Non-esterified fatty acids NEFA

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. 

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. 

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. 

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. 

Factors leading to characteristic dyslipidaemia are complex and not fully understood. Insulin resistance is associated with the failure of normal suppression of hormone-sensitive lipase in adipose tissue and increased lipolysis leading to increased flux of non-esterified fatty acids (NEFAs) to the liver this is partly responsible for increased hepatic output of very low-density lipoprotein (VLDL) [6]. Central obesity is common in insulin resistance and type 2 diabetes and visceral fat is increasingly recognised as an important paracrine and endocrine organ [7]. Adiponectin, an important adipose-specific adipokine, is reduced in insulin resistance and type 2 diabetes [8]. This would favour increased lipolysis as the action of a further important cytokine, TNF-alpha in stimulating lipolysis is unopposed. 

The first hypotheses for cholesterol reduction with niacin pointed toward a steep niacin-induced decrease in non-esterified fatty acid (NEFA) mobilization from adipose tissue via inhibition of lipolysis (reviewed by Carlson 2005). Hormone sensitive lipase mediates lipolysis in response to increased cyclic adenosine monophosphate in adipocytes. A G-protein-coupled cell surface receptor (GPR) inhibiting adenylyl cyclase was proposed, and in 2003, three independent groups identified the human niacin receptors as the low-affinity... 

Fatty acids appear in the bloodstream in one of two forms as non-esterified fatty acids (NEFA) or in lipoproteins. NEFA have a very short half-life in the blood. The bulk of circulating NEFA arise from the hydrolysis of triacylglycerols stored within adipose tissue and are released into the bloodstream, where their transport is facilitated by albumin, which has multiple binding sites for fatty acids (Frayn, 2003). Plasma NEFA are destined to be used mainly as energy sources (see Section E.l on fatty acids as fuels). 

Blood samples were drawn by a jugular vein catheter in 1 h-intervals and plasma concentrations of non-esterified fatty acids ([NEFA]) and of p-hydroxybutyrate ([BHBA]) were determined. The data were analyzed by paired t-test using SPSS (version 15.0). 

Blood samples were taken from all goats at the end of pre-experimental period and of each experimental period. An automated analyzer was used to determine glucose, cholesterol and urea contents in plasma samples. Non-esterified fatty acids (NEFA) and beta-hydroxy butyric acid (BHBA) were analyzed by using commercial kits. Insulin, free triiodothyronine (fT3) and free thyroxine (fT4) were measured in duplicate by ELISA kits... 

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