Decreased Lipoprotein Lipase Research Articles

Beef tallow diet decreases lipoprotein lipase activities in brown adipose tissue, heart, and soleus muscle by reducing sympathetic activities in rats.

Effects of dietary fats consisting of different fatty acids on lipoprotein lipase activities in the interscapular brown adipose tissue, heart, and soleus muscle, and on body fat accumulation were studied in rats. Sprague-Dawley male rats were meal-fed an isoenergetic diet based on either beef tallow or safflower oil for 8 weeks. Lipoprotein lipase activities in the interscapular brown adipose tissue, heart, and soleus muscle before and after a meal were lower in the beef tallow diet group than in the safflower oil diet group. Body fat accumulation was greater in the beef tallow diet group than in the safflower oil diet group. The norepinephrine turnover rats in the interscapular brown adipose tissue, heart, and soleus muscle were lower in the beef tallow diet group. beta-Adrenergic receptor bindings were determined with [125I]iodocyanopindolol. Binding affinities of beta-adrenergic receptor in the interscapular brown adipose tissue, heart, and soleus muscle were lower in the beef tallow diet group probably resulted from lower membrane fluidities. These results suggest that intake of the beef tallow diet promotes body fat accumulation by reducing the lipoprotein lipase activities resulting from lower sympathetic activities in the brown adipose tissue, heart, and skeletal muscle.

Changes in lipoprotein lipase activity and plasma liver lipids in thiram intoxicated rats.

Acute thiram (tetramethyl-bis-thiocarbamyl disulphide) poisoning of rat (a single dose of 50% LD50) caused decreased lipoprotein lipase (LPL) activity in adipose tissue, the greatest inhibition being observed at 72 h after administration of the pesticide. Simultaneously, the levels of total plasma cholesterol, triacylglycerols and the high density lipoprotein (HDL) cholesterol were increased. On repeated pesticide administration (5% LD50) decreased LPL activity was observed after 14 and 30 days of poisoning, whereas after 90 days the LPL activity was distinctly increased. The levels of total cholesterol (in all periods of poisoning) and HDL cholesterol (only after 30 days of poisoning) became increased. These changes were accompanied by decreased content of free fatty acids and increase of hepatic triacylglycerols. The changes observed in the lipoprotein lipase activity of thiram-poisoned rats correspond to the profiles of plasma lipoproteins typical of thyroid hypofunction.

The regulation of adipose tissue and muscle lipoprotein lipase in runners by detraining.

To study the mechanism of lipoprotein lipase (LPL) regulation by exercise, we recruited 16 healthy athletes to undergo a 2-wk period of detraining. Fasting fat and muscle biopsies were performed both before and after the detraining period. In muscle, detraining resulted in a decrease in LPL activity in both the heparin-releasable (HR) (-45%, P < 0.05) and cellular (extractable [EXT]) (-75%, P < 0.005) fractions, with no significant changes in LPL immunoreactive mass and mRNA levels. However, several subjects demonstrated parallel decreases in LPL mass and mRNA levels with detraining, suggesting that there is some degree of heterogeneity in response. In adipose tissue, detraining had the opposite effects on LPL activity. In the HR fraction, detraining resulted in an 86% increase (P < 0.005) in LPL activity, which was paralleled by a 100% (P = 0.02) increase in HR mass. However, there was no significant change in EXT LPL activity or EXT LPL mass. There were no changes in adipose LPL synthetic rate or LPL mRNA levels with detraining. The ratio of adipose tissue/muscle LPL, which may be an important indicator of the tendency for storage of circulating lipids in adipose tissue, increased significantly after detraining. The adipose/muscle LPL ratio was 0.51 +/- 0.17 in the exercising runners, and 4.45 +/- 2.46 in the same runners after detraining (P < 0.05). Thus, detraining of athletes resulted in a decrease in muscle LPL that occurred through post-translational mechanisms, whereas adipose tissue LPL increased, also due to posttranslational changes. This decrease in muscle LPL, coupled with an increase in adipose LPL, yielded a condition favoring adipose tissue storage.

Cytokines stimulate lipolysis and decrease lipoprotein lipase activity in cultured fat cells by a prostaglandin independent mechanism

We previously showed that indomethacin blocked the effect of tumor necrosis factor (TNF) and other cytokines on lipolysis. We now show that TNF stimulates prostaglandin (PG) production, enhances lipolysis and decreases lipoprotein lipase (LPL) activity in 3T3-F442A adipocytes and indomethacin blocks these activities, suggesting that the actions of TNF are mediated by PG's. However, exogenous PGE2 at the levels induced by TNF is not sufficient to affect lipolysis or LPL activity and low doses of indomethacin and flurbiprofen block PG production without affecting TNF's action. Interleukin-1 and interferon-alpha and gamma induce lipolysis and decrease LPL activity but do not stimulate much PG production. These results demonstrate that cytokines enhance lipolysis and decrease LPL activity in 3T3 adipocytes by a PG independent mechanism.

Effects of in vivo estrogen treatment on adipose tissue metabolism and nuclear estrogen receptor binding in isolated rat adipocytes

We have previously demonstrated the existence of nuclear estrogen receptors in isolated adipocytes (Pedersen et al. (1991) Biochim. Biophys. Acta 1093, 80–86). In the present study we have investigated the regulatory properties of these nuclear estrogen receptors, in addition to the metabolic effects of estrogen on adipose tissue metabolism. Estrogen treatment (20 μg 17β-estradiol in NaCl for 7 days) decreased lipoprotein lipase activity (LPL) in the adipose tissue by 62% ( p < 0.05), decreased adipocyte size by 27% ( p < 0.01) and diminished the normal postovariectomy weight gain. Furthermore, estrogen treatment increased the nuclear estrogen receptor binding in adipocytes; in addition, there was a tendency for increased cytosolic estrogen receptor content as well. Time course studies revealed that already 6 h after a single estrogen injection the B max increased from 3.82 ± 0.3 fmol/10 6 cells to 9.8 ± 3.6 fmol/10 6 cells ( p < 0.1) and 24 h after a single injection the B max was maximally increased to 12.7 ± 5.5 fmol/10 6 cells ( p < 0.05). The K d was similar at all time points (about 3–5 nM). Furthermore, the specific insulin receptor binding was increased in adipocytes from estrogen treated rats. The specific insulin binding was maximally increased by 149 ± 6% ( p < 0.001) after 4 days of daily estrogen injections. The increased binding seemed to be due to an increased number of insulin receptors on adipocytes from estrogen treated rats with no alteration of the ED 50 value. In conclusion it was found that estrogen treatment has a positive feedback effect on its own nuclear receptor. In addition, estrogen treatment was found to have several metabolic effects in the adipose tissue. Estrogen treatment increased the insulin receptor number, decreased LPL activity, increased the lipolytic response in adipocytes and finally decreased body weight and adipocyte cell size.

Epinephrine inhibits lipoprotein lipase gene expression in rat adipocytes through multiple steps in posttranscriptional processing.

Previous studies have demonstrated that in vitro treatment of adipocytes with catecholamines results in a decrease in the activity of the enzyme lipoprotein lipase (LPL). To examine the mechanism of this effect, primary cultures of rat adipocytes were cultured in the presence of various concentrations of epinephrine (10(-9)-10(-5) M). Epinephrine yielded a dose-dependent decrease in LPL activity; heparin-releasable LPL activity was reduced to 66% of control values after exposure to 10(-5) M epinephrine for 2 h. However, there was no effect of epinephrine on LPL immunoreactive mass, as measured by enzyme-linked immunosorbent assay. When cells were pulse labeled with [35S]methionine, there was a rapid and dose-dependent decrease in immunoprecipitable LPL. In spite of the decrease in LPL translation, neither epinephrine nor other catecholamines altered the level of LPL mRNA or the rate of LPL transcription. To further examine LPL posttranslational processing, cells were pulse labeled with [35S]methionine in the absence of epinephrine and then chased with unlabeled methionine in the presence of epinephrine. Cells exposed to epinephrine during the chase demonstrated a decrease in LPL secretion into the medium as well as a decrease in LPL degradation. The addition of epinephrine during LPL posttranslational processing did not alter the sensitivity of the newly synthesized LPL protein to endo-beta-N-acetylglucosaminidase-H. Thus, epinephrine had multiple effects on adipocyte LPL. Although there was a rapid decrease in LPL synthesis that was not due to changes in LPL mRNA, the level of LPL protein was unchanged under these conditions due to a decrease in LPL degradation and secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of chlorate on the sulfation of lipoprotein lipase and heparan sulfate proteoglycans. Sulfation of heparan sulfate proteoglycans affects lipoprotein lipase degradation.

In avian-cultured adipocytes 76% of the newly synthesized lipoprotein lipase is degraded before release into the medium (Cupp, M., Bensadoun, A., and Melford, K. (1987) J. Biol. Chem. 262, 6383-6388). The same group (Cisar, L. A., Hoogewerf, A. J., Cupp, M., Rapport, C. A., and Bensadoun, A. (1989) J. Biol. Chem. 264, 1767-1774) has proposed that the interaction of lipoprotein lipase with a class of cell surface heparan sulfate proteoglycans is necessary for degradation to occur. To test further this hypothesis, the binding capacity of the plasma membrane for the lipase was decreased by inhibiting the sulfation of glycosaminoglycans with sodium chlorate, an inhibitor of sulfate adenyltransferase. Chlorate decreased sulfate incorporation into trypsin-releasable heparan sulfate proteoglycans to 20% of control levels. The amount of uronic acid in the trypsin-releasable heparan sulfate proteoglycans remained constant. Therefore, chlorate decreased sulfation density on heparan sulfate chains by approximately 5-fold. In the same fractions, chlorate increased the median heparan sulfate Mr measured on Sephacryl S-300. Chlorate decreased the maximum binding of 125I-lipoprotein lipase to adipocytes by 4-fold, but no significant effects on the affinity constants were observed. Chlorate increased lipoprotein lipase secretion in a dose-dependent relationship up to 30 mM. Utilizing a pulse-chase protocol, it was shown that lipase synthesis in control and chlorate-treated cells was not significantly different and that the increased secretion could be accounted for by a decreased lipoprotein lipase degradation rate. In control cells 77 +/- 11% of the synthesized enzyme was degraded whereas in chlorate-treated cells degradation was reduced to 42 +/- 9% of the synthesized amount. The present study shows that decreased sulfation of heparan sulfate proteoglycans decreases the maximum binding of the lipase for the adipocyte cell surface. Consistent with the model that binding of lipoprotein lipase to cell surface heparan sulfate is required for lipase degradation, degradation is reduced in chlorate-treated cultures. In this report it is also shown that chlorate inhibits lipoprotein lipase sulfation and that desulfation of the enzyme has no effect on its catalytic efficiency or on its binding to cultured adipocytes.

Effect of maternal fasting on fetal and placental lipid metabolism in swine

This experiment was designed to determine whether mobilizing maternal energy stores by fasting pregnant gilts would promote fetal energy storage by altering placental and fetal lipid metabolism. Pregnant gilts were fed a 15% tallow diet from d 80 to 99 and then fed a basal high-carbohydrate diet (control) or fasted from d 100 to 110 of gestation. Caesarean section was performed on d 110. Fasting caused maternal nonesterified fatty acid (NEFA) levels to increase 7.5-fold, beta-hydroxybutyric acid (beta-HBA) levels to increase 4.8-fold triglyceride (TG) levels to decrease 1.8-fold, and no change in plasma glucose concentration compared with controls. Fasted fetuses had a 1.3-fold increase in NEFA, 1.9-fold decrease in TG, 1.5-fold decrease in glucose, and no change in beta-HBA levels compared with control fetuses. Distribution of NEFA in fetal plasma was different from distribution of NEFA in maternal plasma. Esterification of [14C]-palmitate by maternal placenta and fetal adipose tissue was reduced by fasting, but other parameters of fatty acid metabolism were unaffected. Fasting decreased lipoprotein lipase activity per milligram of protein by 33% in maternal placenta and by 44% in fetal adipose tissue. Glycogen content of fetal liver and skeletal muscle was reduced by fasting pregnant gilts, but there was no detectable effect on percentage of carcass lipid of the fetus. These data suggest that fasting mobilizes maternal fuel stores but that these stores are not effectively used by the placenta or transported to the fetus for storage.

Metabolism of endothelial cell-bound lipoprotein lipase. Evidence for heparan sulfate proteoglycan-mediated internalization and recycling.

Lipoprotein lipase (LPL) hydrolyzes triglyceride in plasma lipoprotein primarily while bound to vascular endothelial cells. LPL metabolism by cultured endothelial cells was studied. Purified radioiodinated bovine LPL bound to porcine aortic endothelial cells at 4 degrees C with an association constant of 0.18 x 10(7) m-1. Analysis of the time course of LPL dissociation from endothelial cells at 4 degrees C yielded a dissociation rate constant of 3.9 x 10(-6)s-1. After 1 h at 37 degrees C, 28% of the LPL initially bound to the cell surface was no longer releasable by heparin or trypsin treatments, suggesting that LPL was internalized by the cells. Addition of heparin to the medium or pretreatment of the cells with heparinase markedly reduced the amount of LPL internalized, establishing a requirement for cell surface heparan sulfate proteoglycans in the process. When cells containing internalized LPL were incubated at 37 degrees C, a time-dependent increase in the amount of LPL in the medium and a corresponding decrease in LPL associated with the cells was found. This suggested that internalized LPL was released back into the medium. The catalytic activity, molecular size, and heparin-binding characteristics of the released LPL was similar to native LPL. Addition of either heparin, heparinase, or excess unlabeled LPL to prevent the rebinding of released 125I-LPL to the cell surface increased the amount of 125I-LPL present in the medium, suggesting that there is a process of recycling of 125I-LPL bound to the cell surface. Studies examining the effect of pH on dissociation of LPL from its binding site showed less dissociation of cell surface bound LPL at pH 5.5 compared with pH 7.4 and 8.5. These results suggest that even at acidic pH as in endocytotic vesicles, LPL remains bound to proteoglycans and this may facilitate the recycling of internalized LPL molecules.

Regulation of lipoprotein lipase activity and mRNA content in rat epididymal adipose tissue in vitro by recombinant tumour necrosis factor

Tumour necrosis factor (TNF) has previously been shown to decrease lipoprotein lipase (LPL) activity and mRNA levels in 3T3-L1 cells and in adipose tissue from rats and guinea pigs when injected in vivo, but not to alter LPL activity in human adipocytes incubated in vitro. The effect of recombinant human TNF on LPL activity and mRNA levels in rat epididymal adipose tissue incubated in vitro was examined. LPL activity and mRNA levels fell in adipose tissue taken from fed rats and incubated in Krebs-Henseleit bicarbonate medium with glucose. The addition of insulin and dexamethasone prevented these falls. TNF (400 ng/ml) produced a fall of approx. 50% in LPL activity after 2 h of incubation and of approx. 30% in LPL mRNA levels after 3 h. TNF did not decrease LPL activity in isolated adipocytes. These results demonstrate that rat adipose tissue incubated in vitro is responsive to TNF whereas isolated adipocytes are not.

Smoking depresses adipose lipoprotein lipase response to oral glucose

Adipose tissue lipoprotein lipase was studied in smokers (n = 17) aged 18-47 years and compared with enzyme activity in non-smokers of comparable age (n = 8) and a second time in some of the subjects 5-9 weeks after cessation of smoking (n = 7). Serum cotinine levels served to validate the smoking status of the subjects. Fasting enzyme activity was similar in smokers and non-smokers, when expressed per 10(6) cells, but was significantly increased when normalized for cell size. When lipoprotein lipase was determined in the same individual 4 h after an oral glucose load, a significant decrease (P less than 0.002) occurred in the smokers, while enzyme activity rose in the nonsmokers (P less than 0.02). A tendency for enzyme activity to rise after oral glucose was seen in ex-smokers, which did not reach statistical significance. Even though the mean serum insulin and glucose levels did not differ in the three groups of subjects, the per cent decrease in lipoprotein lipase after oral glucose in smokers was negatively correlated with insulin release into serum in the same subject, i.e., the greater the insulin release, the less the decrease in lipoprotein lipase activity. We would like to propose that the lower body weight in smokers is related to the paradoxical response of adipose tissue lipoprotein lipase to carbohydrate and that the reversal of this behaviour contributes to the weight gain often observed after cessation of smoking.

Tumor necrosis factor induced release of endothelial cell lipoprotein lipase.

The major functional pool of lipoprotein lipase (LPL) that hydrolyzes triglycerides in circulating lipoproteins is located on the vascular endothelium. The macrophage-secreted cytokine tumor necrosis factor (TNF), a molecule known to affect endothelial cell functions, was used to test the hypothesis that alterations of endothelial cell metabolism regulate the binding of LPL to these cells. TNF addition induced rapid (maximum release at 45 minutes) dissociation of LPL protein and activity from its binding sites on cultured porcine aortic endothelial cells. LPL release by TNF required endothelial cell metabolic event(s) which involved cell secretion. In addition, LPL release was inhibited by pertussis toxin, suggesting the involvement of guanine nucleotide regulatory protein(s). Addition of arachidonic acid, a molecule known to be released by endothelial cells due to phospholipase A2 activation by TNF treatment, released LPL from the cell surface. Furthermore, direct modulation of cellular phospholipase A2 activity also led to changes in the release of LPL. Our studies demonstrate that alterations in the cellular metabolism of endothelial cells, for example, by TNF, may release functional pools of LPL from the vascular endothelium. This decrease in LPL on endothelial cell surfaces might be involved in the development of hypertriglyceridemia and redirection of energy flow during infections and inflammation.

Lipid metabolism in renal failure

Many patients with renal failure show abnormalities of lipid metabolism. Hypertriglyceridemia and low levels of high density lipoprotein (HDL) cholesterol are frequent abnormalities in uremic patients. The hypertriglyceridemia and low HDL cholesterol are thought to result from decreased lipoprotein lipase activity. The decreased levels of hepatic lipase observed in renal failure may account for the presence of intermediate density lipoproteins (IDL) and the high HDL2 subfraction. The risk factor for coronary artery disease expressed as the ratio of total cholesterol to HDL cholesterol is elevated in renal failure patients, especially in those with hypertriglyceridemia. Treatment of renal patients with gemfibrozil partially reverses many of the lipid abnormalities including the low HDL cholesterol. However, only the HDL3 subfraction increased while HDL2 remained unchanged.

Influence of age and exercise training on lipid metabolism in Fischer-344 rats

The influence of training on fatty acid and glyceride synthesis by liver and adipose tissue homogenates of young and old Fischer-344 rats was examined. Four groups of rats (10 animals/group) were studied: young untrained, young trained, old untrained, and old trained. Training of each group was for 10 wk at 75% maximal O2 uptake. Young rats were killed at 6 mo of age and old rats were killed at 27 mo of age. Fatty acid synthesis was assessed by measuring the activities of acetyl-CoA carboxylase, fatty acid synthase, ATP citrate-lyase, "malic" enzyme, and glucose-6-phosphate dehydrogenase. Glyceride synthesis was evaluated by determining the rate of incorporation of [14C]glycerol 3-phosphate into lipids. In addition, lipoprotein lipase activity was measured in acetone-ether powders of adipose tissue from the four groups of rats. In liver, training had no effect on fatty acid or glyceride synthesis in either group. However, aging caused a significant decrease in the activities of four of the lipogenic enzymes but had no effect on glyceride synthesis. Training caused an increase in fatty acid synthase and glyceride synthesis in adipose tissue, and aging decreased lipoprotein lipase activity. It was concluded that training enhances the synthetic capacity of lipids by adipose tissue but that aging had a more profound effect in that the activities of the enzymes involved in these processes were lower in the old rats. Furthermore, the decreased activity of lipoprotein lipase in the older rats may explain the higher plasma triglyceride levels that were observed in these animals.

Effect of tumor necrosis factor administration in vivo on lipoprotein lipase activity in various tissues of the rat.

When added to murine adipocytes in culture, tumor necrosis factor (TNF) decreases the levels of lipoprotein lipase (LPL). Semb et al (1987. J. Biol Chem. 262: 8390-8394) have shown that administration of murine TNF to rats decreases lipoprotein lipase (LPL) in the epididymal fat pad with maximal inhibition requiring several hours. We have now tested the effects of treatment of rats with TNF on LPL activity in a variety of tissues and find that few show decreases in LPL under conditions that acutely increase serum triglycerides. Ninety minutes after treatment of male rats with human TNF (25 micrograms/200 g, i.v.), serum triglycerides rose 2.2-fold but there was no decrease in LPL activity in epididymal fat. Sixteen hours after TNF treatment LPL activity had decreased by 44% in epididymal fat, consistent with the previously reported data. In contrast, in female rats, no significant decrease was seen in LPL activity in parametrial adipose tissue at either 90 min or 16 hr after TNF administration despite increases in serum triglycerides (1.8-fold and 1.5-fold, respectively). There was little change in LPL activity in most other adipose tissue sites of male or female rats at either time after TNF treatment. No effect of TNF was seen on heart or diaphragm muscle LPL at any time. TNF treatment of both male and female rats produces consistent increases in de novo hepatic lipogenesis in vivo under conditions that increase serum triglycerides. It is unlikely that the limited effects of TNF on LPL in vivo can account for the rapid and sustained increase in serum triglycerides.

Insulin Deficiency Decreases Lipoprotein Lipase Secretion by Murine Macrophages

We investigated the effects of insulin deficiency and insulin treatment on the secretion of lipoprotein lipase (LPL) by murine macrophages. Streptozocin-induced insulin deficiency caused hyperglycemia and hypertriglyceridemia in mice. Peritoneal macrophages isolated from insulin-deficient mice secreted 70% less LPL activity than control mice. A 65% decrease in LPL activity in epididymal adipose tissue, without any changes in heart LPL activity, was also seen with insulin deficiency. One week of insulin treatment lowered plasma glucose and triglyceride levels in insulin-deficient mice. Additionally, 1 wk of insulin treatment increased LPL secretion by macrophages, but to only one-half of control, while normalizing adipose tissue LPL activity. One injection of insulin also increased LPL secretion by macrophages to one-half of control and normalized adipose tissue LPL activity, even though plasma glucose and triglyceride levels were not affected. In vitro insulin treatment of macrophages isolated from control or insulin-deficient mice had no effect on LPL secretion. The results suggest that insulin does not exert a direct effect on the LPL secretion by macrophages but that deficiency of insulin indirectly causes a profound decrease in macrophage LPL secretion. These changes in macrophage LPL secretion may contribute to the atherosclerotic process in diabetes mellitus.

Insulin deficiency decreases lipoprotein lipase secretion by murine macrophages

Insulin deficiency decreases lipoprotein lipase secretion by murine macrophages

Tissue-specific effects of rapid tumour growth on lipid metabolism in the rat during lactation and on litter removal

1. The effect of tumour burden on lipid metabolism was examined in virgin, lactating and litter-removed rats. 2. No differences in food intake or plasma insulin concentrations were observed between control animals and those bearing the Walker-256 carcinoma (3-5% of body wt.) in any group studied. 3. In virgin tumour-bearing animals, there was a significant increase in liver mass, blood glucose and lactate, and plasma triacylglycerol; the rate of oxidation of oral [14C]lipid to 14CO2 was diminished, and parametrial white adipose tissue accumulated less [14C]lipid compared with pair-fed controls. 4. These findings were accompanied by increased accumulation of lipid in plasma and decreased white-adipose-tissue lipoprotein lipase activity. 5. In lactating animals, tumour burden had little effect on the accompanying hyperphagia or on pup weight gain; tissue lipogenesis was unaffected, as was tissue [14C]lipid accumulation, plasma [triacylglycerol] and white-adipose-tissue and mammary-gland lipoprotein lipase activity. 6. On removal (24 h) of the litter, the presence of the tumour resulted in decreased rates of lipogenesis in the carcass, liver and white and brown adipose tissue, decreased [14C]lipid accumulation in white adipose tissue, but increased accumulation in plasma and liver, increased plasma [triacylglycerol] and decreased lipoprotein lipase activity in white adipose tissue. 7. The rate of triacylglycerol/fatty acid substrate cycling was significantly decreased in white adipose tissue of virgin and litter-removed rats bearing the tumour, but not in lactating animals. 8. These results demonstrate no functional impairment of lactation, despite the presence of tumour, and the relative resistance of the lactating mammary gland to the disturbance of lipid metabolism that occurs in white adipose tissue of non-lactating rats with tumour burden.

Lipoprotein Lipases, Lipoproteins and Tissue Lipids in Rats Fed Fish Oil or Coconut Oil

The effect of fish oil and coconut oil on plasma lipoproteins and lipoprotein-catabolizing enzymes [lipoprotein lipase (LPL) and hepatic endothelial lipase (HL)] was studied in rats. Male rats were fed for 4 wk purified diets containing equlenergetic, amounts of either coconut oil (group A), coconut oil:fish oil, 50:50 (group B) or fish oil (group C). Whole plasma triacylglycerol, cholesterol and phospholipid concentrations were appreciably lower in group C than in group A, mainly due to a fall in very low density lipoprotein (VLDL) and subgroup 2 of high density lipoprotein (HDL2), with less consistent changes in LDL and HDL3. VLDL components of group B were also considerably lower than corresponding ones in group A. LPL and HL activities were about 50% lower in groups B and C than in group A. Increased hepatic triacylglycerol and cholesterol concentrations were observed in groups B and C. It is suggested that the decrease in LPL and HL activity of fish oil—fed rats may be an adaptive response to the low concentration of the substrate (triacylglycerols) for these enzymes.

Multiple effects of tumor necrosis factor on lipoprotein lipase in vivo.

A single dose of recombinant murine tumor necrosis factor (TNF) suppressed lipoprotein lipase activity in adipose tissue of fed rats, mice, and guinea pigs for 48 h, even though TNF itself is rapidly metabolized in vivo. Immunoprecipitation of [35S]lipoprotein lipase from fat pads pulse-labeled with [35S]methionine showed a decrease in relative synthesis of the enzyme, which correlated to the decrease in activity. There was no decrease in general protein synthesis and no change in distribution of the enzyme between adipocytes and extracellular locations in the tissue. This is in contrast to fasting in which case there is redistribution of the enzyme within the tissue, decrease in general protein synthesis, but no change in relative synthesis of lipoprotein lipase. TNF did not decrease lipoprotein lipase activity in any tissue other than the adipose but increased the activity in several cases, most markedly in the liver. No [35S]methionine was incorporated into lipoprotein lipase by liver slices from normal or TNF-treated animals. Thus, the increased activity can not be ascribed to enhanced hepatic synthesis of the enzyme. There was an increase in lipoprotein lipase activity in plasma, which correlated to the increase in liver. Thus, TNF suppresses lipoprotein lipase synthesis in adipocytes, but not in other tissues, and has some as yet undefined effect on lipoprotein lipase turnover in extrahepatic tissues, which results in increased transport of active lipase through plasma to the liver.