Michael P.T. Gillett

Lipoproteins, cell membranes and cellular functions

Abstract Circulating lipoproteins, apart from fulfilling their major physiological role of bulk lipid transport, help maintain the lipid composition of cell membranes, and directly influence several cellular biochemical reactions. These processes involve both lipids and apolipoproteins on the lipoprotein surface, and appear to have broad physiological and pathological significance.

Plasma lipid concentrations for some Brazilian lizards

1. Plasma concentrations of cholesterol, cholesteryl esters, phospholipids and triglycerides were determined for ten species of Brazilian lizards, Iguana iguana, Tropidurus torquatos and T. semitaeniatus (Iguanidae), Tupinambis teguixin, Ameiva ameiva and Cnemidophorus ocellifer (Teiidae), Mabuya maculata (Scincidae), Hemidactylus mabouia (Gekkonidae), Amphisbaenia vermicularis and Leposternon polystegum (Amphisbaenidae). 2. Considerable inter- and intra-species variations in plasma lipid concentrations were observed. 3. The percentage of total cholesterol esterified and the individual phospholipid composition of plasma were relatively constant for each species. 4. Over 60% of the cholesteryl esters present in plasma from three species each of iguanid and teiid lizards were polyenoic.

Evidence for active phospholipase a in mouse plasma

Mouse, rat and human plasma were exposed to minimum concentrations of disulphide or minimum pre-incubation at 55 degrees C in order to inhibit lecithin : cholesterol acyltransferase activity completely. The plasma samples were subsequently incubated at 37 degrees C and changes in individual phospholipid concentrations determined. Significant utilization of phosphatidylcholine and formation of lysophosphatidylcholine occurred only in disulphide-treated mouse plasma and this was accompanied by a decrease in total phospholipid concentration. When disulphide-treated mouse plasma was incubated with [U-14C]phosphatidylcholine radioactivity was additionally recovered in the lysophosphatidylcholine, non-esterified fatty acid and glycero-3-phosphocholine fractions; maximum conversion occurred at close to physiological pH. These observations suggest that phospholipase A and lysophosphatidylcholine hydrolase enzymes are active in mouse plasma but that phospholipase A is either absent or inactive in rat and human plasma.

The phospholipase activities present in preheparin mouse plasma are inhibited by antiserum to hepatic lipase

1. Preheparin plasma from mice, but not rats or man, contains high levels of phospholipase A and lysophospholipase activities which are distinct from lecithin:cholesterol acyltransferase (LCAT). 2. Neither the phospholipase A nor the lysophospholipase activities in preheparin plasma are inhibited by incubation in the presence of protamine sulphate or high salt concentrations. 3. When mouse plasma is incubated in the presence of an antiserum specific for rat hepatic triacylglycerol lipase (HTGL), the phospholipase activities are abolished. 4. These observations suggest that the phospholipase activities are attributable to the action of HTGL, which, in the mouse appears to be a freely circulating enzyme, whereas for other species this enzyme only appears in the blood following administration of heparin.

Changes in the lipid composition of erythrocytes during prolonged fasting in lizard (Tropidurus torquatos) and rat (Rattus norvegicus)

During prolonged fasting in lizard and rat, plasma levels of unesterified cholesterol (UC) and phospholipids (TPL) decreased and there were reductions and increases, respectively, in the molar ratios of lecithin (PC) to sphingomyelin (SPH) and UC to TPL. Plasma lecithin: cholesterol acyltransferase (LCATase) activity in lizard and rat plasma was reduced during prolonged fasting. Erythrocyte lipid composition for fasted animals was also characterized by a reduction in the molar ratio PC/SPH and an increase in UC/TPL, and in both species there were positive correlations between these molar ratios in red cells and those in plasma. In both species these were changes in the morphology of the erythrocytes, and those from fasted rats showed alterations in osmotic fragility and permeability which correlated with alterations in lipid composition. These results suggest that changes in plasma lipoprotein lipid composition, linked to reduced LCATase activity, may cause similar alterations in the lipid composition of red cell membranes leading to altered membrane properties.

Factors influencing lipid levels and lecithin:cholesterol acyltransfer in plasma of the lizard, Tropidurus torquatos.

Abstract 1. 1. Lipid concentrations and lecithin:cholesterol acyltransferase (LCAT) activity in the plasma Tropidurus torquatos were remarkably variable. 2. 2. Both lipid levels and LCAT activity were highest for lizards collected during the early rainy season (March–April) than during other seasons, and were higher for females than for males. 3. 3. Plasma lipid levels and LCAT activity were significantly and inversely correlated with body weight (age) of male lizards, this being associated with an apparent change to an herbivorous diet in older males. 4. 4. During prolonged fasting, plasma lipid levels and lecithin:cholesterol acyltransfer (LCAT) and hepatic phospholipids were markedly reduced. 5. 5. LCAT activity in plasma of fasted and non-fated lizards was significantly correlated with the molar proportion of PC to UC, suggesting that the apparent low LCAT in plasma of fasted lizards is partly due to depletion of PC in the lipoprotein substrates.

Schistosoma mansoni: A comparative study of plasma and erythrocyte lipid alterations in the experimentally infected mouse and in selected human patients

Abstract Alterations of plasma and erythrocyte lipids associated with hepatosplenic schistosomiasis mansoni were studied in the mouse and in human patients. Qualitative and quantitative differences were observed between the two species which indicated that the experimentally infected mouse should not be used as a model for altered lipid metabolism associated with Schistosoma mansoni infections in man. Also blood lipid values should not be used as prophylactic indicators for experimental therapeutical studies in the infected mouse, although lipid determinations could have clinical value in studies of human patients. In infected mice plasma cholesterol and phospholipid were significantly reduced (40 and 25%, respectively), but proportions of individual plasma phospholipids were unchanged. In contrast, only plasma cholesterol was reduced in human patients with compensated or decompensated hepatosplenic schistosomiasis (16 and 29%, respectively); of the individual phospholipids, lecithin was significantly increased and lysolecithin was decreased. The percentage of plasma total cholesterol was reduced in infected mice and patients suggesting that hypocholesterolemia is due mainly to decreased cholesteryl ester. Lipid changes also occurred in erythrocytes. Those of infected mice had significantly elevated membrane phospholipid content and no changes in cholesterol or in the proportions of the individual phospholipid fractions. In marked contrast, the erythrocytes of two groups of human patients had significantly higher levels of cholesterol without a raised total phospholipid concentration. Moreover, decreased proportions of lysolecithin and increased proportions of lecithin were apparent although only the increased membrane lecithin associated with compensated patients was statistically significant.

Alterations of cell membrane composition during prolonged fasting in lizards

Male lizards fasted for 35 days showed significant alterations in the lipid composition of membranes isolated from a variety of organs and tissues. Unesterified cholesterol was significantly increased in membranes from kidney, skeletal muscle, small intestine, testis and heart but not in those from lung, brain and liver; cholesterol/phospholipid molar ratio was also significantly increased in membranes from all organs except brain and liver. Membrane total phospholipids were reduced for all tissues except brain and liver, whilst significant reductions in the molar ratio of membrane phosphatidylcholine to sphingomyelin occurred in kidney, muscle, testis, intestine and liver. Similar alterations in lipid composition were found in plasma and significant correlations between plasma and membrane cholesterol/phospholipid and phosphatidylcholine/sphingomyelin molar ratios were found for those organs in which significant lipid changes occurred during fasting. Lizards fasted for 35 days and then refed a natural diet, such that they started to regain weight, had normal membrane lipid compositions. These observations suggest that during prolonged fasting certain tissues of the lizard are unable to maintain a normal membrane lipid composition and that abnormal plasma lipoproteins may be involved in this process.

Seasonal variation in plasma and hepatic lipids in relation to nutritional status and vitellogenesis in male and female lizards, Ameiva ameiva (Teiidae)

Abstract 1. 1. Separate seasonal cycles in plasma and hepatic lipid levels occurred in male and female A. ameiva . 2. 2. Lipid levels significantly decreased in males during the rainy season (Winter), when these animals were inactive and frequently captured in a fasted state. Males captured during this season but fed a natural diet for 21 days had lipid levels similar to those in lizards captured during Summer. 3. 3. In females plasma and hepatic cholesterol also decreased during Winter, although plasma levels of triglyceride and phospholipid were simultaneously increased as a result of vitellogenesis.

Lipid composition of erythrocytes from reptiles and amphibians

Abstract 1. 1. The concentrations of cholesterol and phospholipids in erythrocytes from seven species of reptiles and two species of amphibians were compared with the lipid composition of human and mouse erythrocytes. 2. 2. The phospholipid composition of reptile and amphibian erythrocytes were all remarkably similar whereas large differences occur between mammalian species. 3. 3. Erythrocyte cholesterol/phospholipid ratio was much lower for reptiles and amphibians than for mammals.