and composition were similar to those in rats fed conventional fats. Histological study showed that intestinal and liver sections were normal after 47 weeks on the MCT-containing diet. In general, rats fed MCT had slightly lower growth rates and caloric efficiency values, less carcass fat and smaller epididymal fat pads than animals fed conventional dietary fats. Little C₈ and C₁₀ were found in depot fat. The MCT diet also supported normal reproducton, as indicated by litter size and number. During lactation the volume of milk secreted by the rats receiving the MCT diet was smaller and contained a lower level of fat than that secreted by the rats receiving an oleo oil diet, resulting in slower gains in weight in the MCT group. After weaning, growth of the rats fed MCT compared favorably with that attained by the animals on the diet containing oleo oil.     

Nutritional properties of medium-chain triglycerides

The biological effects of MCT (medium-chain triglycerides) differed from those of conventional fats, and certain of these suggested examination of the fatty acid composition and triglyceride structure of the adipose tissues and other organs of rats which were fed medium- or long-chain triglyceride mixtures with two levels of linoleic acid. Fatty acid compositions and TG patterns varied with the tissue, with the dietary fat, and with the level of linoleate in the diet. Increasing the latter resulted in the deposition of more linoleate at the expense of oleate and in the deposition of more of the dietary fatty acids. The percentage of completely saturated triglyc-erides (S₃), in adipose tissue with the higher linoleate supplement in the rats fed MCT, decreased in those fed LCT and was unchanged in the controls fed a fat-free diet. The increased deposition of the dietary fatty acids was more pronounced in the S₃ band. Supported by Grants U-1347 and U-1510 from the Health Research Council of the City of New York.     

Effect of continuous enteral medium-chain fatty acid infusion on lipid metabolism in rats

This study compared (i) the relative effects of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT), (ii) the influence of amount of MCT, and (iii) the impact of medium-chain fatty acid position, on plasma and lymphatic triglycerides and portal vein free fatty acids. The animals were fed approximately at 250 kcal/kg · day for 20h. The lymph from lymphatic duct and blood from portal vein and systemic circulation were collected. The results showed that feeding 100% MCT for 20h was sufficiently long to reduce significantly the level of linoleic acid in portal vein fatty acids and plasma and lymph triglycerides. However, this alteration induced by MCT feeding was partially prevented by adding LCT to the diet. The level of arachidonic acid was significantly reduced in plasma triglycerides by any of the diets containing medium-chain fatty acids compared to 100% LCT. When feeding MCT only, palmitoleic acid, presumably reflecting de novo lipogenesis, was increased in lymphatic triglycerides and portal vein fatty acids. Total saturated fatty acids as a total percentage of total fatty acids were also significantly increased in plasma and lymphatic triglycerides and portal vein fatty acids. Thus, when linoleic acid is limiting, the conversion of MCT into long-chain fatty acids by de novo lipogenesis is likely to be an important metabolic route. Providing LCT with MCT or 2-monodecanoin appears to limit this pathway.     

Effect of medium-chain triglycerides on calbindin-D9k expression in the intestine

These studies determined the effect of the saturated fat source in infant formula on the expression of calbindin-D9k (CaBP-9k). Piglets were fed from birth to 8 d with milk or formula containing saturated fatty acids as medium-chain triglycerides (MCT), coconut oil, palm oil (Palm 1), or synthesized triglycerides with 16∶0 directed to thesn-2 position (Palm 2). Levels of intestinal CaBP-9k mRNA were significantly (P<0.01) higher in piglets fed formula with MCT than in piglets fed the other formula or milk; and higher in piglets fed the Palm-1 than in piglets fed Palm-2 formula. This is the first evidence that MCT alter piglet intestinal CaBP-9k mRNA.     

Interactions between medium-chain and long-chain triacylglycerols in lipid and energy metabolism in growing chicks

The combined effects of dietary medium-chain triacylglycerols (MCT) and long-chain triacylglycerols (LCT) on lipid and energy utilization in chicks were investigated. Corn oil was used as the LCT source, and trioctanoin (8∶0) was used as the MCT source. The efficiency of dietary energy utilization (such as metabolizable energy values and fat and energy retention) decreased linearly as the level of MCT increased, but the efficiency of dietary protein utilization (protein retained per protein consumed) was not affected in a consistent manner. Fecal saturated and monounsaturated fatty acid composition was dependent on the dietary fatty acid composition, whereas fecal linoleic acid content was not. It is concluded that dietary MCT and LCT influence each other to some degree, with respect to protein and lipid metabolism in chicks. Moreover, in most cases, the nutritional characteristics of each triacylglycerol, including food efficiency and fat and energy retention, are independent of each other in growing chicks.     

Perfluorodecanoic acid and lipid metabolism in the rat

Alterations in lipid metabolism were axamined in adult male Sprague-Dawley rats seven days after a single intraperitoneal injection of perfluorodecanoic acid (PFDA; 20, 40 or 80 mg/kg). Because PFDA treatment caused a dose-related reduction in feed intake, the response of vehicle-treated rats pair-fed to those receiving PFDA was monitored to distinguish direct effects of the perfluorinated fatty acid from those secondary to hypophagia. Carcass content of lipid phosphorus and free cholesterol decreased in dose-dependent fashion in both PFDA-treated and pair-fed rats. Carcass triacylglycerols diminished in a similar manner, yet PFDA-treated rats at each dose had a higher concentration of neutral acylglycerols than their vehicle-treated, pair-fed counterparts. In vehicle-treated, pair-fed rats at the 80 mg/kg dose level, lipid phosphorus and free cholesterol as a proportion of carcass fat increased, whereas the share of the triacyl-glycerols declined. Because of the higher concentration of triacylglycerols in the carcass of rats treated with 80 mg/kg PFDA, enrichment of lipid phosphorus and free cholesterol in carcass fat was less than in their pair-fed partners. The amount of lipid phosphorus and free cholesterol per hepatocyte was similar in both PFDA-treated rats and their pair-fed partners. Liver triacyl-glycerols were markedly increased in PFDA-treated rats. A similar but less extensive augmentary effect of PFDA on hepatic esterified cholesterol was found. Concentration of triacylglycerols in plasma was not elevated in PFDA-treated rats, in spite of hepatic accumulation of esterified compounds. Also, the plasma level of free fatty acids and 3-hydroxybutyrate was similar in all treatment groups, including those receiving PFDA. Thus, the administration of PFDA appears to divert fatty acids from oxidation toward esterification in the liver.     

Interrelations of linoleic acid with medium-chain and long-chain saturated triglycerides

1. Effects of medium-chain (C₆–C₁₂) saturated triglycerides (MCT) and long-chain (C₁₄–C₁₈) saturated triglycerides (LCT) with and without linoleic acid (LA) supplementation were studied on rats fed purified diets
2. With 2% linoleic acid rats fed MCT and LCT grew somewhat better than those on a low-fat diet with the same supplement. Without linoleic acid those fed MCT grew better, and those fed LCT grew worse than those on the corresponding low-fat diet. MCT seemed to decrease, and LCT to increase linoleic acid requirements.
3. In survival studies 14 out of 18 rats fed 20% MCT were alive after 2 years; of their controls fed 20% lard, 10 out of 19 survived.
4. Reproduction studies in females gave equally poor results on unsupplemented low-fat, MCT, and LCT diets regarding implantation, birth weight, and survival rate. The weaning weights of the young on MCT were however the highest. With 2% LA weaning weights were equally high with LCT and MCT but lower with low-fat diet.
5. In animals fed low-fat diets not supplemented with LA, low serum cholesterol was associated with high liver cholesterol. With MCT, serum values were higher and liver values were significantly lower. With unsupplemented LCT, serum and liver values were high. When the three diets were supplemented with 2% LA, there were no longer any differences in the serum levels and in the liver levels. Whether ar not the presence of some oleate in the MCT and LCT influenced the cholesterol results is not certain.
6. The differences in the effects of MCT and LCT are discussed.

     

Influence of partially hydrogenated vegetable and marine oils on lipid metabolism in rat liver and heart

Partially hydrogenated marine oils containing 18∶1-, 20∶1- and 22∶1-isomers and partially hydrogenated peanut oil containing 18∶1-isomers were fed as 24–28 wt % of the diet with or without supplement of linoleic acid. Reference groups were fed peanut, soybean, or rapeseed oils with low or high erucic acid content. Dietary monoene isomers reduced the conversion of linoleic acid into arachidonic acid and the deposition of the latter in liver and heart phosphatidylcholine. This effect was more pronounced for the partially hydrogenated marine oils than for the partially hydrogenated peanut oil. The content oftrans fatty acids in liver phospholipids was similar in groups fed partially hydrogenated fats. The distribution of various phospholipids in heart and liver was unaffected by the dietary fat. The decrease in deposition of arachidonic acid in rats fed partially hydrogenated marine oils was shown in vitro to be a consequence of lower Δ6-desaturase activity rather than an increase in the peroxisomal β-oxidation of arachidonic acid. The lower amounts of arachidonic acid deposited may be a result of competition in the Δ6-desaturation not only from the C22-and C20-monoenoic fatty acids originally present in the partially hydrogenated marine oil, but also from C18- and C16-monoenes produced by peroxisomal β-oxidation of the long-chain fatty acids. Part of this work was presented at the ISF-AOCS Congress, New York City, 1980.     

Hepatic lipid metabolism in experimental diabetes: III. Synthesis and utilization of triglycerides

Livers removed from normal rats, from alloxan diabetic rats maintained on insulin for two weeks (ADI+), and from insulin-treated diabetic rats from which insulin had been withdrawn two days before use (AD) were perfused in vitro with 120 mg (468 μmoles) palmitic acid-1-C¹⁴. Under these conditions, output of TG (triglyceride) was depressed in livers from ADI+ rats and was negligible with livers from AD animals. The total incorporation of C¹⁴ into perfusate TG paralleled the chemical measurments of TG output. The concentration of hepatic TG increased during perfusion of livers from normal or ADI+ rats but decreased during perfusion of livers from AD animals. A load of 120 mg of palmitic acid/3 hr was inadequate to maintain net accumulation of TG in livers from AD rats; furthermore it is implicit in this observation that the total load of NEFA (nonesterified fatty acid) perfusing livers from AD rats must be increased considerably to obtain a fatty liver. The total incorporation of C¹⁴ into hepatic TG and the specific activity of hepatic TG were depressed during perfusion of livers from AD rats. The production of ketone bodies by livers from AD animals was about five times the normal rates; the output of ketone bodies did not differ from results of other experiments (1) in which the load of palmitic acid added to the medium was varied from 0–80 mg. These observations were discussed with reference to mechanisms for ketogenesis and fatty liver in alloxan diabetes.     

Application of thin-layer chromatography to the quantitative estimation of tissue triglycerides II. Influence of methyl parathion on the composition of liver triglycerides in the rat

Methyl parathion fed at 10 ppm in a high protein low fat diet inhibited 46.9% of the total liver carboxylesterase activity. The total fatty acid composition of liver triglycerides was not significantly altered. However, the methyl parathion-fed rats showed a higher percentage of saturated acids in the 2-position of the glyceride molecule. Triglyceride analysis employing the multiple TLC-GLC technique (5) also showed a slightly higher percentage of saturated glycerides and those containing 1 and 2 double bonds than those in the control group. Triglyceride patterns in both groups were in general agreement with those calculated from the fatty acid distribution as suggested by Vander Wal (11). Presented at the AOCS meeting in Houston, Texas, April, 1965.     

Fatty acid chain length combinations in ascitic fluid triglycerides containing lymphatic absorbed medium-chain fatty acids

Information on the fatty acid chain length combinations in lymph triglycerides containing medium-chain fatty acids was obtained combining the fatty acid composition and the carbon number composition of triglycerides from ascitic fluid of patients on medium-chain triglyceride-containing diets. In these triglycerides, the major part of the medium-chain fatty acids was present in combination with long-chain fatty acids. These results indicate that part of the lymphatic absorbed medium-chain fatty acids are absorbed as triglycerides which also contain long-chain fatty acids.     

Hydrolysis of triglycerides in the isolated perfused rat lung

The purpose of this study was to investigate the hydrolysis of saturated and unsaturated triglycerides by lung lipoprotein lipase and to measure the incorporation of triglyceride fatty acids into lung tissue lipids. Lipolytic activity was studied in the isolated ventilated rat lung, perfused for 100 min in a recycling system with Krebs Ringer bicarbonate containing bovine serum albumin, 5.6 mM glucose, and 1.5 or 10 mM triglyceride. Saturated triglycerides were hydrolyzed at significantly (p<0.05) lower rates than unsaturated triglycerides; tricaprylin, trimyristin and tripalmitin were hydrolyzed at 8.1+1.8, 5.4+1.5 and 9.5+1.8 μmol free fatty acids/g dry wt/100 min, respectively, whereas triolein and trilinolein were hydrolyzed at 20.2+1.8 and 20.6+0.3 μmol free fatty acids/g dry wt/100 min, respectively. The polyunsaturated triglycerides, trilinolein and triarachidonin were hydrolyzed at even higher rates (44.3+3.0 and 50.9+5.4 μmol free fatty acids/g dry wt/100 min, respectively). Intralipid infused at a concentration of 10 mM triglyceride was hydrolyzed at a significantly higher rate than at 1.5 mM triglyceride (58+6.3 μmol free fatty acids/g dry wt/100 min vs 16.6+1.7 μmol free fatty acids/g dry wt/100 min, respectively). Labeled unsaturated triglycerides were broken down at significantly higher rates than labeled saturated triglycerides. Incorporation of triglyceride-fatty acid into lung lipid was greater into neutral lipids than into phospholipids. The data suggest that (a) the factors that appear to affect lung lipoprotein lipase activity are composition and concentration of circulating triglyceride, (b) uptake of fatty acids into the tissue was proportional to the rate of hydrolysis of the emulsion, and (c) triglyceride-fatty acids could therefore be used by the lung for metabolic needs. The data presented in part at the Annual Meetings of the American Physiological Society, Atlanta, GA, April 1981, and the American Thoracic Society, Detroit, MI, May 1981, and published in abstract form-Fed. Proc. 40, 621 (1981), andAm. Rev. Respir. Dis. 123, 219 (1981).     

Effect of a diet rich in sunflower oil on aspects of lipid metabolism in the genetically-obese rat

Aspects of the lipid metabolism of male, obese and lean Zucker rats were compared using animals which had been fed ad libitum for 32 days on a diet (HS) which contained 200 g sunflowerseed oil/kg or one (LS) which contained 50 g/kg of the oil. When compared with the LS diet, the HS diet decreased the characteristic lipid accretion in the liver of obese rats from 126 mg (LS) to 81 mg (HS)/g wet weight; corresponding values for the lean rats were 39 mg and 56 mg/g wet weight of liver, respectively. The HS diet depressed lipid synthesis de novo by liver homogenates and decreased the Δ9-desaturase activity of liver microsomes from obese and clean rats by about 50%. Δ9-Desaturase activity in vitro was also depressed by the addition of linoleic acid to liver microsomes from both obese and lean rats fed ad libitum on a standard laboratory diet. Depressed Δ9-desaturase activity, due to ingestion of the HS diet, was reflected in lower ratios of 16∶1/16∶0 and 18∶1/18∶0 fatty acids in tissue lipids from obese and lean rats. Ingestion of the HS compared with the LS diet resulted in increased proportions of 18∶2ω6 in liver lipids and adipose tissue triacylglycerols of obese and lean rats. The HS diet also increased the proportions of 20∶4ω6 in adipose triacylglycerols of obese and lean rats and in liver lipids of obese animals but not in their lean littermates.     

Influence of sex and gonadal hormones on lipid metabolism in essential fatty acid-deficient rats

Previous work has shown differences between male and female rats in their ability a) to mobilize linoleic acid from adipose tissue when the supply is limited; b) to maintain higher levels of circulating and liver arachidonic acid when dietary linoleic acid is limited; c) to prevent accumulation of cholesteryl ester (CE) in the liver; and d) to increase the proportions of polyunsaturated fatty acids (PUFA) in their plasma lecithins. Recent studies are reviewed which show that a) essential fatty acid (EFA)-deficient rats exhibit the same kinds of sex differences as do rats on complete diets; b) these differences are mediated or at least influenced by estrogen; c) some of the differences may be attributed to differences in body size which result in less need for PUFA in structural phospholipid (PL); d) the rate of conversion of linoleic to arachidonic acid may differ under certain experimental conditions; and e) female rats have higher proportions of stearic and arachidonic acids in their liver lecithins than do males, which may relate to their higher rate of lecithin synthesis via methylation of phosphatidyl-ethanolamine. Presented at the symposium on essential fatty acids in honor of George O. Burr, AOCS Meeting, Loss Angeles, April 1968.     

Influence of hypo- and hyperthyroidism on rat liver glycerophospholipid metabolism

The effects of hyper- and hypothyroidism on enzyme activities involved in phospholipid metabolism in the rat liver were studied. Hyperthyroidism significantly decreases activities of both microsomal acyl-CoA:glycero-3-phosphate acyltransferase (GPAT) (34%, p<0.01) and microsomal acyl-CoA:1-acylglycero-3-phosphocholine acyltransferase (GPCAT) (28–33%, p<0.01). This may contribute to the decreased proportions of certain unsaturated fatty acids found in microsomal phosphoglycerides in hyperthyroidism. Mitochondrial GPAT, phospholipase A₂ and cytosol lysophospholipase are unaffected by hyperthyroidism. In contrast, hypothyroidism stimulates mitochondrial GPAT (38%, p<0.01) and microsomal GPCAT (14–19%) activities but decreases both mitochondrial phospholipase A₂ (36%, p<0.01) and cytosol lysophospholipase (56%, p<0.01) activities. The increased GPCAT activity may contribute to the increased proportions of certain unsaturated fatty acids found in microsomal phosphoglycerides in hypothyroidism. Triiodothyronine (T₃) treatment of the hypothyroid rat (25 μg/100 g body weight/day for four days) corrected phospholipase A₂ and lysophospholipase activities to the level of the control rat, but failed to correct the increased mitochondrial GPAT activity and not only corrected but lowered GPCAT activity to the level of the hyperthyroid rat.     

The structure of rat liver triglycerides

The fatty acid compositions at the 1-, 2-, and 3-positions³ of rat liver triglycerides were determined by using pancreatic lipase and diglyceride kinase. The distribution of acids between the 1- and 3-positions is not random; rather each position has a characteristic composition. The relative abundance of species and positional isomers in the triglyceride mixture was predicted by using values from the stereospecific analysis and assuming that the composition of each position is independent of the other two. The total triglyceride was resolved into species by using TLC with silver nitrate and Silica Gel G, and the relative amounts corresponded closely with those predicted on the basis of this assumption. The major species were isolated, and the distribution of their fatty acids among the three glyceride positions was determined. From these data the relative amount of each positional isomer was calculated. The results indicate that the esterification of fatty acids at each position proceeds with a specificity that is not correlated with the composition of the other positions with the molecule. The relative abundance of the different liver triglyceride species is also found to be related in part to the composition of the 1,2-diglyceride units found in the lecithins of this tissue. Presented at the AOCS Meeting, Philadelphia, October 1966.     

Differential effects of dietary linoleic and α-linolenic acid on lipid metabolism in rat tissues

Comparative effects of feeding dietary linoleic (safflower oil) and α-linolenic (linseed oil) acids on the cholesterol content and fatty acid composition of plasma, liver, heart and epididymal fat pads of rats were examined. Animals fed hydrogenated beef tallow were used as isocaloric controls. Plasma cholesterol concentration was lower and the cholesterol level in liver increased in animals fed the safflower oil diet. Feeding the linseed oil diet was more effective in lowering plasma cholesterol content and did not result in cholesterol accumulation in the liver. The cholesterol concentration in heart and the epididymal fat pad was not affected by the type of dietary fatty acid fed. Arachidonic acid content of plasma lipids was significantly elevated in animals fed the safflower oil diet and remained unchanged by feeding the linseed oil diet, when compared with the isocaloric control animals fed hydrogenated beef tallow. Arachidonic acid content of liver and heart lipids was lower in animals fed diets containing safflower oil or linseed oil. Replacement of 50% of the safflower oil in the diet with linseed oil increased α-linolenic, docosapentaenoic and docosahexaenoic acids in plasma, liver, heart and epididymal fat pad lipids. These results suggest that dietary 18∶2ω6 shifts cholesterol from plasma to liver pools followed by redistribution of 20∶4ω6 from tissue to plasma pools. This redistribution pattern was not apparent when 18∶3ω3 was included in the diet.     

Effect of Lactobacillus plantarum P‐8 on lipid metabolism in hyperlipidemic rat model

Probiotics have been reported to play an important role in the prevention of metabolic disorders. We recently identified a novel probiotic strain Lactobacillus plantarum (L. plantarum) P‐8. The objective of this study was to determine the effects of L. plantarum P‐8 on lipid metabolism of rats fed with high fat diet. All experimental rats were divided into three groups: control group, model group, and L. plantarum P‐8 group. Changes in serum lipid levels, hepatic lipid deposition, serum oxidative stress‐related parameters, activities of liver function marker enzymes, organ indices, gut microflora, and fecal lipids were assessed. Compared with model group, L. plantarum P‐8 exhibited hypolipidemic effects by lowering serum total cholesterol (TC), triglyceride (TG), and low‐density lipoprotein cholesterol levels, accompanied with elevation of high‐density lipoprotein cholesterol level. L. plantarum P‐8 also exerted beneficial effects against high‐fat diet‐induced oxidative stress, curtailed the accumulation of liver lipids and protected healthy liver function. Moreover, L. plantarum P‐8 was able to regulate intestinal bacteria and enhance the fecal excretion of TC, TG, and bile acid. These findings indicate that L. plantarum P‐8 may represent a potential therapeutic agent for controlling hyperlipidemia.     

Improved lipase-catalyzed incorporation of long-chain fatty acids into medium-chain triglycerides assisted by supercritical carbon dioxide extraction

Displacement of the equilibrium of the lipase-catalyzed interesterification between medium-chain triglyceride (MCT) and long-chain polyunsaturated fatty acid was accomplished by the removal of by-products with continuous supercritical carbon dioxide (SC−CO₂) extraction at 60°C and 100 kg/cm². The incorporation of eicosapentaenoic acid to MCT was appreciably improved by this method and was 1.3 times higher than that of the equilibrium state (47 wt%) that was obtained in a closed system. The immobilizedMucor miehei lipase was stable for more than 180 h in SC−CO₂ at 60°C and 100 kg/cm². Presented at ISF-JOCS World Congress, Tokyo, Japan, September 26–30, 1988.