The endocannabinoid (EC) system has a role in metabolic homeostasis. The purpose

of this study was to determine the effect of ECs and the fatty acids they are derived

from on lipid metabolism and mitochondrial function in adipocytes. 3T3-L1

adipocytes on day 8 of differentiation were treated with ECs and fatty acids for 48

hours in the absence or presence of insulin and various inhibitors. Lysates were

analyzed via Western immunoblotting, a lipolysis assay and Seahorse XF Analyzer

for changes in protein levels, phosphorylation state, lipolysis, and oxygen

consumption rate. Results showed that ECs (2-arachidonoyl glycerol) stimulated

lipolysis via a novel AMPK-dependent pathway, while fatty acids had varying effects

on insulin signaling and mitochondrial function . These data suggest adipose tissue

EC receptors may be a suitable target for anti-obesity therapy. Further research is

needed to understand how the dietary fatty acid profile may influence synthesis of

ECs.