Randomly interesterified triacylglycerol containing medium- and long-chain fatty acids stimulates fatty acid metabolism in white adipose tissue of rats

We have reported previously that randomly interesterified triacylglycerol containing medium- and long-chain fatty acids in the same glycerol molecule (MLCT) resulted in significantly lower body fat accumulation and higher hepatic fatty acid oxidation than from long-chain triacylglycerol (LCT) in rats. To understand the metabolic changes occurring in white adipose tissue, the fatty acid oxidation and synthesis, and the adipocytokine level were measured in rats fed with MLCT or LCT for 2 weeks. In comparison with LCT, MLCT lowered not only the fatty acid synthase and glycerol-3-phosphate dehydrogenase activities in perirenal adipose tissue, but also the serum insulin and leptin levels, in addition to significantly reducing the body fat accumulation. In contrast, fatty acid oxidation measured as the carnitine palmitoyltransferase activity in the tissue was significantly higher in the MLCT-fed rats than in the LCT-fed rats. It seems that the altered fatty acid metabolism in adipose tissue per se was also responsible for the lower adiposity by dietary MLCT.     

Components of Total Energy Expenditure in Healthy Young Women Are Not Affected after 14 Days of Feeding with Medium-Versus Long-Chain Triglycerides

PAPAMANDJARIS, ANDREA A., MATTHEW D. WHITE, AND PETER J. H. JONES. Components of total energy expenditure in healthy young women are not affected after 14 days of feeding with medium-versus long-chain triglycerides. Obes Res. Objective: To examine the effect of consumption of medium-chain triglycerides (MCT) vs. long-chain triglycerides (LCT) on total energy expenditure (TEE) and its components in young women during the second week of a 2-week feeding period. Research Methods and Procedures: Twelve healthy lean women (age: 22. 7±0. 7 years, body mass index [BMI]: 21. 5±0. 8 kg/m²) were fed weight maintenance diets containing 15% of energy as protein, 45% as carbohydrate, and 40% as fat, 80% of which was treatment fat, for 2 weeks in a randomized cross-over design separated by a 2-week washout period. Dietary fat was composed of triglycerides containing either 26% medium-chain fatty acids (MCFA) and 74% long-chain fatty acids (LCFA), or 2% MCFA and 98% LCFA. Free-living TEE was measured from day 7 to 14 on each dietary treatment using doubly labeled water (DLW). Basal metabolic rate (BMR) and thermic effect of food (TEF) were measured on days 7 and 14 using respiratory gas exchange analysis (RGE) for 30 minutes and 330 minutes, respectively. Activity-induced energy expenditure (AIEE) was derived as the difference between TEE and the sum of BMR and TEF. Results: The average TEE while consuming the MCT diet (2246±98 kcal/day) did not differ from that of the LCT diet (2186±138 kcal/day. BMR was significantly higher on the MCT diet on day 7 (1219±38 kcal/day vs. 1179±42 kcall day), but not on day 14; there was no effect of diet on TEF. There were no differences in BMR, TEF, or AIEE between diets when expressed as percentages of TEE. On average, BMR, TEF, and AIEE represented 54. 6%, 8. 2%, and 37. 2%, respectively, of TEE. Discussion: Results suggest that between day 7 and day 14 feeding of MCT vs. LCT at these levels, TEE is not affected and that increases seen in energy expenditure following MCT feeding may be of short duration. Thus, compensatory mechanisms may exist which blunt the effect of MCT on energy components over the longer term.     

Effects of medium-chain fatty acids on body composition and protien metabolism in overweight rats

The lack of efficiency of classical treatments for obesity has led to propose alternative strategies. In order to obtain information about the effects of dietary fatty acid composition on body fat and protein metabolism, overweight female rats were fed on isoenergetic diets, using either medium-chain (MCT) or long-chain (LCT) triglycerides as a lipid source. After 23 days, the MCT group had mildly decreased body weight but greatly reduced adipose tissue depots. All fat depots were significantly diminished. MCT-fed rats showed a decrease in some hormones involved in energy balance, such as leptin and triiodothyronine. Feeding MCT resulted in improvements in nitrogen balance. Muscle protein content was similar in both treatments despite an increase in protein degradation in the MCT group. The present data clearly show that a diet with MCT as lipid fuel depresses weight gain and fat stores, relative to a standard LCT diet.     

Triglyceride with medium-chain fatty acids increases the activity and expression of hormone-sensitive lipase in white adipose tissue of C57BL/6J mice

We have previously shown that medium-chain triglyceride (MCT) resulted in significantly less body fat mass than long-chain triglyceride (LCT) did in hypertriglyceridimic subjects. The possible mechanism for this was investigated by measuring and analyzing changes in the body fat, blood lipid profile, enzymatic level and activity of hormone-sensitive lipase (HSL) and its mRNA expression, and levels of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in white adipose tissue (WAT) of C57BL/6J mice fed for 16 weeks on an MCT or LCT diet. MCT induced lower body weight and body fat, and an improved blood lipid profile than LCT did. The enzymatic level and activity of HSL and its mRNA expression, and the levels of cAMP and PKA were significantly higher in WAT of mice fed with the MCT diet. No significant differences in the levels of lipoprotein lipase and peroxisome proliferator-activated receptor-γ in WAT were apparent between the effects of MCT and LCT. It is concluded that lipolysis by the increased level and activity of HSL, which was induced by the activation of cAMP-dependent PKA in WAT, was partially responsible for the lower fat accumulation in C57BL/6J mice fed with MCT.     

Effect of randomly interesterified triacylglycerol containing medium- and long-chain fatty acids on hepatic fatty acid oxidation after a single administration to rats

MLCTs, which are randomly interesterified triacylglycerol containing medium- and long-chain fatty acids in the same glycerol molecule, showed significantly higher acyl-CoA dehydrogenase activity when measured by using butyryl-CoA, octanoyl-CoA, and palmitoyl-CoA as substrates than long-chain triacylglycerol one hour after a single administration to rats. These results suggest that not only medium-chain fatty acid oxidation, but also long-chain fatty acid oxidation were increased in the liver of rats administered with MLCT.     

Effect of diets rich in medium-chain and long-chain triglycerides on lipogenic-enzyme gene expression in liver and adipose tissue of the weaned rat.

The activity and mRNA concentrations of two lipogenic enzymes, fatty-acid synthase and acetyl-CoA carboxylase were measured in the liver and white adipose tissue of rats weaned to a carbohydrate-rich diet containing either long-chain or medium-chain fatty acids, and compared to those of rats weaned on a diet containing less than 1% (total energy) fat (high-carbohydrate diet). In the liver, the diet containing long-chain fatty acids inhibited the increase of both lipogenic-enzyme mRNA concentrations and activities seen at weaning on the high-carbohydrate diet but did not prevent the decrease in phosphoenolpyruvate carboxykinase mRNA and activity. In contrast, the diet containing medium-chain fatty acids induced a slower but finally similar increase in lipogenic-enzyme mRNA concentrations and activities. In adipose tissue, a similar trend was observed, although the inhibitory effect of the diet containing long-chain fatty acids was considerably less marked than in liver. It is concluded that medium-chain and long-chain fatty acids have not the same inhibitory potency of the gene expression of lipogenic enzymes, and that long-chain fatty acids have a more marked effect in the liver.     

Changes in blood lipids during six days of overfeeding with medium or long chain triglycerides

Although medium chain triglyceride (MCT) is less calorically dense than long chain triglyceride (LCT), it produces a greater thermic effect following ingestion. We hypothesized that the previously observed high rate of thermogenesis produced by MCT overfeeding was due to hepatic de novo synthesis of long chain fatty acids (LCFA) from the excess medium chain fatty acids (MCFA). To study this, we compared the effects of overfeeding MCT- and LCT-containing diets on blood lipid profiles. Ten in-patient, nonobese males were overfed (150% of estimated energy requirements) two formula diets for 6 days each, in a randomized crossover design. Diets differed only in the composition of the fat and contained either 40% of energy as MCT or LCT (soybean oil). The major differences between diets in the resulting pattern of blood lipids were: 1) a reduction in fasting serum total cholesterol concentrations with the LCT, but not the MCT diet; and 2) a threefold increase in fasting serum triglyceride concentrations with MCT, but not LCT, diet. Moreover, 10% of the fasting triglyceride fatty acids were medium chain and 40% were 16:0 with the MCT diet. This compared to 1% and 20% for medium chain and 16:0, respectively, with the LCT diet. In addition, there were increases in 16:1, 18:0, and 18:1 in the triglycerides during MCT feeding. The changes in fatty acids in triglycerides with MCT feeding are consistent with the hypothesis that excess dietary MCT cause a significant increase in the hepatic synthesis of these fatty acids from MCFA through de novo synthesis and/or chain elongation and desaturation. These processes could account for the higher rate of postprandial thermogenesis with MCT as compared to LCT.     

Long- and medium-chain triacylglycerols in nutritional support of liver regeneration of partially hepatectomized rats

An appropriate choice for a suitable diet during liver regeneration still remains an enigma. To investigate the effect of isocaloric enteral feeding with medium-chain triacylglycerols (MCT) and long-chain triacylglycerols (LCT) supplement (MCT+LCT, 40%:60% w:w) (178 kJ/kg b.w./24 h), rat liver regeneration was studied 24 and 72 h after partial hepatectomy. The liver DNA synthesis 24 h after partial hepatectomy was significantly higher in the MCT+LCT-supplemented rats (30.2+/-8.2 x 10(3) dpm/mg liver DNA) compared to MCT-treated animals (18.1+/-5.7 x 10(3) dpm/mg liver DNA). Liver protein synthesis was non-significantly elevated both 24 and 72 h after surgery in MCT+LCT-supplemented rats (13.7+/-1.1 and 10.9+/-3.1 x 10(3) dpm/mg liver protein). Seventy-two hours after partial hepatectomy, the hepatocyte mitotic activity was significantly increased in MCT+LCT- supplemented group vs. LCT- or MCT-fed rats (3.3+/-0.7 vs. 1.9+/-0.7 or 1.0+/-0.6 mitoses per 1000 hepatocytes), thus exhibiting an increased proliferative potential. The results showed a qualitative difference according to the proportion of MCT to LCT in the enteral supplements. Overfeeding with MCT decreased body weight, increased liver weight by its fatty infiltration, increased rat mortality rate and reduced spontaneous caloric intake. We conclude that the balanced supplement of MCT+LCT (40%:60% w:w) preserves liver regeneration, whereas overfeeding with MCT seems to be deleterious.     

Metabolic effects of intravenous LCT or MCT/LCT lipid emulsions in preterm infants

Most lipid emulsions for parenteral feeding of premature infants are based on long-chain triacylglycerols (LCTs), but inclusion of medium-chain triacylglycerols (MCTs) might provide a more readily oxidizable energy source. The influence of these emulsions on fatty acid composition and metabolism was studied in 12 premature neonates, who were randomly assigned to an LCT emulsion (control) or an emulsion with a mixture of MCT and LCT (1:1). On study day 7, all infants received [13C]linoleic (LA) and [13C]alpha-linolenic acid (ALA) tracers orally. Plasma phospholipid (PL) and triacylglycerol (TG) fatty acid composition and 13C enrichments of plasma PL fatty acids were determined on day 8. After 8 days of lipid infusion, plasma TGs in the MCT/LCT group had higher contents of C8:0 (0.50 +/- 0.60% vs. 0.10 +/- 0.12%; means +/- SD) and C10:0 (0.66 +/- 0.51% vs. 0.15 +/- 0.17%) than controls. LA content of plasma PLs was slightly lower in the MCT/LCT group (16.47 +/- 1.16% vs. 18.57 +/- 2.09%), whereas long-chain polyunsaturated derivatives (LC-PUFAs) of LA and ALA tended to be higher. The tracer distributions between precursors and products (LC-PUFAs) were not significantly different between groups. Both lipid emulsions achieve similar plasma essential fatty acid (EFA) contents and similar proportional conversion of EFAs to LC-PUFAs. The MCT/LCT emulsion seems to protect EFAs and LC-PUFAs from beta-oxidation.     

Plasma fatty acids and [13C]linoleic acid metabolism in preterm infants fed a formula with medium-chain triglycerides

Most preterm infant formulas contain medium-chain triacylglycerols (MCT), but the effects of MCT on polyunsaturated fatty acid status and metabolism are controversial. Thus, we studied the effects of MCT on linoleic acid metabolism using stable isotopes. Enterally fed preterm infants were randomized to receive for 7 days 40% of fat as MCT (n = 10) or a formula without MCT (n = 9). At study day 5, infants received orally 2 mg/kg body weight of (13)C-labeled linoleic acid. Fatty acids in plasma lipid classes and (13)C enrichment of phospholipid fatty acids were measured and tracer oxidation was monitored. Compared with the control group, the MCT group showed lower breath (13)CO(2) and higher plasma triacylglycerol contents of octanoic acid, of decanoic acid, and of total long-chain polyunsaturated fatty acids (57.1 +/- 4.4 micro mol/l vs. 37.9 +/- 4.8 micro mol/l, P < 0.01). Concentrations of several polyunsaturated fatty acids in plasma phospholipids and non esterified fatty acids were higher in the MCT group. (13)C concentrations in phospholipid n-6 fatty acids indicated no difference in the relative conversion of linoleic to arachidonic acid. We conclude that oral MCT effectively reduce polyunsaturated fatty acid and long chain polyunsaturated fatty acid oxidation in preterm infants without compromising endogenous n-6 long chain polyunsaturated fatty acid synthesis.     

Minor amounts of plasma medium-chain fatty acids and no improved time trial performance after consuming lipids.

Medium-chain triacylglycerols (MCT) have a potential glycogen-saving effect during exercise due to rapid hydrolysis and oxidation. However, studies comparing intake of carbohydrates (CHO) plus 80-90 g MCT with intake of CHO alone have revealed different results. The present study tested performance after consumption of specific structured triacylglycerol, consisting of a mixture of medium-chain fatty acids and long-chain fatty acids, to prevent the adverse effects observed by MCT (pure medium-chain fatty acids) regarding gastrointestinal distress. Seven well-trained subjects cycled 3 h at 55% of maximum O2 uptake during which they ingested CHO or CHO plus specific structured triacylglycerols. Immediately after the constant-load cycling, the subjects performed a time trial of approximately 50-min duration. Breath and blood samples were obtained regularly during the experiment. Fatty acid composition of plasma triacylglycerols, fatty acids, and phospholipids was determined. Performance was similar after administration of CHO plus specific structured triacylglycerol [medium-, long-, and medium-chain fatty acid (MLM)] compared with CHO (50.0 +/- 1.8 and 50.8 +/- 3.6 min, respectively). No plasma 8:0 was detected in the plasma lipid classes, but the amount of phospholipid fatty acids was significantly higher after CHO+MLM compared with CHO intake. The lacking time trial improvement after intake of medium-chain fatty acids might be due to no available 8:0 in the systemic circulation. A higher level of plasma phospholipid fatty acids in the CHO+MLM compared with the CHO group was probably due to endogenous phospholipid release into chylomicrons.     

Impact of maternal dietary n-3 and n-6 fatty acids on milk medium-chain fatty acids and the implications for neonatal liver metabolism

Levels of n-6, n-3, and medium-chain fatty acids (MCFA) in milk are highly variable. Higher carbohydrate intakes are associated with increased mammary gland MCFA synthesis, but the role of unsaturated fatty acids for milk MCFA secretion is unclear. This study addressed whether n-6 and n-3 fatty acids, which are known to inhibit hepatic fatty acid synthesis, influence MCFA in rat and human milk and the implications of varying MCFA, n-6, and n-3 fatty acids in rat milk for metabolic regulation in the neonatal liver. Rats were fed a low-fat diet or one of six higher-fat diets, varying in 16:0, 18:1n-9, 18:2n-6, 18:3n-3, and long-chain (LC) n-3 fatty acids. Higher maternal dietary 18:2n-6 or 18:3n-3 did not influence milk MCFA, but lower maternal plasma triglycerides, due to either a low-fat or a high-fat high-LC n-3 diet led to higher milk MCFA. MCFA levels were inversely associated with 18:1n-9, 18:2n-6, and 18:3n-3 in human milk, likely reflecting the association between dietary total fat and unsaturated fatty acids. High LC n-3 fatty acid in rat milk was associated with lower hepatic Pklr, Acly, Fasn, and Scd1 and higher Hmgcs2 in the milk-fed rat neonate, with no effect of milk 18:1n-9, 18:2n-6, or MCFA. These studies show that the dietary fatty acid composition does not impact MCFA secretion in milk, but the fatty acid composition of milk, particularly the LC n-3 fatty acid, is relevant to hepatic metabolic regulation in the milk-fed neonate.     

Effect of Randomly Interesterified Triacylglycerol Containing Medium- and Long-Chain Fatty Acids on Hepatic Fatty Acid Oxidation after a Single Administration to Rats

MLCTs, which are randomly interesterified triacylglycerol containing medium- and long-chain fatty acids in the same glycerol molecule, showed significantly higher acyl-CoA dehydrogenase activity when measured by using butyryl-CoA, octanoyl-CoA, and palmitoyl-CoA as substrates than long-chain triacylglycerol one hour after a single administration to rats. These results suggest that not only medium-chain fatty acid oxidation, but also long-chain fatty acid oxidation were increased in the liver of rats administered with MLCT.     

Long-term consumption of a diet with moderate medium chain triglyceride content does not inhibit the activity of enzymes involved in hepatic lipogenesis in the rat

The activities of glucose 6-phosphate dehydrogenase (EC 1.1.1.49), malic enzyme (EC 1.1.1.40), ATP-citrate lyase (EC 4.1.3.8), acetyl-CoA carboxylase (EC 6.4.1.2) and fatty acid synthetase were lower (-25 to -60%) in liver of rats fed during 45 days with a moderate long-chain triglycerides (LCT) content diet (32% of metabolizable energy, ME), than in control rats fed with a low fat diet (LCT, 10% of ME). However, the fall in malic enzyme activity was not significant. In contrast, these activities were higher (+40 to +160%) in rats fed with a diet with a moderate medium-chain triglycerides (MCT) content (32% of ME), than in control rats. Nevertheless, the increase in activity of malic enzyme and ATP-citrate lyase was more important. Contrary to LCTs, MCTs had no inhibitory effect on the activity of enzymes involved in hepatic lipogenesis.     

High-level medium-chain triglyceride feeding and energy expenditure in normal-weight women

The objective of this study was to assess how short-term feeding of high levels of dietary medium-chain triglyceride (MCT) affect energy expenditure and postprandial substrate oxidation rates in normal-weight, premenopausal women. Eight healthy women were fed both a MCT-rich and an isocaloric long-chain triglyceride (LCT)-rich diet for two 1-week periods separated by a minimum of 21 days. The energy intake in each diet was 45% carbohydrates, 40% fat, and 15% protein. The 2 diets had either 60.81% or 1.11% of total fat energy from MCT with the remaining fat energy intake from LCT. On days 1 and 7 of each diet, resting metabolic rate and postprandial energy expenditure (EE) were measured by indirect calorimetry with a ventilated hood. Results indicated on days 1 and 7, there were no significant differences between diets for resting metabolic rate or mean postprandial EE. On both days 1 and 7, fat oxidation for the MCT-rich diet was significantly greater (0.0001 相似文献   

Biosynthesis of medium-chain fatty acids by mammary epithelial cells from virgin rats.

Epithelial cells were isolated from the undifferentiated mammary glands of mature virgin female rats, and their lipogenic characteristics were studied. These cells synthesized predominantly medium-chain fatty acids, albeit at a low rate. In contrast, whole tissue from mammary glands of virgin rats synthesized predominantly long-chain fatty acids at a relatively higher rate, indicating that the lipogenic activity is dominated by the adipocyte component of the gland. Enzyme assays revealed that thioesterase II, the enzyme which regulates production of medium-chain fatty acids by the fatty acid synthetase, was present at a high activity in the undifferentiated mammary epithelial cells of virgin rats. Immunohistochemical studies confirmed this observation and showed that the regulatory enzyme was present exclusively in the epithelial cells lining the alveolar and ductal elements of the undifferentiated gland. This study demonstrates that the potential to elaborate tissue-specific medium-chain fatty acids is already expressed in the undifferentiated tissue of virgin rats and is not acquired as a result of the differentiation associated with the lactogenic phase of development. In this species mammary epithelial cells apparently synthesize predominantly medium-chain fatty acids at all stages of development, and only the overall rate of synthesis is increased on induction of the fatty acid synthetase during lactogenesis.     

Increased norepinephrine by medium-chain triglyceride attributable to lipolysis in white and brown adipose tissue of C57BL/6J mice

A further investigation of the lipolysis induced by medium-chain triglyceride (MCT) was conducted on C57BL/6J mice fed with a diet containing 2% MCT or 2% long-chain triglyceride (LCT). Blood norepinephrine, body fat and blood lipid variables, and the protein or mRNA expression of the genes relevant to lipolysis were measured and analyzed in the white and brown adipose tissue (WAT, BAT). Decreased body fat and improved blood lipid profiles attributable to MCT were confirmed. A higher level of blood norepinephrine was observed with the MCT diet. The adipose triglyceride lipase (ATGL) activity and its mRNA expression, the expression of protein and mRNA of the beta 3 adrenergic receptor (β3-AR) in both WAT and BAT, and the hormone-sensitive lipase (HSL) activity and its mRNA expression in BAT were significantly increased in the mice with MCT feeding. The lipolysis induced by MCT might be partially mediated by increasing norepinephrine, thereafter signaling the up-regulation of β3-AR, ATGL, and HSL in WAT and BAT.     

High dietary intake of medium-chain fatty acids during pregnancy in rats prevents later-life obesity in their offspring

We investigated the effects of dietary fatty acids of different chain lengths during pregnancy in the rat on the susceptibility of offspring to later-life obesity and the underlying mechanisms. Pregnant rats were fed three different diets: standard (STD), high medium-chain fatty acids (MCFA); and high long-chain fatty acids (LCFA). The male offspring were assigned to three groups: STD control, MCFA and LCFA according to the maternal diets and suckled by dams fed with STD during pregnancy and lactation. After weaning, the offspring were fed with STD from 3 to 8 weeks of age. At the age of 8 weeks, rats in three groups: high-fat diet (HFD) control, MCFA and LCFA were fed with HFD until 14 weeks of age in an attempt to induce obesity, and rats in the HFD control group were selected randomly from the STD control group. Body weight and body fat content were decreased in the MCFA group accompanied by down-regulated mRNA expression of fatty acid synthase and acetyl-coA carboxylase 1, and increased mRNA and protein expression of adenosine monophosphate (AMP)-activated protein kinase (AMPK), carnitine palmitoyltransferase 1 and uncoupling protein 3 compared with the corresponding controls at 3, 8 and 14 weeks of age. The results suggested that the MCFA diet during pregnancy prevented later-life obesity in the offspring when they were exposed to HFD in later life, which might be related to programming of the expression of genes involved in fatty acid metabolism.     

Transesterification reaction between medium- and long-chain fatty acid triglycerides using surfactant-modified lipase

Transesterification between medium-chain fatty acid triglycerides (MCT) and long-chain fatty acid triglycerides (LCT) in a nonsolvent system was investigated using surfactant modified lipase which is a complex of lipase, Rhizopus japonicus and surfactant, sorbitan monostearate. 74% conversion of was obtained after a 48-h reaction period, and the triglyceride composition was well described by the 1, 3-random 2-random stochastic model. The transesterification reaction between MCT and LCT closely followed the simple kinetic model, and the change in MCT and LCT contents could be simulated using one parameter. The effects of the water activity (A(w)) of modified lipase, the water content of the reaction system and the reaction temperature on the reaction rate were studied. A modified lipase A(w) of 0.35 and a water content of the reaction system at 0.09 wt % showed the highest activity. Inactivation did not occur below 60 degrees C, however, the activity decreased at temperatures over 70 degrees C.