Background: Lipolysis is the pathway responsible for triacylglycerol breakdown into glycerol and non-esterified fatty acids (NEFA) in adipose tissue. Perturbation of this process has been observed in vivo in studies examining the oral administration of short chain fatty acids (SCFA) (3). SCFA, such as acetate, can also increase the concentration of plasma acetate after the consumption of alcohol and carbohydrate-rich meals (1-2), but there is limited tissue-specific evidence for the effects of SCFA on adipocyte lipolysis. Aim: The aim of this study was to examine the effects of the short chain fatty acid, acetate, on the release of NEFA in adipocytes. Methods: The adipose cell line 3T3-L1 was used in all experimental conditions at 7 days post-differentiation. Cells were incubated in a basic media of DMEM with 2% fatty acid-free BSA (Control) for 180 min with either, the β-adrenergic receptor activator isoproterenol (ISO) (5μM), acetate (4mM) and acetate (4mM) plus insulin (1μg/ml). In the conditions where acetate was present cells were pre-incubated for 30 min with acetate. Samples of the media were collected every 60 min and analysed for NEFA concentration and all samples were normalised to total protein. Results: In the presence of acetate, NEFA release decreased and was lower at 120 and 180min compared with the control (Figure 1). A smiliar effect was observed in the presence of insulin plus acetate where NEFA release was lower compared with the control at 120 and 180 min (Figure 1). Under the conditions of stimulated lipolysis, ISO increased NEFA release by ~20 fold compared with the basal NEFA release over a 3 hour period (Figure 2). In the ISO-stimulated cells acetate inhibited NEFA release, and by 180 min this had been reduced to about 40% compared with ISO alone (acetate, 0.78; ISO, 1.33 μmol/mg protein). Insulin also inhibited NEFA release in the ISO-stimulated cells at 120 and 180 min. Conclusions: These data demonstrate that acetate has a small inhibitory effect on the basal release of NEFA. Under conditions of adrenergic stimulation the effect of acetate is similar to insulin in inhibiting NEFA release. Future work identifying the mechanism(s) of action would lead to a greater understanding of adipocyte metabolism and function and provide further insight into the abnormal metabolism associated with disorders, such as obesity and type II diabetes.