Influence of thermal acclimation on membrane lipid composition of rainbow trout liver.

Rainbow trout (Salmo gairdneri) acclimated to 5 degrees C possessed larger livers and less neutral lipid per gram of liver than 20 degrees C-acclimated animals; quantities of liver glycolipid, phospholipid, and cholesterol did not vary significantly with acclimation temperature. The relative proportions of phosphatidylethanolamine increased significantly following cold exposure, whereas the quantities of sphingomyelin and cardiolipin declined. For all phosphatides examined (phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, phosphatidylinositol, lysolecithin, cardiolipin, sphingomyelin) cold acclimation resulted in 1) an increase in the quantity of polyunsaturated fatty acids, 2) a reduction in the level of saturated fatty acids, and 3) little change in the total content of monoenes and dienes. The increased content of polyunsaturated fatty acids in choline and ethanolamine phosphatides following cold acclimation was confined to the 2-position and occurred at the expense of monoenes and dienes. The relative proportions of n - 3 fatty acids, and less frequently n - 6 fatty acids, increased in phosphatides of cold-acclimated trout, whereas the relative proportions of n - 9 fatty acids declined. These data suggest a preferential incorporation of fatty acids belonging to the linolenic acid family at reduced temperatures. Temperature-induced changes in the chemical composition of trout liver phospholipids counteracted the effects of acute temperature change on nonelectrolyte permeability of isolated liposomes.     

Metabolic responses in feline “red” and “white” skeletal muscle to shock and ischemia

In order to investigate possible differences in the reaction to hypoxic conditions between “red” and “white” skeletal muscle, cats were subjected to a 2 h period of either hemorrhagic shock or hind limb tourniquet ischemia, and the hypoxia induced changes were studied in the soleus and lateral gastrocnemius muscles. Muscle biopsies were analysed for ATP, CP, glucose, G 6–P and lactate. Using microelectrodes, the resting membrane potential was repeatedly measured. Both experimental models resulted in increased tissue lactate levels and a successive decrease in the membrane potential of both muscles studied. No reduction of the high energy phosphagen content (ATP+CP) occurred in any of the muscles during shock. The tourniquet ischemia resulted in a 40% reduction of the ATP+CP content in the soleus muscle, whereas in the gastrocnemius muscle no significant reduction occurred. A significant correlation was found between the tissue lactate content and the membrane potential under both conditions and in both muscles studied. It is concluded that “red” muscles are more susceptible to metabolic derangement than “white” muscles during total ischemia, whereas during hypovolemia “red” muscles appear to be protected from early hypoxic damage, probably due to a redistribution of skeletal muscle blood flow.     

Metabolic responses in feline "red" and "white" skeletal muscle to shock and ischemia.

In order to investigate possible differences in the reaction to hypoxic conditions between "red" and "white" skeletal muscle, cats were subjected to a 2 h period of either hemorrhagic shock or hind limb tourniquet ischemia, and the hypoxia induced changes were studied in the soleus and lateral gastrocnemius muscles. Muscle biopsies were analysed for ATP, CP, glucose, G 6-P and lactate. Using microelectrodes, the resting membrane potential was repeatedly measured. Both experimental models resulted in increased tissue lactate levels and a successive decrease in the membrane potential of both muscles studied. No reduction of the high energy phosphagen content (ATP + CP) occurred in any of the muscles during shock. The tourniquet ischemia resulted in a 40% reduction of the ATP + CP content in the soleus muscle, whereas in the gastrocnemius muscle no significant reduction occurred. A significant correlation was found between the tissue lactate content and the membrane potential under both conditions and in both muscles studied. It is concluded that "red" muscles are more susceptible to metabolic derangement than "white" muscles during total ischemia, whereas during hypovolemia "red" muscles appear to be protected from early hypoxic damage, probably due to a redistribution of skeletal muscle blood flow.     

Effect of creatine supplementation on creatine and glycogen content in rat skeletal muscle

The effects of high dose creatine feeding (5 g kg(-1) BW day(-1), 5 days) on creatine content, glucose transport, and glycogen accumulation in white gastrocnemius, red gastrocnemius and soleus muscles of the rat was investigated. Isolated rat hindquarters of creatine fed and control rats were perfused with a standard medium containing either insulin alone (0, 100 or 20 000 microU mL(-1)) or in combination with creatine (2 or 10 mmol L(-1)). Furthermore, plasma insulin concentration was measured in normal rats during creatine feeding, as well as in anaesthetized rats during intravenous creatine infusion. Five days of creatine feeding increased (P < 0.05) total creatine content in soleus (+ 20%) but not in red gastrocnemius (+15%, n.s.) and white gastrocnemius (+ 10%, n.s.). In parallel, glycogen content was markedly elevated (P < 0.05) in soleus (+ 40%), less (P < 0.05) in red gastrocnemius (+ 15%), and not in white gastrocnemius (+ 10%, n.s.). Glucose transport rate, muscle GLUT-4 content, glycogen synthase activity in perfused muscles and glycogen synthesis rate were not significantly altered by creatine feeding in either muscle type. Furthermore, high dose creatine feeding raised (P < 0.05) plasma creatine concentration fivefold but did not alter circulating insulin level. It is concluded that short-term high dose creatine feeding enhances creatine disposal and glycogen storage in rat skeletal muscle. However, the creatine and glycogen response to creatine supplementation is markedly greater in oxidative than in glycolytic muscles.     

Hidden anti-phospholipid antibodies in normal human sera circulate as immune complexes whose antigen can be removed by heat,acid, hypermolar buffers or phospholipase treatments

Heat treatment of normal human serum reveals otherwise masked anti-cardiolipin antibodies (aCL). We studied the mechanism of masking and the nature of the inhibitor of these aCL IgG. Other forms of treatment, besides heating for 30 min at 56 °C, can also unmask hidden aCL IgG. These include acid pH, hypermolar buffers and phospholipase digestion. When unmasked, these aCL recognize other anionic and zwitterionic phospholipids, but do not react with DNA, cell antigens or IgG. Using thin layer chromatography we demonstrate that the heat-labile inhibitor(s) of these aCL are phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylcholine. These antibodies are not β₂ -glycoprotein-I dependent and actually compete with this protein for phospholipid binding. The hidden antibodies are comprised of two populations of IgG autoantibodies: one reactive with cardiolipin, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, phosphatidylethanolamine and sphingomyelin, and the other reactive almost exclusively with phosphatidylcholine and phosphorylcholine on enzyme-linked immunosorbent assay plates or when exposed by bromelain on the erythrocyte surface. Our data suggest that hidden aCL are natural oligoreactive IgG anti-phospholipid autoantibodies that circulate masked by their antigen.     

Phospholipid liposomes enhance the infectivity of purified simian virus 40 virions

When simian virus 40 virions purified after treatment with sodium deoxycholate were incubated with the extract of monkey kidney CV-1 cells, infectivity of the virions was enhanced. The infectivity-enhancing activity was recovered from the phospholipid fraction of CV-1 cells. The constructed liposomes composed of phosphatidylserine were able to enhance the infectivity of the purified virions, but those composed either of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, or phosphatidylinositol could not. The liposomes constructed with a mixture of phosphatidylethanolamine and phosphatidylcholine at a ratio of 1:1 (w:w) also enhanced the infectivity of the purified virions. Pretreatment of cells with liposomes either of phosphatidylserine or of phosphatidylethanolamine did not enhance susceptibility of the cells to infection with the purified virions. These observations suggest that the major phospholipids of the cellular membrane, when associated with virions, play a vital role in activation of purified virions.     

Effects of voluntary wheel running and amino acid supplementation on skeletal muscle of mice

The aims of the present study were as follows: (1) to examine the adaptational changes to chronic endurance voluntary exercise and (2) to investigate the effects of amino acid supplementation on the adaptational changes induced by endurance training in hindlimb (gastrocnemius, tibialis, soleus) and respiratory (diaphragm) muscles of mice. Male C57Bl6 mice were divided in four groups: control sedentary, sedentary supplemented with amino acid mixture (BigOne, 1.5 mg g day^–1 in drinking water for 8 weeks), running (free access to running wheels for 8 weeks), and running supplemented with amino acid mixture. Myosin heavy chain (MHC) isoform distribution was determined in all muscles considered. Fiber cross-sectional area (CSA) was measured in the soleus muscle. In all muscles except the tibialis, endurance training was associated with an overall shift towards the expression of slower MHC isoforms. Amino acid supplementation produced a shift towards the expression of faster MHC isoforms in the soleus and diaphragm muscles, and partially antagonized the effects of training. Immunohistochemical analysis of CSA of individual muscle fibers from the soleus muscle suggests that voluntary running produced a decrease in the size of type 1 fibers, and amino acid supplementation during training resulted in an increase in size in both type 1 and type 2A fibers. Collectively, these results suggest that the endurance adaptations induced by voluntary running depend on the muscle type, and that amino acid supplementation is able to modulate both fiber size and MHC isoform composition of skeletal muscles in sedentary and exercised mice.     

Accumulation of caesium and rubidium in vivo by red and white muscles of the rat

1. Rats were given drinking water containing either 20 mM-CsCl or 20 mM-RbCl for a period of 2 weeks. Samples of blood were then taken from the rats under anaesthetic. They were immediately centrifuged and the plasma taken for analysis. Soleus muscles, diaphragm, extensor digitorum longus, white gastrocnemius and vastus lateralis muscles were then taken from the dead animals and these and the plasma were analysed for potassium, and for caesium or rubidium by means of the flame photometer.2. The concentrations of potassium and rubidium or caesium in the fibre water of these various muscles and in the samples of plasma water were then calculated.3. It was found that the red muscles including soleus and diaphragm generally tended to accumulate caesium and rubidium to a greater extent than did the white muscles such as the white gastrocnemius and vastus lateralis.4. When the concentration ratio [K](i)/[K](o) was divided into the ratio [Rb](i)/[Rb](o) for the different muscles, values of about 1.3 were obtained for the red muscles compared with values about 1.14 for white muscles.5. When in the case of the caesium-treated rats the ratio [K](i)/[K](o) was divided into the ratio [Cs](i)/[Cs](o) values ranged from 1.94 +/- 0.12 for the red soleus to 1.08 +/- 0.09 for the white gastrocnemius.6. When these values in the caesium-treated animals were plotted against the percentage of red fibres in the five muscle types (as obtained from the data of Sreter & Woo, 1963) the graph indicated that the white fibres had similar ionic gradients for Cs(+) and K(+) and that affinity for Cs(+) was confined to the red fibres.7. The membrane potential measured in soleus and extensor muscles immersed in plasma from the same animal was not significantly different from E(K) but was much less than E(Cs).8. These results are interpreted in terms of permeability differences between the slow red fibres and white twitch fibres.     

Muscle and brown adipose tissue fatty acid profiles in cold-exposed rats

Effects of cold acclimation and cold exposure for 25 generations on triglyceride (TG)-, total phospholipid (PL)-, and cardiolipin (CL)-fatty acid (FA) compositions were studied in the different types of skeletal muscles (red and white muscles from quadriceps, and soleus) as well as brown adipose tissue (BAT) in rats. TG: in cold-acclimated rats (CA) and rats reared in cold for 25 generations (25G) white muscle showed the decreased saturated FA (SA) and increased polyunsaturated FA (PU). In soleus of 25G, monounsaturated FA (MU) and PU increased, and SA decreased. In BAT, SA increased and MU decreased in CA, and SA and PU decreased, and MU increased in 25G. PL: in red muscle of CA, SA increased and PU decreased. In red muscle of 25G the similar but more marked changes were found accompanied by lowered arachidonic acid and unsaturation index (UI). In BAT, SA, PU, arachidonic acid, and UI increased in CA, and arachidonic acid increased in 25G. CL: in red and white muscles of 25G, oleic acid and MU increased. In BAT, arachidonic acid increased in CA and 25G, and UI increased in 25G. These results suggest that FA unsaturation of CL in the muscles as well as BAT is involved in an enhanced thermogenesis in cold-exposed rats.     

Skeletal muscle and heart antioxidant defences in response to sprint training

Although endurance training enhances the antioxidant defence of different tissues, information on the effect of sprint training is scanty. We examined the effect of sprint training on rat skeletal muscle and heart antioxidant defences. Male Wistar rats, 16–17 weeks old, were sprint trained on a treadmill for 6 weeks. Total glutathione levels and activities of glutathione peroxidase, glutathione reductase, glutathione S-transferase and superoxide dismutase in heart and various skeletal muscles were compared in trained and control sedentary animals. Lactate dehydrogenase and citrate synthase enzyme activities were measured in muscle to test the effects of training on glycolytic and oxidative metabolism. Sprint training significantly increased lactate dehydrogenase activity in predominantly fast glycolytic muscles and enhanced total glutathione contents of the superficial white quadriceps femoris, mixed gastrocnemius and fast-glycolytic extensor digitorum longus muscles. Oxidative metabolic capacity increased in plantaris muscle only. Compared with the control group, glutathione peroxidase activities in gastrocnemius, extensor digitorum longus muscles and heart also increased in sprint trained rats. Glutathione reductase activities increased significantly in the extensor digitorum longus muscle and heart. Glutathione S-transferase activity was also higher in the sprint trained extensor digitorum longus muscle. Sprint training did not influence glutathione levels or glutathione-related enzymes in the soleus muscle. Superoxide dismutase activity remained unchanged in skeletal muscle and heart. Sprint training selectively enhanced tissue antioxidant defences by increasing skeletal muscle glutathione content and upregulating glutathione redox cycle enzyme activities in fast and mixed fibre leg muscles and heart.     

Changes in phospholipid composition of synaptic membranes in medulla oblongata and frontal lobes of the cerebral hemispheres in cats with hemorrhagic shock

We studied phospholipid composition of brain synaptic membranes isolated from cats with severe hemorrhagic shock. Changes in the medulla oblongata were most pronounced and manifested in decreased content of phosphatidylcholine. Changes in the phospholipid composition of synaptic membranes in the frontal lobes included an increase in phosphatidylinositol content and reduced content of phosphatidylserine. Accumulation of phosphatidylethanolamine in synaptic membranes was found in both the medulla oblongata and frontal lobes. These data help to understand the mechanisms underlying exhaustion of compensatory reserves in brain cells during severe hemorrhagic shock.     

Changes in Phospholipid Composition of Cardiomyocyte Plasma Membranes during Hemorrhagic Shock

Changes in the phospholipid composition of cardiomyocyte plasma membranes during hemorrhagic shock suggest that disturbances in phosphatidylethanolamine metabolism serve as one of the major factors for myocardial alteration in shock. Depletion of membrane phosphatidylcholine causes destruction of cardiomyocytes. The enhanced breakdown of membrane sphingomyelin at the late stage of hemorrhagic shock is considered as a mechanism, which induces apoptosis in cardiomyocytes and Ca²⁺ accumulation in these cells. A simultaneous increase in the content of membrane phosphatidylserine is the mechanism of activation of opioid receptors, which plays a compensatory role.     

Monoclonal hybridoma anti-cardiolipin antibodies from SLE mice.

To determine whether the anti-cardiolipin antibodies are identical with the lupus anticoagulant and other antibodies to phospholipids and DNA, we prepared monoclonal hybridoma autoantibodies to cardiolipin from SLE-prone MRL/lpr mice and characterized their specificity. Using a somatic cell hybridization technique, we established three hybridoma clones which produce antibodies to cardiolipin (CAL-1: IgG2b, k, CAL-2: IgM, k and CAL-3: IgM, k). These hybridoma antibodies preferentially reacted with cardiolipin and phosphatidylserine, weakly reacted with phosphatidylinositol, but not with other phospholipids such as phosphatidylcholine, sphingomyelin, phosphatidylethanolamine and VDRL antigen. Two hybridoma anti-cardiolipin antibodies bound to ssDNA and were found to act as the lupus anticoagulant when mixing activated partial thromboplastin time with cephalin. These autoantibodies may prove to be good tools for elucidating mechanisms of thrombosis, thrombocytopenia, fetal loss and other related manifestations found in patients with systemic lupus erythematosus.     

Muscle myoglobin as determined by electrophoresis in thermally acclimated rat

Quantitative analysis of myoglobin (Mb) was established using the sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis in order to determine the influence of thermal acclimation on Mb levels in muscles. Myoglobin was measured in the red and white parts of quadriceps, soleus, diaphragm and heart of young adult male rats (11 weeks old). It was higher in the red muscle (0.92 +/- 0.043 mg/g fresh weight) than in the white muscle (0.08 +/- 0.007), and similar in the red muscle and soleus (1.17 +/- 0.117). Heart showed the highest level (1.52 +/- 0.073) among the tissues studied. The level in diaphragm (0.74 +/- 0.039) was intermediate between red muscle and heart. Cold acclimation (5 degrees C for 4 weeks, 11 weeks old) caused significant increases in Mb levels in white muscle (0.27 +/- 0.031, p less than 0.001), heart (1.95 +/- 0.094, p less than 0.01), and diaphragm (1.01 +/- 0.060, p less than 0.01), but not in red muscle and soleus. The rats reared in cold for many generations (20 generations at 5 degrees C, 11 weeks old) manifested significant increases in Mb levels of all tissues (p less than 0.05-0.001) examined. Heat acclimation (33 degrees C for 4 weeks, 11 weeks old) did not influence Mb levels of the tissues. The above findings suggest that skeletal muscle Mb may be partly involved in an enhanced thermogenesis in cold acclimation by favouring an oxidative capacity of muscles.     

Acyl-coenzyme A binding protein expression is fibre-type specific in rat skeletal muscle but not affected by moderate endurance training

The metabolic active form of free fatty acids, long-chain acyl-coenzyme A (lc-acyl-CoA), binds to its 10-kDa binding protein with high affinity. In the present study, we investigated the content of lc-acyl-CoA binding protein (ACBP) in different skeletal muscle fibre types. Soleus had the highest expression of ACBP (0.33+/-0.02 microg mg protein(-1)) and the content was as high as in heart muscle. The content in mixed gastrocnemius (0.27+/-0.02 microg mg protein(-1)), extensor digitorum longus (0.21+/-0.01 microg mg protein(-1)) and white gastrocnemius (0.16+/-0.01 microg mg protein(-1)) were lower than in soleus and differed from each other ( P<0.05). The ACBP content correlated positively with the fraction of myosin heavy chain I in the skeletal muscles (Spearman rank correlation rho=0.90; P<0.0001), and negatively with the myosin heavy chain IIB fraction ( rho=-0.92; P<0.0001). The content of ACBP also correlated with 3-hydroxy-acyl-CoA dehydrogenase (HAD) and citrate synthase (CS). Five weeks of endurance training increased HAD and CS activities in soleus and mixed gastrocnemius but did not affect the ACBP content. These findings demonstrate that ACBP expression is fibre-type specific in skeletal muscles and correlates with beta-oxidative potential. Training-induced increase in oxidative capacity was not paralleled by an increase in ACBP content.     

Relation between membrane potential and lactate in gastrocnemius and soleus muscle of the cat during tourniquet ischemia and postischemic reflow

The relation between the lactate content and the membrane potential was investigated in the gastrocnemius and soleus muscle of the cat during and after a 4 h period of ischemia. The skeletal muscle content of ATP and glucose was also measured. No change occurred in the ATP content of the gastrocnemius muscle during the period of ischemia, whereas in the soleus a 40% reduction of ATP occurred. The glucose content decreased during ischemia and increased above initial values after reflow in both muscles. The lactate content increased, and the membrane potential decreased linearly in both muscles during the ischemic period. The final lactate accumulation was higher and the decrease in membrane potential was less in the gastrocnemius than in the soleus. After release of the tourniquet both variables returned to normal or near normal values within 1.5 h in both muscles. A significant correlation was found between the lactate content and the membrane potential in both muscles during the entire experimental period. It is suggested that the depolarisation occurring in skeletal muscle during hypoxia is partly caused by changes in intracellular pH.This work was supported by grants from the Medical Faculty, University of Göteborg and from the Göteborg Medical Society     

Antibodies against oxidized phospholipids in laboratory tests exploring lupus anti-coagulant activity

Lupus anti-coagulants (LA) are a variety of anti-phospholipid antibodies characterized by their capacity to interfere with phospholipid-dependent coagulation assays. LA are increasingly recognized as important predictors of thrombosis. However, the antigen specificity of LA is still poorly characterized. Growing evidence indicates that oxidized phospholipids are among the targets of anti-phospholipid antibodies. This prompted us to investigate the role of IgG directed against different oxidized phospholipids in 164 subjects without clotting factor defects that were tested for the presence of LA using a LA-sensitive activate partial thromboplastin time (aPTT-FSL) and a screening/confirmation assay based on diluted Russell's viper venom test (dRVVT-PL). The response to aPTT-FSL was significantly (P < 0.0005) associated with high titres of IgG against oxidized phosphatidylserine, phosphatidylethanolamine and phosphatidylinositol, whereas positivity to dRVVT-PL was associated with the elevation of IgG against oxidized phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine (P < 0.0005) and phosphatidylinositol (P < 0.01). No difference in reactivity against oxidized cardiolipin was evident between the different groups. Positivity to the dRVVT-PL test was also associated significantly (P < 0.005) with the elevation of anti-cardiolipin and anti-beta(2)-glycoprotein-1 IgG. However, stepwise logistic regression demonstrated that IgG recognizing oxidized phosphatidylethanolamine and oxidized phosphatidylcholine were the only independent predictors of the response to dRVVT-PL assay, while IgG recognizing oxidized phosphatidylethanolamine and oxidized phosphatidylinositol were independent predictors of the response to aPTT-FSL test. In conclusion, autoantibodies against defined oxidized phospholipids are independent predictors of LA detection by aPTT-FSL or dRVVT-PL assays and might contribute to the variability often observed in the responses to the functional tests detecting LA.     

Lipid composition of human alveolar macrophages

Lipids from human alveolar macrophages were characterized. The cells were obtained from a patient with pulmonary fibrosis and alveolar monocytosis. Phospholipids accounted for 80% of the total lipids, with the remainder neutral lipids. Phosphatidylcholine was the major phosphatide. Phosphatidylethanolamine, sphingomyelin, phosphatidylglycerol, and lyso-(bis)phosphatidic acid were the other phosphatides present. Arachidonic acid, especially in phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol, was present in significantly high amounts. The lipids from the human cells were compared with those obtained from normal rabbit alveolar macrophages. Five major differences are observed between the lipids from these two species. First, phosphatidylcholine and sphingomyelin from human cells contained predominantly palmitic acid, whereas those from rabbit cells consisted mainly of fatty acids with 18 carbon atoms. Second, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol from the patient underwent partial oxidation, whereas the lipids of rabbit macrophages were not oxidized. Third, the lyso(bis)phosphatidic acid from the human cells contained significantly less arachidonic acid than that from rabbit cells. Fourth, all phosphatides, except phosphatidylglycerol, in human macrophages contained significantly less linoleic acid compared with those from rabbit cells. In the case of phosphatidylglycerol, the reverse was true. Fifth, free fatty acids were present only in the cells obstained from the patient.Abbreviations used in this paper PC phosphatidylcholine - PE phosphatidylethanolamine - Sph sphingomyelin - PS phosphatidylserine - PI phosphatidylinositol - PG phosphatidylglycerol - LBPA lyso(bis)phosphatidic acid - FFA free fatty acids - chol cholesterol     

Pro- and macroglycogenolysis in contracting rat skeletal muscle

Glycogen is present in skeletal muscle in smaller acid-insoluble proglycogen particles and larger acid-soluble macroglycogen particles. The present study was designed to investigate the relative contribution of pro- and macroglycogen to glycogenolysis during muscle contractions. Rats were subjected to a glycogen-depleting exercise bout and refed with either a carbohydrate-rich or fat-rich diet, resulting in widely different muscle glycogen contents. The following day, isolated hindlimbs were perfused and electrically stimulated to contract for 10 min. Pre- and postcontraction muscle samples of soleus, white and red gastrocnemius were analysed for pro- and macroglycogen. Contractions caused significant reductions in both pro- and macroglycogen in all glycogen groups and muscle types. In glycogen-supercompensated gastrocnemius muscles, the relative utilization of macroglycogen was significantly higher than the relative utilization of proglycogen. In muscles with normal to low initial glycogen contents, proglycogen was much more abundant than macroglycogen and therefore contributed more to glycogenolysis in absolute numbers. In conclusion, both proglycogen and macroglycogen are suitable substrates during skeletal muscle contractions, although macroglycogen, when amply available, seems to be more easily broken down. This may provide an explanation for the dependence of the glycogenolytic rate on the total muscle glycogen content.     

Skeletal muscle susceptibility to clofibrate induction of lesions in rats

Morphological changes induced by clofibrate in type-1 predominant soleus, type-2 predominant tensor fasciae latae, and type-1 and -2 mixed biceps femoris muscles and diaphragm in rats were investigated. Administration of the agent at 500 or 750 mg/kg/day by oral gavage for 14 or 28 days caused lesions in the soleus muscle and diaphragm, bur no changes in the tensor fasciae latae and biceps femoris muscles. In soleus muscle, vacuolation of muscle fibers was observed in all animals treated with clofibrate, and degeneration of muscle fibers and infiltration of leukocytes were noted at 750 mg/kg/day. In diaphragm, vacuolation of muscle fibers was also observed in all animals treated with clofibrate, and these lesions were located in type-1 skeletal muscles densely stained with NADH-TR. The vacuoles seen in soleus muscle and diaphragm were positive for oil red O staining. In addition, increase of lipid droplets and mitochondrial hypertrophy was seen in soleus muscle, ultrastructurally. These data suggest that sensitivity to clofibrate-induced muscle toxicity differs among muscles, with type-1 fibers being susceptible.