The metabolic syndrome is defined as the coexistence of 3 or more components, some of which indicate alterations in glucose and lipid metabolism. The prevalence of the metabolic syndrome is rapidly increasing in relation to obesity, and it is considered to be an important predictor of cardiovascular disease. Increased intakes or supplements of n-3 marine fatty acids may improve defects in insulin signaling and prevent alterations in glucose homeostasis and the further development of type 2 diabetes. This is largely mediated through a reduction in fatty acid accumulation in muscle and liver. n-3 Polyunsaturated fatty acids (n-3 PUFAs) reduce plasma triacylglycerols and improve the lipoprotein profile by decreasing the fraction of atherogenic small, dense LDL. However, n-3 PUFAs do not lower LDL cholesterol. These effects are likely mediated through the activity of transcription factors relating to expression of genes involved in lipid oxidation and synthesis. Other pleiotrophic effects of n-3 PUFAs may contribute to decreasing the burden of the metabolic syndrome, such as modulating inflammation, platelet activation, endothelial function, and blood pressure. Although studies comparing the effect of both major n-3 PUFAs are limited, docosahexaenoic acid appears at least as efficient as eicosapentaenoic acid in correcting several risk factors. The use of n-3 PUFAs should be considered in more global strategies including changes in lifestyle, such as adhering to a healthy Mediterranean type of diet and practicing regular physical exercise.

a b s t r a c tSince heterozygous familial hypercholesterolemia (HeFH) is a disease that exposes the individual from birth onwards to severe hypercholesterolemia with the development of early cardiovascular disease, a clear consensus on the management of this disease in young patients is necessary. In Belgium, a panel of paediatricians, specialists in (adult) lipid management, general practitioners and representatives of the FH patient organization agreed on the following common recommendations.

Lipoprotein lipase (LPL) catalyzes the fluxgenerating step in transport of fatty acids from lipoprotein triacylglycerols into tissues for use in metabolic reactions. In viro studies have shown that fatty acids can bind to the enzyme and impede its other interactions. In this study we have searched for evidence of fatty acid control of LPL in vivo by rapid infusion of a triacylglycerol emulsion to healthy volunteers. During infusion the activity of LPL but not of hepatic lipase increased in plasma, but to different degrees in different individuals. The time course for the increase in LPL activity differed from that for triacylglycerols but followed the plasma levels of free fatty acids. This was true during infusions and when the emulsion was given as a bolus iijection. In particular there were several instances when plasma triacylglycerol levels were very high but free fatty acids and LPL activity remained low. Model studies with bovine LPL showed that fatty acids displace the enzyme from heparin-agarose. We suggest that in situations when fatty acids are generated more rapidly by LPL than they are used by the local tissue, they cause dissociation of the enzyme from its binding to endothelial heparan sulfate and are themselves released into circulation.Triacylglycerol (TG) transport is a major pathway in energy metabolism and handles more than 100 g of lipid per day in individuals on a typical Western diet. The TGs are unloaded from the lipoproteins through hydrolysis by lipoprotein lipase (LPL) at the vascular endothelium in extrahepatic tissues (for review, see refs. 1 and 2). It is generally assumed that the rate-limiting factor is the amount of LPL available at the endothelium (3). In support of this, studies in animals have shown a correlation between the activity of LPL in a tissue and its uptake of fatty acids from chylomicra (1,2,4). Inherent in this view is the assumption that the tissue can assimilate the fatty acids at the rate that the enzyme provides them. The possibility that fatty acid assimilation can be rate-limiting has been raised (5) but has received little attention. In vitro studies have, however, shown that LPL has a built-in mechanism for product control. The enzyme can bind fatty acids, which reduces its affinity for lipid droplets (6, 7) as well as for heparin-like polysaccharides (8) and abolishes the activation by apolipoprotein C-II (9). This suggests that accumulation of fatty acids at the endothelium might inhibit further lipolysis and disrupt the binding of LPL to heparan sulfate. Whether this mechanism ever comes into play in vivo is not known. To demonstrate it one would need a condition in which the clearing capacity was overloaded. In this study we have tried to create such a situation by rapid infusion of a lipid emulsion. Analyses. Blood samples (5 ml) were collected in EDTA and immediately put in ice water. Plasma was rapidly separated by centrifugation for 5 min at 1000 x g using a Beckman refrigerated centrifuge. Plasma lipids were determined by the following enzy...

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The present study was undertaken to determine intracellular amino acid patterns in patients with multiple trauma, whether or not complicated by sepsis and during convalescence. A percutaneous muscle biopsy was performed three to four days following major accidental injury in ten patients and analyzed for muscle free amino acids. Venous blood was drawn at the time of the biopsy and analyzed for plasma free amino acids. Five patients developed sepsis and a repeat biopsy was performed on days 8 to 11. In five of the patients a biopsy was performed during the late convalescent period (anabolic phase). A marked depletion of nonessential amino acids in muscle occurred in both injury and sepsis due to a decrease (50%) in glutamine, which was equally marked in both states. The essential amino acids in muscle increased in injury. During sepsis, a further increase was observed with a return toward normal in the convalescent period. In injury, the most marked rise was in the branched-chain amino acids, phenylalanine, tryosine and methionine. With sepsis, a further rise in muscle branched-chain amino acids, phenylalanine and tryosine occurred, while plasma levels remain unchanged. During convalescence, muscle glutamine, arginine, histidine and plasma branched-chain amino acids were below normal, whereas muscle phenylalanine and methionine were elevated. The muscle free amino acid pattern observed after major trauma was essentially the same as earlier described following elective operation. This suggests a common response of intracellular amino acids irrespective of the degree of injury, and may indicate that the pump settings which regulate amino acid transport follow the "all or none" rule. The high intracellular levels of branched-chain amino acids in sepsis suggest that the energy deficit of this state is due to an impairment of substrate use rather than intracellular availability. The high concentrations of the aromatic amino acids and methionine may be due to altered liver function. During the late convalescent period (anabolic phase) the low levels of certain key amino acids suggests inadequate nutrition. The difficulties in nourishing the injured or septic patient are well recognized. The period following these catabolic states may be an important period for the application of an optimal, aggressive nutritional regimen.

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The acute phase reactions, associated with injury, inflammation, or sepsis, markedly affect the concentration and composition of plasma lipids and lipoproteins. Hepatic production of triglycerides and very low density lipoprotein formation are increased, but do not necessarily result in high plasma triglyceride levels. In contrast, all conditions lower plasma cholesterol by decreasing its content in both low-density and high-density lipoproteins. In addition, substantial changes in protein and lipid composition of lipoproteins are observed that may redefine the function of these particles, but also increase their atherogenic and inflammatory properties.

To explore how enzyme affinities and enzyme activities regulate hydrolysis of water-insoluble substrates, we compared hydrolysis of phospholipid-stabilized emulsions of medium-chain (MCT) versus long-chain triacylglycerols (LCT). Because substrate solubility at the emulsion surface might modulate rates of hydrolysis, the ability of egg yolk phosphatidylcholine to solubilize MCT was examined by NMR spectroscopy. Chemical shift measurements showed that 11 mol % of [13C]carbonyl enriched trioctanoin was incorporated into phospholipid vesicles as a surface component. Similar methods with [13C]triolein showed a maximum solubility in phospholipid bilayers of 3 mol % (Hamilton & Small, 1981). Line widths of trioctanoin surface peaks were half that of LCT, and relaxation times, T1, were also shorter for trioctanoin, showing greater mobility for MCT in phospholipid. In assessing the effects of these differences in solubility on lipolysis, we found that both purified bovine milk lipoprotein lipase and human hepatic lipase hydrolyzed MCT at rates at least 2-fold higher than for LCT. With increasing concentrations of MCT, saturation was not reached, indicating low affinities of lipase for MCT emulsions, but with LCT emulsion incubated with lipoprotein lipase, saturation was reached at relatively low concentration, demonstrating higher affinity of lipase for LCT emulsions. Differences in affinity were also demonstrated in mixed incubations where increasing amounts of LCT emulsion resulted in decreased hydrolysis of MCT emulsions. Increasing MCT emulsion amounts had little or no effect on LCT emulsion hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS)