Unesterified Fatty Acid Levels Research Articles

Considerations on goat milk biochemical composition

Abstract The benefits of human consumption of goat's milk are given by the presence in this milk of short-chain fatty acids (approximately 20% are short-chain fatty acids) and medium-chain fatty acids (55%), this milk being easier to digest. An important qualitative indicator of goat's milk with technological, nutritional and dietary impact is the fat content. Our data show that the percentage of milk fat increases immediately after parturition, then decreases for most of the lactation. This is due to two factors: a diluting effect, by increasing the volume of milk to the maximum level of lactation and a decreasing effect of lipid mobilization, which leads to a decrease in the plasma level of unesterified fatty acids (especially C18:0 and C18:1), with a role in lipid synthesis in the mammary gland. From the third month of lactation, the average daily amount of milking milk undergoes only slight variations. Also, the fat and protein percentage remain relatively constant during June-August. In summer there was an increase in the levels of monounsaturated, polyunsaturated fatty acids and of conjugated linoleic acids in milk, compared to spring. Our results indicate that multiparous Carpathian breed females, whose food comes mostly from grazing, produce milk during the summer with a ratio between omega-6 and omega-3 below 4.

Influence biologically of active substances to amaranth on composition of lipids in organism of quails

Influence biologically of active substances to amaranth on composition of lipids in organism of quails

Microsomal triglyceride transfer protein contributes to lipid droplet maturation in adipocytes.

Previous studies in our laboratory have established the presence of MTP in both white and brown adipose tissue in mice as well as in 3T3-L1 cells. Additional studies demonstrated an increase in MTP levels as 3T3-L1 cells differentiate into adipocytes concurrent with the movement of MTP from the juxtanuclear region of the cell to the surface of lipid droplets. This suggested a role for MTP in lipid droplet biogenesis and/or maturation. To probe the role of MTP in adipocytes, we used a Cre-Lox approach with aP2-Cre and Adipoq-Cre recombinase transgenic mice to knock down MTP expression in brown and white fat of mice. MTP expression was reduced approximately 55% in white fat and 65–80% in brown fat. Reducing MTP expression in adipose tissue had no effect on weight gain or body composition, whether the mice were fed a regular rodent or high fat diet. In addition, serum lipids and unesterified fatty acid levels were not altered in the knockdown mice. Importantly, decreased MTP expression in adipose tissue was associated with smaller lipid droplets in brown fat and smaller adipocytes in white fat. These results combined with our previous studies showing MTP lipid transfer activity is not necessary for lipid droplet initiation or growth in the early stages of differentiation, suggest that a structural feature of the MTP protein is important in lipid droplet maturation. We conclude that MTP protein plays a critical role in lipid droplet maturation, but does not regulate total body fat accumulation.

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.

Phylogenetically Theory of General Pathology. Nutritive Disturbance Is the Basis of Metabolic Syndrome Pathogenesis, Overeating Syndrome. Leptin and Adiponectin Role

Metabolic syndrome (overeating) is a phylogenetically-determined sequence of symptoms with the same pathogenesis. There is only one etiological factor, namely, increased consumption of physiologically optimal food. Enterocytes and omentum fat cells are phylogenetically paracrine-regulated cell community that realizes the biological reactions of exo- and endotrophy. Visceral obesity, high level of unesterified fatty acids (FA), formation of a pool of micellar FA in the blood, integration of these FA into endothelial cell plasma membrane and enlargement of adipocytes are the causes of hydrodynamic hypertension. Toll-like receptors recognize the albumin associates with greater amount of FA than physiologically required as non- self and initiate inflammatory process. Endoplasm stress forms in lipid-laden cells, protein synthesis (folding) impairs and induces apoptosis-like cell death. Visceral fat is a phylogenetically repository of FA to fulfill the biological function of homeostasis, trophology, endoecology and adaptation; it is regulated at the early level of paracrine communities and is anatomically limited. The subcutaneous fat repository fulfills the phylogenetically late function of locomotion; the repository size is not anatomically limited. Visceral fat cells don't have receptors for phylogenetically late insulin (INS); specialized adipoсytes laden with INS and GLUT4 receptors are cells that form the subcutaneous repository. These cells are regulated by phylogenetically late humoral factors at the body level. Leptin is the initiator of humoral hypothalamic regulation of in vivo sized ontogenetically programmed number of visceral INS-insensitive fat cells. It prevents endoplasm stress and apoptosis, being designed to regulate the amount of consumed food. Leptin initiates transformation of FA storing from visceral repository into subcutaneous repository. Adiponectin is phylogenetically late humoral hypothalamic regulatory factor that controls optimal number of fat cells in vivo. Its biological role is to regulate the number (proliferation) of insulin- dependent adipocytes in subcutaneous fatty tissue.

Oleic acid inhibits lung Na/K-ATPase in mice and induces injury with lipid body formation in leukocytes and eicosanoid production.

BackgroundAcute respiratory distress syndrome (ARDS) can emerge from certain pathologies, such as sepsis, fat embolism and leptospirosis, in which the levels of unesterified fatty acids are increased in the patient’s plasma. ARDS is characterized by edema formation, and edema resolution occurs mainly due to the pneumocyte Na/K-ATPase activity. As previously described, increased oleic acid (OA) plasma concentrations induce lung injury by interfering with sodium transport. The first aim of this study was to develop a radioactivity-free assay to detect Na,K-ATPase activity ex vivo using a model of OA-induced lung injury in mice. We also investigated the relationship between Na/K-ATPase inhibition and OA-induced lung injury using ouabain-induced lung injury as a comparison, because of the well-described effect of ouabain as a Na/K-ATPase inhibitor.MethodsWe developed a Na/K-ATPase assay based on the capture of non-radioactive Rb+ ions by mice lung tissue in the absence or presence of ouabain, a specific Na/K-ATPase inhibitor. Rb+ incorporation into the lung was measured by inductively coupled plasma-optical emission spectrometry (ICP-OES) after lung tissue mineralization. Na/K-ATPase activity was considered as the difference between Rb+ incorporation in the absence and in the presence of ouabain. Bronchoalveolar lavage fluid was collected for lung injury assessment. For this assessment, cell counting, lipid body enumeration and lipid mediator concentrations were measured. Histological analyses were used to determinate lung pathology. Whole body plethysmographic analysis was performed to assay lung function.ResultsThe lung Na/K-ATPase activity of mice was completely inhibited by an OA dose of 10 μmol, an effect also obtained with 10-3 μmol of ouabain, as demonstrated by the decreased Rb+ incorporation in the lungs. The same OA dose induced lung edema and inflammation with cell influx, lipid body formation, and leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) production. Ouabain also induced lung inflammation, as detected by histological examinations. As far as we know, this is the first time that ouabain-induced lung injury was shown. Both OA and ouabain induced functional lung pathology in mice simultaneously with inhibition of the lung Na/K-ATPase activity.ConclusionsWe developed a new non-radioactive assay to quantified Na/K-ATPase in vivo. OA and ouabain inhibited in vivo Na/K-ATPase activity in the lungs and induced lung injury. Our data reinforce the idea that Na/K-ATPase inhibitors may worsen lung injury in specific pathological conditions.

Inhibitors of Fatty Acid Synthesis Induce PPARα-Regulated Fatty Acidβ-Oxidative Genes: Synergistic Roles of L-FABP and Glucose

While TOFA (acetyl CoA carboxylase inhibitor) and C75 (fatty acid synthase inhibitor) prevent lipid accumulation by inhibiting fatty acid synthesis, the mechanism of action is not simply accounted for by inhibition of the enzymes alone. Liver fatty acid binding protein (L-FABP), a mediator of long chain fatty acid signaling to peroxisome proliferator-activated receptor-α (PPARα) in the nucleus, was found to bind TOFA and its activated CoA thioester, TOFyl-CoA, with high affinity while binding C75 and C75-CoA with lower affinity. Binding of TOFA and C75-CoA significantly altered L-FABP secondary structure. High (20 mM) but not physiological (6 mM) glucose conferred on both TOFA and C75 the ability to induce PPARα transcription of the fatty acid β-oxidative enzymes CPT1A, CPT2, and ACOX1 in cultured primary hepatocytes from wild-type (WT) mice. However, L-FABP gene ablation abolished the effects of TOFA and C75 in the context of high glucose. These effects were not associated with an increased cellular level of unesterified fatty acids but rather by increased intracellular glucose. These findings suggested that L-FABP may function as an intracellular fatty acid synthesis inhibitor binding protein facilitating TOFA and C75-mediated induction of PPARα in the context of high glucose at levels similar to those in uncontrolled diabetes.

Effect of exposure to hypoxia from birth on aldosterone in rabbits: role of unesterified fatty acids

Hypoxia and fluid and electrolyte disturbances are serious risks to normal postnatal development. Because a decrease in inspired O2 (hypoxic hypoxia) inhibits aldosterone synthesis in the adult and aldosterone controls water and electrolyte balance, we studied adrenocortical function in rabbits exposed to normobaric normoxia or hypoxic hypoxia (fraction of inspired O2 0.09) from birth. At 21 days of age, rabbits were anesthetized, the adrenals were rapidly removed, and the adrenal capsules containing mostly zona glomerulosa cells were separated. Cells were dispersed with collagenase and studied in vitro. Hypoxia in vivo resulted in a 73% decrease in basal aldosterone release and a 86% decrease in adenosine 3',5'-cyclic monophosphate-stimulated aldosterone release in vitro. We hypothesized that increased unesterified fatty acids could be partly responsible for inhibition of aldosterone synthesis. Total serum unesterified fatty acids in hypoxic kits were significantly increased (298 +/- 14 micromol/l) compared with normoxic kits (184 +/- 31 micromol/l). When cells from hypoxic rabbits were washed with fatty acid-free albumin and studied under conditions devoid of fatty acids, aldosterone production was partially restored. Corticosterone production was not affected by washing. Washing had no effect on aldosterone synthesis by cells from normoxic rats. Finally, exposing washed zona glomerulosa cells to oleic acid (10-50 microM) inhibited aldosteronogenesis. We conclude that exposure to hypoxia from birth attenuates aldosterone production in part due to an increase in levels of unesterified fatty acid levels.

The role of lipid peroxidation in McArdle's disease: Applications for treatment of other myopathies

Experimental therapies for McArdle's disease have been directed toward increasing substrate availability to exercising muscle. Such therapies to date have proven largely unsuccessful. These include administration of isoproterenol to increase blood flow, glucagon treatment to elevate serum glucose and increased dietary fat intake. Each of these therapies also results in greater levels of unesterified fatty acids in blood. More recently, a high protein diet is suggested to provide increased amounts of amino acids which would be available as fuel sources. We hypothesize that the absence of myophosphorylase in McArdle's disease creates an imbalance between the enzymes of the redox systems that control the generation, propagation and inactivation of free radicals. This occurs because muscle cells are forced to rely more heavily on fatty acid oxidation. The resulting free radical damage to cellular components disrupts metabolic control and increases the permeability of membranes. Elevated levels of Ca2+ in the sarcoplasm activate proteases, phospholipases and other catabolic enzymes initiating muscle fatigue and cramping. Lipid peroxidation is a consequence of normal muscle activity and may occur unchecked in individuals with McArdle's disease. Continued muscle activity in the absence of a favorable nutritional environment may promote the progression of the disease by increasing susceptibility to oxidative stress.

Salt loads raise plasma fatty acids and lower insulin.

Some fatty acids are potent inhibitors of angiotensin binding and aldosterone production in adrenal glomerulosa cells and thereby may be involved in regulating salt and water balance. To study the possible regulation of fatty acids by salt, we measured the levels of unesterified fatty acids in plasma from patients subjected to extremes of dietary salt intake and saline infusion. Insulin and catecholamines, two known regulators of plasma fatty acids, also were measured. Infusion of 2 l saline over 4 hours caused the levels of most unesterified fatty acids to rise. Total unesterified fatty acids rose 60-100%. A high salt diet caused a smaller rise in total unesterified fatty acids (approximately 33%). In both instances, oleic and palmitoleic acids showed the greatest proportionate increases, whereas stearic acid was relatively unaffected. When salt loads were administered by either intravenous or dietary routes, plasma insulin levels fell by approximately 50%. Plasma norepinephrine increased after saline infusion but not during a high salt diet. Postsaline levels of fatty acids correlated inversely with postsaline levels of aldosterone, supporting a possible role for fatty acids as physiological regulators of the adrenal glomerulosa. A rise in plasma fatty acids and fall in insulin in response to salt loads could act in concert to increase sodium excretion, constituting a physiological mechanism contributing to salt and water balance.

Short Tertatolol Treatment Does not Impair the Hormone and Metabolic Responses to Exercise and Hypoglycemia in Diabetics

Beta-blockers can precipitate hypoglycemia and mask its warning signs. Ten male insulin-dependent, otherwise healthy diabetic patients underwent two submaximal exercise tests and two insulin-induced hypoglycemic events (0.2 u/Kg short-acting insulin IV) after six days administration of placebo followed by tertatolol, a non selective beta-blocker (5 mg once daily). Tertatolol modified neither the exercise-induced changes in blood glucose, lactate and plasma unesterified fatty acid levels, nor those of counter regulatory hormones (glucagon, growth hormone, cortisol), while blood pressure, heart rate and plasma renin activity were significantly reduced, proving that tertatolol had actually been ingested, and was active. During the insulin-induced hypoglycemia, similarly tertatolol did not modify the course of the plasma fuels and hormones. Particularly, hypoglycemia was neither deeper nor more prolonged in the presence than in the absence of tertatolol. Warning symptoms were not affected except for palpitations which were not perceived. These results suggest that tertatolol did not precipitate hypoglycemia following exercise, and did not aggravate insulin-induced hypoglycemia in short term administration, and in otherwise healthy diabetic patients.

Energy thresholds that determine membrane integrity and injury in a renal epithelial cell line (LLC-PK1). Relationships to phospholipid degradation and unesterified fatty acid accumulation.

This study related ATP levels with membrane damage, lipid abnormalities, and cell death in energy-depleted LLC-PK1 cells. Oxidative phosphorylation was inhibited by antimycin A, and glycolysis was regulated by graded glucose deprivation to achieve stepwise ATP depletion. Over a range of ATP levels down to approximately equal to 5% of normal, over 5 h, cells were altered only minimally, or injured reversibly. Such cells maintained mitochondrial potential, and retained more K+ than cells without an energy source. Over the same duration, cells without an energy source were lethally injured. Treatment with antimycin induced increments of triglycerides and decreases of phospholipids. With severe ATP depletion (approximately equal to 5-10% of normal after 5 h), decrease of phospholipids was marked. Cells in which ATP was not measurable (or was less than 5% of normal) showed comparable phospholipid declines but, in addition, showed massive and progressive increase of unesterified fatty acids. The results identified a low threshold of ATP, at best 5-10% of normal, which preserved viability in LLC-PK1 cells despite major loss of membrane phospholipids. This threshold also determined the ability of cells to maintain their normally low levels of unesterified fatty acids. Failure of energy-dependent mechanisms that normally metabolize unesterified fatty acids may be a correlate of the extent of energy depletion that determines lethal injury.

Augmentation of unesterified arachidonic acid in the renal inner medulla of dexamethasone-treated rats. Relationship to altered triglyceride metabolism.

The present study was designed to investigate the effect of dexamethasone treatment for 2 weeks (2.5 mg/kg/week, subcutaneously) on the level of unesterified fatty acids, particularly arachidonic acid, in the renal medulla of rats, and to relate the observed effect to changes in the tissue concentration and the fatty acid composition of renal medulla phospholipids and triglycerides. Dexamethasone treatment caused an increase in the renal inner medulla level of unesterified fatty acids, including arachidonic acid, that was associated with a reduction of triglycerides and of arachidonic acid esterified into triglycerides, and with an increase in the rate of fatty acids esterification into triglycerides. In contrast, dexamethasone treatment did not affect the renal medulla concentration of phospholipids, the arachidonic acid content of renal medulla phospholipids, or the rate of esterification of fatty acids into renal medulla phospholipids. In the face of increased fatty acid esterification into triglycerides, the finding of reduced triglyceride levels in the renal medulla of dexamethasone-treated rats suggests excessive triglyceride breakdown. If so, fatty acids including arachidonic acid liberated from triglycerides may contribute to elevation of unesterified fatty acid levels in the renal medulla during dexamethasone treatment. The increased level of free arachidonic acid in the renal medulla of dexamethasone-treated rats may explain in part the reported effect of this steroid in increasing urinary prostaglandins.

Effects of different energy intakes before and after calving on food intake, performance and blood hormones and metabolites in dairy cows

ABSTRACTAn experiment with 25 dairy cows was performed to investigate the effects of different energy intakes on food intake, performance and blood hormone and metabolite levels during the last 70 days of pregnancy and the first 125 days after parturition. Compared with animals fedad libitumbefore parturition, cows fed only according to requirements during the same time showed no decrease of food intake at calving. Cows fed at a restricted level also showed a faster increase in food intake, a smaller energy deficiency at the onset of lactation and a smaller weight loss after parturition. Peak milk yield was also lower, but the peak was maintained for a longer period, and during the first 2 months of lactation these cows had higher concentrations of glucose and lactic acid, and lower concentrations of non-esterified fatty acids and ketone bodies in the blood. Weight losses, and decrease of milk production during the 1st weeks of lactation were higher in cows fed only 0·75 of requirements during the first 60 days of lactation than in animals whose energy intake was planned to cover energy requirements, and during the first 2 months of lactation levels of unesterified fatty acids, ketone bodies and urea were higher, whereas levels of insulin, thyroxine and triiodothyronine were lower. Endocrine and metabolic changes seen during early lactation suggested improved glucose homeostasis, diminished fat mobilization and ketogenesis in cows given reduced amounts of energy during the dry period compared to animals fedad libitum. To prevent the development of acetonaemia an adequate energy supply during the first part of lactation is, however, of greater importance.

Effects of CDPcholine and CDPethanolamine on the alterations in rat brain lipid metabolism induced by global ischemia.

The fast turnover pool of rat brain lipids was labeled by intracerebral injection of [3H]acetate. Cerebral ischemia for a duration of 5 min after decapitation caused a 2.2-fold increase in radioactivity in the free fatty acids and loss of more than 20% of the radioactivity from choline and ethanolamine glycerophospholipids. An intracerebral injection of 0.6 mumol each of cytidine diphosphocholine (CDPcholine) and cytidine diphosphoethanolamine (CDPethanolamine) prevented the loss of radioactivity from the glycerophospholipids and decreased the amount of radioactivity in the free fatty acids by 59% as compared with control values and 82% as compared with ischemia values. By GLC assays of the mass of the free fatty acids there was a threefold increase of free fatty acids in ischemic brains. Pretreatment of ischemic brains with CDPcholine and CDPethanolamine reduced the levels of unesterified fatty acids to 60% of the control values. Thus, a prior injection of cytidine nucleotides prevented the release of free fatty acids observed in ischemic brains.

Activation of milk lipase by serum proteins: possible role in the occurrence of lipolysis in raw bovine milk.

The increase in unesterified fatty acid content of unpasteurized bulk milk in storage at 4 degrees C in the presence of known effectors of bovine milk lipoprotein lipase originating from bovine serum was studied. Bovine serum and high density lipoprotein (HDL) caused an increase in developed unesterified fatty acid levels whilst lipoprotein-free serum, apo-HDL, all individual apo-HDL tested, and the unfractionated C-peptide fraction were without lipolytic effect. In the presence of HDL-lipids, 2 C-peptides stimulated considerable lipolysis, as did the combination of HDL-lipid with unfractionated C-peptides. These characteristics of unesterified fatty acid development could be duplicated in milk whose endogenous lipolytic activity had been destroyed by heat treatment (75 degrees C for 5 min) and then restored by addition of purified bovine milk lipoprotein lipase. Radioactively labelled glycerol trioleate in milk was not hydrolysed in the same way as milk fat on the addition of serum liproproteins.

The effects of pure saturated and unsaturated fatty acids bon breadmaking and on lipid binding, using chorleywood bread process doughs containing a ‘model fat’

AbstractWhen a fresh flour dough containing a model fat prepared from pure saturated and unsaturated triglycerides was supplemented with pure oleic or linoleic acids in amounts sufficient to raise the level of unesterified fatty acids to that obtained with a flour badly deteriorated by age, the acids were equally detrimental to loaf volume. Margaric acid added at the same level was not deleterious. Lipid binding studies showed that both unsaturated fatty acids behaved similarly during doughmixing, not only becoming largely ‘bound’ themselves, but also causing increased binding of glyceryl trioleate and flour lipids. Conversely, margaric acid remained largely ‘free’ and did not affect the binding of other dough lipid constituents.

Acetate intolerance in chronic uremic patients.

The metabolic effects of an acute acetate load have been investigated in chronic uremic patients and in controls. The decay rate of blood acetate levels was significantly lower in patients than in controls. Higher levels of blood acetoacetate and 2-oxoglutarate and plasma triglycerides were observed in the patients after the load. No difference was detectable in plasma levels of unesterified fatty acids and cholesterol between the two groups of subjects. Acetate oxidation in citric acid cycle may be reduced in uremia owing to a lack of coenzyme A. These observations raise the possibility that chronic acetate administration with the dialysate induces hypertriglyceridemia and accelerates the development of atherosclerosis in hemodialysis patients.

Increase [formula omitted] of unesterified fatty acids, prostaglandin F 2α but not thromboxane B 2 in rat brain during drug induced convulsions

The amount of free arachidonic acid and prostaglandin F 2α in rat cerebral hemispheres was increased following convulsions induced by carbachol and metrazol. The level of thromboxane B 2 was not affected and prostaglandin endoperoxides could only be “trapped” after a very short convulsive period. Unesterified fatty acid levels at 2 minutes post-mortem were decreased by 50% in the cerebral hemispheres of phenytoin treated rats. Under the same conditions, phenobarbital and diazepam had little effect on the levels of free fatty acids in rat brain.

The relation between fatty acid mobilization and contractility in the isolated, perfused rat heart

The contractility of hearts from normal fed rats is decreased by 70% during perfusion with 50 μM chloroquine, which is a potent inhibitor of endogenous lipolysis. In triacylglycerol-rich hearts, obtained by feeding rats rapeseed-oil, chloroquine depresses lipolysis much less, while contractility was found to be inhibited only 30%. In both groups of hearts the effect of chloroquine was decreased by adding fatty acids, prostaglandin E 1, the Ca 2+ Mg 2+ ionophore X-537A or more Ca 2+ to the perfusion fluid. Norepinephrine and glucagon also stimulate chloroquine-depressed hearts. The conclusion is therefore reached that fatty acids act as Ca 2+-vehicles in heart cells and that chloroquine, by inhibiting lipolysis, decreases Ca 2+-transport by lowering unesterified fatty acid levels.