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.

     

Lipid Emulsions Differentially Affect LPS-Induced Acute Monocytes Inflammation: In Vitro Effects on Membrane Remodeling and Cell Viability

The aim of this study was to assess how lipid emulsions for parenteral nutrition affect lipopolysaccharide (LPS)‐induced acute monocyte inflammation in vitro. An 18 h long LPS induced human monocyte leukemia cell stimulation was performed and the cell‐growth medium was supplemented with three different industrial lipid emulsions: Intralipid^®, containing long‐chain triglycerides (LCT—soybean oil); Medialipid^®, containing LCT (soybean oil) and medium‐chain triglycerides (MCT—coconut oil); and SMOFlipid^®, containing LCT, MCT, omega‐9 and ‐3 (soybean, coconut, olive and fish oils). Cell viability and apoptosis were assessed by Trypan blue exclusion and flow cytometry respectively. Monocyte composition and membrane remodeling were studied using gas chromatography and NR12S staining. Microparticles released in supernatant were measured by prothrombinase assay. After LPS challenge, both cellular necrosis and apoptosis were increased (threefold and twofold respectively) and microparticle release was enhanced (sevenfold) after supplementation with Medialipid^® compared to Intralipid^®, SMOFlipid^® and monocytes in the standard medium. The monocytes differentially incorporated fatty acids after lipid emulsion challenge. Finally, lipid‐treated cells displayed microparticles characterized by disrupted membrane lipid order, reflecting lipid remodeling of the parental cell plasma membrane. Our data suggest that lipid emulsions differentially alter cell viability, monocyte composition and thereby microparticle release. While MCT have deleterious effects, we have shown that parenteral nutrition emulsion containing LCT or LCT and MCT associated to n‐3 and n‐9 fatty acids have no effect on endotoxin‐induced cell death and inflammation.     

Incubation of lipid emulsions with plasma lipoproteins modifies the fluidity of each particle

Lipid emulsions (LE) contain triglyceride (TG)-rich particles (TGRP) and phospholipid-rich particles (PLRP). Various lipid and protein exchanges take place during in vitro incubations of LE with lipoproteins. These composition changes affect physical properties of particles. The aim of this study was to determine the role of different LE particles and the effect of TG composition on physical modifications. Low density lipoproteins (LDL: 1.025<d<1.040 g/mL) or high density lipoproteins (HDL: 1.085<d<1.150 g/mL) were incubated with the following four LE or their TGRP or PLRP, which were manufactured with the same phospholipid emulsifier: long-chain triglycerides (LCT): 100% soybean oil; medium-chain triglycerides (MCT)/LCT (MCT/LCT, 5∶5, w/w); FO (100% fish oil); and MLF541 (MCT/LCT/FO, 5∶4∶1, by wt). After incubation, modified LE particles and lipoproteins were analyzed by fluorescence polarization. Observed physical modifications were significant in emulsion particles (ordering effect) but not in lipoporteins and also were significant for TG composition effect. Since intact emulsion contained a large excess of TGRP over PLRP, it is not surprising that intact emulsion had the same behavior as TGRP alone, and that PLRP had the same physical characteristics as lipoproteins. TG loss and cholesterol and protein acquisitions by emulsion particles rigidify their envelope. The two emulsions containing FO were less ordered after incubation. In conclusion, incubation of LE with lipoproteins changes physical properties of each kind of particle, and TG composition of the emulsion affects emulsion particle changes but has no effect on LDL and HDL. These order modifications induce more effective exchanges between LE particles and lipoproteins and modify their metabolism; HDL changes may increase the reverse cholesterol transport.     

Cholestyramine alters the lipid and energy metabolism of chicks fed dietary medium-or long-chain triacylglycerol

The effects of cholestyramine, a bile acid binding polymer, on the lipid and energy metabolism of chicks given dietary medium-chain triacylglycerol (MCT) or long-chain triacylglycerol (LCT) were investigated. Chicks (from 8 to 17 days of age) were fed diets containing MCT or LCT at 200 g oil/kg diet with or without 2% cholestyramine under equalized feeding conditions. An adjusted LCT diet was formulated in order to supply another group with daily nutrients and dietary metabolizable energy (ME) equal to MCT groups, except for corn starch. ME intakes of chicks given MCT or LCT diets were reduced by cholestyramine; consequently, fat and energy retention was reduced, though the reduction was more drastic in chicks fed LCT. This was caused by a change in amounts of the fecal excretion of fat and bile acids. Cholestyramine enhanced the excretion of octanoic acid (8∶0) in the feces, which suggests that bile acids are needed for 8∶0 absorption. Cholestyramine affects the utilization of dietary MCT and LCT by lowering fat and energy retention in chicks. However, the effect of cholestyramine on MCT utilization was smaller than its effect on utilization of LCT.     

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.     

Olive Oil-Based Lipid Emulsions Do Not Influence Platelet Receptor Expression in Comparison to Medium and Long Chain Triglycerides In vitro

Lipid emulsions influence platelet aggregation and receptor expression. However, the effect on platelet function is not fully explained. Therefore, the aim of this study was to examine the influence of the lipids Lipofundin^®, Lipidem^® and ClinOleic^® on surface expressions of P‐selectin, GPIb and GPIIb/IIIa on platelets in vitro. Whole blood was incubated in two different concentrations (0.06 and 0.6 mg/ml) of LCT/MCT, n‐3/LCT/MCT and LCT‐MUFA for 30 min, followed by activation with TRAP‐6 or ADP for flow‐cytometric assay. Rates of P‐selectin, GPIb and GPIIb/IIIa expression were analyzed. There was a significant increase in GPIIb/IIIa‐ and P‐selectin‐expression after incubation with LCT/MCT and n‐3/LCT/MCT at the concentration of 0.6 mg/ml, without and after stimulation with TRAP‐6 and ADP. GPIb was significantly decreased. Accordingly, LCT‐MUFA had no effect on receptor expression of platelets in vitro. We demonstrated that LCT‐MUFA did not activate receptor expression of platelets whereas LCT/MCT significantly increased platelet aggregation in vitro. This finding should be noted for parenteral nutrition of intensive care patients and, in the future, might provide further insight into the pathogenic pathways of acute thromboembolic events. However, prospectively designed clinical studies are needed to support our results.     

A comparison of the effect of medium- vs. long-chain triglycerides on the <Emphasis Type="Italic">in vitro</Emphasis> solubilization of cholesterol and/or phytosterol into mixed micelles

Despite clinical evidence of the cholesterol-lowering effects of phytosterols, the exact mechanisms involved are still unclear. Displacement of cholesterol by phytosterols from mixed micelles, which is due to their greater hydrophobicity, is one of the hypotheses for the lumenal effects contributing to the reduction of intestinal cholesterol absorption. In this study a dynamic in vitro lipolysis method was used to examine the solubilization behavior of cholesterol and/or phytosterols during lipolysis to probe the efficacy of cholesterol displacement from mixed micelles by phytosterols. The effects of lipid chain length on sterol solubilization were studied by using microcrystalline suspensions containing 17% phytosterol or cholesterol, formulated in long-chain TG (LCT) and medium-chain TG (MCT). When digesting cholesterol suspended in LCT, the entire cholesterol dose was incorporated into the micellar phase. For the cholesterol formulation suspended in MCT, 50.3% of the initial dose was recovered in the micelles. Under the respective conditions, we observed lower solubilization of phytosterols than of cholesterol (roughly fourfold). Only 25% of the initial phytosterol dose was solubilized from suspensions formulated with LCT, and 13% was solubilized from MCT formulations. Co-administration of phytosterol and cholesterol suspensions showed a significant reduction of cholesterol solubilization, particularly when dosed in MCT, with ≈25% of the cholesterol dose solubilized. Insignificant amounts of cholesterol were displaced by phytosterols when cholesterol was presolubilized in the mixed micelles. The results show that, compared with LCT, mixed micelles containing MCT lipolysis products have a reduced solubilizing capacity for cholesterol, which adds to the effectiveness of the phytosterols in displacing cholesterol. This suggests potential benefits of using medium chain length lipids in cholesterol-lowering phytosterol products.     

Lipid Emulsions Containing Medium Chain Triacylglycerols Blunt Bradykinin-Induced Endothelium-Dependent Relaxation in Porcine Coronary Artery Rings

Lipid emulsions for parenteral nutrition are used to provide calories and essential fatty acids for patients. They have been associated with hypertriglyceridemia, hypercholesterolemia, and metabolic stress, which may promote the development of endothelial dysfunction in patients. The aim of the present study was to determine whether five different industrial lipid emulsions may affect the endothelial function of coronary arteries. Porcine coronary artery rings were incubated with lipid emulsions 0.5, 1, or 2% (v/v) for 30 min before the determination of vascular reactivity in organ chambers and the level of oxidative stress using electron paramagnetic resonance. Incubation of coronary artery rings with either Lipidem^®, Medialipid^® containing long- and medium-chain triacylglycerols (LCT/MCT), or SMOFlipid^® containing LCT, MCT, omega-9, and -3, significantly reduced the bradykinin-induced endothelium-dependent relaxation, affecting both the nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) components, whereas, Intralipid^® containing LCT (soybean oil) and ClinOleic^® containing LCT (soybean and olive oil) did not have such an effect. The endothelial dysfunction induced by Lipidem^® was significantly improved by indomethacin, a cyclooxygenase (COX) inhibitor, inhibitors of oxidative stress (N-acetylcysteine, superoxide dismutase, catalase) and transition metal chelating agents (neocuproine, tetrathiomolybdate, deferoxamine and l-histidine). Lipidem^® significantly increased the arterial level of oxidative stress. The present findings indicate that lipid emulsions containing LCT/MCT induce endothelial dysfunction in coronary artery rings by blunting both NO- and EDH-mediated relaxations. The Lipidem^®-induced endothelial dysfunction is associated with increased vascular oxidative stress and the formation of COX-derived vasoconstrictor prostanoids.     

Effect of SMP-500, a novel ACAT inhibitor,on hepatic cholesterol disposition in rats

The effects of SMP-500, a novel ACAT inhibitor, on serum lipid levels, hepatic lipid secretion rate, and hepatic lipid disposition in rats were studied to clarify its lipid-lowering action. SMP-500 reduced the serum cholesterol level in a dose-dependent manner in rats fed a hypercholesterolemic diet. SMP-500 also reduced hepatic free cholesterol content in addition to hepatic total and esterified cholesterol contents. Biliary concentrations of cholesterol and bile acid were increased by SMP-500; however, the bile flow and lithogenic index were not affected. SMP-500 increased cholesterol 7α-hydroxylase mRNA level. Therefore, it is suggested that the increase in concentrations of cholesterol and bile acid in bile is due to both the increase of bile acid production through the increase of cholesterol 7α-hydroxylase and the decrease of hepatic free cholesterol content. An inhibitory effect of SMP-500 both on the cholesterol secretion and on the TG secretion from liver was observed. SMP-500 reduced the serum TG level in sucrose-fed rats. From these results, one may hypothesize that the suppression of hepatic VLDL secretion probably plays an important role on both cholesterol- and TG-lowering effects of SMP-500.     

The effect of medium and long chain triglyceride on human adipose tissue metabolism

Studies have been performed to assess the effects, in vivo and in vitro, of lipid emulsions on human adipose tissue prostaglandin production. Subcutaneous adipose tissue obtained either during elective surgery or by needle aspiration was studied in tissue culture or by using a perifusion apparatus. Physical mixtures of emulsions of long chain triglyceride (LCT) and/or medium chain triglyceride (MCT) were added to the tissue culture medium so that the final concentration was 400 mg/dl. After a 3-day incubation period the tissue was harvested, placed in buffer and used to determine in vitro production of prostaglandin E₂, prostacyclin I₂ (measured as its stable end product 6-keto PGF_1α) and thromboxane A₂ (measured as TXB₂) by radioimmunoassay. The results demonstrated that samples incubated in 100% MCT had the most significant increase in prostaglandin production, while those incubated in 100% LCT had the most significant decrease in activity of the three prostaglandins assayed. The addition of LCT to MCT caused a stepwise decrease in adipose tissue prostaglandin production. The data suggest a pharmacological rather than a physiological effect of lipid emulsions containing MCT and/or LCT on adipose tissue prostaglandin production. In vivo effects of a 20% safflower oil emulsion, containing high levels of the essential fatty acid linoleate, were assessed in five pediatric patients. Adipose tissue was obtained before and after two and four weeks of treatment. Fatty acid profiles and prostaglandin production were determined. The results demonstrated that intravenous fat infusion increased the concentrations of linoleic and arachidonic acids found in adipose tissue within a short interval. The effect of intravenous fat infusion on human adipose tissue prostaglandin production was less predictable and may have been a function of the patients' disease and subsequent clinical course. These findings suggest that lipid emulsions should not be viewed solely as a source of intravenous energy, because they may have the potential to elicit changes in prostaglandin production as demonstrated by a human adipose tissue model. Presented in part at the symposium on “Specialty Lipids and Their Biofunctionality,” at the annual meeting of the American Oil Chemists' Society, Philadelphia, May 1985.     

Serum fatty acid profiles after intravenous medium chain triglyceride administration

The serum fatty acid profiles of patients receiving either intravenous medium or long chain triglycerides were studied. Seventeen hospitalized patients, dependent on total parenteral nutrition, were randomly enrolled into a prospective study. The total parenteral nutrition (TPN) delivered amino acids and glucose and either a 75% medium chain triglyceride and 25% long chain triglyceride (MCT group) physical mixture or all long chain triglyceride (LCT group), as the respective fat sources. The amino acids and glucose were given continously, and the lipid was given for 10 hours each day over five days. Fatty acid profiles on serum triglycerides and free fatty acids were done in the morning before any lipid was given and also later in the afternoon, near the end of the lipid administration, on days 1, 3 and 5. Medium chain fatty acids rose quickly in the triglyceride fraction in patients given MCT. Rapid MCT hydrolysis occurred as evidenced by the appearance of medium chain fatty acids in the free fatty acid fraction in the afternoon sampling. Clearance of the hydrolyzed medium chain free fatty acids (MCFFA) occurred so that little, if any, were present in the morning sampling one day later. Long chain fatty acids, as either triglycerides or free fatty acids, showed expected increases during the daily infusion, but not of such relative magnitude as the medium chain fatty acids. Medium chain fatty acid incorporation into the phospholipid or cholesterol ester fractions by the end of the five-day feeding period was present but minimal. As opposed to conventional long chain triglycerides, intravenously administered medium chain triglycerides are hydrolyzed and cleared rapidly and do not accumulate in other lipid fractions, and are therefore a more readily available lipid fuel.     

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.     

Efficacy of a long-term home parenteral nutrition regimen containing fish oil-derived n-3 polyunsaturated fatty acids: a single-centre,randomized, double blind study

Background

Data on the use of lipid emulsions containing fish-oil (FO) derived n-3 polyunsaturated fatty acids (n-3 PUFAs) in addition to medium- and long-chain triglycerides (MCT/LCT) for long-term home parenteral nutrition (HPN) are limited. This study aimed to compare HPN regimens containing either MCT/LCT/FO-derived n-3 PUFAs (test group) or MCT/LCT (control group) with respect to efficacy and safety during 8?weeks of HPN using a non-inferiority trial design with change of body mass index (BMI) as primary endpoint.

Methods

This prospective, randomized, double-blind study was conducted at the Charité, Berlin, Germany, from 02/2008 until 01/2014. Adult patients (n?=?42; aged 18 to 80?years) requiring HPN for at least 8?weeks were randomly assigned to the test or control group. Assessments included weight, height, physical examination (cardiovascular system, abdomen, respiratory tract, liver, spleen, kidney, urine tract, skin, mucous membrane, neurology, psyche, musculoskeletal system, lymph nodes), bio impedance analysis, calorimetry, blood samplings (haematology, biochemistry, fatty acid analysis) and quality of life questionnaire.

Results

BMI increased in both groups with 8?weeks of HPN (ΔBMI_{(test group)}?=?1.3?±?1.1?kg/m²; ΔBMI_{(control group)}?=?0.6?±?0.9?kg/m²) demonstrating non-inferiority of the test regimen regarding nutritional efficacy. Assessment of secondary efficacy endpoints revealed that after 8?weeks of HPN with the test regimen, the proportion of n-3 PUFAs in serum, platelet and red blood cell phospholipids significantly increased, while the proportion of n-6 PUFAs decreased. The fatty acid pattern in the control group remained mostly stable. No statistically significant differences were detected between groups regarding inflammatory markers or quality of life. Laboratory parameters reflecting the safety endpoints liver function, bone metabolism, renal function, metabolic activity, lipid metabolism, coagulation and haematology were stable in both groups and no group differences were detected regarding (serious) adverse events.

Conclusions

The HPN regimen prepared with MCT/LCT/FO-derived n-3 PUFAs was at least as efficient in maintaining or even improving nutritional status during HPN as the control MCT/LCT regimen. Administration of FO-derived n-3 PUFAs for 8?weeks altered the fatty acid pattern of serum, platelet and red blood cell phospholipids. Both regimens were safe and well tolerated.

Trial registration

www.clinicaltrials.gov, registration number: NCT00530738.

     

Detergent induced changes in serum lipid composition in rats

The influence ofin vivo administration of detergents on serum lipid composition was studied in rats. Male Wistar rats received 50 mg Emulgen 913 (polyoxyethylene nonylphenylether, a nonionic detergent) or SDS (sodium dodecylsulfate, an anionic detergent) per kg of body weight intraperitoneally for 3 consecutive days. Emulgen 913 and SDS administration increased the level of cholesterol esters and phospholipids, respectively. But Emulgen 913 administration reduced the level of triglycerides in the Serum, and SDS administration reduced also the levels of triglycerides and cholesterol esters. In spite of the changes in serum lipid composition, the administration of these detergents did not affect the amount of total lipids in rat serum. The proportion of palmitic, oleic, and docosahexaenoic acids in phospholipids was decreased by the administration of Emulgen 913 while the level of arachidonic acid was raised. However, the level SDS administration had no effect on the fatty acid composition of the serum phospholipids. On the other hand, both Emulgen 913 and SDS administration showed an effect on the fatty acid composition of triglycerides. It is postulated that liver damage due to administration of detergents is responsible for the changes in serum lipid and fatty acid composition in detergent-treated rats.     

Lymphatic transport of a physical mixture of medium-and long-chain TAG in rats

Lymphatic transport of a mixture of medium-chain TAG (MCT) and long-chain TAG (LCT) was studied in lymph-cannulated rats. Animals were administered a test emulsion containing either triolein, tricaprylin, or a 1∶1 mixture of triolein and tricaprylin, and the lymph was collected for 24 h. The lymphatic recovery rate of medium-chain FA (MCFA) was significantly higher in rats given the TAG mixture than in those given MCT alone. The lymphatic recovery rate of long-chain FA (LCFA) also was significantly higher in rats given the TAG mixture than in those given LCT alone. No TAG containing three MCFA (i.e., MCT) was detected, and 37.7% of TAG containing one or two MCFA was detected in the lymph TAG when rats were given the TAG mixture. These results indicate that lymphatic transport of MCFA and LCFA can be modified by the combination of MCT and LCT.     

Nonessential fatty acids in formula fat blends influence essential fatty acid metabolism and composition in plasma and organ lipid classes in piglets

The n-6 and n-3 fatty acid status of developing organs is the cumulative result of the diet lipid composition and many complex events of lipid metabolism. Little information is available, however, on the potential effects of the saturated fatty acid chain length (8:0–16:0) or oleic acid (18:1) content of the diet on the subsequent metabolism of the essential fatty acids 18:2n-6 and 18:3n-3 and their elongated/desaturated products. The effects of feeding piglets formulas with fat blends containing either coconut oil (12:0±14:0) or medium chain triglycerides (MCT, 8:0±10:0) but similar levels of 18:1, 18:2n-6 and 18:3n-3, or MCT with high or low 18:1 but constant 18:2n-6 and 18:3n-3 on the fatty acid composition of plasma, liver and kidney triglycerides, phospholipids and cholesteryl esters, and of brain total lipid, were studied. Diet-induced changes in the fatty acid composition of lipid classes were generally similar for plasma, liver and kidney. Dietary 18:1 content was reflected in tissue lipids and was inversely associated with levels of 18:2n-6. Lower percentage of 18:2n-6, however, was not associated with lower levels of its elongated/desaturated product 20:4n-6 but was associated with higher levels of 22:6n-3. Feeding coconut oilvs. MCT resulted in lower 18:1 levels in all lipids, and higher percentages of 20:4n-6 in tissue phospholipid. Increasing the dietary n-6/n-3 ratio from 5 to 8 significantly increased tissue percentage of 18:2n-6 and decreased phospholipid 22:6n-3. In contrast to plasma, liver and kidney, brain lipid fatty acid composition was not influenced by the formula saturated fatty acid chain length, content of 18:1, or n-6/n-3 ratio. In summary, the studies show that the dietary requirement for n-6 and n-3 fatty acids may be influenced by the nonessential saturated and monounsaturated fatty acids fed concurrently.     

Mechanism of suckling-rat hypercholesteremia. II. Cholesterol biosynthesis and cholic acid turnover studies

Cholesterol biosynthesis from acetate-2-¹⁴C by the livers of suckling rats, which is known to be relatively slow, was increased 2–3-fold within 24 hours after severing the bile duct. Cholesterol synthesis by sham-operated litter mates showed no change under similar treatment. Mevalonate biosynthesis from acetate-2-¹⁴C in vitro by recombined liver microsomal supernatant (105,000×g) fractions from suckling rats also was only 10% of that of comparable recombined fractions from normal controls (young adult rats which were consuming colony diet). Activity was not improved by combining either the microsomal or supernatant fraction from suckling rat livers with the complementary fraction from normal adult livers. On the other hand, activity was restored to 100% when microsomes from livers of duct-served suckling rats were combined with the supernatant fraction from normal controls. Likewise, recombined liver fractions prepared from adult rats fed synthetic diets exhibited low activity for mevalonate biosynthesis. Activity was restored by bile duct cannulation, but inhibited when cholic acid was infused into the cannulated animal. Therefore, surgical procedures which interrupt the enterohepatic recirculation of bile components lead to a restoration of cholesterol biosynthesis and, at least in the adult animal where cannulation studies are practicable, this effect can be reversed readily by bile acid infusion. A slow rate of fecal excretion of¹⁴C-cholic acid was observed in suckling rats and rats fed synthetic diets, apparently reflecting an efficient enterohepatic recirculation of bile salts. The data suggest that under these dietary conditions bile salt retention either directly or indirectly influences hepatic synthesis of cholesterol. Presented in part before Federation of American Societies for Experimental Biology, Fed. Proc.24, 1078, 1965 (abstract). and in part at the AOCS Meeting, Los Angeles, April 1966. Journal Paper No.2835, Purdue University Agricultural Experiment Station.     

Medium chain triglyceride in early life: Effects on growth of adipose tissue

Effects of feeding early in life a diet high in either long chain (LCT) or medium chain triglyceride (MCT) were studied on the development of adipose tissue in post-weanling rats. The diets were similar in calorie distribution and identical in nutrients except for type of fat. The caloric distribution of the two diets by percent was LCT (corn oil)/protein/carbohydrate, 70/18/12 and MCT/corn oil/protein/carbohydrate, 66/4/18/12. Male littermates with less than 5% weight difference were pair-fed the two diets randomly at age 18–20 days. One-fourth of the rats were killed at 10, 16, 22 and 28 weeks of age and analyzed for adipose depots and adipose tissue cellularity. Results showed that the LCT-fed rats were significantly heavier, with larger epididymal, retroperitoneal, omental and subcutaneous fat pads than the respective pair-fed MCT rats. Also, LCT-fed rats had larger size and number of adipocytes than MCT-fed littermates. It is concluded that the type of fat in the diet, namely LCT or MCT, when fed early in life can influence the development of adipose tissue. MCT appears less lipogenic than LCT. The mechanism for the diminished adiposity of MCT-fed rats is related to extensive oxidation of MCT and its enhancement of thermogenesis leading to lessened energy efficiency. Presented at the symposium on “Specialty Lipids and Their Biofunctionality” at the annual meeting of the American Oil Chemists' Society, Philadelphia, May 1985.     

Effects of triton WR 1339 and orotic acid on lipid metabolism in rats

In order to investigate the effect of hepatic cholesterol flux on biliary bile acids, Triton WR 1339 and orotic acid were administered to rats, and the biliary cholesterol, phospholipids and bile acids were analyzed together with serum lipoproteins and hepatic lipids. Triton, which raised serum very low density lipoprotein and lipid levels and decreased serum high density lipoprotein liver lipid levels, increase the biliary cholic acid group/chenodeoxycholic acid group ratio (CA/CDCA) in the bile without affecting the total amount of bile acids and the other biliary lipids. Orotic acid, which decreased serum lipid and lipoprotein concentrations and increased liver lipid levels, increased the biliary excretion of cholesterol and phospholipids, but produced no significant change in the total amount of bile acids and in the CA/CDCA ratio in bile.