Free Fatty Acid Depression Research Articles

Addition of glucose to a fatty meal delays chylomicrons and suppresses VLDL in healthy subjects.

Postprandial lipemia has been shown in a number of studies to be associated with atherosclerosis. However, the test meals used in these studies were heterogeneous particularly in their carbohydrate content, which may be important for the resulting lipemia and which makes comparison between different studies difficult. We studied the effect of 75 g glucose added to a fatty meal on various lipoproteins and on gastric emptying. Fourteen healthy young volunteers were studied in the fasting state and until 7 h postprandially. In a crossover design, each subject received an oral fat load (1 g fat kg(-1) body weight) with or without 75 g glucose. Triacylglycerol (TG) and free fatty acids (FFA) were then measured in whole blood and lipoproteins were separated off by ultracentrifuging. Gastric emptying was determined by the (13)C breath test. The addition of 75 g glucose to a fatty meal had two different effects. Gastric emptying was delayed by about 2 h and the chylomicron response was consequently postponed. In addition, the postprandial increase in VLDL triacylglycerol was reduced by 40%, which may be due to the pronounced FFA depression during the glucose-induced rise in insulin. 75 g glucose added to an oral fat load causes a delay of the chylomicron response and a marked suppression of the postprandial increase in VLDL.

Acipimox-mediated plasma free fatty acid depression per se stimulates growth hormone (GH) secretion in normal subjects and potentiates the response to other GH-releasing stimuli

Acipimox-mediated plasma free fatty acid depression per se stimulates growth hormone (GH) secretion in normal subjects and potentiates the response to other GH-releasing stimuli

Relationship between plasma free fatty acid levels and human placental lactogen secretion in late pregnancy.

In order to determine whether changes in free fatty acid (FFA) levels affect hPL secretion in late human pregnancy in the same way as they affect human growth hormone (hGH) secretion, two types of experiments were performed: 1) I g of nicotinic acid (NA) was infused for 60 min inII patients and 1.5 g of NA was infused for 90 min in 8 additional patients; 2) triglycerides and heparin were administered iv for 120 min in 5 control cases and, in 11 other patients 0.3 U insulin/kg BW was injected at the 45th min of the triglycerideheparin infusion. Maternal blood glucose (BG), plasma triglycerides (TG), FFA, immunoreactive insulin (IRI) and hPL levels were sequentially determined in the course of these experiments. In both series of patients, the NA infusion resulted in substantial depression of FFA levels to around 50% of mean basal levels. The hPL levels displayed only negligible fluctuations, although FFA depression persisted for more than 2 hours. During the lipid-heparin infusion, an increase in plasma TG...

Growth hormone, glucagon, and insulin response to depression of plasma free fatty acids and the effect of glucose infusion.

It has previously been shown that nicotinic acid (NA)-induced depression of free fatty acids (FFA) stimulates the secretion of GH and glucagon. To evaluate this hormonal response further, we studied the influence of different doses of glucose administered by continuous iv infusion on the GH and glucagon increase during NA-induced FFA depression. In ten male non-obese volunteers, FFA depression by the infusion of NA (2.3 g over a period of 210 min) resulted in a late rise (from 150 min on) of GH (From 1.1 to 25.9 ng/ml) and an early increase (from 30 min on) of glucagon (from 71.7 to 138.2 pg/ml). When glucose was infused (approximately 60, 120 and 180 g, respectively, over a period of 270 min) during NA-induced FFA depression, the GH rise was reduced and delayed in relation to the amount of glucose infused, but could not be completely abolished (maximal GH concentration during the three NA-plus-glucose infusions: 16.5, 8.0 and 6.1 ng/ml, respectively). The glucagon rise was entirely reversed by the high glucose dose. Insulin did not rise during NA infusion alone. Its secretion in response to glucose infusion was not significantly influenced by FFA depression. Thus, during NA-induced FFA depression the secretion of two lipolytic hormones--GH and glucagon--is stimulated while the secretion of the lipogenetic hormone insulin remains low. Glucose has an inhibitory effect on the GH and glucagon response which, however, is different for each of the hormones.

Metabolic effects of N6-substituted adenosines in rats

In vitro studies using isolated fat cells of fed rats demonstrated that certain N 6-substituted adenosine derivatives are highly effective antilipolytic agents. The compounds are thought to interfere with the binding of ATP to adenylate cyclase. Enzymatic reactions which provide or depend on ATP were not influenced. Substances which exhibit antilipolytic activity in vitro lowered serum free fatty acids (FFA) in normal rats after oral administration. No symptoms of tachyphylaxis were observed after oral treatment for four weeks. Blood glucose, cholesterol, triglycerides, corticosterone and adrenal wt were unaltered. Liver glycogen was decreased, presumably as a consequence of FFA depression. Isolated fat cells from treated animals exhibited a higher response towards added dibutyrylcAMP than controls. The mobilization of glucose from glycogen by glucagon in the anesthetized rat was not altered after treatment with tN 6-substituted adenosines. Despite good tolerance after oral treatment, rats died after i.v. injections of low doses of adenosine derivatives, presumably of heart failure.

Studies on the relationship between plasma free fatty acids and growth hormone secretion in man.

The influence of plasma free fatty acid (FFA) concentration on the secretion of human growth hormone (HGH) was investigated. (a) FFA depression was produced by means of a nicotinic acid (NA) infusion for either 1 or 5 hr in the presence of glucose-induced hyperglycemia. Controls received only saline. (b) FFA depression was also produced by a 90 min NA infusion and then rapid FFA elevation by a lipid-plus-heparin (lipid) infusion. This procedure was compared with a similar NA infusion not followed by lipid. (c) FFA elevation was produced either by a lipid or by a norepinephrine (NE) infusion and then HGH secretion was stimulated by insulin-induced hypoglycemia. Each subject in this group received both the lipid and the NE infusion on seperate days as well as two control tests (insulin alone and NE alone). Depression of FFA resulted in an increase of HGH with a lag period of approximately 2 hr. Maximal HGH rise after 1 hr NA infusion was 7.7+/-1.9 ng/ml and with 5 hr NA infusion 14.3+/-3.6 ng/ml (both significantly higher than during saline infusion, P < 0.025 and < 0.005 respectively) and occurred despite continuous hyperglycemia. Lipid infusion just before the expected HGH increase prevented the HGH response to FFA depression. HGH rise during insulin hypoglycemia (32.2+/-6.5 ng/ml) was significantly inhibited by prior FFA elevation whether achieved by lipid infusion (maximum HGH rise 11.4+/-1.6 ng/ml) or by NE infusion (maximum HGH rise 19.0+/-6.2 ng/ml). The results are suggestive of a negative feedback loop between plasma FFA and HGH secretion, of importance for subacute rather than acute changes in the plasma FFA concentration. FFA lack itself seems to be the signal for HGH release despite the lag period between FFA decrease and HGH increase. Glucose and FFA can at least not fully replace each other in their respective influence on HGH release.

Effect of lipids on growth hormone secretion in humans.

To determine the effect of elevations of plasma lipids on growth hormone secretion in humans, paired insulin hypoglycemia tests and paired arginine infusion tests were performed on eight and six normal female volunteers respectively. On 1 of the 2 test days for each growth hormone stimulus, subjects were given 60 g corn oil (Lipomul) 3 hr before testing followed by intravenous heparin (5000 U) at the time of insulin or arginine administration. Lipomul plus heparin administration inhibited both insulin- and arginine-induced plasma HGH elevations with almost complete suppression of the response to arginine. The plasma HGH (human growth hormone) inhibition was associated with elevation in plasma triglycerides and inhibition of plasma FFA (free fatty acid) depression after insulin or arginine. Neither the hypoglycemic response to insulin nor the blood glucose and plasma immunoreactive-insulin responses to arginine were altered by Lipomul plus heparin administration. In four additional subjects in whom Lipomul was given without heparin, the elevated plasma triglyceride values were not associated with suppression of arginine-induced plasma HGH elevations. In the same four subjects, heparin administration without Lipomul neither suppressed arginine-induced plasma HGH elevations nor prevented the depression in plasma FFA after arginine as much as when Lipomul plus heparin had been given. These latter observations suggest that the elevation in plasma FFA was responsible for suppression of growth hormone secretion by Lipomul plus heparin. These studies indicate a possible role of plasma FFA in regulation of growth hormone secretion.

The biphasic effect of nicotinic acid on plasma FFA levels

Nicotinic acid, which has been shown to be a potent inhibitor of lipolysis in vitro (1), depresses plasma free fatty acid (FFA) levels in rats, dogs (2) and man (3,4). In each of these species the initial FFA depression is followed by a rise to markedly elevated concentrations (FFA rebound). Earlier studies in rats have demonstrated that the FFA rebound response is mediated by the pituitary-adrenal system (2). An increase in plasma corticosterone levels was associated with the rise in plasma FFA concentrations. Studies of the time course of changes in plasma FFA levels suggested the possibility that the rebound response and the elevated levels of corticosterone were evoked by the initial depression of plasma FFA concentrations. To investigate this possibility studies of the effects of a wide range of doses of nicotinic acid on plasma FFA and corticosterone levels were undertaken.

Effect of adrenergic receptor blockade on nicotinic acid-induced plasma FFA rebound

Nicotinic acid administration causes an initial depression in plasma free fatty acids (FFA) followed by a rebound above baseline concentrations. Beta adrenergic blockade with propranolol had no effect on the FFA rebound. Alpha adrenergic blockade with phentolamine completely abolished the FFA rebound and also partially inhibited the initial plasma FFA depression. No relationship between FFA rebound and plasma growth hormone levels was observed. A significant correlation was demonstrated between FFA depression and rebound following nicotinic acid administration. It is proposed that the abolishment of the FFA rebound by alpha adrenergic blockade is related to its inhibition of the initial FFA depression which in turn may be related to antagonistic effects of alpha adrenergic blockers and nicotinic acid on adenyl cyclase activity.

Observations on the cholesterol-lowering mechanism of nicotinic acid and nicotinyl alcohol tartrate

Summary A single dose of nicotinic acid or nicotinyl alcohol tartrate was found to inhibit normal, fasting, epinephrine, norepinephrine and theophylline-induced release of free fatty acids (FFA) in rats. Serum FFA concentrations were also lowered in the dog within 2 min of drug injection. Serum total cholesterol, phospholipids and triglycerides and liver triglyceride levels were also reduced at various time intervals during a 24 h study in the fasted rat. Cholesterol depletion occurred much later than FFA depletion. The magnitude of the FFA depression and the temporal relationship of the FFA to total cholesterol and other serum lipids constituents was sufficient to suggest that cholesterol lowering was an indirect consequence of the inhibition of FFA release.

Effects of prostaglandin E, on lipolysis and dasma free fattv acids in the fasted rat

Contrary to published reports, prostaglandin E(1) (PGE(1)) in vitro and in vivo inhibited fasting lipolysis in rats. Adipose tissue lipolysis was inhibited when the tissue was incubated in the presence of PGE(1) and when the compound was administered intravenously. A biphasic plasma free fatty acid (FFA) response was obtained in fasted rats after intravenous injection of 80 micrograms of PGE(1) per kg body weight; plasma FFA concentrations were lowered at 7 min, elevated at 15 min, and at normal concentrations at 30 min. The FFA depression at 7 min was independent of the animal's nutritional state, but the rebound at 15 min did not occur in fed rats. The plasma FFA rebound in fasted rats at 15 min may be a consequence of rapid inactivation of PGE(1), followed by unopposed activity of factors which enhance fasting lipolysis.