NEFA

Abstract: There is a widespread acceptance in the literature that plasma nonesterified fatty acids (NEFA), also called free fatty acids (FFA), can mediate many adverse metabolic effects, most notably insulin resistance. Elevated NEFA concentrations in obesity are thought to arise from an increased adipose tissue mass. It is also argued that the process of fatty acid mobilization from adipose tissue, normally suppressed by insulin, itself becomes insulin resistant—thus, lipolysis is further increased, potentially leading to a vicious cycle. Although we have also accepted this model for many years (1,2), recently there has been a steady accumulation of data, both in the literature and from our own research, that has forced us to realize that this simple story is not always true. Here we review the background to the idea of “fatty acids as metabolic villains,” together with data from the literature and from our own studies, which tend to show another side to the fatty acids/insulin resistance story. We will first examine the relationship between systemic concentrations of NEFA and obesity/insulin resistance and then study adipose tissue in the obese state with regard to its adaptation for NEFA release. NEFA circulate in the plasma bound to plasma albumin. Their function was largely elucidated in the 1950s through the work of Vincent Dole (3) at the Rockefeller Institute in New York and Robert Gordon (4,5) at the National Institutes of Health. Gordon demonstrated the origin of plasma NEFA from adipose tissue and their use by tissues such as the liver and myocardium, but not the brain. We now recognize that NEFA are the vehicle by which triacylglycerol (TG) stored in adipose tissue is transported to its sites of utilization. NEFA turnover is rapid, with a plasma half-life around 2–4 min (6). The only significant site of NEFA liberation …

Abstract: In this study concentration and composition of non-esterified fatty acids (NEFA) in follicular fluid (FF) of high-yielding dairy cows were determined during the period of negative energy balance (NEB) early post partum. NEFA were then added during in vitro maturation at concentrations measured previously in FF to evaluate their effect on the oocyte's developmental competence. At 16 and 44 days post partum, FF of the dominant follicle and blood were collected from nine high-yielding dairy cows. Samples were analysed for NEFA concentration and composition. NEFA concentrations in FF (0.2-0.6 mmol/l) during NEB remained +/- 40% lower compared with serum (0.4-1.2 mmol/l). The NEFA composition differed significantly between serum and FF with oleic acid (OA), palmitic acid (PA) and stearic acid (SA) being the predominant fatty acids in FF. Based on these results, 5115 oocytes were matured for 24 h in serum-free media with or without (negative control) the addition of 0.200 mmol/l OA, 0.133 mmol/l PA or 0.067 mmol/l SA dissolved in ethanol or ethanol alone (positive control). Matured oocytes were fertilized and cultured for 7 days in SOF medium. Addition of PA or SA during oocyte maturation had negative effects on maturation, fertilization and cleavage rate and blastocyst yield. More (late) apoptotic cumulus cells were observed in cumulus-oocyte complexes matured in the presence of SA or PA. Ethanol or OA had no effect. These in vitro results suggest that NEB may hamper fertility of high-yielding dairy cows through increased NEFA concentrations in FF affecting oocyte quality.