Plasma free fatty acids

The free fatty acid uptake by tissues is related directly to the plasma free fatty acid concentration, which in turn is determined by the rate of lipolysis in adipose tissue. After dissociation of the fatty acid-albumin complex at the plasma membrane, fatty acids bind to a membrane tty acid transport protein that acts as a transmembrane cotransporter with Na. On entering the cytosol, free fatty acids are bound by intracellular fatty acid-binding proteins. The role of these proteins in intracellular transport is thought to be similar to that of serum albumin in extracellular transport of long-chain fatty acids. 

The free fatty acids formed by lipolysis can be reconverted in the tissue to acyl-CoA by acyl-CoA synthetase and reesterified with glycerol 3-phosphate to form triacylglycerol. Thus, there is a continuous cycle of lipolysis and reesterification within the tissue. However, when the rate of reesterification is not sufficient to match the rate of lipolysis, free fatty acids accumulate and diffuse into the plasma, where they bind to albumin and raise the concentration of plasma free fatty acids. 

Otfier fiormones accelerate tfie release of free fatty acids from adipose tissue and raise tfie plasma free fatty acid concentration by increasing the rate of lipolysis of the triacylglycerol stores (Figure 25—8). These include epinephrine, norepinephrine, glucagon, adrenocorticotropic hormone (ACTH), a- and P-melanocyte-stimulat-ing hormones (MSH), thyroid-stimulating hormone (TSH), growth hormone (GH), and vasopressin. Many of these activate the hormone-sensitive hpase. For an optimal effect, most of these lipolytic processes require the presence of glucocorticoids and thyroid hormones. These hormones act in a facilitatory or permissive capacity with respect to other lipolytic endocrine factors. 

There is a small fall in plasma glucose upon starvation, then little change as starvation progresses (Table 27-2 Figure 27-2). Plasma free fatty acids increase with onset of starvation but then plateau. There is an initial delay in ketone body production, but as starvation progresses the plasma concentration of ketone bodies increases markedly. 

Glucocorticoids not only break down protein but also stimulate the catabolism of lipids in adipose tissue and enhance the actions of other lipolytic agents. This occurrence results in an increase in plasma free fatty acids and an enhanced tendency to ketosis. The mechanism of this lipolytic action is unknown. The net effect of the biochemical changes induced by the glucocorticoids is antagonism of the actions of insulin. These biochemical events promote hyperglycemia and glycosuria, which are similar to the diabetic state. 

ATP sensitive K channels. They lower down the blood sugar level in type 11 diabetics and non-diabetic individuals. They also decrease the elevated plasma free fatty acid levels. They also sensitize the target tissues to action of insulin by increasing the number of insulin receptors. 

Fate of fatty acids The free (unesterified) fatty acids move through the cell membrane of the adipocyte, and immediately bind to albumin in the plasma. They are transported to the tis sues, where the fatty acids enter cells, get activated to their CtA derivatives, and are oxidized for energy. [Note Active transport of fatty acids across membranes is mediated by a membrane fatty acid binding protein.] Regardless of their blood levels, plasma free fatty acids cannot be used for fuel by erythrocytes, which have no mitochondria, or by the brain because of the imperme able blood-brain barrier. rr f-... 

More recently, Bortolotti et al. (2008) provided evidence to refute this calcium-mediated mechanism of weight loss, presenting results from a placebo-controlled crossover study of 10 obese adults with habitually low calcium intakes (<800 mg/day). Results indicated that dietary supplementation of 800 mg of calcium/day had no effect on circulating plasma free fatty acid concentrations or glycerol turnover. Theoretically, a calcium-mediated stimulation of lipolysis would have resulted in an increase in plasma free fatty acid concentrations and glycerol turnover, thus indicating a need for further research. 

Insulin is probably the most important inhibitor of lipolysis. In contrast to adults, in whom catecholamines represent the most important stimulators of lipolysis, thyrotropin (TSH) is the most important stimulator of lipolysis in the newborn. Plasma free fatty acid concentrations rise markedly in the first hours after birth in response to a marked increase in the TSH concentration and a fall in the insulin concentration. The fatty acids released from lipid stores are oxidized by some extrahepatic tissues (e.g., heart and skeletal muscle, kidney, intestine, and lung). Because the respiratory quotient (the ratio of carbon dioxide production to oxygen use) falls from a value of 1.0 (showing that carbohydrate oxidation is the primary source of energy) to a value of 0.8 to 0.9 (showing increasing oxidation of protein or fatty acids) at 2 to 12 hours of age, at a time when protein catabolism is usually insignificant, fatty acid oxidation must represent... 

Hickson, R. C., Rennie, M. J., Conlee, R. K., Winder, W, W. and Holloszy, J. 0. (1977) Effects of Increased plasma free fatty acids on glycogen utilization and endurance. J. Appl. 

During the early minutes of exercise, carbohydrate (plasma glucose and muscle glycogen) is the predominant fuel for the working muscles. When the exercise is prolonged and intensive, carbohydrate remains a predominant fuel with lipids (plasma free fatty acids and muscle triglycerides) being of lesser importance. When the exercise is of moderate intensity, lipids eventually become the primary fuel as carbohydrate stores are reduced. 

Intestinal Handling of FFA In the cells of the small intestine, several enzymes can act on free but not on esterified fatty acids. In contrast to MAGs, FFA are diluted with fatty acids originating from the plasma free fatty acid pool (44). After activation they can be oxidized, elongated, chain desaturated, and converted into complex lipids (45, 46). The relative rates depend on the nature of the fatty acids and on the presence of other components in the intestinal cells (47). Conversion of saturated fatty acids in monounsaturated ones when they are absorbed as FFA, i.e., when they were present in the outer position of the dietary TAGs, could... 

Free thyroxine levels are affected by plasma free fatty acids which are increased in the postoperative period. Normal variations and induced increases in free fatty acids produced no change in free thyroxine levels (K4). 

Nestel, R J., Ishikawa, T., and Goldrick, R, B, (1978) Diminished plasma free fatty acid clearance in obese subjects, Matalwiism 27, 589-596. 

Kaminsky, 1,. A., Knowiton, R. G-, Perkins, R. M-, and Hetzler, R. K. (1966). Relationship of aerobic capacity and percent body fat with plasma free fatty acid following walking. 

Lipids have an adverse effect on carbohydrate metabolism under basal conditions. The infusion of 20% triglyceride emulsion with heparin during basal insulin and glucose turnover conditions resulted in a rise of plasma free fatty acids from 0.4 to 0.8 mmol/1 at a low rate of infusion (0.5 ml/minute for 2 hours) to between 1.6 and... 

Caffeine has a marked effect on lipid metaboflsm. Ingestion of two cups of coffee may increase the plasma free fatty acid concentration by as much as 30% and glycerol, total... 

Y. Suzuki, M. Nanno, R. Gemma, T. Yoshimi, Plasma free fatty acids, inhibitor of extrathyroidal conversion of T4 to T3 and thyroid hormone binding inhibitor in patients with various nonthyroidal illness,Endocrinol Jpn 39, 445-53 (1992). 

Plasma free fatty acids (FFA) are elevated during the early phase of myocardial infarction. Rapid reduction of FFA following the administration of the nicotinic acid analog 5"fluoro-3 hydroxymethylpyridine hydrochloride (6) to patients with infarction was associated with decreased incidence of ventricular arrhythmias.10 Amiodarone (j) was reported to be effective in the treatment of atrial and ventricular arrhythmias in a recent trial.19... 

G.M. Reaven, C. Hollenbeck, C.-Y. Jeng, M.S. Wu, and Y.-D.I. Chen, Measurement of plasma free fatty acid, lactate and insulin for 24 h in patients with NIDDM, Diabetes, 1988, 37, 1020-1024. 

---