CONTEXT: Little is known about the link between the endocannabinoid (EC) system and the in vivo metabolic function of white adipose tissue (WAT). OBJECTIVE: We aimed to evaluate whether ECs are linked to postprandial fatty acid metabolism and WAT metabolic function. METHODS: Men and women, with (IGT, n = 20) or without impaired glucose tolerance (NGT, n = 20) underwent meal testing with oral and intravenous stable isotope palmitate tracers and positron emission tomography with intravenous [11C]-palmitate and oral [18F]-fluoro-thia-heptadecanoic acid to determine systemic and organ-specific dietary fatty acid (DFA) and nonesterified fatty acid (NEFA) metabolism and partitioning. We determined fasting and postprandial plasma levels of EC by ultra-high performance liquid chromatography-tandem mass spectrometry. RESULTS: All ECs of the 2-monoacylglycerol (2-MAG) family displayed a progressive postprandial increase up to 360 minutes after meal intake that was more pronounced in women with IGT. N-acylethanolamine (NAE) levels decreased between fasting and 180 minutes, followed by a return to preprandial values at 360 minutes and were also increased in women with IGT. Postprandial area under the curve (AUC) of palmitate appearance rate was significantly and independently associated with postprandial AUC of anandamide (AEA
P = .0003) and total energy expenditure (P = .0009). DFA storage in abdominal subcutaneous adipose tissue was positively predicted by fasting 2-arachidonoylglycerol (2-AG
P <
.04). CONCLUSION: EC levels of the NAE family independently follow plasma NEFA metabolism, whereas 2-MAG closely follow the spillover of triglyceride-rich lipoprotein intravascular lipolytic products. Whether these associations are causal requires further investigation.