Comparison of adjuvant mechanisms of medium-chain triacylglycerol in a mouse FITC-induced contact hypersensitivity model.

The number of allergy sufferers has been increasing with the increase in chemicals to which we are potentially exposed. We have discovered that tributyrin, a short-chain triacylglycerol (TAG), enhanced fluorescein isothiocyanate (FITC)-induced contact hypersensitivity in a mouse model. Medium-chain triacylglycerols (MCTs) are used in cosmetics, with which we come into direct contact frequently, to maintain skin conditions and as a thickening agent for cosmetics. In this study, we examined whether MCTs with different side chain lengths enhanced skin sensitization to FITC in the mouse model. During skin sensitization to FITC, the presence of tributyrin (side chain carbon number, 4; C4) as well as that of each MCT, tricaproin (C6), tricaprylin (C8), or tricaprin (C10), resulted in enhanced skin sensitization, whereas that of trilaurin (C12) did not. As to the mechanism underlying the enhanced sensitization, three MCTs (C6, C8 and C10) facilitated migration of FTIC-presenting CD11c+ dendritic cells to draining lymph nodes. These results indicated that not only tributyrin but also MCTs, up to side chain carbon number 10, have an adjuvant effect on FITC-induced skin hypersensitivity in mice.

Green Formulation of Triglyceride/Phospholipid-Based Nanocarriers as a Novel Vehicle for Oral Coenzyme Q10 Delivery.

This study was aimed to develop a novel nanocarrier for coenzyme Q10 (CoQ10) by a green process that prevented the use of surfactants and organic solvents. Triglyceride/phospholipid-based nanocarriers were developed through high-pressure homogenization (an industrial feasible process), and a 25-1 fractional factorial design was adopted to assess the influences of formulation variables on the considered responses, including vesicle size, entrapment efficiency, loading capacity, and solubility of the vehicles in simulated gastrointestinal fluids. The optimized formulation was further in-depth characterized in terms of morphology, release behavior, biocompatibility (Caco-2 cell cytotoxicity and histological examination), thermal behavior, and Fourier transform infrared analysis. Optimal nanocarriers were found to have mean particle size of 75 nm, narrow particle distribution, and CoQ10 entrapment of 95%. The optimized formulation was stable upon incubation in simulated gastrointestinal fluids without considerable leakage of cargo, which was in agreement with their sustained release behavior. Microscopic observations also confirmed nanosized nature of the vesicles and revealed their spherical shape. Moreover, toxicity evaluations at the cellular and tissue levels revealed their nontoxic nature. In conclusion, triglyceride/phospholipid-based nanocarriers proved to be a green safe vehicle for delivery of CoQ10 with industrial-scale production capability and could provide a new horizon for delivery of hydrophobic nutraceuticals. PRACTICAL APPLICATION: Green nanostructure formulation approaches have recently gained tremendous attraction for their safe profile especially when it comes to supplements, which are generally recommended for daily use. However, their sufficient association with cargoes and industrial-scale production have remained considerable challenges. This study focuses on the development of lipid-based nanocarriers for CoQ10 by an industrial feasible process that prevents the use of any surfactants or organic solvents.

Toxicological aspects of interesterified fat: Brain damages in rats.

In recent years, interesterified fat (IF) has been used to replace hydrogenated vegetable fat (HVF), rich in trans isomers, being found in processed foods. Studies involving IF have shown deleterious influences on the metabolic system, similarly to HVF, whereas no studies regarding its influence on the central nervous system (CNS) were performed. Rats from first generation born and maintained under supplementation (3g/Kg, p.o.) of soybean-oil or IF until adulthood were assessed on memory, biochemical and molecular markers in the hippocampus. IF group showed higher saturated fatty acids and linoleic acid and lower docosahexaenoic acid incorporation in the hippocampus. In addition, IF supplementation impaired short and long-term memory, which were related to increased reactive species generation and protein carbonyl levels, decreased catalase activity, BDNF and TrkB levels in the hippocampus. To the best of our knowledge, this is the first study to show that lifelong IF consumption may be related to brain oxidative damage, memory impairments and neurotrophins modifications, which collectively may be present indifferent neurological disorders. In fact, the use of IF in foods was intended to avoid damage from HVF consumption; however this substitute should be urgently reviewed, since this fat can be as harmful as trans fat.

Safety assessment of medium- and long-chain triacylglycerols containing 30% (w/w) medium-chain fatty acids in mice and rats.

A novel medium- and long-chain triacylglycerols (MLCT), with 30% (w/w) medium-chain fatty acids (MCFA) was evaluated for its safety as a dietary fat in mice and rats. The subacute oral toxicity study showed that the maximum tolerated dose exceeded 54.33 g/kg body weight (kg bw)/day. In the 90-day feeding study, no dose-related adverse effects were observed in rats administered diets formulated with different levels of MLCT (2.0, 4.0, and 8.0 g/kg bw/day) as compared to the rapeseed oil control diet. Further safety assessment in pregnant rats did not reveal any significant difference relative to the control at a treatment level up to 8.0 g MLCT/kg bw/day. The results from this study indicated the safe use of MLCT with high contents of MCFA in food products for improving human health.

The physical state of lipid nanoparticles influences their effect on in vitro cell viability.

Although lipid nanoparticles represent potent drug carriers, for many formulations toxicity data are rare. Thus, in this study, the effect of different lipid nanoparticles on the cell viability of L929 mouse fibroblasts was systematically investigated using the MTT assay. The formulations were composed of trimyristin, tristearin or cholesteryl myristate stabilized with poloxamer 188, polysorbate 80, polyvinyl alcohol or a blend of soybean phospholipid and sodium glycocholate. Depending on lipid and storage conditions, the nanoparticles were prepared in different physical states or crystal modifications leading to different particle shapes. The cell viability was influenced considerably by the physical state of the particle matrix with crystalline nanoparticles causing a stronger decrease in viability than the corresponding liquid or liquid crystalline particles. Effects on the cell viability were also related to the type of matrix lipid, stabilizer and the particle shape. However, the effects of differently shaped particles of different polymorphic modifications of crystalline tristearin were comparable. The low viability caused by poloxamer 188-stabilized particles could be correlated with a strong cell uptake which was investigated by confocal laser scanning microscopy.

Safety assessment of EPA-rich triglyceride oil produced from yeast: genotoxicity and 28-day oral toxicity in rats.

The 28-day repeat-dose oral and genetic toxicity of eicosapentaenoic acid triglyceride oil (EPA oil) produced from genetically modified Yarrowia lipolytica yeast were assessed. Groups of rats received 0 (olive oil), 940, 1880, or 2820 mg EPA oil/kg/day, or fish oil (sardine/anchovy source) by oral gavage. Lower total serum cholesterol was seen in all EPA and fish oil groups. Liver weights were increased in the medium and high-dose EPA (male only), and fish oil groups but were considered non-adverse physiologically adaptive responses. Increased thyroid follicular cell hypertrophy was observed in male high-dose EPA and fish oil groups, and was considered to be an adaptive response to high levels of polyunsaturated fatty acids. No adverse test substance-related effects were observed on body weight, nutritional, or other clinical or anatomic pathology parameters. The oil was not mutagenic in the in vitro Ames or mouse lymphoma assay, and was not clastogenic in the in vivo mouse micronucleus test. In conclusion, exposure for 28 days to EPA oil derived from yeast did not produce adverse effects at doses up to 2820 mg/kg/day and was not genotoxic. The safety profile of the EPA oil in these tests was comparable to a commercial fish oil.

Inner ear biocompatibility of lipid nanocapsules after round window membrane application.

Nanoparticle-mediated drug delivery represents the future in terms of treating inner ear diseases. Lipid core nanocapsules (LNCs), 50 nm in size, were shown to pass though the round window membrane (RWM) and reached the spiral ganglion cells and nerve fibers, among other cell types in the inner ear. The present study aimed to evaluate the toxicity of the LNCs in vitro and in vivo, utilizing intact round window membrane delivery in rats. The primary cochlear cells and mouse fibroblast cells treated with LNCs displayed dosage dependant toxicity. In vivo study showed that administration of LNCs did not cause hearing loss, nanoparticle application-related cell death, or morphological changes in the inner ear, at up to 28 days of observation. The cochlear neural elements, such as synaptophysin, ribbon synapses, and S-100, were not affected by the administration of LNCs. However, expression of neurofilament-200 decreased in SGCs and in cochlear nerve in osseous spiral lamina canal after LNC delivery, a phenomenon that requires further investigation. LNCs are potential vectors for the delivery of drugs to the inner ear.

Potential use of nanostructured lipid carriers for topical delivery of flurbiprofen.

The potential use of nanostructured lipid carriers (NLC) composed of a fatty acid [stearic acid (SA)] or a triglyceride (glyceryl behenate) as solid lipids, and a mixture of medium chain triglycerides and castor oil as liquid lipids, for skin administration of flurbiprofen (FB), has been explored. Two different optimized NLC formulations (FB-SANLC based on SA vs. FB-C888NLC based on glyceryl behenate), with respect to the morphometrical properties (particle size and polydispersity index) and the entrapment efficiency, were used in this study. The ex vivo permeation profiles of FB-C888NLC, FB-SANLC and conventional FB solution were evaluated using human skin. An improved FB permeation was observed when the drug was delivered by skin application of FB-C888NLC, attributed to the particle size and matrix crystallinity. The differential scanning calorimetry and X-ray diffraction studies suggested major polymorphic transitions in the lipid matrix of FB-C888NLC. A good correlation between polymorphic transitions and increased drug permeation was observed. However, both NLC dispersions showed a penetration-enhancing ratio (ER) higher than conventional FB solution. The in vitro and in vivo irritancy and local tolerability were assessed by running, respectively, the SKINTEX™ and Draize test. Both FB-C888NLC and FB-SANLC were classified as nonirritant.

Blood D-(-)-3-hydroxybutyrate concentrations after oral administration of trioctanoin, trinonanoin, or tridecanoin to newborn rhesus monkeys (Macaca mulatta).

Premature newborn infants are born with limited stores of glycogen and fat. Energy, such as medium-chain triglycerides (MCT), which can spare the use of body protein as metabolic energy, may be beneficial. This study compares MCT containing C8, C9, or C10 fatty acids as oral sources of energy for newborn rhesus monkeys (Macaca mulatta). On day 1 of life, 4 groups of 5 monkeys were given a single dose of water or MCT by nasogastric tube. The dose provided approximately 80% of the expected energy requirement. Plasma C8:0, C9:0, and C10:0 fatty acids and whole-blood D-(-)-3-hydroxybutyrate (3HB) concentrations were measured at 0, 1, and 3 h after dosing. Concentrations of free fatty acids (C8, C9, or C10) and ketone (3HB) increased with time after the dose. At 1 and 3 h, concentrations of C8 and C9 did not differ, but C9 was greater than C10. At 1 h, blood 3HB concentrations due to C8 triglyceride were higher than C9 or C10 (503 versus 174 and 225 µmol/L respectively). As MCT chain length increased from C8 to C10, blood concentration of 3HB decreased. Odd-chain MCT (C9 versus C8) resulted in lower whole-blood ketone (3HB), perhaps due to C9 metabolism or the rate of release or uptake of fatty acids. These results have implications for the use of MCT in nutritional supplements for preterm infants.

Biodegradation kinetics and toxicity of vegetable oil triacylglycerols under aerobic conditions.

The aerobic biodegradation of five triacylglycerols (TAGs), three liquids [triolein (OOO), trilinolein (LLL), and trilinolenin (LnLnLn)] and two solids [tripalmitin (PPP) and tristearin (SSS)] was studied in water. Respirometry tests were designed and conducted to determine the biochemical oxygen demand (BOD) parameters of the compounds. In the case of the solid lipids, the degradation process was limited by their extremely non-polar nature. When added to water, PPP and SSS formed irregular clumps or gumballs, not a fine and uniform suspension required for the lipase activity. After 30 days, appreciable mineralization was not achieved; therefore, first-order biodegradation coefficients could not be determined. The bioavailability of the liquid TAGs was restricted due to the presence of double bonds in the fatty acids (FAs). An autoxidation process occurred in the allylic chains, resulting in the production of hydroperoxides. These compounds polymerized and became non-biodegradable. Nevertheless, the non-oxidized fractions were readily mineralized, and BOD rate constants were estimated by non-linear regression: LLL (k=0.0061h(-1)) and LnLnLn (k=0.0071h(-1)) were degraded more rapidly than OOO (k=0.0025h(-1)). Lipids strongly partitioned to the biomass and, therefore, Microtox toxicity was not observed in the water column. However, EC(50) values (<15% sample volume) were measured in the solid phase.

Safety evaluation of a medium- and long-chain triacylglycerol oil produced from medium-chain triacylglycerols and edible vegetable oil.

To reduce the incorporation of dietary lipids into adipose tissue, modified fats and oils have been developed, such as medium-chain triacylglycerols (MCT). Typical dietary lipids from vegetable oils, termed long-chain triacylglycerols (LCT), are degraded by salivary, intestinal and pancreatic lipases into two fatty acids and a monoacyl glycerol; whereas, MCT are degraded by the same enzymes into three fatty acids and the simple glycerol backbone. Medium-chain fatty acids (MCFA) are readily absorbed from the small intestine directly into the bloodstream and transported to the liver for hepatic metabolism, while long-chain fatty acids (LCFA) are incorporated into chylomicrons and enter the lymphatic system. MCFA are readily broken down to carbon dioxide and two-carbon fragments, while LCFA are re-esterified to triacylglycerols and either metabolized for energy or stored in adipose tissue. Therefore, consumption of MCT decreases the incorporation of fatty acids into adipose tissue. However, MCT have technological disadvantages precluding their use in many food applications. A possible resolution is the manufacture and use of a triacylglycerol containing both LCT and MCT, termed medium- and long-chain triacylglycerol (MLCT). This manuscript describes studies performed for the safety evaluation of a MLCT oil enzymatically produced from MCT and edible vegetable oil (containing LCT), by a transesterification process. The approximate fatty acid composition of this MLCT consists of caprylic acid (9.7%), capric acid (3.3%), palmitic acid (3.8%), stearic acid (1.7%), oleic acid (51.2%), linoleic acid (18.4%), linolenic acid (9.0%), and other fatty acids (2.9%). The approximate percentages of long (L) and medium (M) fatty acids in the triacylglyerols are as follows: L, L, L (55.1%), L, L, M (35.2%), L, M, M (9.1%), and M, M, M (0.6%). The studies included: (1) acute study in rats (LD50>5000 mg/kg); (2) 6 week repeat-dose safety study via dietary administration to rats (NOAEL of 3500 mg/kg/day), (3) in vitro genotoxicity studies using Salmonella typhimurium and Escherichia coli (negative at 5000 mg/plate), and (4) a four-week, placebo-controlled, double blind, human clinical trial utilizing 20 test subjects (no effects at 42 g MLCT/day). These data are corroborated by other studies published in the peer-reviewed literature on analogous MLCTs.

A review of the safety of DHA45-oil.

Polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA), are natural constituents of the human diet; however, dietary intakes of these fatty acids are below recommended values. The main dietary source of DHA is fatty fish, with lesser amounts provided by shellfish, marine mammals, and organ meats. The addition to traditional food products of refined oils produced by marine microalgae represents potential sources of supplemental dietary DHA. DHA45-oil is manufactured through a multi-step fermentation and refining process using a non-toxigenic and non-pathogenic marine protist. Comprising approximately 45% DHA, and lesser concentrations of palmitic acid and docosapentaenoic acid, DHA45-oil is intended for use in foods as a dietary source of DHA. The safety of DHA45-oil was evaluated in various genotoxicity and acute, subchronic, and reproductive toxicity studies. DHA45-oil produced negative results in genotoxicity assays and demonstrated a low acute oral toxicity in mice and rats. Dietary administration of DHA45-oil to rats in subchronic and one-generation reproductive studies produced results consistent with those observed in oral studies using high concentrations of omega-3 PUFAs from fish or other microalgal-derived oils. The results of these studies, as well as those of various published metabolic, toxicological, and clinical studies with DHA-containing oils, support the safety of DHA45-oil as a potential dietary source of DHA.

Dietary epoxy fatty acids are absorbed in healthy women.

BACKGROUND: Epoxy fats in the diet may adversely affect human health. There are no data on the absorption of these fats in humans. METHODS: Triglycerides were synthesized containing two U-13C-labelled monoepoxy or diepoxy stearic acid molecules. Apparently healthy women consumed a standardized fatty meal (30 g fat) containing either 20 mg monoepoxy or 25 mg diepoxy fat (n = 6 and n = 7, respectively). Plasma lipid [U-13C]monoepoxy and diepoxy stearate concentrations were determined (0-24 h) by gas chromatography-mass spectrometry. RESULTS: Plasma triglycerides increased from 1.05 +/- 0.12 to 1.83 +/- 0.13 mmol L-1 (n = 6) and from 1.10 +/- 0.19 to 1.41 +/- 0.27 mmol L-1 (n = 7) (both P < 0.001). Plasma [U-13C]monoepoxy and diepoxy stearate levels increased to 0.18 +/- 0.07 micromol L-1 (n = 6) and to 0.08 +/- 0.03 micromol L-1 (n = 7), respectively. Monoepoxy triglyceride was better absorbed than diepoxy triglyceride: 17 +/- 4 vs. 8 +/- 1% of dose (determined from area under curve (plasma 13C) normalized to that of absorbed triglycerides (plasma 12C); P < 0.02 after log transformation). The absorption of monoepoxy- and diepoxy-labelled triglycerides was related to that of normal triglycerides (r = 0.80, P < 0.05 and r = 0.91, P < 0.001, respectively). CONCLUSIONS: Monoepoxy fats are better absorbed than diepoxy fats in women (17 +/- 4 vs. 8 +/- 1% of dose, P = 0.02). This difference in absorption is important when considering the relative toxicity of epoxidized material in the food chain.

Review of the toxicologic properties of medium-chain triglycerides.

Medium chain triglycerides (MCTs) are a family of triglycerides, containing predominantly, caprylic (C(8)) and capric (C(10)) fatty acids with lesser amounts of caproic (C(6)) and lauric (C(12)) fatty acids. MCTs are widely used for parenteral nutrition in individuals requiring supplemental nutrition and are being more widely used in foods, drugs and cosmetics. MCTs are essentially non-toxic in acute toxicity tests conducted in several species of animals. In ocular and dermal irritation testing MCTs exhibit virtually no potential as ocular or dermal irritants, even with prolonged eye or skin exposure. MCTs exhibit no capacity for induction of hypersensitivity. Ninety-day toxicity tests did not result in notable toxicity, whether the product was administered in the diet up to 9375mg/kg body weight/day or by intramuscular (im) injection (up to 0. 5ml/kg/day, rabbits). There was no evidence that intravenous (iv) or dietary administration of MCTs adversely affected the reproductive performance of rats or resulted in maternal toxicity, foetal toxicity or teratogenic effects at doses up to 4.28g/kg body weight/day (iv) or 12,500mg/kg body weight/day (dietary). There was no evidence that dietary administration of MCTs adversely affected the reproductive performance of pigs or resulted in maternal toxicity, foetal toxicity or teratogenic effects at doses up to 4000mg/kg body weight/day in the diet. In rabbits, following iv administration, the maternal and foetal no-observed-adverse-effect levels (NOAELs) were between 1.0 and 4.28g/kg body weight/ day. A 2-year study in rats, conducted with a closely related compound (tricaprylin, a triglyceride with C(8) fatty acids), provided no evidence of a carcinogenic effect when the material was administered by oral gavage at levels up to 10ml/kg (9.54g/kg) per day. Although tricaprylin was found to be positive in one of five strains of Salmonella typhimurium in the presence of metabolic activation in an Ames mutagenicity assay, the results of the carcinogenicity test with tricaprylin and mutagenicity tests with caprylic acid indicate that MCTs do not have the potential to be carcinogenic or mutagenic. The safety of human dietary consumption of MCTs, up to levels of 1g/kg, has been confirmed in several clinical trials.

High levels of dietary arachidonic acid triglyceride exhibit no subchronic toxicity in rats.

Arachidonic acid (AA), an n-6 long-chain polyunsaturated fatty acid (LC-PUFA), serves an important role in the body as a structural fatty acid of many tissues including neurological tissues. It is also a precursor of the n-6 class of eicosanoids and is the most abundant n-6 LC-PUFA found in human breast milk. We have optimized the production of a microfungal source of a triglyceride oil (ARASCO) which is enriched in AA to about 40% by weight. To establish the safety of this oil as a food, we evaluated the effect of ARASCO in Sprague-Dawley rats (20/sex/group) gavaged at dose levels of 1.0 and 2.5 g/kg/d for a period of 90 d, paying special attention to any potential neurotoxicity of the oil. Two groups of control animals received either untreated standard laboratory diet (untreated control) or the same diet and vehicle oil at the same dose volume administered to the treated animals (vehicle control). Physical observations, ophthalmoscopic examinations, body weight, food consumption, clinical chemistry, hematology parameters, neurobehavioral assessments, and macroscopic as well as microscopic postmortem evaluations were performed. Tissue fatty acid analyses indicated that the AA levels in the brain, heart, and liver of the high-dose ARASCO-fed animals increased by 8, 59, and 76%, respectively, indicating that the AA in the oil was readily incorporated into tissue lipids. In spite of this high elevation in tissue AA levels, no developmental, histopathological, or neuropathological differences were seen in the animals administered ARASCO compared with the vehicle control animals. Being highly enriched in AA, ARASCO offers the means to study the effect of this fatty acid in experimental settings and in human metabolic studies.

A 91-day feeding study in rats with caprenin.

Caprenin, a randomized triglyceride primarily comprising caprylic (C8:0), capric (C10:0), and behenic (C22:0) acids, was administered in a semi-purified diet to weanling Sprague-Dawley rats (25/sex/group) at dose levels of 5.23, 10.23 or 15.00% (w/w) for 91 days. Corn oil was added at 8.96, 5.91 and 3.00%, respectively, to provide essential fatty acids and digestible fat calories. Corn oil alone (12.14%) and a blend of medium-chain triglyceride (MCT) oil plus corn oil (11.21 and 3.13%, respectively) served as controls. All diets were formulated to provide about 4000 kcal/kg of diet and 26.8% of digestible calories from fat by assuming that corn oil, MCT oil, and caprenin provided 9, 7 and 5 kcal/g, respectively. Survival, clinical signs, body weight, feed consumption, feed efficiency, organ weights, organ-to-body-weight ratios, organ-to-brain-weight ratios, haematological values and clinical chemistry parameters were evaluated in all groups. Histopathology of a full complement of tissues was evaluated in the corn oil and MCT oil control groups as well as the high-dose caprenin group. Additional rats (n = 5/sex/group) were included in the study to determine whether there was marked storage of C22:0 in heart, liver or perirenal fat at the end of the 91-day feeding period. No significant differences in body weight gain were measured with the balanced caloric diets, although feed conversion efficiency was reduced in the high-dose caprenin group. No adverse effects from the ingestion of caprenin were detected, nor were significant amounts of C22:0 present in the fat extracted from the selected fat depot sites. These results establish a no-observable-adverse-effect level (NOAEL) of more than 15% (w/w) caprenin in the diet (or more than 83% of total dietary fat), which is equal to a mean exposure level of more than 13.2 g/kg/day for male rats and more than 14.6 g/kg/day for female rats.

Metabolism of meadowfoam oil fatty acids in mice.

Meadowfoam oil is unusual because over 95% of the fatty acids are 20- and 22-carbon aliphatic acids with cis double bonds located principally at the 5- and/or 13-position. Since little information is available on the metabolism of the 5c-20:1 and 5c,13c-22:2 fatty acids, an exploratory study in mice was conducted to investigate the metabolism of purified samples of the free fatty acids isolated from meadowfoam oil, and to determine the effect of meadowfoam oil on weight gain and tissue lipid composition. Mice fed diets containing 5% by wt of the purified 5c-20:1 or 5c,13c-22:2 for 6 days exhibited no apparent physiological problems. Total liver lipids from mice fed the purified fatty acid diets contained mean values of 2.0% 5c-20:1 and 2.1% 5c,13c-22:2; total heart lipids contained 1.7% 5c-20:1 and 10.7% 5c,13c-22:2. Liver total phospholipids from mice fed a 5% meadowfoam oil diet for 19 wk contained 1.4% 5c-20:1 and 1.9% 5c,13c-22:2. There was no evidence of desaturation, elongation or retroconversion. Weight gain for mice fed the meadowfoam oil diet for 19 wk was similar to mice fed corn oil, and was higher than for mice fed hydrogenated cottonseed oil. Considering the high 5c-20:1 and 5c,13c-22:2 content of the diets, the percentages of these fatty acids in mouse tissue lipids from both the short- and long-term studies were low. Weight gain was surprisingly good since the meadowfoam oil diet was essential fatty acid-deficient. Results of this initial investigation suggest that the 5c-20:1 and 5c,13c-22:2 fatty acids were utilized primarily for energy.(ABSTRACT TRUNCATED AT 250 WORDS)

Toxicity of rac-1(3)-palmitoyl glycerol in weanling mice.

Reinvestigation of the previously reported toxicity of saturated fat on weanling mice has shown rac-1(3)-palmitoyl glycerol to be a more potent toxic agent than free palmitic acid when fed as the sole source of dietary fat. As shown before, protection against this toxicity can be afforded by the addition of 2 to 4% safflower oil. We have now shown that if the rac-1(3)-palmitoyl glycerol is acetylated the toxicity is much less. The protective effect of diacetyl rac-1(3)-palmitoyl glycerol cannot be totally ascribed either to the presence of acetate itself or to the blocking of the free hydroxyls of palmitoyl glycerol by acylation. In vivo absorption studies coupled with in vitro experiments with pancreatic lipase suggest that the major protective effects result from increased lipolysis of the acylated palmitoyl glycerol, causing conversion to the less toxic free palmitic acid.