scholarly journals Prevention of peroxisomal proliferation by carnitine palmitoyltransferase inhibitors in cultured rat hepatocytes and in vivo

1987 ◽  
Vol 245 (2) ◽  
pp. 387-392 ◽  
Author(s):  
R Hertz ◽  
J Bar–Tana
Keyword(s):  
Rat Hepatocytes ◽  
Carnitine Palmitoyltransferase ◽  
Long Chain Fatty Acids ◽  
Beta Oxidation ◽  
Carnitine Acyltransferase ◽  
Cultured Rat Hepatocytes ◽  
Acyltransferase Inhibitors ◽  
Long Chain

1. The induction of peroxisomal beta-oxidation activities by bezafibrate in cultured rat hepatocytes and in the rat in vivo was prevented by inhibitors of carnitine acyltransferase, e.g. 2-bromopalmitate, 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate or 2-tetradecylglycidic acid. 2. The prevention of peroxisomal proliferation by carnitine palmitoyltransferase inhibitors could not be accounted for by inhibition of mitochondrial beta-oxidation, since 2-bromo-octanoate, acting as an inhibitor of beta-oxidation, did not prevent the induction of peroxisomal activities in cultured rat hepatocytes. 3. The putative role of the acylcarnitine derivative of bezafibrate was analysed by studying the formation of bezafibroylcarnitine with bezafibroyl-CoA as substrate. However, no bezafibroylcarnitine formation was demonstrated in the presence of rat liver preparations capable of catalysing transfer to carnitine of medium- or long-chain fatty acids. 4. The prevention of peroxisomal proliferation by carnitine acyltransferase inhibitors may help in dissecting the causal relationship between the multiple effects mediated by peroxisomal proliferators.

scholarly journals Fatty acid metabolism in hepatocytes cultured with hypolipidaemic drugs. Role of carnitine

1988 ◽  
Vol 253 (1) ◽  
pp. 161-167 ◽  
Author(s):  
P Gerondaes ◽  
K G M M Alberti ◽  
L Agius
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Rat Hepatocytes ◽  
Beta Oxidation ◽  
Carnitine Acyltransferase ◽  
Periportal Zone ◽  
Palmitate Metabolism

The direct effects of clofibrate analogues on carnitine acyltransferase activities and fatty acid metabolism were studied in cultured hepatocytes. Rat hepatocytes cultured with bezafibrate or ciprofibrate (0.1-10 micrograms/ml) for 48 h had increased activities of carnitine acetyltransferase (CAT; 4-6-fold) and carnitine palmitoyltransferase (CPT; 12-34%). The increase in CAT was higher in hepatocytes from the periportal zone (440%) of rat liver compared with cells from the perivenous zone (266%). In human hepatocytes, in contrast with rat, the fibrates did not cause a marked increase in CAT activity. The effects of fibrates on palmitate metabolism were dependent on the carnitine status. In the presence of exogenous carnitine (1 mM), rat hepatocytes cultured with bezafibrate had higher rates of total palmitate metabolism (29-34%) without increased partitioning of palmitate towards beta-oxidation, relative to control cultures. At low endogenous carnitine concentrations, cells cultured with bezafibrate had a greater increase in palmitate metabolism, esterification and cellular accumulation of triacylglycerol compared with the corresponding increases in the presence of carnitine. The changes in palmitate metabolism at either high or low carnitine concentrations were small in comparison with the changes in CAT activity. It is concluded that the increase in hepatic carnitine that occurs in vivo after fibrate feeding probably plays the major role in the changes in partitioning of fatty acid between beta-oxidation and esterification.

scholarly journals Induction of peroxisomal β-oxidation by a microbial catabolite of cholic acid in rat liver and cultured rat hepatocytes

1993 ◽  
Vol 295 (1) ◽  
pp. 217-220 ◽  
Author(s):  
T Nishimaki-Mogami ◽  
A Takahashi ◽  
K Toyoda ◽  
Y Hayashi
Keyword(s):  
Cholic Acid ◽  
Rat Hepatocytes ◽  
Peroxisome Proliferator ◽  
Beta Oxidation ◽  
Oxidation Activity ◽  
Cultured Rat Hepatocytes ◽  
Coa Reductase ◽  
Increased Activity

The capability of (4R)-4-(2,3,4,6,6a beta,7,8,9,9a alpha,9b beta-decahydro-6a beta-methyl-3-oxo-1H-cyclopental[f]quinolin-7 beta-yl)valeric acid (DCQVA), a catabolite of cholic acid produced by enterobacteria, to induce peroxisome proliferation in vivo and in vitro was studied. Rats given 0.3% DCQVA in the diet for 2 weeks showed marked increases in peroxisomal beta-oxidation, mitochondrial 2,4-dienoyl-CoA reductase and microsomal laurate omega-oxidation activities in the liver compared with control rats given the diet without DCQVA. Cultured rat hepatocytes treated with DCQVA for 72 h also exhibited greatly enhanced beta-oxidation activity. The increased activity was concentration-dependent and the effective concentrations were comparable with those of clofibric acid that produced the same degree of induction in the assay. The results demonstrate that DCQVA is a potent peroxisome proliferator that occurs naturally in rat intestine.

scholarly journals The Role of Long-Chain Fatty Acids in Inflammatory Bowel Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Chunxiang Ma ◽  
Reshma Vasu ◽  
Hu Zhang
Keyword(s):  
Inflammatory Bowel Disease ◽  
Fatty Acids ◽  
Bowel Disease ◽  
Mucosal Healing ◽  
Long Chain Fatty Acids ◽  
Inflammatory Bowel ◽  
Underlying Mechanisms ◽  
Long Chain ◽  
Chain Fatty Acids

Inflammatory bowel disease (IBD) is a complicated disease involving multiple pathogenic factors. The complex relationships between long-chain fatty acids (LCFAs) and the morbidity of IBD drive numerous studies to unravel the underlying mechanisms. A better understanding of the role of LCFAs in IBD will substitute or boost the current IBD therapies, thereby obtaining mucosal healing. In this review, we focused on the roles of LCFAs on the important links of inflammatory regulation in IBD, including in the pathogen recognition phase and in the inflammatory resolving phase, and the effects of LCFAs on immune cells in IBD.

scholarly journals Non-esterified Long-chain Fatty Acid Metabolism in Fed Sheep at Rest and During Exercise

1987 ◽  
Vol 40 (2) ◽  
pp. 221 ◽  
Author(s):  
DW Pethick ◽  
N Harman ◽  
JK Chong
Keyword(s):  
Skeletal Muscle ◽  
Ketone Bodies ◽  
Long Chain Fatty Acids ◽  
Entry Rate ◽  
Long Chain Fatty Acid ◽  
Pregnant Sheep ◽  
Arteriovenous Difference ◽  
Long Chain ◽  
Sustained Increase

The role of circulating, non-esterified, long-chain fatty acids (NEFA) as a source of energy for the whole animal and skeletal muscle was investigated in fed non-pregnant sheep at rest and during exercise. Infusion of tracer quantities of [1-14C]oleic or [l-14C]stearic acid was combined with the use of arteriovenous difference studies on fed sheep at rest or during a 2 h period of exercise on a belt treadmill moving at 4� 5 km h -I. At rest all parameters of NEFA metabolism indicated a minimal role for oxidation. Thus the concentration in plasma (0'07 � 0�01 mmol I-I), entry rate (0'08 � 0�02 mmol h- I kg-I body wt), contribution to whole animal oxidation (1'2 � 0'3%) and utilization of NEFA by skeletal muscle (0'046 � 0�008 mmol h- I kg-I muscle) were all low. Exercise prompted a shift to lipolysis and accordingly the above parameters increased markedly some 13-24-fold. The circulating concentration of ketone bodies showed only a small increase during exercise and consequently the role of ketone bodies as an energy source during exercise was minimal. Glucose utilization by skeletal muscle was considerable in animals at rest and it represented the most significant potential fuel of skeletal muscle. Exercise resulted in a sustained increase of 3-4-fold in the utilization of glucose by skeletal muscle. Thus the traditional view that NEF A and not glucose is a predominant fuel of skeletal muscle of fed sheep should be appraised.

scholarly journals Interactions of insulin, glucagon and dexamethasone in controlling the activity of glycerol phosphate acyltransferase and the activity and subcellular distribution of phosphatidate phosphohydrolase in cultured rat hepatocytes

1985 ◽  
Vol 230 (2) ◽  
pp. 525-534 ◽  
Author(s):  
R A Pittner ◽  
R Fears ◽  
D N Brindley
Keyword(s):  
Neutral Lipids ◽  
Relative Proportion ◽  
Rat Hepatocytes ◽  
Glycerol Phosphate ◽  
Acyltransferase Activity ◽  
Phosphatidate Phosphohydrolase ◽  
Cultured Rat Hepatocytes ◽  
Total Glycerol

Rat hepatocytes were incubated in monolayer culture for 8 h. Glucagon (10nM) increased the total phosphatidate phosphohydrolase activity by 1.7-fold. This effect was abolished by adding cycloheximide, actinomycin D or 500 pM-insulin to the incubations. The glucagon-induced increase was synergistic with that produced by an optimum concentration of 100 nM-dexamethasone. Theophylline (1mM) potentiated the effect of glucagon, but it did not affect the dexamethasone-induced increase in the phosphohydrolase activity. The relative proportion of the phosphohydrolase activity associated with membranes was decreased by glucagon when 0.15 mM-oleate was added 15 min before the end of the incubations to translocate the phosphohydrolase from the cytosol. This glucagon effect was not seen at 0.5 mM-oleate. Since glucagon also increased the total phosphohydrolase activity, the membrane-associated activity was maintained at 0.15 mM-oleate and was increased at 0.5 mM-oleate. This activity at both oleate concentrations was also increased in incubations that contained dexamethasone, particularly in the presence of glucagon. Insulin increased the relative proportion of phosphatidate phosphohydrolase that was associated with membranes at 0.15 mM-oleate, but not at 0.5 mM-oleate. It also decreased the absolute phosphohydrolase activity on the membranes at both oleate concentrations in incubations that also contained glucagon and dexamethasone. None of the hormonal combinations significantly altered the total glycerol phosphate acyltransferase activity. However, glucagon significantly increased the microsomal activities, and insulin had the opposite effect. Glucagon also decreased the mitochondrial acyltransferase activity. There was a highly significant correlation between the total phosphatidate phosphohydrolase activity and the synthesis of neutral lipids from glycerol phosphate and 0.5 mM-oleate in homogenates of cells from all of the hormonal combinations. Phosphatidate phosphohydrolase activity is increased in the long term by glucocorticoids and also by glucagon through cyclic AMP. In the short term, glucagon increases the concentration of fatty acid required to translocate the cytosolic reservoir of activity to the membranes on which phosphatidate is synthesized. Insulin opposes the combined actions of glucagon and glucocorticoids. The long-term events explain the large increases in the phosphohydrolase activity that occur in vivo in a variety of stress conditions. The expression of this activity depends on increases in the net availability of fatty acids and their CoA esters in the liver.

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