[Lipolysis in very low density lipoproteins - locus minoris resistentiae - in the pathogenesis of hypertriglyceridemia. Positive effects of diet, polyenic fatty acids, statins and fibrates.]

Inhibition of hydrolysis of palmitic and oleic triglycedires (TG) in very low density lipoproteins (VLDL), slow formation of active apoВ-100 conformation, blockade of апоЕ/В-100 ligand formation in VLDL and their reduced uptake by insulin-dependent cells cause hypertriglyceridemia (HTG). Palmitic and oleic VLDL (>80% total VLDL) are not converted in low density lipoproteins (LDL). Atherosclerosis is not an alimentary deficiency of polyenic fatty acids (PFA), but results from low in vivo bioavailability of PFA in LDL against the background of high dietary palmitic FA and palmitic LDL. Plasma PFA content and cellular PFA deficiency are as high as LDL cholesterol (CL). Primary prevention of atherosclerosis should be based on a decrease in dietary content of palmitic saturated FA, trans FA and a moderate increase in PFA. It seems highly unlikely that the xeobiotics statins, fibrates and probucol produce pleiotropic biological effects in vivo. These effects are brought about by phylogenetically early humoral mediators eicosanoids: prostacyclins, prostaglandins, thromboxanes, leukotrienes, and resolvins. It is reasonable to suggest that all preparations which act according to the same algorithm activate TG hydrolysis in VLDL and normalize cellular uptake of PFA in linoleic and linolenic LDL via apoВ-100 endocytosis. Atherosclerosis is a syndrome of cellular deficiency of essential polyenic FA.

[The positional isomers of palmitic and oleic triglycerides, lipolysis, conformation of apoB-100, formation of apoE/B-100 ligand and absorption of lipoproteins of very low density by insulin-dependent cells under action of statins.]

The study was carried out to trace back quantitative alterations of positional isomers, oleic and palmitic triglycerides and individual fatty acids in blood serum. After two weeks of taking of Simvastatin (40, 80 mg), analysis of blood serum established decreasing of content of Рhosphatidylcholine and more reliable decreasing of amount of non-etherized alcohol cholesterol. No alterations of content of particular fatty acids were detected. In apoB-100, Рhosphatidylcholine and non-etherized alcohol cholesterol form polar mono-layer; it covers mass of oleic and palmitic triglycerides that was bound by apoB-100 in oleic and palmitic lipoproteins of very low density disturbing bio-availability of substrate (oleic and palmitic triglycerides) for post-heparin lipase. This very pool of non-etherized alcohol cholesterol is inhibited by statins activating lipolysis in oleic and palmitic lipoproteins of very low density. In blood was detected amount of palmitic positional isomersin oleic and palmitic triglycerides (palmitoyl-palmitoyl-palmitate and palmitol-palmitoyl-oleate) and oleic positional isomers (oleyl-oleyl-palmitate and oleyl-oleyl-oleate). The significant difference was marked in content of positional isomers both of oleyl-oleyl-oleate and oleyl-oleyl-palmitate; their content is less in blood of patients of experimental group as compared with healthy people. In case of treatment with Simvastatin (40 mg) the level of palmitic positional isomers and palmitol-palmitoyloleate is decreased. In case of treatment with Simvastatin (80 mg) significant decreasing of positional isomers-palmitolpalmitoyl-oleate and oleyl-oleyl-palmitate as compared with data before treatment. The detection of content of positional isomers triglycerides permits: a) to characterize disorders of metabolism of palmitic fatty acid, oleic fatty acid, oleic and palmitic triglycerides and oleic and palmitic lipoproteins of very low density of the same name; b) to form individual diet therapy; c) to obtain objective information concerning compliance of prescribed recommendations b y patient. The basis of primary prevention of atherosclerosis and atheromatosis is in decreasing up to physiological level in food the content of longchained saturated fatty acids mainly palmitic acid.

[The positional specificity of individual triglycerides-substrates for lipase action. The oleic triglycerides of palm oil, palmitic triglycerides of milk, ions of calcium and magnesium.]

The counter-insulin effect of surplus of palmitic fatty acid in food is implemented under: a) formation in vivo of palmitic type of fatty acids metabolism with deficiency of substrate for ATP synthesis and permanent shortage of energy for accomplishment of biologic functions; b) compensatory activation of biologic function of adaptation, biologic reaction of compensation. The activation with catecholamines in visceral fatty cells of gland the hormone-dependent lipase which is not blocking insulin, increases content of unesterified fatty acids in blood plasma. Until in blood plasma the level of unesterified fatty acids is increased the cells phylogenetically justified stop absorption of glucose along with development of hyperglycemia and hypertriglyceridemia - insulin resistance syndrome. Thew increasing of content of triglycerides (alcohol glycerin) always increases cholesterol - low density lipoproteins; the highest numbers of cholesterol result in no increasing of triglycerides concentration in blood. All triglycerides of milk positionally are palmitic ones and all triglycerides of palm oil are oleic ones. The surplus of palmitic unesterified fatty acids in small intestine under hydrolysis of oleic triglycerides decreases bio-availability and absorption of ions of Ca++ and Mg++ by enterocytes. This occurrence is absent in case of hydrolysis of palmitic triglycerides of maternal milk in intestine since all released unesterified fatty acids are oleic ones. The position of fatty acids in the composition of triglyc erides is a functional characteristic of substrate under impact of positionally specific lipases in all biologic mediums.