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Comparison of effects of long-chain and medium-chain triglyceride emulsions during hepatic regeneration in rats.

We examined the effect of long-chain triglyceride (LCT) and medium-chain triglyceride (MCT) emulsions on hepatic regeneration. After approximately 70% hepatectomy, Sprague-Dawley rats were maintained for 96 hours on total parenteral nutrition (TPN) (250 kcal/kg per day; nonprotein calories-nitrogen 160:1) with LCT or MCT as 30% of nonprotein calories. There were no significant differences in the body weight, cumulative nitrogen balance, urinary 3-methylhistidine excretion, or changes in the energy stores between the two groups; but the fatty acid composition of the phospholipid fraction of the regenerating liver differed significantly between the LCT and the MCT groups. The extent of hepatic regeneration by weight was 88.7 +/- 10.5% in the MCT group and 99.1 +/- 10.6% in the LCT group by 96 hours after hepatectomy. Furthermore, the incorporation of 3H-orotic acid into DNA and RNA of regenerating liver cells in the LCT group was higher than in the MCT group 24 hours after hepatectomy. These observations indicate that essential fatty acids--components of the cell membrane and precursors as functional mediators--are very important to hepatic regeneration.

Animals↗

Acyl-CoA synthetases in guinea-pig liver mitochondria. Purification and characterization of a distinct propionyl-CoA synthetase.

Guinea-pig liver mitochondria contain three soluble ATP-dependent acyl-CoA synthetases: (a) a medium-chain acyl-CoA synthetase, (b) a salicylate activating enzyme, and (c) a propionyl-CoA synthetase. A complete separation of these enzymes has been accomplished and the resulting preparation of propionyl-CoA synthetase (Spec. act. 4 units/mg protein) accepts acetate, propionate and butyrate as substrates with a high preference for propionate.

Acetates↗

Effects of different lipid sources in total parenteral nutrition on whole body protein kinetics and tumor growth.

This study examined the short-term effects of three total parenteral nutrition solutions, each containing a different lipid source, on host and tumor protein metabolism in a rat cancer model. Each diet contained 220 kcal/kg per day, including 2 g of nitrogen/kg per day and 50% of nonprotein calories as either a structured lipid of medium-chain triglycerides and fish oil, a physical mix of medium-chain triglycerides and fish oil, or Liposyn II, a long-chain triglyceride. A 3-day intravenous feeding infusion began on day 7 after tumor implantation. Tumor growth rate, nitrogen balance, energy expenditure, and plasma albumin, glucose, and free fatty acids were measured, and whole body protein kinetics and fractional synthetic rates in liver, muscle, and tumor tissues were assessed using a constant infusion of 14C-leucine. The results revealed that tumor growth rate was slowed in structured lipid-fed animals (p = .06, one-way analysis of variance) with significant increases in rates of tumor protein synthesis and tumor protein breakdown (p < .001, one-way analysis of variance). Although muscle fractional synthetic rates were significantly decreased in tumor-bearing animals (p < .05, two-way analysis of variance), the rates in structured lipid-fed animals were restored. Nitrogen balance improved significantly in structured lipid-fed animals. The results demonstrate that the source of lipid in total parenteral nutrition solutions can influence tumor and host protein metabolism, and that a structured lipid composed of medium-chain triglycerides and fish oil seems to improve protein metabolism in host tissue without stimulating tumor growth.

Animals↗

Medium-chain triglyceride feeding in premature infants: effects on calcium and magnesium absorption.

The effect of medium-chain triglycerides (MCT) on the absorption of calcium and magnesium in premature infants was studied in 34 infants with birth weights lower than 2,000 gm. The infants were divided into three groups and fed three formulas similar in nutrient content except for the type of fat, as follows: group 1 (control): corn oil, oleo, and coconut oil (39:41:20); group 2: MCT, corn oil, and coconut oil (40:40:20); group 3: MCT and corn oil (80:20). The infants fed MCT-containing formulas absorbed significantly more calcium than the control group. Magnesium absorption was significantly increased in the 80% MCT group.

Absorption↗

Medium-chain triglyceride feeding in premature infants: effects on fat and nitrogen absorption.

The effect of medium-chain triglycerides (MCT) on the "physiological" steatorrhea of prematurity was studied in 34 infants with birthweights below 2,000 gm. The infants were divided into three groups and fed three formulas identical in nutrient content except for the type of fat, as follows: group 1 (control): corn oil, oleo, and coconut oil (39:41:20); group 2: MCT, corn oil, and coconut oil (40:40:20); group 3: MCT and corn oil (80:20). The infants fed MCT-containing formulas had striking diminution in stool volume and frequency. Their total fat absorption was significantly improved when compared with controls; nitrogen absorption was slightly but significantly improved in the 80% MCT group. The results also suggest that nitrogen sparing may be enhanced in premature infants fed MCT-containing formulas.

Birth Weight↗

Medium-chain acyl-CoA dehydrogenase deficiency: molecular aspects.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an autosomal recessive disorder which is known to cause Reye-like syndrome in children and sudden infant death. A point mutation of lysine329-to-glutamic acid329 substitution in the MCAD gene was recently identified as the most common mutation in patients with MCAD deficiency. This mutation is responsible for about 90% of mutant MCAD alleles in Caucasians. Patients with this type of mutation have a variety of symptoms, indicating that the clinical heterogeneity of MCAD deficiency may not be caused entirely by genetic heterogeneity. Screening for the mutation among newborns in England, Australia, and United States of America indicates the prevalence of carriers to be 1 in 40-107, suggesting the high incidence of the mutation. Since presymptomatic diagnosis and appropriate dietary management are important in MCAD deficiency to prevent life-threatening complications, the relatively high incidence of this disorder may warrant population screening. The most common MCAD mutation can now be detected by DNA diagnostic methods using Guthrie cards. This makes it possible to screen a population efficiently for this potentially fatal disorder.

Acyl-CoA Dehydrogenase↗

Iron-Deprivation Liposomes for Cancer Therapy.

Targeting iron homeostasis in tumor cells represents a promising anticancer strategy, as iron plays essential roles in tumor growth, invasion, and metastasis. Although deferoxamine can effectively chelate iron, its clinical application is limited by poor membrane permeability, short half-life, and lack of targeting capability. To overcome these challenges, we designed and synthesized a family of DFO-bearing lipids by modifying the molecule with dual fatty acid chains of varying lengths, and co-assembled them with auxiliary lipids via microfluidics to construct "iron-deprivation" liposomes. Among them, the medium-chain DFO-C12-liposomes exhibited the highest cellular uptake, iron-deprivation efficiency, and anticancer activity in vitro, markedly depleting mitochondrial iron, disrupting Fe-S cluster synthesis, suppressing mitochondrial respiration, and inducing autophagy. Furthermore, DFO-C12-liposomes efficiently coordinated Mn2 + via DFO-Mn2 + chelation, providing MRI capability while inducing iron deprivation-mediated ferroptosis. In addition, the iron-deprivation liposomes can encapsulate anticancer drugs such as doxorubicin, leading to an enhanced antitumor effect through the combination of iron deprivation and chemotherapy for osteosarcoma treatment. In summary, the "iron-deprivation" liposomes integrate iron chelation, imaging functionality, and chain-length-dependent cellular uptake into a versatile nanoplatform for regulating tumor iron homeostasis and achieving enhanced antitumor efficacy through multimodal therapeutic strategies.

alkyl chain&#x2010;length engineering↗

Inhibition of enoyl-CoA hydratase by long-chain L-3-hydroxyacyl-CoA and its possible effect on fatty acid oxidation.

The kinetics of bovine liver enoyl-CoA hydratase (EC 4.2.1.17) or crotonase with 2-trans-hexadecenoyl-CoA as a substrate were studied because different rates were obtained with two assay methods based on measurements of substrate utilization and product formation, respectively. L-3-Hydroxyhexadecanoyl-CoA, the product of the crotonase-catalyzed hydration of 2-trans-hexadecenoyl-CoA, was found to be a strong competitive inhibitor of the enzyme with a Ki of 0.35 microM. In contrast the short-chain product, L-3-hydroxybutyryl-CoA, is a weak competitive inhibitor with a Ki of 37 microM. L-3-Hydroxyhexadecanoyl-CoA is a much stronger inhibitor of crotonase than are other short-chain and long-chain intermediates of beta-oxidation and crotonase is more severely inhibited by this compound than are all beta-oxidation enzymes tested so far. Determination of true kinetic parameters for the crotonase-catalyzed hydration of long-chain substrates requires the removal of product in a coupled assay. When this was done, the Km for 2-trans-hexadecenoyl-CoA with bovine liver crotonase was found to be only 9 microM. It is suggested that under conditions of restricted beta-oxidation, when 3-hydroxyacyl-CoAs accumulate in mitochondria, the inhibition of crotonase by long-chain 3-hydroxyacyl-CoAs may limit the further degradation of medium-chain and short-chain intermediates of beta-oxidation.

Acyl Coenzyme A↗

A disorder of muscle lipid metabolism and myoglobinuria. Absence of carnitine palmityl transferase.

Two brothers, 29 and 33 years of age, had recurrent myoglobinuria, renal failure and azotemia, but were otherwise normal, without apparent muscle weakness or exercise intolerance. Ischemic exercise resulted in normal lactate production. Muscle glycogen content and activities of phosphorylase and phosphofructokinase were normal. Plasma triglycerides were elevated (500 mg per deciliter) on a regular diet and rose during fasting. During a 72-hour fast, serum creatine phosphokinase rose more than 10 times, and myoglobin was detected in urine. Plasma ketone production was minimal during fasting, but prompt ketonemia ( a normal response) occurred after ingestion of medium-chain triglycerides. Carnitine palmityl transferase activity was virtually absent in crude muscle extracts and mitochondrial fractions. Lack of this enzyme impairs long-chain fatty acid utilization, reflected in increased content of plasma free fatty acids and plasma triglycerides. Depletion of ATP because of this metabolic block in muscle may account for the attacks of myoglobinuria.

Acute Kidney Injury↗

Necessity of vitamin B12 for growth of rats fed on an odd- or even-carbon-number fat.

1. The effect of vitamin B12 on growth was studied in young male and female rats fed on diets sufficient (+B12) or deficient (-B12) in vitamin B12 containing 30% of the dietary energy as fat, either maize oil (CO) or triundecanoin (TUD). 2. Vitamin B12 deficiency severely depressed growth. After 6 weeks the weight gain of CO(-B12) rats was only 72% of that of CO(+B12) rats and the gain of TUD(-B12) rats was only 47% of TUD(+B12) rats. 3. After fasting 24 or 96 h TUD-fed rats, both +B12 and -B12, had greater glycogen reserves and higher plasma glucose levels than CO-fed rats. 4. It is concluded that vitamin B12 is required for the metabolism and utilization of both an odd-carbon-number medium-chain fat, TUD, and an even-C-number long-chain fat, CO, during growth in rats.

Animals↗

On the mechanism of malonyl-CoA-independent fatty-acid synthesis. Different properties of the mitochondrial chain elongation and enoylCoA reductase in various tissues.

1. NADPH-specific mitochondrial enoyl-CoA reductase can be assayed by a sensitive radioactive test, employing tritium-labelled NADPH, synthesized in a prefixed reaction from D-[1-3H]-glucose via the hexokinase and glucose-6-phosphate dehydrogenase reactions. 2. Liver, kidney cortex, heart muscle, skeletal muscle, brown adipose tissue, brain cortex, and aortic intimal tissue are investigated concerning chain lengths specificity of the chain elongation and the enoyl-CoA reductase. Medium-chain acyl-CoA compounds prove to be the best primers for the chain elongation. Enoyl-CoA reductases still show large incorporation rates with hexadecenoyl-CoA. 3. The differences in the chain lengths specificity of the chain elongation and enoyl-CoA reductase can be explained by the inhibitory effect of long-chain acyl-CoA derivatives on the 3-hydroxyacyl-CoA dehydrogenase. 4. The nucleotide specificity in the different tissues reveals two types of chain elongation: In addition to liver and kidney cortex, mitochondria of brown adipose tissue need NADH + NADPH for optimal chain elongation, whereas heart muscle, skeletal muscle and aortic intimal mitochondria only need NADH. 5. Different physiological roles are proposed for the two types. The "heart type" may be of importance in the conservation of reducing equivalents or acetate units in the anaerobic state, the "liver type" may play a role in the transfer of hydrogen from NADPH to the respiratory chain. In addition, the mitochondrial chain elongation may serve as bypass of the first part of the respiratory chain.

Adipose Tissue, Brown↗

Free fatty acid and glucose metabolism during hypothermic perfusion of canine kidneys.

Canine kidneys were subjected to continuous nonpulsatile perfusion using 200 ml of a perfusate containing 50 g/l albumin. When optimal oxygenation was achieved, perfusate K+ contents were unchanged for 24 h, indicating adequate membrane function but tended to increase thereafter. Lowered oxygen pressures resulted in significant cellular K+ loss during the first hours of perfusion. During oxygenated perfusion, glucose and free fatty acids (FFA) were oxidized in considerable amounts with a preferential consumption of octanoate. A capacity for long-chain FFA oxidation became obvious when the octanoate had been used up, but the amount of these FFA in the perfusate depended preferentially on FFA being liberated from tissue lipids during the 1st day of perfusion. Glucose consumption rates were highest during the first 2 days of perfusion but the subsequent reduction of the metabolic rate was not accompanied by an accumulation of lactate. Thus medium-chain FFA and glucose should be supplied to the continuously perfused kidney in hypothermia and optimal oxygenation of the perfusate should be guaranteed. However, it seems to be unnecessary to supply exogenous long-chain FFA.

Albumins↗

Lipid infusion with different triglyceride cores (long-chain vs medium-chain/long-chain triglycerides): effect on plasma lipids and bilirubin binding in premature infants.

The possible beneficial effects of infusing a lipid emulsion containing 50% by weight of medium-chain triglycerides (MCT) compared with a standard long-chain triglyceride (LCT) emulsion were studied in 18 premature neonates (gestational age less than 34 weeks) requiring parenteral nutrition. The infants were assigned in a double-blind manner to receive one of the two lipid emulsions over 17 hours a day as a supplemental regimen for total parenteral nutrition. A lipid load of 1 g/kg per day was initiated on the third day of life and was increased at the rate of 1 g/kg per day until a maximal dose of 3 g/kg per day was obtained on the fifth day of life and maintained thereafter. Both bound and unbound bilirubin decreased with both infusion regimens during the study period. Despite a marked increase in plasma free fatty acid levels (260% in the MCT/LCT group compared with 210% in the LCT group), the fraction of unbound (free) bilirubin was significantly lower in the MCT/LCT group (34% vs 13%). Free fatty acid levels, corrected to albumin, were positively correlated to the percentage of free bilirubin only for the LCT lipid infusion. The finding of a significant elevation of plasma cholesterol levels only in the MCT/LCT group is now under investigation. Use of the MCT-containing emulsion was not associated with a higher frequency of adverse effects than the commonly used LCT-containing emulsion.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilirubin↗

Metabolic clearance of a fat emulsion containing medium-chain triglycerides in cirrhotic patients.

Medium-chain triglycerides (MCTs) may be advantageous in cirrhotic patients, but data on the clearing capacity are lacking. Intravenous fat tolerance test (IVFTT) was performed on 28 cirrhotic patients (Child's A, n = 9; Child's B, n = 13; Child's C, n = 6) to determine the clearance rate of Lipofundin MCT 20%, which contains a physical mixture of MCT and long-chain triglycerides (LCT). The mean fractional elimination rate (k2) of MCT/LCT physical blend in the cirrhotic patients (7.72%/min) was comparable with that of the healthy control subjects (n = 9, k2 = 5.43%/min). Significantly higher serum free fatty acid (FFA) levels were found in the cirrhotic patients during IVFTT. The difference could be accounted for by their higher basal levels. In all patients, serum FFA concentrations returned to basal value at the end of 1 hour. Prompt appearance of glycerol and beta-hydroxybutyrate was seen during IVFTT, indicating that hydrolysis of triglycerides and release of ketone bodies from the liver were rapid. It was concluded that the ability to eliminate MCT/LCT physical blend was not impaired in the cirrhotic patients.

3-Hydroxybutyric Acid↗

Comparison of long term lipogenic effects of two different medium-chain triglycerides (tri C8: O and tri C12 : O) in the growing rat.

During the growth (35 g-340 g), and as compared to results obtained with a lipid-free diet or a diet containing long-chain fatty acids, high levels of Tri C8 : O or Tri C12 : O did not change the quantitative aspects of proteinogenesis and lipogenesis balances. The incorporation of Tri C8 : O into the diet did not change the fatty acid composition of body lipid stores while the incorporation of Tri C12 : O induced a lipogenesis characterized by the disappearance of about 50% of the n-9 and n-7 unsaturated fatty acids, the emergence of an equivalent amount of saturated fatty acids in C12 and C14, and the decrease of hexadecanoic or palmitic acid concentration. Titers of saturated fatty acids with a melting point higher than 40 degrees C increased from 34% to 64%. Results suggested an efficient inhibition of fatty acid biosynthesis de novo by C12 : O, associated with an impossibility for microsomal enzymes to assume the elongation of a sufficient amount of C12 : O to maintain C16 : O concentration and to furnish an important amount of substrate (C18 : O) to delta-9-stearoyl coenzyme A desaturase for oleic acid synthesis. Introducing dodecanoic acid into the diet of growing animals appears to be the most efficient method for increasing the degree of saturation of body lipids without changing the concentrations of long-chain saturated fatty acids.

Animals↗

Composition and flavor of milk and butter from cows fed unsaturated dietary fat and receiving bovine somatotropin.

Composition and flavor of milk and butter were evaluated from cows divided into four treatments including a control, control with bST, added dietary fat from sunflower seeds with bST, or added dietary fat from safflower seeds with bST. Feeding added unsaturated dietary fat resulted in lower concentrations of short-and medium-chain and higher concentrations of long-chain fatty acids in milk fat and butter. Milk fat unsaturated fatty acid concentrations were 25.0, 28.4, 39.6, and 37.9%, and butter unsaturated fatty acid concentrations were 23.0, 26.9, 37.8, and 36.2% for control, control with bST, sunflower seeds with bST, and safflower seeds with bST, respectively. Sensory evaluations indicated that butters from the bST with sunflower seed and bST with safflower seed treatments were equal or superior in flavor to the control butter. Milk from cows receiving bST or fed added unsaturated dietary fat and receiving bST was no more susceptible to oxidized off-flavors than control milk. Butters from sunflower seed and safflower seed treatments with bST contained higher concentrations of unsaturated fatty acids, were softer at 4 and 20 degrees C, and possessed acceptable flavor and processing characteristics compared with butters from control and control with bST.

Animals↗

Medium-chain triglycerides and long-term parenteral nutrition in children.

There are no data concerning long-term utilization of medium-chain triglycerides (MCTs) in parenteral nutrition (PN) in children. Our study included 12 children, aged 1.5-17 yr, on total PN at home, supplying a daily intake of 214 +/- 92 mg/kg nitrogen and 47 +/- 17 kcal/kg nonprotein energy (NPE). NPE included 10-32% long-chain triglycerides (LCTs) (Intralipid 20%). After switching to emulsion containing 50% MCT and 50% LCT (Medialipide) at the same dosage regimen and infusion rate as before, the subjects were monitored at 1, 3, and 6 mo. No signs of clinical intolerance were observed. Among the laboratory parameters evaluated, the only significant (p < 0.05) changes were 1) an increase in apolipoproteins A-I and A-II at 1, 3, and 6 mo and 2) a decrease in gamma-glutamyltransferase (gamma-GT) at 6 mo. There were no changes in the status of essential fatty acids in plasma or in phospholipids (in erythrocyte membranes). Moderate urinary excretion of dicarboxylic acids (adipic, suberic, and sebacic) was evidence of peroxysomal omega-oxidation. The results support the proposal for use of MCT-rich emulsion in long-term PN, given its metabolic advantages relative to LCT.

Adolescent↗

[Fatty acids: their biochemical and functional classification].

Fatty acids (FA) constitute the main component of phospholipids, triglycerides and cholesterol esters. FA are acidic, monocarboxylic linear chains of variable length: short-chain FA (2-4 carbon atoms), medium-chain FA (6-12 carbon atoms), long-chain FA (14-18 carbon atoms), very long-chain FA (derived from parental 18-carbon molecules). They can be further subdivided into saturated (no double bond), monounsaturated (one double bond) and polyunsaturated (two or more double bonds). They are all involved in energetic, metabolic and structural activities. Short-chain FA act as growth factors; medium chain FA are readily available as energy source; saturated long-chain FA constitute a source of energy but may be implicated in the development of the atherosclerotic process; unsaturated long-chain FA include oleic acid and the essential fatty acids (linoleate and linolenate), and are all implicated in fundamental metabolic processes; very-long chain FA are the most characteristic molecules in biologic membranes. From recent works it is clearly established that the physiological role of FA depends on the chain length, and that the very-long chain molecules could determine the quality of human development. A functional classification of FA today must be based not only on the rate of unsaturation, but also (and most importantly) on the chain length.

Biochemical Phenomena↗