In-plane stress development in mesoporous thin films.

Ordered mesoporous thin films of TiO2 and CexZr1-xO2 (x = 0, 0.5, 1) were prepared via an evaporation-induced self-assembly (EISA) process and subsequently investigated in terms of the developing intrinsic and residual in-plane stress. These mechanical properties were determined by the curvature method, which is based on the determination of the deflection of light due to concave or convex bending of the films on a substrate. The films were investigated with regard to the intrinsic stress during heat treatment up to 500 °C and to the residual stress at room temperature for several annealing temperatures. Following this strategy, the influence of the decomposition of a block copolymer template on the intrinsic stress as well as the pore collapsing on the residual stress was analyzed. Nanoporous TiO2 thin films were prepared using two different block copolymers (PIB50-b-PEO45 and Pluronic® F127). A comparison between the templated and non-templated TiO2 films showed the lowest intrinsic and residual stress for the ordered mesoporous material prepared with PIB50-b-PEO45 indicating that the distributed polymer and the corresponding mesopores act as relaxing agents for the system. This was verified by mesoporous CexZr1-xO2 (x = 0, 0.5, 1) thin films showing a comparable behavior in terms of the experienced intrinsic stress. This work reveals an increase in the residual in-plane stress during pore collapse, which lays the foundation for further understanding of the stress-related mechanical properties of mesoporous thin films.

Regulation of palmitoyl-CoA chain elongation and linoleoyl-CoA chain elongation in rat liver microsomes and the differential effects of peroxisome proliferators, insulin and thyroid hormone.

Treatment of rats with p-chlorophenoxyisobutyric acid (clofibric acid), 2,2'-(decamethylenedithio)diethanol, di(2-ethylhexyl)phthalate or acetylsalicylic acid caused an increase in activity of palmitoyl-CoA chain elongation in hepatic microsomes. The activity of palmitoyl-CoA chain elongation decreased in both hypothyroid-state and diabetic-state rats, increased in hyperthyroid-state rats and did not change in adrenalectomized rats. The administration of clofibric acid to these rats in an altered hormonal state caused an increase in the activity of palmitoyl-CoA chain elongation, but no additional increase in the activity was observed with treatment of hyperthyroid rats with clofibric acid. The activity of linoleoyl-CoA chain elongation did not respond to the changes in either the nutritional conditions or the hormonal state of insulin so sensitively as the activity of palmitoyl-CoA chain elongation. The treatment of rats with triiodothyronine caused a marked increase in the activity of linoleoyl-CoA chain elongation; nevertheless, the activity of linoleoyl-CoA chain elongation was not changed by the treatment of rats with clofibric acid. The results suggest that rat liver microsomes contain at least two fatty acid chain elongation systems and that these chain elongation systems are regulated differently by hormones and drugs.

Increased activity of stearoyl-CoA desaturation in liver from rat fed clofibric acid.

Male rats were fed a diet containing 0.5% (w/w) p-chlorophenoxyisobutyric acid (clofibric acid), a hypolipidemic drug. Activities of stearoyl-CoA desaturation in hepatic microsomes were increased approx. 4 times following the administration of clofibric acid for 7 days. An increase in the activity of desaturation of stearic acid was also observed in the liver of clofibric acid-fed rats in vivo. The increase in the activity of microsomal stearoyl-CoA desaturation by clofibric acid-feeding was due to the increase in the activity of terminal desaturase as measured by the rate constant for cytochrome b5 reoxidation, but not due to the changes in cytochrome b5 content and NADH-cytochrome b5 reductase activity. Increases in the activity of stearoyl-CoA desaturation by clofibric acid-feeding were also observed in rats of hormonally altered state, such as diabetic rats, hyperthyroid rats and hypothyroid rats. Percentages of octadecenoic acid in total fatty acid of hepatic lipid were increased with the increase in the activity of stearoyl-CoA desaturation.

Alterations by clofibric acid of glycerolipid metabolism in rat-kidney.

Alterations induced by p-chlorophenoxyisobutyric acid (clofibric acid) in glycerolipid metabolism in rat-kidney were studied. (1) The treatment of rats with clofibric acid markedly decreased renal level of triacylglycerol, which seemed to be due to a reduced formation of triacylglycerol, since the in vivo incorporation of [14C]oleic acid (18:1), [14C]linoleic acid (18:2) and [3H]glycerol into triacylglycerol was decreased in clofibric acid-fed rats. (2) The administration of clofibric acid to rats increased proportions of 18:1 and 18:2 and decreased a proportion of arachidonic acid (20:4) in phosphatidylcholine; the contents of two major molecular species of renal diacylglycerophosphocholine (diacyl-GPC), palmitoyl-arachidonoyl (16:0-20:4) and stearoylarachidonoyl (18:0-20:4), were both decreased markedly. The treatment did not alter renal content of phosphatidylcholine. (3) By contrast, clofibric acid changed, to a lesser extent, the composition of molecular species of diacylphosphatidylethanolamine. (4) The decrease in the level of diacyl-GPC that contains 20:4 seemed to be due to the clofibric acid-caused reduction in the concentration of free 20:4 in kidney. The reduction in renal concentration of free 20:4 seemed to be caused by a decrease in serum concentration of lipids that contain 20:4, but not by a decrease in the activities of desaturation and chain elongation that participate in biosynthesis of 20:4. (5) The reduction by clofibric acid in the renal content of diacyl-GPC containing 20:4 resulted in the decrease in the formation of prostaglandin E2 in kidney.

Modulation by dietary oils and clofibric acid of arachidonic acid content in phosphatidylcholine in liver and kidney of rat: effects on prostaglandin formation in kidney.

The manipulation of 20:4(n - 6) contents in phosphatidylcholine of liver and kidney of rats by dietary oils and p-chlorophenoxyisobutyric acid (clofibric acid) as well as the effects on the formation of prostaglandin E2 in kidney were studied. Three groups of rats were fed diets that contained either safflower oil (SO) or perilla oil (PO) or fish oil (FO) for 1 week. Each dietary group was divided into two groups. One group continued the same diet for another 1 week; the second group continued the same diet and received subcutaneous injections of clofibric acid once a day for 1 week. The content of 20:4(n - 6) in hepatic phosphatidylcholine was markedly lowered by feeding either FO or PO and was further decreased by the administration of clofibric acid. Feeding either FO or PO lowered the content of 20:4(n - 6) in hepatic phosphatidylethanolamine, whereas clofibric acid increased it. The decrease in the level of 20:4(n - 6) in serum phospholipid was produced by feeding either FO or PO and by the administration of clofibric acid as well. There was a high correlation for the levels of 20:4(n - 6) between hepatic phosphatidylcholine and serum phospholipid. The changes brought about by dietary oils and clofibric acid in renal phosphatidylcholine was similar to those observed in liver. The content of 20:4(n - 6) in renal phosphatidylcholine was highly correlated with the level of 20:4(n - 6) in serum phospholipid. Other phospholipids in kidney responded less sensitively to the manipulation by dietary oils and clofibric acid. These results suggest that the level of 20:4(n - 6) in renal phosphatidylcholine is regulated by the level of 20:4(n - 6) in hepatic phosphatidylcholine through the changes in serum level of 20:4(n - 6). Formation of prostaglandin E2 in kidney slices was dependent on the content of 20:4(n - 6) in renal phosphatidylcholine.

Sex-related difference in the effect of clofibric acid on induction of two novel long-chain acyl-CoA hydrolases in rat liver.

The sex differences in the induction of two novel long-chain acyl-CoA hydrolases in hepatic cytosol of rats by clofibric acid (p-chlorophenoxyisobutyric acid)-feeding and the properties of the induced acyl-CoA hydrolases were investigated. Marked sex-related difference was observed in the induction of acyl-Coa hydrolase activity. The sex difference was mainly due to the difference in the induction of acyl-CoA hydrolase with higher molecular weight (hydrolase I), but not to the difference in the induction of acyl-CoA hydrolase with lower molecular weight (hydrolase II). The extent of the induction of the hydrolase I in hepatic cytosol of male rats was 3.5 times over that of female rats. Castration of male rats resulted in the marked depression of the ability to induce hydrolase I. The administration of testosterone to the castrated male rats recovered completely the ability to induce hydrolase I. Unlike hydrolase I, the ability to induce hydrolase II did not respond to the changes in state of androgen. The administration of di-(2-ethylhexyl)phthalate also induced both hydrolase I and II, although the extent of the induction of hydrolase I was less compared to that by clofibric acid treatment. Likewise, marked sex difference was observed in the induction of the hydrolase I on di-(2-ethylhexyl)phthalate administration. These two hydrolases showed different kinetic properties and different substrate specificities to each other. Hydrolase I was inhibited by bovine serum albumin in vitro, but was not affected by Mg2+. Hydrolase II was activated slightly in the presence of lower concentrations of bovine serum albumin, Mg2+ or Ca2+.

Differential effects of altered hormonal state on the induction of acyl-CoA hydrolases and peroxisomal beta-oxidation by clofibric acid.

Induction of hydrolase I, hydrolase II, peroxisomal beta-oxidation and hepatomegaly caused by clofibric acid (rho-chlorophenoxyisobutyric acid) administration was investigated in relation to alterations in hormonal state of glucocorticoid, thyroid hormone and insulin. (1) In adrenalectomized rats, the ability to induce hydrolase I was depressed effectively and little hepatomegaly was produced. Hydrolase II and peroxisomal beta-oxidation were induced to a similar extent, compared to those of intact rats. (2) In hypothyroid rats, induction of hydrolase I, hydrolase II, peroxisomal beta-oxidation and hepatomegaly was reduced. In hyperthyroid rats, the ability to induce hydrolase I, hydrolase II and peroxisomal beta-oxidation was depressed, although hepatomegaly was produced by the same or a greater extent as in intact rats. (3) In diabetic rats, marked reduction of ability to induce both hydrolase I and II was observed and induction of hepatomegaly was depressed slightly, although peroxisomal beta-oxidation was induced normally. Differences in the response of four parameters (hydrolase I, hydrolase II, peroxisomal beta-oxidation and liver size) to alterations in hormonal state suggest that the four biological responses to clofibric acid may each be mediated through distinct mechanism(s) other and regulated by distinct hormone(s).

Modification by clofibric acid of acyl composition of glycerolipids in rat liver. Possible involvement of fatty acid chain elongation and desaturation.

Administration of p-chlorophenoxyisobutyric acid (clofibric acid) to rats induced a marked change in acyl composition of hepatic glycerolipids; a considerable increase in the proportion of octadecenoic acid (18:1) was accompanied by a marked decrease in the proportion of octadecadienoic acid (18:2). Among the glycerolipids, the changes in the proportions of 18:1 and 18:2 were the most marked in phosphatidylcholine. The change in the acyl composition of phosphatidylcholine paralleled the change in free fatty acid composition in microsomes. The treatment of rats with clofibric acid resulted in a 2.3-fold increase in activity of microsomal palmitoyl-CoA chain elongation and a 4.8-fold increase in activity of stearoyl-CoA desaturation. The activities of acyl-CoA synthetase, 1-acylglycerophosphate acyltransferase and 1-acylglycerophosphorylcholine acyltransferase in hepatic microsomes were increased approx. 3-, 1.7- and 3.6-times, respectively, by the treatment of rats with clofibric acid. These findings are discussed with respect to the role of fatty acid modification systems in the regulation of acyl composition of phosphatidylcholine.

Selective increase in acylation of 1-acylglycerophosphorylcholine in livers of rats and mice by peroxisome proliferators.

Rats were fed a diet containing p-chlorophenoxyisobutyric acid (clofibric acid). Activity of microsomal 1-acylglycerophosphorylcholine (1-acyl-GPC) acyltransferase in liver was increased approx. 3-fold by the treatment with clofibric acid. The treatment of rats with clofibric acid did not increase activity of microsomal 2-acyl-GPC acyltransferase. Feeding a diet containing 2,2'-(decamethylenedithio)diethanol (tiadenol), di(2-ethylhexyl)phthalate or acetylsalicylic acid also resulted in a selective increase in the activity of 1-acyl-GPC acyltransferase in rat liver. Treatment with clofibric acid increased the activity of 1-acyl-GPC acyltransferase in liver of mouse as well as rat, but did not change the activity in liver of guinea-pig. The relative rate of acylation of 1-acyl-GPC with various acyl-CoAs by hepatic microsomes was not changed by the treatment of rats with clofibric acid.

The mechanism for the increased supply of phosphatidylcholine for the proliferation of biological membranes by clofibric acid, a peroxisome proliferator.

The metabolic changes induced by p-chlorophenoxyisobutyric acid (clofibric acid), a peroxisome proliferator, in hepatic glycerolipids for the supply of membrane phospholipids were studied. The administration of clofibric acid to rats caused hepatomegaly and an increase in hepatic contents of phosphatidylcholine (PtdCho) (1.13-fold on the basis of g liver and 1.50-fold on the basis of whole liver). The administration of the drug enhanced the formation in vivo of PtdCho from [3H]glycerol, which seemed to be due to the increase in activity of CTP:phosphocholine cytidylyltransferase. On the other hand, clofibric acid depressed the activity of phosphatidylethanolamine N-methyltransferase. The in vivo study using [3H]glycerol revealed that clofibric acid slightly reduced the secretion of PtdCho into circulation. On the other hand, the drug did not affect the turnover of PtdCho. These results may elucidate the metabolic alterations by which clofibric acid increases hepatic mass of PtdCho. The facilitated biosynthesis of PtdCho by the drug seemed to lead to the increased formation of phosphatidylserine and subsequently phosphatidylethanolamine. Physiological significance of the alterations in glycerolipid metabolism by clofibric acid was discussed in relation to biological action of the drug.

Induction of microsomal stearoyl-CoA desaturation by the administration of various peroxisome proliferators.

Male rats were fed a diet containing 0.5% p-chlorophenoxyisobutyric acid (clofibric acid), 1% acetylsalicylic acid, 2% di-(2-ethylhexyl)phthalate, 2% dibutylphthalate, 2% di-(2-ethylhexyl)adipate or 0.5% 4,4'-(isopropylidenedithio)bis(2,6-di-tert-butylphenol)) (probucol) for 7 days. Activity of microsomal stearoyl-CoA desaturation in rat liver was increased, ranging from 2.1 to 3.6 times, in association with an increase in the activity of peroxisomal beta-oxidation and catalase following the administration of clofibric acid, di-(2-ethylhexyl)phthalate, dibutylphthalate or di-(2-ethylhexyl)adipate. The increase in the activity of stearoyl-CoA desaturation by peroxisome proliferators appears to be due to an increase in activity only of the terminal desaturase, but not to changes in either NADH-cytochrome b5 reductase activity or cytochrome b5 content. Unlike peroxisome proliferators, probucol increased little the activity of either microsomal desaturation or peroxisomal beta-oxidation. The percentage of octadecenoic acid in total fatty acid of hepatic microsomes, homogenates and serum was increased markedly by the administration of peroxisome proliferators.

Induction of hepatic long-chain acyl-CoA hydrolase by clofibric acid administration.

The induction of hepatic long-chain acyl-CoA hydrolase in the cytosolic fraction by administration of clofibric acid (p-chlorophenoxyisobutyric acid) was compared in rats, mice and guinea-pigs. In rats, two long-chain acyl-CoA hydrolases were induced by the administration of clofibric acid. In mice, only one long-chain acyl-CoA hydrolase was induced, and this hydrolase had properties similar to those of the lower-molecular-weight hydrolase induced in the hepatic cytosol of rats. In hepatic cytosol of guinea-pig, no hydrolase was induced by the administration of clofibric acid.

Effects of peroxisome proliferators on fatty acid-binding protein in rat liver.

The relationship between hepatic fatty acid-binding protein and peroxisomal beta-oxidation was studied. Rats were fed a diet containing p-chlorophenoxyisobutyric acid (clofibric acid), 2,2'-(decamethylenedithio)-diethanol (tiadenol), di-(2-ethylhexyl)-phthalate (DEHP), di-(2-ethylhexyl)-adipate (DEHA) and acetylsalicylic acid. On the administration of these peroxisome proliferators, both [1-14C]oleic acid-binding capacity and content of fatty acid-binding protein were increased, in association with an increase in peroxisomal beta-oxidation activity. The order of the increase in binding capacity and content of fatty acid-binding protein was tiadenol greater than DEHP greater than or equal to clofibric acid greater than DEHA = acetylsalicylic acid. The order of the increase in peroxisomal beta-oxidation activity in liver was tiadenol greater than clofibric acid greater than or equal to DEHP greater than DEHA = acetylsalicylic acid. Linear regression analysis between the binding capacity or content of fatty acid-binding protein and peroxisomal beta-oxidation activity was highly significant.

Role of stearoyl-CoA desaturase and 1-acylglycerophosphorylcholine acyltransferase in the regulation of the acyl composition of phosphatidylcholine in rat liver.

The role of stearoyl-CoA desaturase and 1-acylglycerophosphorylcholine (1-acylGPC) acyltransferase in regulating acyl composition of microsomal phosphatidylcholine was investigated in rat liver, using rats in five different kinds of physiological state: clofibric acid-fed rats, diabetic rats, insulin-treated diabetic rats, starved rats and starved-refed rats. There was a reverse linear correlation between 18:1 and 18:2 in the C-2 position, and a similar correlation was found between 18:1 and 18:2 in microsomal free fatty acids. The proportion of 18:1 or 18:2 in the C-2 position of phosphatidylcholine correlated with the proportion of the respective fatty acids in microsomal free unsaturated fatty acids which could be incorporated effectively, except for the group of clofibric acid-fed rats. In this group alone, 1-acylGPC acyltransferase was induced markedly. The proportion of 18:1 in microsomal free fatty acids correlated well with the activity of stearoyl-CoA desaturase. The physiological significance of stearoyl-CoA desaturase and 1-acylGPC acyltransferase was discussed in relation to the regulation of the acyl composition of phosphatidylcholine.

Inducing effects of clofibric acid on 1-acylglycerophosphorylcholine acyltransferase in kidney and intestinal mucosa of rats.

Administration of p-chlorophenoxyisobutyric acid (clofibric acid) markedly increased the activity of microsomal 1-acylglycerophosphorylcholine (1-acyl-GPC) acyltransferase in kidney, intestinal mucosa and liver, but not in brain, heart, lung, spleen, testis or skeletal muscle. In both kidney and liver, a marked dose-dependent increase in the activities of both microsomal 1-acyl-GPC acyltransferase and peroxisomal beta-oxidation was observed. In the rats treated with clofibric acid at a relatively low dose, the increase in the activity of 1-acyl-GPC acyltransferase in kidney was more marked than that in liver. The extent of the relative increase in the activity of 1-acyl-GPC acyltransferase to the activity of peroxisomal beta-oxidation in kidney was more marked than that in liver. The increased activity of 1-acyl-GPC acyltransferase in both kidney and liver lasted throughout the 8-week treatment period of rat with clofibric acid.

Effects of clofibric acid and tiadenol on cytosolic long-chain acyl-CoA hydrolase and peroxisomal beta-oxidation in liver and extrahepatic tissues of rats.

The effects of two peroxisome proliferators, p-chlorophenoxyisobutyric acid (clofibric acid) and 2,2'-(decamethylenedithio)diethanol (tiadenol), on cytosolic long-chain acyl-CoA hydrolase and peroxisomal beta-oxidation were studied in several organs of rat. Among organs of control rats, the brain had the highest activity of long-chain acyl-CoA hydrolase, followed by testis, and a low activity was found in other tissues. Administration of the peroxisome proliferators caused a marked increase in activity of long-chain acyl-CoA hydrolase in both liver and intestinal mucosa and a slight increase in the activity in kidney, but little affected acyl-CoA hydrolase activity in either brain, testis, heart, spleen and skeletal muscle. In accordance with the change in the activity of acyl-CoA hydrolase, the activity of peroxisomal beta-oxidation was markedly increased in liver, intestinal mucosa and kidney, and a slight increase was found in brain and testis, whereas peroxisome proliferators little affected the activity in other organs tested. Gel filtration of cytosol from intestinal mucosa showed that clofibric acid caused an appearance of a new peak in intestinal mucosa. Although cytosol of liver, intestinal mucosa, brain and testis contained two 4-nitrophenyl acetate esterases with different molecular weights (about 105,000 and about 55,000), these esterases are different from cytosolic long-chain acyl-CoA hydrolases of these four organs in respect of molecular weight. The administration of clofibric acid little affected cytosolic 4-nitrophenyl acetate esterases. Comparative studies on cytosolic long-chain acyl-CoA hydrolases from these four organs showed that liver hydrolase I (molecular weight of about 80,000) had properties similar to those of brain and testis enzymes. On the other hand, intestinal mucosa enzyme was different from either hepatic hydrolase I or II (molecular weight of about 40,000). The results from the present study suggest that inductions of peroxisomal beta-oxidation and cytosolic long-chain acyl-CoA hydrolases are essential responses of rats to peroxisome proliferators not only in liver but also in intestinal mucosa and that induced hydrolases are not attributable to non-specific esterases.

Induction of microsomal 1-acylglycerophosphocholine acyltransferase by peroxisome proliferators in rat kidney; co-induction with peroxisomal beta-oxidation.

Induction of microsomal 1-acyl-glycerophosphocholine (GPC) acyltransferase in rat tissues by four peroxisome proliferators, clofibric acid, tiadenol, DEHP and PFOA, was examined. Among the nine tissues examined, kidney, liver and intestinal mucosa responded to the challenges by the peroxisome proliferators to induce the enzyme. The treatment of rats with various dose of clofibric acid, tiadenol, DEHP or PFOA resulted in an induction of kidney microsomal 1-acyl-GPC acyltransferase in a dose-dependent manner. Despite the structural dissimilarity of peroxisome proliferators, the induction of microsomal 1-acyl-GPC acyltransferase was highly correlated with the induction of peroxisomal beta-oxidation. The activity of microsomal 1-acyl-GPC acyltransferase was not affected by changes in hormonal (adrenalectomy, diabetes, hyperthyroidism and hypothyroidism) and nutritional (starvation, starvation-refeeding, fat-free-diet feeding and high-fat-diet feeding) states. The induction of renal microsomal 1-acyl-GPC acyltransferase was seen in mice subsequent to the administration of clofibric acid and tiadenol and in guinea pigs subsequent to the administration of tiadenol. These results may indicate that kidney microsomal 1-acyl-GPC acyltransferase is a highly specific parameter responsive to the challenges by peroxisome proliferators and may suggest that the possibility that the inductions by peroxisome proliferators of microsomal 1-acyl-GPC acyltransferase and peroxisomal beta-oxidation in kidney are co-regulated.

Co-induction by peroxisome proliferators of microsomal 1-acylglycerophosphocholine acyltransferase with peroxisomal beta-oxidation in rat liver.

Administration of clofibric acid, 2,2'-(decamethylenedithio)diethanol, di(2-ethylhexyl)phthalate or perfluorooctanoic acid to male rates increased markedly microsomal 1-acylglycerophosphocholine (a-acyl-GPC) acyltransferase in a dose-dependent manner in liver. Simultaneous administration of actinomycin D or cycloheximide completely abolished the increase in the enzyme activity. The treatment of rats with clofibric acid did not affect the rate of decay of 1-acyl-GPC acyltransferase. Regardless of a great difference in the chemical structures of the peroxisome proliferators, high correlation was observed between the induced activities of microsomal 1-acyl-GPC acyltransferase and peroxisomal beta-oxidation. Stearoyl-CoA desaturase was induced by peroxisome proliferators in a dose-dependent manner; nevertheless, high correlation was not seen between the induced activities of desaturase and peroxisomal beta-oxidation. Hormonal (adrenalectomy, diabetes, hyperthyroidism and hypothyroidism) and nutritional (starvation, starvation-refeeding, fat-free diet feeding and high-fat diet feeding) alterations hardly affected the activity of 1-acyl-GPC acyltransferase. The present results indicate that microsomal 1-acyl-GPC acyltransferase is a useful parameter responsive to the challenges by peroxisome proliferators and suggest that a similar regulatory mechanism operates for the inductions of microsomal 1-acyl-GPC acyltransferase and peroxisomal beta-oxidation.

Effects of long-term administration of clofibric acid on stearoyl-CoA desaturase, 1-acylglycerophosphorylcholine acyltransferase and fatty acyl composition of microsomal phosphatidylcholine in rat liver.

Long-term effects of p-chlorophenoxyisobutyric acid (clofibric acid) on inductions of stearoyl-CoA desaturase and 1-acylglycerophosphorylcholine (1-acyl-GPC) acyltransferase, and on changes in fatty acyl composition of microsomal lipid in rat liver were studied. Male rats were fed clofibric acid at a dietary concentration of 0.25% for 2 or 22 weeks. Inductions of stearoyl-CoA desaturase and 1-acyl-GPC acyltransferase lasted throughout the long-term treatment and were the same as those of either young or aged rats which were treated with clofibric acid for 2 weeks. The long-term treatment of rats with clofibric acid scarcely affected components of stearoyl-CoA desaturation system other than terminal desaturase. In accordance with the induction of stearoyl-CoA desaturase, the increase in the proportion of octadecenoic acid in hepatic lipid lasted throughout the 22-week treatment. In the case of both of the long-term treatment and the short-term treatment of rats, the increase in the proportion of octadecenoic acid in microsomal phosphatidylcholine was due to the marked increase in the proportion of octadecenoic acid in position 2, but not position 1, of phosphatidylcholine. These changes in fatty acyl composition of phosphatidylcholine were not due to the alteration of the content of phosphatidylcholine in liver.

Reduction by clofibric acid of serum arachidonic acid in rats. Effect on the acyl composition of renal phospholipids.

Alterations induced by p-chlorophenoxyisobutyric acid (clofibric acid) in the composition of phosphatidylcholine and cholesterol esters in serum and their influence on the composition of phosphatidylcholine in the kidney were studied. Rats of different ages responded differently to the drug in terms of the levels of arachidonic acid (20:4) and linoleic acid (18:2) in the phosphatidylcholine and cholesterol esters in the serum. Administration of clofibric acid to 26-week-old rats for 2 weeks caused a marked decreased in the relative level of 20:4 in phosphatidylcholine and cholesterol esters in serum, whereas similar treatment of 6-week-old rats resulted in a reduction of 18:2 and, to a lesser extent, of 20:4 in serum lipids. The decrease in phosphatidylcholine that contained 20:4 in the serum of old rats was mainly due to a decrease in the concentration of stearoyl-arachidonoyl (18:0-20:4) species. The decrease in cholesterol arachidonate in serum caused by the treatment of old rats with clofibric acid seemed to be due to a reduction in the relative level of serum phosphatidylcholine containing 20:4. The marked reduction in serum lipids that contained 20:4 caused a decrease in the relative level of 20:4 in renal phospholipids, in particular, a decrease in the proportion of palmitoyl-arachidonoyl (16:0-20:4) and 18:0-20:4 phosphatidylcholine.