Changes In Free Fatty Acid Concentrations Research Articles

Short-term acipimox treatment is associated with decreased cardiac parasympathetic modulation.

The nicotinic acid analogue acipimox is an antilipolytic agent, which acutely inhibits lipolysis and suppresses systemic levels of free fatty acids (FFA) and improves insulin sensitivity in obese patients. These effects of acipimox are transient due to a counter-regulatory increase in growth hormone levels that reverse the antilipolytic effect of acipimox. Hypopituitary patients constitute a viable model to study the growth hormone-independent effects of acipimox and the impact of isolated changes in FFA concentrations and insulin sensitivity on parasympathetic nervous activity. The aim of the present study was to investigate if pharmacological antilipolysis with acipimox acutely affects autonomic tone. We studied heart rate variability as a measure of autonomic tone in eight hypopituitary men with and without acipimox treatment. The standard deviation of normal-to-normal intervals, root mean square of successive differences and high frequency were measured as heart rate variability parameters. The patients were studied in the basal and insulin-stimulated state with clamped plasma glucose on two occasions in a randomized, double-blind and placebo-controlled crossover study. Plasma glucose (4.7 vs. 4.9mmoll-1 , P=0.02) and serum FFA (0.05 vs. 0.41mmoll-1 , P<0.001) were significantly decreased during acipimox treatment. Acipimox had an inhibitory effect on standard deviation of normal-to-normal intervals (41.3 vs. 45.3ms, P=0.01), root mean square of successive differences (23.2 vs. 11ms, P=0.03) and high frequency (3.79 vs 3.60 ln (ms2 ), P=0.02) and these effects were reversed during clamping. Short-term inhibition of lipolysis by acipimox treatment lowered circulating FFA levels, improved insulin sensitivity, and was accompanied by reduced parasympathetic tone. The effect of acipimox on the parasympathetic modulation was reversed by hyperinsulinaemia.

Free fatty acids as a cardiovascular risk factor

Free fatty acids (FFAs) serve as physiologically important energy substrates and their release from the adipose tissue by lipolysis is regulated according to the energy demands of the body. FFAs are increased in obese patients and contribute to type 2 diabetes, hepatic steatosis and several cardiovascular diseases. In patients with heart failure and acute coronary syndromes, elevated FFA levels are a consequence of an increased lipolysis due to a surge in catecholamines and natriuretic peptides. FFAs contribute to myocardial dysfunction and are proarrhythmic, and their oxidation requires more oxygen than does glycolysis. Therapeutic approaches have already emerged that aim to reduce the uptake and/or oxidation of fatty acids in the myocardium. The routine use of FFAs as a diagnostic tool is limited by their high variability, this being strongly influenced by nutrition and the effects of several hormones. In addition, it remains to be clarified whether fasting or postprandial values or dynamic measurements such as changes in FFA concentrations induced by stress are better parameters for evaluating cardiovascular risk. In this review, we present an overview of the metabolism and role of FFAs as a cardiovascular risk factor and discuss the potential of FFAs in the diagnosis and treatment of cardiovascular diseases.

Fatty acids as precursors for aroma volatile biosynthesis in pre-climacteric and climacteric apple fruit

Abstract Changes in the concentration of free fatty acids (FA) and FA as constituents of neutral and polar lipids were determined during the course of ripening in the peel of ‘Golden Delicious’ apple fruit. The concentration of these FA was then related to previously examined volatile aroma substances in order to evaluate a possible quantitative relationship between both variables. In particular, the concentrations of the C18:1 and C18:2 FA in the free FA fraction were low in pre-climacteric fruit but rapidly increased three- to fourfold during the climacteric rise. Changes in FA concentrations during maturation were less pronounced in the neutral lipid fraction and almost absent in the polar lipid fraction. Treatment of immature fruit (harvested almost 5 weeks before the climacteric rise) with 100 μl l−1 ethylene increased the concentration of FA in the free and neutral lipid fraction but not in polar lipids. The increase in the free and ‘neutral lipid’ 18:2 FA after ethylene treatment in immature apples exceeded the concentration of this FA found in mature climacteric fruit. A hypothesis is discussed linking the examined dynamic changes of FA with previous results of ATP and aroma volatiles in an attempt to explain deficiencies in aroma volatile production in unripe and long-term stored apple fruit.

Effect of eicosapentaenoic acid ethyl ester on hypothyroid function.

Thyroid hormones affect reactions in almost all pathways of lipid metabolism. It has been reported that plasma free fatty acid (FFA) concentration in hypothyroidism is generally within the normal range. In this study, however, we show that plasma FFA concentration in some hypothyroid patients is higher than the normal range. Symptoms of thyroid dysfunction in these individuals were less severe than those of patients with lower plasma FFA concentrations. From these findings we hypothesized that the change in FFA concentration must correlate with thyroid function. Using an animal model, we then examined the effect of highly purified eicosapentaenoic acid ethyl ester (EPA-E), a n-3 polyunsaturated fatty acid derived from fish oil, on thyroid function in 1-methyl-2-imidazolethiol (MMI)-induced hypothyroid rats. Oral administration of EPA-E inhibited reduction of thyroid hormone levels and the change of thyroid follicles in MMI-induced hypothyroid rats. These findings suggest that FFA may affect thyroid functions and EPA-E may prevent MMI-induced hypothyroidism.

Infusion of nicotinic acid stimulates leucine oxidation and inhibits protein synthesis in pigs before and during a meal.

Leucine metabolism was measured isotopically in immature female pigs to assess the effect of acute infusions of nicotinic acid (NA) on leucine kinetics in both the fed and fasting states. After an overnight fast, immature pigs were infused with 3H-alpha-ketoisocaproate (KIC) and 14C-leucine. After a 2-hour equilibration period, an infusion of either saline or 0.4 mg/kg.min of NA was begun. NA caused a decrease in plasma glucose and an increase in plasma glucagon. During the fasting period, NA increased KIC oxidation 2-fold over controls. After feeding, plasma free fatty acids (FFA) in both groups were equivalent, but KIC oxidation was still approximately 80% higher in NA-infused animals. In addition, NA stimulated proteolysis and inhibited protein synthesis during the meal. Because plasma FFA concentrations were equal during the fed period, it is unlikely that changes in FFA concentrations are responsible for the changes in leucine metabolism observal during NA infusion.

FREE FATTY ACID METABOLISM DURING INTRALIPID INFUSION

Fatty acid composition of intralipid (IL) differs from that of milk in that iL consists of 50% linoleic acid (L) and 10% palmitic acid (P) as compared with 8% (L) and 42% (P) in milk. To determine the effects of IL infusion on plasma free fatty acid (FFA) patterns, 6 neonates received 1 gin/kg of IL over 4 hours. The infants ranged from 32 - 38 weeks gestation and were of appropriate birth weight. Samples were obtained during infusion and at 2 hours post infusion for FFA pattern analysis by gas liquid chromatography. Results: During infusion, the change in FFA concentration was significant (p<0.02). There was a significant decrease in P/FFA ratio (p<0.01) and increase in L/FFA ratio (p<0.001) and reversal of P/L ratio (p<0.001). In the post infusion period from 4 to 6 hours, there was a reversal of these altered ratios towards baseline values, but this change was not statistically significant. There are both quantitative and qualitative changes in plasma FFA during intralipid infusion. These alterations reflect the fatty acid composition of intralipid. Slow return of FFA to the normal pattern, after stopping intralipid infusion, depends on the rate of ceftilar uptake or metabolism of the FFA.

Regulation of plasma free fatty acid turnover.

Plasma free fatty acid (FFA) turnover rates have been estimated in dogs by a technique involving measurement of FFA specific activities during constant intravenous infusion of trace amounts of C14-labeled palmitic acid. In order to determine the relationship between FFA concentration and turnover, variations in plasma FFA levels ranging from 0.081 to 3.31 µEq/ml were induced by a variety of physiological and pharmacological treatments. Calculated FFA turnover rates ranged from 2.1 to 58.8 µEq/kg/min, with a highly significant linear regression of FFA turnover on FFA level. It is concluded that under a variety of conditions changes in FFA concentration are brought about by changes in FFA production rate and that changes in FFA uptake are simple mass-action effects of changes in FFA concentration. Respiratory C14O2 data are presented indicating that about one-fourth of the total expired CO2 is derived from FFA in the postabsorptive state. This accounts for the immediate fate of about one-fourth of the total FFA leaving the plasma.