Stearoyl-CoA desaturase activity in adipose tissue and liver of the cardiomyopathic hamster

Stearoyl-CoA desaturase activity and the fatty acid composition of lipids of adipose tissue and liver were determined in 35- and 180-day-old cardiomyopathic hamsters and age-matched normal controls. Enzyme activity was unchanged in the adipose tissue of 35-day-old animals but was significantly depressed in the 180-day-old cardiomyopathic hamsters. In the liver, stearoyl-CoA desaturase activity was significantly lower in the 35-day-old disease animals but was unchanged in the 180-day-old animals. The analysis of the fatty acid composition of the lipids isolated from adipose tissue showed an increase in the relative percentage of saturated fatty acids accompanied by a decrease in the relative percentage of unsaturated fatty acids in both age groups of the cardiomyopathic hamsters. However, linoleic acid content was increased in the diseased animals. Similar changes in fatty acid composition of lipids from the livers of 35-day-old cardiomyopathic hamsters were observed, but no significant differences in the fatty acid composition between 180-day-old cardiomyopathic hamsters and normal controls were observed. The changes in the fatty acid composition appear to be related to the observed changes in desaturase activity. In is concluded that such changes in desaturase activity and fatty acid composition could affect the normal structure and functions of membranes and membrane-related processes.     

Lipid content and fatty acid composition of heart and muscle of the BIO 82.62 cardiomyopathic hamster

Microscopic and analytical studies of the lipids in the heart and muscle of the BIO 82.62 myopathic hamsters and agematched normal animals at the average ages of 33, 67, and 108 days were performed. Microscopic examinations did not show increased lipid depositions in the hearts of the diseased animals as was found in the BIO 14.6 strain. No consistent differences in the lipid content of the cardiomyopathic hamsters (BIO 82.62) and age-matched controls were observed in the three age groups except in the cholesterol content of muscle. Cholesterol increased significantly (P<0.01) in the 67 and 108 day old animals. This increase elevated the cholesterol/phospholipid ratio. Analysis of the fatty acid composition of triglycerides showed that the cardiomyopathic hamsters store more saturated fatty acids in both heart and muscle than do their normal counterparts. The abundance of more saturated fatty acids may imply that either the desaturation mechanism is altered in the diseased animals or that unsaturated fatty acids are preferentially utilized in other processes.     

The effects of streptozotocin diabetes on tissue specific lipase activities in the rat

Fasting in normal rats produced a fall in hepatic triglyceride lipase (H-TGL) activity as well as lipoprotein lipase (LPL) activities of adipose tissue and psoas minor muscle. On the other hand, LPL activities of heart and diaphragm were not decreased by fasting; the former, in fact, was increased significantly. Changes in tissue specific lipase activity caused by withdrawal of insulin from insulin-treated diabetic animals paralleled in direction the changes induced by starvation of normal rats. Furthermore, it was shown in the present paper that the tissue specific lipase activity of diabetic rats became stuck in the starve phase of the starve-feed cycle regardless of dietary intake. The changes of the tissue specific lipase activities, especially of liver, adipose tissue and heart, appeared to coincide with those of plasma insulin levels. These results strongly suggest that the tissue specific lipase system is under hormonal regulation by insulin. Streptozotocin diabetes produced hypertriglyceridemia. The possible mechanism of the hypertriglyceridemia in diabetic animals was discussed in connection with the role of the tissue specific lipase system in the serum triglyceride metabolism.     

The effect of dietary fish oil on muscle and adipose tissue lipoprotein lipase

The activity of lipoprotein lipase (LPL) in the adipose tissue and skeletal muscle of rats fed glucose- or fructose-based diets containing fish oil, corn oil or tallow was examined. In addition, heart LPL activity was measured in rats fed a glucose-based diet containing either corn oil or fish oil. Adipose tissue LPL activity was unaffected by dietary fat. In both heart and skeletal muscle, LPL activity was higher in rats fed the fish oil diet. These results suggest that increased removal of triglyceride by muscle may contribute to the blood triglyceride lowering effect of dietary fish oil.     

Failure of the nonselective β-blocker propranolol to affect lipoprotein lipase gene expression in the rat

Treatment with β-blockers has been reported to be associated with the development of hypertriglyceridemia. The etiology, even the existence, of this phenomenon is controlverisal. The purpose of our study was to examine whether the nonselective β-blocker propranolol causes hypertriglyceridemia in the rat and whether its action is mediated by the modulation of lipoprotein lipase (LPL) messenger RNA (mRNA) accumulation or activity. LPL activity was assayed in fresh tissue by incubation with tritiated triglycerides. LPL mRNA was quantified in total RNA by slot-blot analysis using a mouse LPL complementary DNA probe. We have conducted three series of experiments in unanaesthetized rats in order to study the effects of different single doses of propranolol (1.5 to 6 mg i.p.) and different durations of treatment (15 min to 4 wk). We measured triglyceride and cholesterol levels in plasma as well as the LPL activity and mRNA levels in the heart and adipose tissue before and after propranolol administration. In these experiments we did not find any significant decrease in either the activity or the amount of mRNA of lipoprotein lipase nor was there any change in plasma lipids following treatment. Our results lead us to the conclusion that the nonselective β-blocker propranolol affects neither the activity nor, the mRNA level of LPL in the rat.     

Lipoprotein lipase in rats fed fish oil: Apparent relationship to plasma insulin levels

To investigate the role of lipoprotein lipase (LPL) and hepatic lipase in the triacylglycerol lowering effects of fish oil, rats were fed lard (L), corn oil (CO) or menhaden oil (MO) as the primary fat source in otherwise identical diets. After 2 weeks, soleus muscle LPL differed between groups (MO>CO>L). Hepatic lipase did not differ between CO- and MO-fed rats but was elevated in L-fed rats. Adipose LPL did not differ between diet groups. Total epididymal fat weight was reduced in MO-fed rats. There was a significant positive correlation between adipose tissue weight and plasma free fatty acids. MO-fed rats had lower plasma insulin levels. Insulin was directly correlated with plasma triacylglycerol and glucose, consistent with a hyperinsulinemic, insulin-resistant state in CO-and L-fed rats, and a protective effect with MO feeding. In addition, insulin was directly correlated with adipose LPL. A negative relationship between soleus muscle LPL and insulin approached significance. Soleus muscle LPL was significantly inversely correlated with triacylglycerol. The data indicate that increased skeletal muscle LPL, in response to MO or a MO-induced decrease in insulin, may contribute to the triacylglycerol-lowering effects of fish oil. Decreased fat weight and adipose LPL and increased soleus muscle LPL and decreased plasma triacylglycerol suggest a shift from fat deposition to oxidation with MO feeding. The lack of response of hepatic lipase to MO feeding suggests that this enzyme does not contribute to the fish oil-stimulated lowering of plasma triacyglycerolvia hepatic reuptake of very low density lipoproteins or other triacylglycerol-rich lipoproteins.     

Lipoprotein lipase and hepatic lipase in Wistar and Sprague-Dawley rat tissues. Differences in the effects of gender and fasting

To evaluate the effects of strain, gender and fasting in the regulation of lipoprotein lipase (LPL) and hepatic lipase (HL) activities were measured in tissues of male and female Wistar and Sprague-Dawley rats after feeding or a 24-h starvation period. It is noteworthy that an effect of gender on LPL activity was observed in Wistar, but not in Sprague-Dawley rats, not in the basal (fed) activity in several tissues, such as white and brown adipose tissues, heart, and brain, but also in response to fasting which affected LPL activity in brown adipose tissue, heat and lung of female but not of male Wistar rats. By contrast, HL activity in liver, plasma and adrenals of Sprague-Dawley rats was higher in females than in males. No effect of gender on HL activity was observed in Wistar rats. Our results indicate that differences exist between Wistar and Sprague-Dawley rats in the regulation of both LPL and HL. Some of the contradictory results found in the literature may be explained by the differences between rat strains and gender, as well as differences in the nutritional status of the animals.     

Characterization of the adipose tissue atrophy induced by peroxisome proliferators in mice

In the present study, we characterized the effects of peroxisome proliferators (PP) on adipose tissue in mice. Treatment with potent PP, such as perfluorooctanoic acid (PFOA), 2-methyl-2-(p(1,2,3,4-tetrahydroxy-naphthyl)-phenoxy)propionic acid, (4-chloro-6-(2,3-xylidino)2-pyrimidinylthio) acetic acid, and di(2-ethylhexyl)phthalate, caused dramatic decreases in adipose tissue weight, whereas the moderately potent PP, acetylsalicylic acid, had a relatively weak effect. This decrease in weight reflects a loss of fat from adipocytes rather than a loss of cells, as demonstrated by constant DNA content. The dose-dependency and time-course experiments indicate that peroxisome proliferation occurs simultaneously with or prior to adipose tissue atrophy. Thus, hepatic peroxisome proliferation might result in the increased mobilization of lipids and lipid utilization in liver. The enhanced adipose tissue hormonesensitive lipase (HSL) activity and down-regulated lipoprotein lipase (LPL) activity observed upon PP treatment might, at least in part, explain the loss of fat via increase FA release from adipocytes and/or decreased FA uptake from the circulation, respectively. In addition, the possible involvement of the increased tumor necrosis factor α expression found upon PFOA treatment in reducing the insulin sensitivity of adipose tissue and thereby altering LPL and HSL activities is discussed.     

Effect of magnesium deficiency on post-heparin lipase activity and tissue lipoprotein lipase in the rat

Previous studies have provided evidence that Mg deficiency affects lipid metabolism. The present experiments were designed to assess whether the hypertriglyceridemia associated with Mg deficiency was related to alterations in post-heparin lipase activity (PHLA). Mg-deficient and control diets were pair-fed to weanling Wistar rats for eight days and plasma lipoproteins were separated into various density classes by sequential preparative ultracentrifugation. Triglycerides were significantly increased in chylomicrons and in the very low density lipoprotein, low density lipoprotein and high density lipoprotein (HDL) fractions. Cholesterol and phospholipid levels were significantly lower in the HDL fraction. PHLA in deficient rat was substantially lower than in control rats. The inverse correlation between plasma triglyceride concentration and PHLA strongly suggests that hypertriglyceridemia is the result of defective lipolysis of plasma triglycerides in Mg-deficient rats. Further examination of the PHLA was carried out by salt-mediated inhibition of lipoprotein lipase (LPL) and by heparin sepharose affinity chromatography and purified rat LPL antiserum. The results indicate that hepatic lipase is significantly decreased in Mg-deficient rats but the low PHLA is due mainly to a decline in LPL. However, total LPL activity, that is, both the intracellular and the extracellular oools of LPL in adipose tissue, heart and diaphragm, were unaffected by Mg deficiency. The results suggest that the decrease of LPL activity in the plasma of Mg-deficient rats may be due to a selective decrease in the heparin-releasable pool of enzyme.     

Cholesteryl esterase activities in ventricles,isolated heart cells and aorta of the rat

Cholesteryl esterase activities were determined in homogenates of rat heart (ventricles), isolated, calcium-tolerant, cardiac myocytes and aortic tissue and were compared with acid and neutral triglyceride lipase activities in these fractions. Using cholesteryl oleate/phosphatidylcholine/taurocholate emulsions and digitonin pretreatment of the enzyme fractions, acid and neutral cholesteryl esterase activities were measured in all tissue preparations. In contrast to the acid and neutral triglyceridase and acid cholesteryl esterase activity, the neutral cholesteryl esterase activity was subject to substrate inhibition. Upon isolation of cardiac myocytes, and in contrast with the recovery of neutral triglyceride lipase activity, only a small portion of the neutral cholesteryl esterase (6%) was recovered, suggesting that nonmyocyte neutral cholesteryl esterase activity markedly contributes to the relatively high activity detectable in whole ventricular homogenates. The recovery of large amounts of neutral cholesteryl esterase activity in the supernatant of collagenase-digested heart tissue, obtained during the isolation of myocytes, which is also markedly enriched in activities of two endothelial marker enzymes (5′-nucleotidase and angiotesine-converting enzyme) may indicate the predominant contribution of neutral cholesteryl esterase activity from coronary endothelial cells to this activity detectable in ventricular homogenates. Relative to the activity in ventricular and myocyte homogenates, aorta homogenates possessed the highest specific neutral cholesteryl esterase activity. We propose that in addition to coronary endothelium, smooth muscle cells also contribute to the neutral cholesteryl esterase activity in ventricular homogenates. Pretreatment of rats with carrageenan an agent toxic to macrophages, lymphocytes and fibroblasts, induced a significant drop in myocardial neutral cholesteryl esterase and triglyceride lipase activity, suggesting that interstitially trapped macrophages may also contribute to lipolytic activities present in whole ventricular homogenates. Our data indicate that caution has to be taken upon extrapolation of experimental findings in heart homogenates to myocardial muscle cells.     

Hepatic and Adipose Tissue Depot-Specific Changes in Lipid Metabolism in Late-Onset Obese (LOB) Rats

Transgenic Late-onset OBesity (LOB) rats slowly develop a male-specific, autosomal dominant, obesity phenotype with a specific increase in peri-renal white adipose tissue (WAT) depot and preserved insulin sensitivity (Bains et al. in Endocrinology 145:2666–2679, 2004). To better understand the remarkable phenotype of these rats, the lipid metabolism was investigated in male LOB and non-transgenic (NT) littermates. Total plasma cholesterol (C) levels were normal but total plasma triacylglycerol (TAG) (2.8-fold) and hepatic TAG content (25%) was elevated in LOB males. Plasma VLDL-C and VLDL-TAG levels were higher while plasma apoB levels were 60% lower in LOB males. Increased hepatic TAG secretion explained the increased VLDL levels in LOB males. The hepatic gene expression of FAS, SCD-1, mitochondrial (mt)GPAT, and DGAT2 was up-regulated in both old obese and young non-obese LOB rats. Lipoprotein lipase (LPL) activity in heart and epididymal white adipose tissue (WAT) was unchanged, while LPL activity was increased in peri-renal WAT (30%) and decreased in soleus muscle (40%). Moreover, FAS, SCD-1 and DGAT2 gene expression was increased in peri-renal, but not in epididymal WAT. Basal lipolysis was reduced or unchanged and β-adrenergic stimulated lipolysis was reduced in WAT from both old obese and young non-obese LOB rats. To summarize, the obese phenotype of LOB male rats is associated with increased hepatic TAG production and secretion, a shift in LPL activity from skeletal muscle to WAT, reduced lipolytic response in WAT depots and a specific increase in expression of genes responsible for fatty acid and TAG synthesis in the peri-renal depot. F. Frick and R. Hume contributed equally to this work.     

Effect of a diet rich in sunflower oil on aspects of lipid metabolism in the genetically-obese rat

Aspects of the lipid metabolism of male, obese and lean Zucker rats were compared using animals which had been fed ad libitum for 32 days on a diet (HS) which contained 200 g sunflowerseed oil/kg or one (LS) which contained 50 g/kg of the oil. When compared with the LS diet, the HS diet decreased the characteristic lipid accretion in the liver of obese rats from 126 mg (LS) to 81 mg (HS)/g wet weight; corresponding values for the lean rats were 39 mg and 56 mg/g wet weight of liver, respectively. The HS diet depressed lipid synthesis de novo by liver homogenates and decreased the Δ9-desaturase activity of liver microsomes from obese and clean rats by about 50%. Δ9-Desaturase activity in vitro was also depressed by the addition of linoleic acid to liver microsomes from both obese and lean rats fed ad libitum on a standard laboratory diet. Depressed Δ9-desaturase activity, due to ingestion of the HS diet, was reflected in lower ratios of 16∶1/16∶0 and 18∶1/18∶0 fatty acids in tissue lipids from obese and lean rats. Ingestion of the HS compared with the LS diet resulted in increased proportions of 18∶2ω6 in liver lipids and adipose tissue triacylglycerols of obese and lean rats. The HS diet also increased the proportions of 20∶4ω6 in adipose triacylglycerols of obese and lean rats and in liver lipids of obese animals but not in their lean littermates.     

Dietary proteins modulate the effects of fish oil on triglyceridemia in the rat

Sprague-Dawley rats were fed purified diets varying in both protein (20%) and lipid (11%) content for 28 d to verify the independent and interactive effects of dietary proteins and lipids on serum and hepatic lipids, and on tissue lipoprotein lipase (LPL) activity in both fasted and postprandial states. These diets consisted of either casein-menhaden oil, casein-coconut oil, soy protein-menhaden oil (SPMO), soy protein-coconut oil, cod protein-menhaden oil, or cod protein-coconut oil. A randomized 3×2 factorial design was used. A significant protein-lipid interaction was seen on serum triglyceride levels: menhaden oil, compared with coconut oil, induced a decrease in serum triglyceride levels when combined with soy protein but not when combined with cod protein and casein. The lower serum triglyceride concentrations observed in the SPMO-fed rats could be the result of decreased hepatic triglycerides when soy protein was compared with casein and when menhaden oil was compared with coconut oil. Total LPL activity in the heart was higher in menhaden oil-fed rats than in coconut oil-fed rats in the postprandial state. The higher LPL activity in the heart could, however, explain only 10% of the reduction of serum triglycerides, contributing slightly to the lowering effects of SPMO diet on serum triglycerides. Therefore, the present results indicate that dietary proteins can modulate the effects of fish oil on triglyceridemia in the rat, and that could be mainly related to specific alterations in hepatic lipid concentrations.     

Clofibrate and Nafenopin (SU-13437): Effects on plasma clearance and tissue distribution of chylomicron triglyceride in the dog

Adult male dogs, which received orally for 21 days either no drug, 75 mg/kg/day of clofibrate or 25 mg/kg/day of nafenopin, were injected iv with¹⁴C-labeled chylomicron-lipid, essentially chylomicron-triglyceride fatty acid, at 0.2 g of fat per kilogram body weight. At times from 2–160 min after injection, samples of blood, liver, skeletal muscle and adipose tissue were removed, weighed and assayed for¹⁴C-lipid content. Also, in other dogs treated for 14 days, samples of skeletal muscle and adipose tissue were removed before and after treatment by biopsy for measurement of lipoprotein lipase activity. Chylomicron-¹⁴C was cleared more rapidly from the plasma of nafenopin-treated and to a lesser extent of clofibrate-treated dogs than controls. Thet _0.5 for clearance was ca. 31 min for control, 12 min for nafenopin-treated and 20 min for clofibrate-treated dogs. The total skeletal muscle mass of nafenopintreated animals took up 40–50% of the injected chylomicron-triglyceride during the first 20 min after injection, as compared with ca. 25–30% for clofibratetreated and 20–25% for control dogs. Also in treated dogs lesser percentages of the cleared chylomicron-¹⁴C appeared in the liver soon after injection and more in adipose tissue at later times. These observations could be related partially to a measured ability of clofibrate to increase adipose tissue lipoprotein lipase activity (ca. 50%) and of nafenopin to increase a lipase activity of skeletal muscle (ca. 20%). These data suggest that clofibrate and particularly nafenopin lower plasma triglycerides by increasing their clerance by the peripheral tissues.     

Combined effects of EFA deficiency and tumor necrosis factor-α on circulating lipoproteins in rats

Both tumor necrosis factor-α (TNF-α) and EFA deficiency (EFAD) have been established as causes of marked perturbations in lipid and lipoprotein metabolism. Excessive levels of circulating TNF-α can coexist with EFAD in various clinical disorders such as cystic fibrosis and type I diabetes. The present study therefore aimed to investigate their combined effects on lipid profile and lipoprotein composition by administering TNF-α to EFAD rats. Lipoprotein lipase (LPL), the ratelimiting enzyme in TG catabolism, was also measured in epididymal adipose tissue. EFAD, after a 4-wk period, induced significant increases in plasma TG (80%, P<0.001), total cholesterol (TC, 27%, P<0.025), and HDL-cholesterol (HDL-C, 62%). Two hours after the administration of TNF-α, a further rise in TG (43%, P<0.05) was noted in controls, but not EFAD animals. TC and HDL-C were unaffected by TNF-α treatment. In addition, TNF-α modified lipoprotein-lipid composition. VLDL and HDL₂ derived from EFAD rats were depleted in apolipoprotein (apo) E and apo A-II, and enriched in apo A-12 h after TNF-α administration. Finally, TNF-α decreased adipose tissue LPL activity in both control and EFAD animals. The TNF-α-induced inhibition was more marked in EFAD rats. The present results demonstrated that TNF-α can amplify or antagonize the effects of EFAD on lipid profile, lipoprotein composition, and LPL activity. These data also suggest that the host's nutritional status is a determining factor for the modulating effect of TNF-α on lipid metabolism.     

Effects of dietary methionine and cystine on lipid metabolism in hepatoma-bearing rats with hyperlipidemia

Abnormal lipid metabolism and its restoration by dietary methionine (Met) and cystine (Cys) were studied in Donryu rats subcutaneously implanted with an ascites hepatoma cell line of AH109A. The hepatoma-bearing rats exhibited byperlipidemia characterized by rises in serum triglyceride and cholesterol levels. Decreased lipoprotein lipase (LPL) activities in epididymal adipose tissue, cardiac muscle, and gastrocnemius as well as increased fatty acid mobilization from adipose tissue were considered to be responsible for the hepatoma-induced hypertriglyceridemia, while increased hepatic cholesterogenesis and decreased steroid excretion into feces were thought to be responsible for the hepatoma-induced hypercholesterolemia. Dietary-supplemented Met or Cys reduced the AH109A-induced hypertriglyceridemia with suppression of fatty acid synthesis in the host liver. Met restored the fall of LPL activities, while Cys did not. Dietary Met or Cys also reduced the hypercholesterolemia with restoration of decreased bile acid excretion into feces. These results suggest that dietary Met or Cys is hypolipidemic in the hepatoma-bearing rats with slight differences in their modes of action.     

Impaired lipoprotein metabolism in obese offspring of streptozotocin-induced diabetic rats

The time course of changes in lipoprotein metabolism of obese offspring of mildly diabetic rats was studied with respect to serum lipoprotein composition as well as LCAT and tissue lipoprotein lipase (LPL) activities. Mild hyperglycemia in pregnant rats was induced by intraperitoneal injection of streptozotocin on day 5 of gestation. Control pregnant rats were injected with citrate buffer. At birth, obese pups had higher serum glucose, insulin, and lipoprotein (VLDL, LDL-HDL₁, HDL_2–3) levels than control pups. After 1 mon of life, all of these parameters in obese rats became similar to those of controls. However, LCAT, adipose tissue LPL, and hepatic triacylglycerol lipase activities were high. At 2 mon of age, VLDL-TAG levels were higher in obese females than in controls. By the age of 3 mon, obese offspring had developed insulin resistance with hyperglycemia, hyperinsulinemia, and higher serum lipoprotein concentrations. Indeed, qualitative abnormalities of lipoproteins were seen and were typical of obese and diabetic human beings. Fetal hyperinsulinemia should be considered as a risk factor for later metabolic diseases, including dyslipoproteinemia.     

Inhibition of myocardial lipoprotein lipase by U-57,908 (RHC 80267)

U-57,908 (RHC 80267) was shown to inhibit lipoprotein lipase (LPL) activity in cardiac myocytes from rat hearts; the concentrations required for inhibition to 50% of control activity were 1.1 μM and 2.5 μM for myocyte homogenates and a post-heparin medium preparation, respectively. The inhibition of LPL activity by U-57,908 was not changed when the concentration of the triolein substrate and apolipoprotein CII activator in the assay was reduced. The availability of U-57,908 as a potent and selective LPL inhibitor may provide a useful experimental approach in studies on lipoprotein metabolism.     

Changes in the fatty acid composition of rat lung lipids during development and following age-dependent lipid peroxidation

Analyses of the fatty acid content and composition of various lung lipids were conducted in rats 1 day, 5 days, and 12 days after birth and in adult animals in order to define more clearly the specific lipid peroxidizing system found in neonatal rat lungs. Lipid peroxidation occurs in the 900×g supernatant fraction of rat lung homogenates in an age-dependent manner independent of the addition of any factor and is maximal at 5 days of age. No lipid peroxidation is evident in similar preparations of either newborn or adult lung tissue. As the animals develop, arachidonic and docosahexaenoic acids, fatty acids which are both highly susceptible to lipid peroxidation in the presence of a suitable catalyst, decrease gradually when measured as the percentage of the total fatty acids in the triglyceride fraction of the lung. The total quantity of triglycerides, however, is significantly lower in lungs from 1-day-old rats than at any other age. The fatty acid composition and total quantity of both lung phospholipids and lung free fatty acids do not show similar changes. Following in vitro incubation of the 900×g supernatant fraction of peroxidizing lung homogenates, an appreciable decrease in the amount of arachidonic and docosa-hexaenoic acid could be detected in lung triglycerides. Less extensive decreases were observed in the phospholipid fraction. No changes in these components were observed in newborn or adult animals. The addition of triarachidonin to the 900×g supernatant fraction of lung homogenates resulted in increased malondialdehyde release at all ages tested while added arachidonic acid increased the formation of malondialdehyde only in 5- and 12-day-old rat lung preparations. The addition of triolein, cholesterol arachidonate, and diarachidonyl phosphatidylcholine had no effect on malondialdehyde formation at any age. The age-dependent lipid peroxidation observed after in vitro incubation of rat lung homogenate preparations, therefore, may result from the relatively high concentration of triglycerides containing polyunsaturated fatty acids present in the neonatal tissue. As the susceptible polyunsaturated fatty acids of lung triglycerides are replaced by less unsaturated species, this activity may diminish concomitantly. Recipient of Public Heath Service Research Career Development Award 5-K04-HD00068 from the National Institute of Child Health and Human Development.