199-LB: Artemisia scoparia Attenuates Glucocorticoid-Induced Lipolysis in Adipocytes

Abstract

Prescription glucocorticoid use is widespread across developed countries for the treatment of several inflammatory conditions. Elevated glucocorticoids are known to promote lipolysis and often result in metabolic disorders such as insulin resistance and hepatic lipid accumulation. An extract of Artemisia scoparia (SCO) has been shown to reduce lipolysis and promote metabolic health but has not been investigated in the context of glucocorticoid-mediated metabolic disease. We assessed the ability of SCO to modulate glucocorticoid-induced lipolysis in 3T3-L1 adipocytes. Mature adipocytes were pretreated with vehicle (DMSO) , SCO (50 ug/mL) , or rosiglitazone for three days. Cells from each condition were then exposed to either vehicle (ethanol/BSA) , Dexamethasone (synthetic glucocorticoid; 500 nM) , or TNFa (0.75 nM) , in the presence or absence of RU486 (glucocorticoid receptor (GR) antagonist; 250 nM) for 20 hours. Separate experiments were performed to determine the involvement of the GR in SCO’s effects using an siRNA approach. Glycerol and free fatty acids (FFA’s) were measured from the media to evaluate changes in lipolysis. The expression and phosphorylation status of several lipolytic genes and proteins were also assessed via qPCR and western blot, respectively. SCO significantly attenuated dexamethasone-induced glycerol and FFA release, with the combination of SCO and RU486 resulting in the greatest effects. SCO led to significant reductions in the monomeric forms of PDE3B and PDE4D, but greater expression of multimeric complexes were observed. Reduction in GR expression did not interfere with the effects of SCO, suggesting the GR is not required for SCO-mediated attenuation of lipolysis. These observations shed some light on the protective effects of SCO under conditions of elevated glucocorticoids, but additional studies are needed to identify the underlying mechanisms that confer beneficial effects of SCO to combat both diet- and glucocorticoid-induced metabolic dysfunction. Disclosure I. Harvey: None. J. M. Stephens: None. Funding National Center for Complementary and Integrative Health T32 (AT004094)