Effect of thyroid state on the phospholipid regeneration rate of rat liver mitochondria

The rate of phospholipid renewal in mitochondria of normal, hypothyroid, hyperthyroid and thyrotoxic rats was studied. Mitochondria were isolated from rat livers 24 and 48 hrs after administration of 3H-glycerol and 14C-palmitic acid. In mitochondria of hypothyroid animals, practically no phospholipid renewal is observed. In mitochondria of hyperthyroid and thyrotoxic rats, the rate of degradation of phospholipids labelled with glycerol, was approximately 1.5 times as low as that in controls. The decrease in the rate of renewal of the fatty acid residues in mitochondrial phospholipids was still more pronounced in hyperthyroid and thyrotoxic animals. Possible reasons for these changes connected with the thyroid state are discussed.     

Induction of Ca-independent PLA(2) and conservation of plasmalogen polyunsaturated fatty acids in diabetic heart

Diabetes-induced changes in phospholipase A(2) (PLA(2)) activity have been measured in several tissues but are undefined in diabetic myocardium. We measured ventricular PLA(2) activity in control, streptozotocin-induced diabetic, and insulin-treated diabetic rats and characterized myocardial phospholipids to determine whether diabetes altered myocardial phospholipid metabolism. Increased membrane-associated Ca(2+)-independent PLA(2) (iPLA(2)) activity was observed in diabetes that was selective for arachidonylated phospholipids. Increased iPLA(2) activity was accompanied by an increase in choline lysophospholipids. Diabetes was associated with marked alterations in the phospholipid composition of the myocardium, characterized by decreases in esterified arachidonic and docosahexaenoic acids and increases in linoleic acid. The decrease in polyunsaturated fatty acids was confined to diacylphospholipids, whereas the relative amount of these fatty acids in plasmalogens was increased. Diabetes-induced changes in PLA(2) activity, lysophospholipid production, and alterations in phospholipid composition were all reversed by insulin treatment of diabetic animals. Diabetes-induced changes in membrane phospholipid content and phospholipid hydrolysis may contribute to some of the alterations in myocardial function that are observed in diabetic patients.     

Effect of different levels of thyroid hormones on the fatty acid composition of lipids from rat liver mitochondria

The abundance or deficiency of thyroid hormones in rat organism influence the unsaturation and desaturation indices of total lipid fatty acids and phospholipids in liver mitochondria. The most conspicuous changes were observed in the fatty acid composition of the phospholipid fraction. The changes in the structure and function of rat liver mitochondria are considered to be due to alterations in the fatty acid composition of mitochondrial phospholipids.     

Thyroid hormones control lipid composition and membrane fluidity of skeletal muscle sarcolemma.

Sarcolemma membrane lipid phase of skeletal muscles of hyperthyroid animals was compared to that of control (euthyroid) ones. Hyperthyroidism caused 15% decrease in cholesterol and 70% increase in the phospholipid content of the membrane. This was accompanied by the alterations in proportions between individual phospholipid classes, and was followed by changes in the composition of phospholipid fatty acids. The calculated fatty acid unsaturation index was higher for membrane lipid phase of hyperthyroid animals than of euthyroid ones. Thyroxine-induced alterations in the lipid composition of sarcolemma caused changes in the membrane fluidity and the activity of calmodulin-stimulated (Ca(2+)-Mg(2+)-ATPase. Measurements of the steady-state fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene indicated that the lipid phase transition of membrane vesicles occurred at 25.9 degrees C and at 28.9 degrees C for preparations isolated from hyperthyroid and euthyroid rabbits, respectively. Arrhenius plot break-point temperature for CaM-stimulated (Ca(2+)-Mg(2+)-ATPase activity was lower in membrane preparations isolated from hyperthyroid (26.9 degrees C) than from euthyroid ones (30.0 degrees C). Thus, the increase of the membrane fluidity presumably caused that the enzyme was characterized by the lower activation energy value. This phenomenon may be viewed as a supplementary mechanism for activation of the enzyme by thyroid hormones to previously reported elevation of the amount of (Ca(2+)-Mg(2+)-ATPase protein exerted by hyperthyroidism (Famulski et al. (1988) Eur. J. Biochem., 171, 363-368; Famulski and Wrzosek (1988) in The Ion Pumps-Structure, Function and Regulation (Stein, W.D., ed.), pp. 355-360, Alan R. Liss, New York).     

Influence of hyper‐ and hypothyroidism on lipid peroxidation,unsaturation of phospholipids,glutathione system and oxidative damage to nuclear and mitochondrial DNA in mice skeletal muscle

While the biochemical literature on free radical metabolism is extensive, there is little information on the endocrine control of tissue oxidative stress, and in the case of thyroid hormones it is mainly limited to liver tissue and to short-term effects on a few selected biochemical parameters. In this investigation, chronic hypothyroidism and hyperthyroidism were successfully induced in mice, and various oxidative-stress-related parameters were studied in skeletal muscle. In vivo and in vitro lipid peroxidation significantly increased in hyperthyroidism and did not change in the hypothyroid state. The fatty acid composition of the major phospholipid classes was affected by thyroid hormones, leading to a significant decrease in total fatty acid unsaturation both in hypothyroid and hyperthyroid muscle in phosphatidylcholine and phosphatidylethanolamine fractions. In cardiolipin, however, the double bond content significantly increased as a function of thyroid status, leading to a 2.7 fold increase in the peroxidizability index from euthyroid to hyperthyroid muscle. Cardiolipin content was also directly and significantly related to thyroid state across the three groups. Glutathione system was not modified by thyroid state. The oxidative damage marker 8-oxo-7,8-dihydro-2'-deoxyguanosine did not change in mitochondrial DNA, and decreased in genomic DNA both in hypothyroid and hyperthyroid muscle. The results indicate that chronic alterations in thyroid status specially affect oxidative damage to lipids in skeletal muscle, with a probably stronger effect on mitochondrial membranes, whereas the cytosolic redox potential and DNA are better protected possibly due to homeostatic compensatory reactions on the long-term.     

Change of synaptic membrane lipid composition and fluidity by chronic administration of lithium

The effect of chronic administration of lithium salts on the lipid composition and physical properties of the synaptosomal plasma membrane was examined in rat brain. The effect of lithium treatment has been studied on the fluorescence polarization of synaptosomal plasma membrane and artificial lipid vesicles and on the lipid composition of the membranes. Fluorescence polarization of lipophilic probes was used to study membrane lipid structure. Steady-state polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH), a probe of the hydrophobic core, was significantly lower in plasma membranes from lithium-treated animals. Altered DPH polarization was due to a decrease in the order parameter of the probe. The lithium-treatment also changed the fluorescence of 1-anilino-8-naphthalene sulfonate (ANS), a probe that binds to the polar head group of the phospholipids and to proteins on the membrane surface. Synaptic plasma membranes from treated rats presented no significant changes on the cholesterol-to-phospholipid ratio, although the phospholipid class distribution was altered and the membrane phospholipid unsaturation increased. In summary, the neural plasma membranes became disorder after chronic lithium administration at therapeutic levels. This structural change may be due to changes in plasma membrane phospholipid distribution and to the degree of unsaturation of phospholipid fatty acids.     

Fatty acid composition of brown adipose tissue in genetically heat-tolerant FOK rats

The phospholipid fatty acid composition of brown adipose tissue (BAT) was examined in inbred heat-tolerant FOK rats and compared with that in conventional Wistar rats not previously exposed to heat. The FOK rats showed higher unsaturation states, as indicated by higher levels of polyunsaturated fatty acids and a higher unsaturation index and polyunsaturated fatty acids/saturated fatty acids ratio. This higher level of unsaturation was characterized by the higher amount of polyunsaturated fatty acids such as linoleic acid, arachidonic acid and docosahexaenoic acid. It may be concluded that the increased docosahexaenoic acid level in BAT phospholipids brings about the hyperplasia of BAT, causing an enhancement of its in vivo thermogernic activity as well as the systemic non-shivering thermogenesis observed in heat-tolerant FOK rats. Received: 17 May 2000 / Revised: 21 August 2000 / Accepted: 21 September 2000     

The mechanism of the increase in mitochondrial proton permeability induced by thyroid hormones.

Three possible mechanisms by which different levels of thyroid hormones in rats might cause the observed sevenfold change in the apparent proton permeability of the inner membrane of isolated liver mitochondria were investigated. (a) Cytochrome c oxidase was isolated from the livers of hypothyroid, euthyroid and hyperthyroid rats and incorporated into liposomes made with soya phospholipids. There was no difference between the proton current/voltage curves of the three types of vesicles. The hormonal effects, therefore, were not an inherent property of the enzymes, and were not due to different coupling of electron flow through the enzyme to proton transport. (b) The surface area of the mitochondrial inner membrane was shown by three different assays to be greater by a factor of between two and three in mitochondria from hyperthyroid animals than in mitochondria from hypothyroid animals; euthyroid controls were intermediate. This difference in surface area of the inner membrane explains less than half of the difference in apparent proton permeability. (c) The proton permeability of liposomes prepared from phospholipids extracted from mitochondrial inner membranes of hyperthyroid rats was three times greater than the proton permeability of those from hypothyroid rats; euthyroid controls were intermediate. This suggests, first, that the proton permeability of the phospholipid bilayer is an important component of the proton permeability in intact mitochondria and, second, thyroid hormone-induced changes in the bilayer are a major part of the mechanism of increased proton permeability. Such changes may be due to the known differences in fatty acid composition of mitochondrial phospholipids in different thyroid states. Thus we have identified two mechanisms by which thyroid hormone levels in rats change proton flux/mass protein in isolated liver mitochondria: a change in the area of the inner membrane/mass protein and a change in the intrinsic permeability of the phospholipid bilayer.     

The Na+,K+-ATP-ase Activity and Lipids of Trout and Rat Brain Cell Membranes at the Pressure of 101 Atmospheres

The effect of elevated heliox pressure (101 ATA) on activity of Na⁺,K⁺-ATP-ase and some characteristics of fatty acid composition was studied in membrane phospholipids of trout and rat brain synaptosomal and mitochondrial fractions. The Na⁺,K⁺-ATP-ase activity was shown to decrease by 25% in both fractions of the rat brain; in mitochondrial fraction of the trout brain it decreased by 47%, while in synaptosomal fraction, only by 11%. It has also been established that under experimental conditions, the unsaturation index of fatty acids of phosphatidylcholine and phosphatidylethanolamine of trout synaptosomes decreased, with no changes in these lipids in mitochondrial fraction. The phosphatidylcholine unsaturation index in rats did not practically change in both fractions, while in rat phosphatidylethanolamine it increased in mitochondrial fraction and slightly decreased in synaptosomal fraction. Thus, under conditions of high pressure the reduction of the enzyme activity is also determined, specifically, by peculiarities of the phospholipid fatty acid composition in the subcellular fractions studied. A possibility of changes of the enzyme activity as a result of transition of its lipid component from the liquid crystalline to the gel state under effect of an enhancement of lipid peroxidation under conditions of elevated pressure is discussed.     

Effect of thyroid status on lipid composition and peroxidation in the mouse liver

In order to analyze the possible relationship between metabolic rate and oxidative stress, OF1 female mice were rendered hyper- or hypothyroid for 4–5 weeks by administration of 0.0012%l-thyroxine (T₄) or 0.05% 6-n-propyl-2-thiouracil (PTU), respectively, in their drinking water. Treatment with T₄ resulted in increased basal metabolic rate measured by oxygen consumption and liver cytochrome oxidase activity without altering the glutathione redox system. Endogenous lipid peroxidation, sensitivity to lipid peroxidation and fatty acid unsaturation were decreased in the hyperthyroid group. Hypothyroidism also decreased phosphatidylcholine and cardiolipin fatty acid unsaturation but not in total lipids, and thus lipid peroxidation was not altered. Cardiolipin, a mainly mitochondrial lipid, was the most profoundly altered fraction by both hyper- and hypothyroidism. It is suggested that the lipid changes observed in hyperthyroid animals can protect them against an increased oxidative attack to tissue lipids due to their increased mitochondrial activities.     

Temperature adaptation of biological membranes. Compensation of the molar activity of cytochrome c oxidase in the mitochondrial energy-transducing membrane during thermal acclimation of the carp (cyprinus carpio L.)

The phospholipid composition, fatty acid pattern and cholesterol content are studied in mitochondria of red lateral muscle of carp acclimated to high and low environmental temperatures.The results of the experiments are: mitochondria from cold-acclimated carp contain higher proportions of ethanolamine phosphatides than mitochondria from warm-acclimated fish, the opposite is true for the choline phosphatides. Thus, at constant pH, the membrane phospholipids are slightly more negatively charged at low acclimation temperature. The total plasmalogen content is reduced in the cold; this reduction is caused by a decrease in the proportion of the choline plasmalogens. The ethanolamine phosphoglycerides contain approx. 20% of the alk-1-enyl acyl type, irrespective of the acclimation temperature. There is no temperature-dependent difference in the low proportion of cholesterol.The fatty acids of total mitochondrial phospholipids are characterized by large amounts of the n-3 and n-6 families. The ratio of unsaturated to saturated fatty acids and the unsaturation index are remarkably higher than those reported for comparable mammalian phospholipids. Cold acclimation of carp does not significantly increase the unsaturation of total phospholipids. A fatty acid analysis of the main isolated phospholipids, however, shows that cold acclimation considerably increases unsaturation of the neutral phosphatidylcholine, whereas it dramatically decreases unsaturation of the negatively charged cardiolipin. It is suggested that the observed fatty acid substitution in phosphatidylcholine indicates a temperature-induced fluidity adaptation within the mitochondrial lipid bilayer, whereas the inverse acclimation pattern of cardiolipin provides a suitable lipid to accommodate the temperature-dependent modifications in the dynamic surface shape of integral membrane proteins.     

Adaptive modification of membrane phospholipid fatty acid composition and metabolic thermosuppression of brown adipose tissue in heat-acclimated rats

Thermogenesis, especially facultative thermogenesis by brown adipose tissue (BAT), is less important in high ambient temperature and the heat-acclimated animals show a lower metabolic rate. Adaptive changes in the metabolic activity of BAT are generally found to be associated with a modification of membrane phospholipid fatty acid composition. However, the effect of heat acclimation on membrane phospholipid fatty acid composition is as yet unknown. In this study, we examined the thermogenic activity and phospholipid fatty acid composition of interscapular BAT from heat-acclimated rats (control: 25±1°C, 50% relative humidity and heat acclimation: 32±0.5°C, 50% relative humidity). Basal thermogenesis and the total thermogenic capacity after noradrenaline stimulation, as estimated by in vitro oxygen consumption of BAT (measured polarographically using about 1-mm³ tissue blocks), were smaller in the heat-acclimated group than in the control group. There was no difference in the tissue content of phospholipids between the groups when expressed per microgram of DNA. The phospholipid fatty acid composition was analyzed by a capillary gas chromatograph. The state of phospholipid unsaturation, as estimated by the number of double bonds per fatty acid molecule, was similar between the groups. The saturated fatty acid level was higher in the heat-acclimated group. Among the unsaturated fatty acids, heat acclimation decreased docosahexaenoic acid and oleic acid levels, and increased the arachidonic acid level. The tissue level of docosahexaenoic acid correlated with the basal oxygen consumption of BAT (r=0.6, P<0.01) and noradrenaline-stimulated maximum values of oxygen consumption (r=0.5, P<0.05). Our results show that heat acclimation modifies the BAT phospholipid fatty acids, especially the n-3 polyunsaturated fatty acid docosahexaenoic acid, which is possibly involved in the metabolic thermosuppression. Received: 9 August 1999 / Revised: 8 November 1999 / Accepted: 24 November 1999     

Effect of ionizing radiation on the functional state of snail neurons. Phospholipid composition and levels of free fatty acids

A study was made of the effect of ionizing radiation on the phospholipid composition and the level of free fatty acids in nervous ganglia of edible snails (Helix pomatia). Ionizing radiation was shown to decrease the total content of phospholipids and to change certain fractions and accumulation of lysoforms. The increase in the free fatty acid content indicated an activation of endogenous phospholipase hydrolysis. Model experiments on treatment of nervous ganglia with phospholipase A2 demonstrated a similarity of radiation-induced changes in the phospholipid content.     

Lipids in mammalian hibernation and artificial hypobiosis

Membrane lipids—phospholipids, fatty acids, and cholesterol—participate in thermal adaptation of ectotherms (bacteria, amphibians, reptiles, fishes) mainly via changes in membrane viscosity caused by the degree of fatty acids unsaturation, cholesterol/phospholipids ratio, and phospholipid composition. Studies of thermal adaptation of endotherms (mammals and birds) revealed the regulatory role of lipids in hibernation. Cholesterol and fatty acids participate in regulation of the parameters of torpor, gene expression, and activity of enzymes of lipid metabolism. Some changes in lipid metabolism during artificial and natural hypobiosis, namely, increased concentration of cholesterol and fatty acids in blood and decreased cholesterol concentration in neocortex, are analogous to those observed under stress conditions and coincide with mammalian nonspecific reactions to environmental agents. It is shown that the effects of artificial and natural hypobiosis on lipid composition of mammalian cell membranes are different. Changes in lipid composition cause changes in membrane morphology during mammalian hibernation. The effect of hypobiosis on lipid composition of membranes and cell organelles is specific and seems to be defined by the role of lipids in signaling systems. Comparative study of lipid metabolism in membranes and organelles during natural and artificial hypobiosis is promising for elucidation of adaptation of mammals to low ambient temperatures.     

Effects of triiodothyronine and propylthiouracil on plasma lipoproteins in male rats

Hyperalphalipoproteinemia, characterized by increased plasma concentrations of apoA-I and of HDL lipid and protein, was observed in rats treated with triiodothyronine (T(3)) for 7 days. The increase in the plasma HDL apoproteins was general for apoC, apoE plus A-IV, and apoA-I, as determined by isoelectric focusing. Hypotriglyceridemia, characterized by decreased concentrations of VLDL and apoB, was also observed in the hyperthyroid state. Although in the mildly hypothyroid animals (propylthiouracil-treated), hepatic metabolism of free fatty acid is shifted toward esterification to triglyceride and VLDL formation, as we reported previously, plasma HDL and apoA-I concentrations were not different from control plasma values, while the d 1.006-1.063 g/ml (IDL + LDL) lipoprotein fraction tended to be increased. In general, the proportion of apoE in the (IDL + LDL) fraction of the hypothyroid rat was greater than in controls and hyperthyroid animals, while the proportion of apoE tended to be lower in VLDL from both hypo- and hyperthyroid rats than in VLDL from controls. An enhanced release of apoA-I by perfused livers isolated from rats treated with T(3) was also observed; this enhanced output of apoA-I may explain, in part, the hyperalphalipoproteinemia observed in these rats. The depressed net output of apoA-I in vitro by perfused livers from rats treated with propylthiouracil (PTU) was not expressed in a statistically significant diminished plasma concentration of HDL or apoA-I in the intact animals. Treatment with T(3) also resulted in modification of the content of essential fatty acids in various lipid classes. Linoleic acid residues were significantly reduced and arachidonic acid content was increased in plasma phospholipids and esterified cholesterol in T(3)-treated rats. However, the relative fatty acid composition of unesterified fatty acids and triglyceride fatty acids was not altered by T(3) treatment. PTU treatment had no effect on fatty acid distribution in any of the plasma lipids. Secretion of biliary lipids was increased in perfused livers from T(3)-treated rats, while treatment with PTU did not affect release of lipids in the bile. These observations suggest a regulatory role for thyroid hormones that determine concentration and composition of plasma HDL and other lipoproteins.-Wilcox, H. G., W. G. Keyes, T. A. Hale, R. Frank, D. W. Morgan, and M. Heimberg. Effects of triiodothyronine and propylthiouracil on plasma lipoproteins in male rats.     

Temperature adaptation of biological membranes. The effects of acclimation temperature on the unsaturation of the main neutral and charged phospholipids in mitochondrial membranes of the carp (cyprinus carpio L.)

The phospholipid composition, fatty acid pattern and cholesterol content are studied in mitochondria of red lateral muscle of carp acclimated to high and low environmental temperatures.The results of the experiments are: mitochondria from cold-acclimated carp contain higher proportions of ethanolamine phosphatides than mitochondria from warm-acclimated fish, the opposite is true for the choline phosphatides. Thus, at constant pH, the membrane phospholipids are slightly more negatively charged at low acclimation temperature. The total plasmalogen content is reduced in the cold; this reduction is caused by a decrease in the proportion of the choline plasmalogens. The ethanolamine phosphoglycerides contain approx. 20% of the alk-1-enyl acyl type, irrespective of the acclimation temperature. There is no temperature-dependent difference in the low proportion of cholesterol.The fatty acids of total mitochondrial phospholipids are characterized by large amounts of the $\text{n-3}\text{and}\text{n-6}$ families. The ratio of unsaturated to saturated fatty acids and the unsaturation index are remarkably higher than those reported for comparable mammalian phospholipids. Cold acclimation of carp does not significantly increase the unsaturation of total phospholipids. A fatty acid analysis of the main isolated phospholipids, however, shows that cold acclimation considerably increases unsaturation of the neutral phosphatidylcholine, whereas it dramatically decreases unsaturation of the negatively charged cardiolipin. It is suggested that the observed fatty acid substitution in phosphatidylcholine indicates a temperature-induced fluidity adaptation within the mitochondrial lipid bilayer, whereas the inverse acclimation pattern of cardiolipin provides a suitable lipid to accommodate the temperature-dependent modifications in the dynamic surface shape of integral membrane proteins.     

Effect of chronic ethanol administration on energy metabolism and phospholipase A2 activity in rat liver.

1. For a period of 31 days male rats were given a liquid diet containing 36% of its energy as ethanol. Liver mitochondria from these animals demonstrated lowered respiratory control with succinate as substrate, a diminished energy-linked anilinonaphthalene-sulphonic acid fluorescence response, and lowered endogenous ATP concentrations. The phospholipid/protein ratio in mitochondria from these animals was unchanged; only minor alterations in the phospholipid fatty acid composition were observed. 2. In experiments where mitochondria were incubated at 18 degrees C in iso-osmotic sucrose (aging experiments), the above energy-linked properties were lost at an earlier time in organelles from ethanol-fed animals. Phospholipase A2 acitivty was depressed in mitochondria from control animals until respiratory control was lost and ATP was depleted. In contrast, no lag in the expression of phospholipase activity was observed in mitochondria from ethanol-fed rats. This loss of control of the phospholipase resulted in an earlier degradation of membrane phospholipids under the conditions of the aging experiments. 3. The ATPase (adenosine triphosphatase) activities, measured in freshly prepared tightly coupled mitochondria and in organelles uncoupled with carbonyl cyanide p-trifluoromethoxyphenylhydrazone, were not significantly different in ethanol-fed and liquid-diet control animals. When the mitochondria were aged at 18 degrees C, the activity increased with time of incubation in organelles from both groups of animals. A lag was observed, however, as the ATPase activity increased in control preparations. This lag was not present as APTase activity increased in mitochondria from ethanol-fed animals. 4. The significantly lowered values observed for energy-linked functions with succinate as an energy source demonstrate that ethanol elicits an alteration in liver mitochondria that affects the site II-site III regions of the oxidative-phosphorylation system. The apparent lack of control of the phospholipase A2 and ATPase activities in mitochondria from ethanol-fed animals suggests that the membrane microenvironment of these enzymes has been altered such that they can exert their catabolic effects more readily under conditions of mild perturbation. The fatty acid analyses demonstrate that the observed alterations both in the energy-linked functions and in control of the phospholipase and ATPase are not mediated through changes in the acyl chain composition of bulk-phase phospholipids.     

The effect of membrane phospholipid acyl-chain composition on the activity of brain-beta-N-acetyl-D-glucosaminidase.

The phospholipid acyl-chain dependence of the membrane-bound lysosomal beta-N-acetyl-D-glucosaminidase has been examined on control membranes from rat brain primary cell cultures and on membrane modified by culturing the cells in media supplemented with polyunsaturated fatty acids. The relationship between beta-N-acetyl-D-glucosaminidase activity and the membrane phospholipid acyl-chain composition has been evaluated. An increase in the unsaturation level of phosphatidyl ethanolamines and phosphatidylcholines, the most abundant phospholipids in this membrane fraction, is related to the rate of the enzymic reaction. The Arrhenius plot of the enzyme activity in modified membranes shows break-temperatures, starting from approximately 15 degrees C. The apparent activation energy below and above the break-temperature is not correlated with phospholipid acyl-chain unsaturation.     

Hypothyroidism down-regulates mitochondrial citrate carrier activity and expression in rat liver

The effect of hypothyroidism on citrate carrier (CiC) activity has been investigated in rat-liver mitochondria. The rate of citrate transport was reduced by approximately 50% in mitochondria from hypothyroid as compared with euthyroid rats. In parallel, a decrease in the rate of de novo fatty acid synthesis was observed in the cytosol of the former animals. Kinetic analysis of citrate transport revealed that only the Vmax was reduced by hypothyroidism, while Km was almost unaffected. Hypothyroidism increased the mitochondrial percentage of phosphatidylcholine while decreased that of phosphatidylethanolamine; an altered fatty acid pattern but no significant difference in the sum of saturated and unsaturated fatty acids as well as in the unsaturation index was observed. The CiC Arrhenius plot did not show appreciable difference between the two groups of rats. However, Western blot analysis associated with mRNA quantitation indicated that both protein level and mRNA accumulation of hepatic CiC were noticeably decreased in hypothyroid state. Therefore, a reduced content of the carrier protein can represent a plausible mechanism to explain the decline in the CiC activity observed in rat liver mitochondria of hypothyroid rats.     

Plasma and muscle phospholipids are involved in the metabolic response to long-distance migration in a shorebird

We studied: (1) concentrations and fatty acid compositions of plasma non-esterified fatty acids, neutral lipids, and phospholipids, and (2) fatty acid composition of flight muscle phospholipids in wintering, premigratory, and spring and fall migrating western sandpipers ( Calidris mauri). Plasma neutral lipid and phospholipid levels were elevated in migrants, reflecting high rates of fat deposition. An important role of phospholipids in fattening is suggested by the fact that the amount of fatty acids in plasma phospholipids was similar to, or in spring as much as twice, that of neutral lipids. Changes in the ratio of plasma neutral lipids to phospholipids may indicate seasonal changes in triacylglycerol stores of invertebrate prey. Monounsaturation and total unsaturation of plasma neutral lipids and phospholipids increased during migration. Muscle phospholipids were more monounsaturated in spring and fall, but total unsaturation was reduced in fall. Arachidonic acid [20:4(n-6)] was especially abundant in muscle phospholipids in winter (29%) and declined during migration (19-22%), contributing to a decline in the ratio of n-6 to n-3 fatty acids. The abundance of plasma phospholipids and variability of neutral lipid to phospholipid ratio indicates that measurement of plasma phospholipids will improve methods for assessment of fattening rates of birds. The functional significance of changes in muscle phospholipids is unclear, but may relate to depletion of essential n-6 fatty acids during exercise.