The proportions of different lecithins in the livers of rats deficient in essential fatty acids

1. Lecithin was prepared from the livers of rats deficient in essential fatty acids and analysed by means of countercurrent distribution. Thin-layer chromatography showed that only lecithin was present. 2. The distributions of phosphorus and the fatty acids at the 3 and 2 positions were determined. 3. It has been shown that 26% of the fatty acids in the 3 position were unsaturated and that most of the Delta(5,8,11)-eicosatrienoic acid and the arachidonic acids occur as the stearoyl or oleoyl lecithins.     

Very low density lipoproteins and lipoprotein lipase in serum of rats deficient in essential fatty acids

Rats fed a diet deficient in essential fatty acids have a low level of serum very low density lipoproteins (VLDL). It was found that after intraperitoneal injection of heparin, deficient rats had a higher level of lipoprotein lipase activity in their plasma than did normal rats. VLDL isolated from serum of normal and deficient rats were compared as substrates for postheparin lipase of rat plasma. There was no significant difference in V(max) between the two preparations of lipoproteins, but the apparent K(m) for lipoproteins from deficient animals was significantly less than that for normal animals. These observations suggest that the low concentration of VLDL in deficient rats may be explained (a) by an increased activity of lipoprotein lipase in the tissues of these animals and (b) by the VLDL of deficient rats being more rapidly hydrolyzed at low concentrations by lipoprotein lipase than VLDL from normal rats.     

Free fatty acids and skeletal muscle insulin resistance

PURPOSE OF REVIEW: Acute exposure to fatty acids causes insulin resistance in muscle, and excess dietary lipid and obesity are also strongly associated with muscle insulin resistance. Relevant mechanisms, however, are still not fully elucidated. Here we examine the latest evidence as to why lipids might accumulate in muscle and the possible mechanisms for lipid-induced insulin resistance. RECENT FINDINGS: Muscle lipid metabolites such as long chain fatty acid coenzyme As, diacylglycerol and ceramides may impair insulin signalling directly. Crosstalk between inflammatory signalling pathways and insulin signalling pathways, mitochondrial dysfunction and oxidative stress have also been put forward as major contributors to the development or maintenance of lipid-induced insulin resistance in muscle. Several animal models with gene deletions in pathways of fatty acid synthesis and storage also show increased metabolic rate, reduced intramuscular lipid storage and improved insulin action when challenged with a high lipid load. SUMMARY: Studies in genetic and dietary obese animal models, genetically modified animals and humans with obesity or type 2 diabetes suggest plausible mechanisms for effects of fatty acids, lipid metabolites, inflammatory pathways and mitochondrial dysfunction on insulin action in muscle. Many of these mechanisms, however, have been demonstrated in situations in which lipid accumulation (obesity) already exists. Whether the initial events leading to muscle insulin resistance are direct effects of fatty acids in muscle or are secondary to lipid accumulation in adipose tissue or liver remains to be clarified.     

Inhibition of sheep vesicular gland oxygenase by unsaturated fatty acids from skin of essential fatty acid deficient rats

Unsaturated fatty acids present in the lipids of essential fatty acid (EFA)-deficient rats were found to inhibit the oxygenase activity of sheep vesicular gland in an instantaneous, reversible manner. However, competitive inhibition by high levels of these acids cannot account fully for the reported loss of prostaglandin synthetic capacity of these EFA-deficient animals. A similar competitive inhibition pattern was observed with several anti-inflammatory drugs tested, whereas others also exhibited a time-dependent destructive effect on the oxygenase of the sheep vesicular gland. The relative effectiveness of these drugs in treating inflammations of the skin paralleled their effects on the vesicular gland oxygenase.     

Prostaglandins and sleep. Awaking effect of prostaglandins and sleep pattern of essential fatty acids deficient (EFAD) rats.

The experiments were carried out to investigate the effects of prostaglandins (PGs) on the sleep pattern in the cat, and in normal and EFAD rats. The data indicate that the duration of slow wave sleep (SWS) was significantly longer in EFAD rats compared with the normal rats. However, no difference in the REM sleep was observed between the two groups. Intraventricular (i.vc. )administration of PGE1, PGE2 and PGF2alpha increased wakefulness without a significant alteration of REM sleep. PGE1 administered i.vc. did not alter the duration of SWS or REM sleep in the chronic cat, but induced ponto-geniculo-occipital (PGO) waves (spikes) which are the phasic phenomenon of REM sleep. The fact that previous administration of 5-hydroxytryptophane abolished the PGE1-induced PGO spiking, might indicate that this drug triggered the spikes mainly via the functional inhibition of the serotonergic system.     

Prostaglandins and sleep. Awaking effect of prostaglandins and sleep pattern of essential fatty acids deficient (EFAD) rats

The experiments were carried out to investigate the effects of prostaglandins (PGs) on the sleep pattern in the cat, and in normal and EFAD rats.The data indicate that the duration of slow wave sleep (SWS) was significantly longer in EFAD rats compared with the normal rats. However, no difference in the REM sleep was observed between the two groups. Intraventricular (i.vc.) administration of PGE₁, PGE₂ and PGF_2α increased wakefulness without a significant alteration of REM sleep.PGE₁ administered i.vc. did not alter the duration of SWS or REM sleep in the chronic cat, but induced ponto-geniculo-occipital (PGO) waves (spikes) which are the phasic phenomenon of REM sleep.The fact that previous administration of 5-hydroxytryptophane abolished the PGE₁-induced PGO spiking, might indicate that this drug triggered the spikes mainly via the functional inhibition of the serotonergic system.     

Non-shivering thermogenesis and brown adipose tissue activity in essential fatty acid deficient rats.

The effects of essential fatty acid (EFA) deficiency on energetic metabolism and interscapular brown adipose tissue (BAT) activity were examined in the cold acclimated rat. Weanling male Long-Evans rats were fed on a low fat semipurified diet (control diet, 2% sunflower oil; EFA deficient diet, 2% hydrogenated coconut oil) for 9 weeks. They were exposed at 5 degrees C for the last 5 weeks. In EFA deficient rats, compared to controls, growth retardation reached 22% at sacrifice. Caloric intake being the same in the two groups, it follows that food efficiency was decreased by 40%. Resting metabolism in relation to body surface area was 25% increased. Calorigenic effect of norepinephrine (NE) in vivo (test of non-shivering thermogenesis) underwent a marked decrease of 34%. BAT weight was 21% decreased but total and mitochondrial protein content showed no variation. A 26% increase in purine nucleotide binding per BAT (taken as an index of thermogenic activity) was observed, suggesting that the enhancement in resting metabolism observed was mainly due to increased BAT thermogenesis. However, BAT mitochondria respiratory studies which are more direct functional tests showed a marked impairment of maximal O2 consumption of about 30% with palmitoyl-carnitine or acetyl-carnitine (both in presence of malate) or with alpha-glycerophosphate as substrate. It is likely that this impaired maximal BAT oxidative capacity may explain the impaired NE calorigenic effect in vivo. A possible increase in mitochondrial basal permeability is also discussed.     

Selective incorporation of n-3 and n-6 fatty acids in essential fatty acid deficient rats in response to short-term oil feeding

Essential fatty acid deficient male Sprague Dawley rats were fed for 7 days a fat-free semi-synthetic diet supplemented with 10% by weight of different oil supplements. The oil supplement was a mixture of olive, safflower and linseed oils prepared at different proportions so the dietary n-9/n-6/n-3 ratios were approximate 2/1/1, 1/2/1, 1/1/2, and 1/1/1. The fatty acid compositions of plasma and liver lipids were then examined. Our results show polyunsaturated n-6 and n-3 fatty acids were selectively incorporated into plasma and liver phospholipids, and also into plasma cholesteryl esters. A preferential incorporation of n-6 over n-3 fatty acids into plasma cholesteryl esters and phospholipids was also observed.     

Biosynthesis of branched-chain fatty acids in Bacillus subtilis. A decarboxylase is essential for branched-chain fatty acid synthetase

Branched long-chain fatty acids of the iso and anteiso series are synthesized in many bacteria from the branched-chain alpha-keto acids of valine, leucine, and isoleucine after their decarboxylation followed by chain elongation. Two distinct branched-chain alpha-keto acid (BCKA) and pyruvate decarboxylases, which are considered to be responsible for primer synthesis, were detected in, and purified in homogenous form from Bacillus subtilis 168 strain by procedures including ammonium sulfate fractionation and chromatography on ion exchange, reversed-phase, and gel absorption columns. The chemical and catalytic properties of the two decarboxylases were studied in detail. The removal of BCKA decarboxylase, using chromatographic fractionation, from the fatty acid synthetase significantly reduced its activity. The synthetase activity was completely lost upon immunoprecipitation of the decarboxylase. The removal of pyruvate decarboxylase by the above two methods, however, did not affect any activity of the fatty acid synthetase. Thus, BCKA decarboxylase, but not pyruvate decarboxylase, is essential for the synthesis of branched-chain fatty acids. The very high affinity of BCKA decarboxylase toward branched-chain alpha-keto acids is responsible for its function in fatty acid synthesis.     

Time-dependent effects of fatty acids on skeletal muscle metabolism

Increased plasma levels of free fatty acids (FFA) occur in states of insulin resistance such as type 2 diabetes mellitus, obesity, and metabolic syndrome. These high levels of plasma FFA seem to play an important role for the development of insulin resistance but the mechanisms involved are not known. We demonstrated that acute exposure to FFA (1 h) in rat incubated skeletal muscle leads to an increase in the insulin-stimulated glycogen synthesis and glucose oxidation. In conditions of prolonged exposure to FFA, however, the insulin-stimulated glucose uptake and metabolism is impaired in skeletal muscle. In this review, we discuss the differences between the effects of acute and prolonged exposure to FFA on skeletal muscle glucose metabolism and the possible mechanisms involved in the FFA-induced insulin resistance.