Effect of 1,3 butanediol on hepatic fatty acid synthesis and metabolite levels in the rat (original) (raw)
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Journal of Nutrition
Diets containing graded levels of 1,3-butanediol (BD) substituted for approximately equal amounts of glucose energy were fed to rats. Body weight gain was not affected by addition of 10 parts (17% of dietary energy) BD to the diet; however, addition of 15 parts BD (25% of dietary energy) or mode did depress weight gain. Plasma /3-hydroxybutyrate and acetoacetate levels were elevated as dietary BD was increased. Increasing the BD content of the diet decreased plasma glucose, insulin and triglycéridelevels. Plasma free fatty acids were increased by addition of BD to the diet. Hematocrit was increased slightly in rats fed the BD-containing diets and may have been related to the increased rate of urination associated with elevated plasma ketones. Hepatic rates of in vitro fatty acid synthesis were markedly depressed when BD was added to the diet. The in vitro rates of fatty acid synthesis in adipose tissue were not affected by dietary BD. Malic enzyme activity was depressed in both liver and adipose tissue only when high levels of BD were added to the diets. It is suggested that dietary BD affects hepatic fatty acid synthesis in the rat by its effect on the hepatic NADH/ NAD+ ratio.
Journal of Nutrition
The influence of dietary 1,3-butanediol (BD) on body weight gain, blood and liver metabolites, and on lipogenesis in pigs and chicks was studied. Body weight gain and energy intake of both pigs and chicks were depressed when the dietary energy derived from BD exceeded about 20%. Circulating /3-hydroxybutyrate and acetoacetate levels were markedly increased as the level of BD in the diet increased. Blood lactate levels were also increased by dietary BD. Plasma triglycéridelevels were in creased in pigs and unchanged in chicks fed BD-containing diets. In vitro rates of fatty acid synthesis and the activities of fatty acid synthetase and malic enzyme in pig adipose tissue were not affected by dietary BD. Neither addition of 18% dietary energy in the form of BD to the diet nor addition of BD to the incubation buffer affected ["C] glucose conversion to fatty acids by chick liver slices. Dietary BD did not affect long-chain acyl CoA levels in freeze-clamped chick liver but did increase the free CoA levels slightly. The hepatic lactate :pyruvate ratio was decreased when chicks were fed a BD-contain ing diet.
Hepatic fatty acid metabolism in rats fed diets with different
2003
In the present study the effects of some C 18 fatty acids on hepatic fatty acid metabolism have been compared. Male rats were fed cholesterol-free diets containing either C 18 : 0 , C 18 : 1 cis or C 18 : 1 trans isomers as the variables. In accordance with previous work, oleic acid in the diet caused an increase in cholesterol concentration in the liver and in the lipoprotein fraction of density (d; kg/l) , 1•006. Oleic acid also reduced the triacylglycerol:cholesterol value in this fraction. Surprisingly, the C 18 : 1 trans isomers diet induced a decrease in the amount of cholesterol in total plasma as well as in the 1•019 , d , 1•063 lipoprotein fraction. Both oleic acid and C 18 : 1 trans isomers increased the concentration of triacylglycerols in the liver. The two C 18 : 1 fatty acids differently influenced the hepatic activities of carnitine palmitoyltransferase-I and 3-hydroxy-acyl-CoA dehydrogenase; both enzymes were inhibited by C 18 : 1 trans isomers, while no change was induced by oleic acid. The activity of the citrate carrier was lower in the oleic acid-and C 18 : 1 trans isomers-fed rats, when compared with the rats fed stearic acid. No diet effects were seen for the activities of acetyl-CoA carboxylase, fatty acid synthase, diacylglycerol acyltransferase, citrate synthase and phosphofructokinase. The results are interpreted in that oleic acid raised liver triacylglycerol by reducing the secretion of it with the d , 1•006 lipoprotein fraction whereas the C 18 : 1 trans isomers enhanced liver triacylglycerol by lowering the hepatic oxidation of fatty acids.
2010
Rats were trained to eat a fat-free high carbohydrate diet from 800 to 1100 hours each day. After adaptation to meal-eating, the fatfree diet was supplemented with 8% methyl stéarate(Ci8;o) or 3% methyl linoleate (Ci8:2) for 7 days. Relative to the fat-free group, hepatic utiliza tion of acetate unit equivalents (C2 units) for fatty acid synthesis per mg soluble protein by the Ci8:o group was not significantly altered, whereas Ci8:2 supplementation significantly depressed hepatic fatty acid synthesis. Supplemental Ci8:2 also caused a significant decline in liver fatty acid synthetase and acetyl CoA carboxylase while fat-free and Ci8:o groups dis played similar enzyme activities. Within a treatment, C2 unit utilization tor in vivo fatty acid synthesis was identical to that of acetyl CoA car boxylase and fatty acid synthetase activities in vitro. Therefore, shortly after a meal, the hepatic activities of these two enzymes appear to be functioning at near capacity. Ci8:2 supplementation to the fat-free diet for 7 days caused a 25% decline in glucokinase and pyruvate kinase activ ities, but only pyruvate kinase was significantly depressed. In contrast, citrate cleavage enzyme and fatty acid synthetase were both significantly reduced in activity by 50%. Plasma unesterified fatty acid levels in rats fed Ci8:2 for 5 days were not significantly elevated prior to a meal, al though dietary Ci8:2 did cause a fourfold rise in plasma free linoleate. Quantitation of long chain acyl CoA esters in freeze-clamped liver tissue of rats fed fat-free or fat-free plus 3% Ci8:2 or Ci8:3 diets revealed no con centration differences between treatments either before or after a meal. Similarly, lactate and pyruvate concentrations as well as the lactate: pyru vate ratios were not significantly changed by dietary Ci8:2 or Ci8:3. The inhibitory effects of C18:2 or Ci8;3 appear not to be mediated through changes in total plasma free fatty acid levels, in total hepatic long chain acyl CoA concentration or in hepatic cytosolic redox state.
The Journal of Nutrition, 1977
Rats were trained to eat a fat-free high carbohydrate diet from 800 to 1100 hours each day. After adaptation to meal-eating, the fatfree diet was supplemented with 8% methyl stéarate(Ci8;o) or 3% methyl linoleate (Ci8:2) for 7 days. Relative to the fat-free group, hepatic utiliza tion of acetate unit equivalents (C2 units) for fatty acid synthesis per mg soluble protein by the Ci8:o group was not significantly altered, whereas Ci8:2 supplementation significantly depressed hepatic fatty acid synthesis. Supplemental Ci8:2 also caused a significant decline in liver fatty acid synthetase and acetyl CoA carboxylase while fat-free and Ci8:o groups dis played similar enzyme activities. Within a treatment, C2 unit utilization tor in vivo fatty acid synthesis was identical to that of acetyl CoA car boxylase and fatty acid synthetase activities in vitro. Therefore, shortly after a meal, the hepatic activities of these two enzymes appear to be functioning at near capacity. Ci8:2 supplementation to the fat-free diet for 7 days caused a 25% decline in glucokinase and pyruvate kinase activ ities, but only pyruvate kinase was significantly depressed. In contrast, citrate cleavage enzyme and fatty acid synthetase were both significantly reduced in activity by 50%. Plasma unesterified fatty acid levels in rats fed Ci8:2 for 5 days were not significantly elevated prior to a meal, al though dietary Ci8:2 did cause a fourfold rise in plasma free linoleate. Quantitation of long chain acyl CoA esters in freeze-clamped liver tissue of rats fed fat-free or fat-free plus 3% Ci8:2 or Ci8:3 diets revealed no con centration differences between treatments either before or after a meal. Similarly, lactate and pyruvate concentrations as well as the lactate: pyru vate ratios were not significantly changed by dietary Ci8:2 or Ci8:3. The inhibitory effects of C18:2 or Ci8;3 appear not to be mediated through changes in total plasma free fatty acid levels, in total hepatic long chain acyl CoA concentration or in hepatic cytosolic redox state.
Hepatic Fatty Acid Metabolism as a Determinant of Plasma and Liver Triacylglycerol Levels
European Journal of Biochemistry, 2008
To investigate the importance of factors influencing substrate availability for triacylglycerol biosynthesis on lipoprotein metabolism, the effects of two opposite-acting sulphur-substituted fatty acid analogues, tetradecylthioacetic acid and tetradecylthiopropionic acid were studied. Administration of tetradecylthioacetic acid to rats resulted in a reduction of plasma levels of triacylglycerols (44%) and cholesterol (26 %). This was accompanied by a reduction in very-low-density lipoprotein (VLDL) triacylglycerols (48 %), VLDL cholesterol (36% j, low-density lipoprotein (LDL) cholesterol (36 %) and high-density lipoprotein (HDL) triacylglycerols (50 %), whereas HDL cholesterol levels did not change. Subsequently, the HDLLDL-cholesterol ratio increased by 40 %. The cholesterol-lowering effect was accompanied by a reduction in hydroxymethylglutaryl CoA (HMG-CoA) reductase activity (37 %). Both mitochondrial and peroxisomal fatty acid oxidation increased (1.7-fold and 5.3-fold, respectively). Furthermore, there was a significant negative correlation between plasma triacylglycerols and mitochondrial fatty acid oxidation. Hepatic triacylglycerol synthesis was retarded, as indicated by a decrease in VLDL triacylglycerol secretion (40%), and by a reduced liver triacylglycerol content (29%). The activities of lipoprotein lipase and hepatic lipase in post-heparin plasma were not affected. Microsomal and cytosolic phosphatidate phosphohydrolase activities were inhibited (28 % and 70 %, respectively j. Hepatic malonyl-CoA levels decreased by 29% and the total activity of acetyl-CoA carboxylase was reduced (23%). In hepatocytes treated with tetradecylthioacetic acid, mitochondrial fatty acid oxidation increased markedly (100 %) and triacylglycerol secretion was reduced (40%). In tetradecylthiopropionic-acid-treated rats, a significant increase in both plasma and VLDL triacylglycerols was found (46 % and 72 %, respectively) but VLDL triacylglycerol secretion was unaffected. However, no effect on either plasma or lipoprotein cholesterol levels was seen. Mitochondrial fatty acid oxidation was decreased by 50 % and hepatic triacylglycerol levels increased by 33 %. In hepatocytes exposed to tetradecylthiopropionic acid, triacylglycerol synthesis increased (100 %) while triacylglycerol secretion and fatty acid oxidation remained unaltered. The results illustrate that lipoprotein triacylglycerol levels can be modulated by changes in the availability of fatty acid substrate for triacylglycerol biosynthesis, mainly by affecting mitochondrial fatty acid oxidation. In addition, we demonstrate that suppression of rat hepatic HMG-CoA reductase activity during treatment with tetradecylthioacetic acid may contribute to a cholesterol-lowering effect.
Impact of essential fatty acid deficiency on hepatic sterol metabolism in rats
Hepatology, 1996
EFA in the major mechanisms involved in the mainte-The major aim of the current investigation was to denance of hepatocyte sterol balance. (HEPATOLOGY fine whether essential fatty acid (EFA) deficiency modi-1996;23:848-857.) fies the intrahepatic metabolism and biliary output of sterols in rats. EFA-deficient diet caused an impoverishment in linoleic, arachidonic, and docosahexaenoic
European Journal of Biochemistry, 1995
To investigate the importance of factors influencing substrate availability for triacylglycerol biosynthesis on lipoprotein metabolism, the effects of two opposite-acting sulphur-substituted fatty acid analogues, tetradecylthioacetic acid and tetradecylthiopropionic acid were studied. Administration of tetradecylthioacetic acid to rats resulted in a reduction of plasma levels of triacylglycerols (44%) and cholesterol (26 %). This was accompanied by a reduction in very-low-density lipoprotein (VLDL) triacylglycerols (48 %), VLDL cholesterol (36% j, low-density lipoprotein (LDL) cholesterol (36 %) and high-density lipoprotein (HDL) triacylglycerols (50 %), whereas HDL cholesterol levels did not change. Subsequently, the HDLLDL-cholesterol ratio increased by 40 %. The cholesterol-lowering effect was accompanied by a reduction in hydroxymethylglutaryl CoA (HMG-CoA) reductase activity (37 %). Both mitochondrial and peroxisomal fatty acid oxidation increased (1.7-fold and 5.3-fold, respectively). Furthermore, there was a significant negative correlation between plasma triacylglycerols and mitochondrial fatty acid oxidation. Hepatic triacylglycerol synthesis was retarded, as indicated by a decrease in VLDL triacylglycerol secretion (40%), and by a reduced liver triacylglycerol content (29%). The activities of lipoprotein lipase and hepatic lipase in post-heparin plasma were not affected. Microsomal and cytosolic phosphatidate phosphohydrolase activities were inhibited (28 % and 70 %, respectively j. Hepatic malonyl-CoA levels decreased by 29% and the total activity of acetyl-CoA carboxylase was reduced (23%). In hepatocytes treated with tetradecylthioacetic acid, mitochondrial fatty acid oxidation increased markedly (100 %) and triacylglycerol secretion was reduced (40%). In tetradecylthiopropionic-acid-treated rats, a significant increase in both plasma and VLDL triacylglycerols was found (46 % and 72 %, respectively) but VLDL triacylglycerol secretion was unaffected. However, no effect on either plasma or lipoprotein cholesterol levels was seen. Mitochondrial fatty acid oxidation was decreased by 50 % and hepatic triacylglycerol levels increased by 33 %. In hepatocytes exposed to tetradecylthiopropionic acid, triacylglycerol synthesis increased (100 %) while triacylglycerol secretion and fatty acid oxidation remained unaltered. The results illustrate that lipoprotein triacylglycerol levels can be modulated by changes in the availability of fatty acid substrate for triacylglycerol biosynthesis, mainly by affecting mitochondrial fatty acid oxidation. In addition, we demonstrate that suppression of rat hepatic HMG-CoA reductase activity during treatment with tetradecylthioacetic acid may contribute to a cholesterol-lowering effect.
Analytical methods for evaluation of the fatty acid metabolism in rat liver
Acta Scientiarum. Biological Sciences
The liver is an essential organ for body energy homeostasis, controlling the biosynthesis, uptake and the disposal of carbohydrates and lipids. The hepatic steatosis is a common condition frequently associated with metabolic diseases and is characterized by the excessive accumulation of triglycerides in the liver. In recent years, many efforts have been devoted to prevent and treat the hepatic steatosis, but it remains being pointed out as the major cause for chronic hepatic diseases in Western countries. A considerable part of the knowledge about the physiopathology of hepatic steatosis, the effects of diets and drugs on the metabolic capacity of the liver to metabolize fatty acids, as well as the potential therapeutic approaches for hepatic steatosis derived from experimental animal models using rodents. Here, in this article, we present the details of some of the most common techniques used to evaluate fatty acid metabolism in liver of rats, including quantification of total lipid content, measurement of fatty acid oxidation in isolated subcellular fractions and procedures to measure the activities of important lipogenic enzymes. Classical protocols previously described to be performed using samples from other tissues were adapted to liver samples and different techniques with equivalent aims were compared. The principles and the advantages in terms of reliability and costs were discussed and the procedures here described can be applied for a low-cost broad evaluation of the fatty acid metabolism in liver of rats submitted to different experimental conditions.