NEFA fatty acids

Free fatty acids—also called unesterified (UFA) or non-esterified (NEFA) fatty acids—are fatty acids that are in the unesterified state. In plasma, longer-chain FFA are combined with albumin, and in the cell they are attached to a fatty acid-binding protein, so that in fact they are never really free. Shorter-chain fatty acids are... 

Plasma non-esterified fatty acids (NEFA) were elevated by infusion of a lipid emulsion and heparin with a constant rate of 1.5 ml/min (lipid emulsion, protocols [1] and [3]) and 0.4 lU/kg per minute (heparin). In protocol [2] a solution of 0.9% saline was infused as a control for the lipid emulsion. 

Circulating glucose and insulin levels are the key values for a diagnosis of type II diabetes. Obesity and elevated levels of non-esterified fatty acids (NEFA) are known to cause insulin resistance and diabetes. Comorbidity of T2DM and dyslipidemia are common in animal models and in clinical populations and therefore, cholesterol, triglycerides, inflammation markers, and blood pressure are often measured within the same experiments. However, for the purpose of this chapter, we will cover only values directly linked to T2DM. 

Free fatty acids are elevated in the plasma of obese patients and are known to cause muscle and liver insulin resistance. The Wako HR series NEFA-HR(2) is an in vitro enzymatic colorimetric method assay for the quantitative determination of non-esterified fatty acids (NEFA) in serum. Perform the assay on serum collected from mice fasted for a period greater than 4 h, but less than 16 h. Perform the test on samples immediately after collection, without freezing. Also note that hemolysis in the serum samples may interfere with the assay. 

NEFA Non-esterified Fatty Acids (also called free fatty acids, FFA)... 

GH administered to hypophysectomized rats in vivo causes a drop in the level of plasma non-esterified fatty acids (NEFA), followed by a prolonged increase in this level [89]. This appears to be due to increased utilization of lipids - increased uptake of NEFA by muscle preceding increased output by adipose tissue. As a consequence GH diverts the energy metabolism of the organism from carbohydrate utilization to lipid utilization, and acts to oppose the effects of insulin. Actions of GH on lipid metabolism are particularly marked in man, where GH levels become elevated on fasting and presumably serve to help stimulate the increased lipid utilization seen in this condition. In contrast, in the rat, GH levels fall on fasting. 

MSH-R, melanoc5de stimulating hormone receptor MTP, microsomal triglyceride transfer protein NEFA, non-esterified fatty acids NO, nitric oxide NPY, neuropeptide Y... 

StrooWE, HookJB. Dissociation of renal organic anion transport from renal lipid metabolism. I. Endogenous nonesterified fatty acids (NEFA) as determinants of transport. J Pharmacol ExpTher 1983 227(1) 55-59. 

Fig. 3. Time-related changes in plasma glucose, non-esterified (or free) fatty acids (NEFA), insulin and glucagon concentrations in controls (— —) and normal-weight NIDDM patients (—O—) during insulin clamp. P<0.()1. (Source Golay et al., 1988.)...

Fig. 4. The fatty acid composition of serum FAEEs and serum triglycerides from hospital emergency-room patients and plasms non-esterified fatty acids (NEE A) of healthy subjects. The values represent the percent of each fatty acid within either FAEE, triglyceride, or NEFA pools. (From Doyle 1994 with permission.)...

This has been reviewed in an earlier section. Normally, the proportion of total plasma tryptophan bound to albumin is 85 to 90%. This equilibrium can be shifted under conditions which raise plasma nonesterified fatty acid (NEFA) concentrations, such as during fasting or stress.198 Since NEFA... 

Findings by Zammarchi et al.43 on blood free tryptophan levels in jaundiced newborn infants during phototherapy are of interest. They reported a significant decrease in free tryptophan levels 24 h after phototherapy. This was explained by the decrease in nonesterified fatty acids (NEFA) during phototherapy. Since both tryptophan and NEFA are bound to serum albumin and NEFA can displace tryptophan from their binding sites, the decrease in free tryptophan may be secondary to the change in NEFA levels. 

The ability of L-tryptophan to bind to plasma proteins of the blood and circulate as free and bound tryptophan is a unique feature for an amino acid. This binding is affected by and competes with other compounds that bind plasma proteins, such as nonesterified fatty acids (NEFA) and certain drugs. This relationship in blood affects its transport from the blood to the brain because only the free tryptophan is transplanted through the blood-brain barrier. Free tryptophan s concentration in blood in relation to other amino acids, particularly branched-chain amino acids (BCAA), affects its transport to the brain. 

As might be expected following administration of either inhibitor in vivo, non-esterified fatty acids (NEFA) rise, but with chronic administration of the drugs, their levels reportedly fall back to those normally found in the plasma [113]. The rise is probably due to the decreased utilization of the NEFA, but the reason for the transient nature of this rise has remained unexplained. Either lipolytic inhibition occurs to restrict inflow of NEFA into the plasma or the processes of esterification and re-esterification are increased store excess NEFA as triacylglycerols in some tissue or tissues [95, 114]. Chronic use of the drug has resulted in a fatty liver, but it is unclear whether this explains the transient nature of the rise in NEFA. 

There has been some speculation that, with the chronic use of a fatty acid oxidation inhibitor, an impairment of exercise capacity and/or the counter-regulatory mechanisms involved in glucose homeostasis might occur. In normal [ 117] or streptozotocin-diabetic [118] rats, MeTDGA caused no decrease in the ability of the animals to perform strenuous or prolonged, moderately strenuous exercise. However, based on a reduced ability by tissues to use NEFA, one might expect that the ability to sustain exhaustive exercise would be reduced, particularly once glycogen levels had been depleted. 

The terms NEFA, unesterified fatty acids, and free fatty acids have been used synonymously in the literature, although these fatty acids are mainly bound to plasma proteins. Enzymatic assays are convenient with NEFA in the presence of added acyl-coenzyme A (CoA) synthetase forming acyl CoA esters, which are then oxidized by acyl CoA oxidase to yield hydrogen peroxide. The hydrogen peroxide produced is measured by a peroxidase-linked colorimetric detection reaction. Plasma samples should be separated promptly and stored frozen to prevent in vitro lipolysis (Zambon, Hashimoto, and Brunzell 1993). 

Non-esterified fatty acid (NEFA) levels are elevated in patients with cirrhosis. This change might be expected because basal hepatic glucose output is low in these patients. As a result, more NEFA are presumably required (via increased lipolysis) to meet the fasting energy requirements of peripheral tissues. 

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