Adipose tissue plays a vital role in the development of obesity and related diseases. The aim of the present study was to investigate the effects of N-Oleoyl glycine (OLGly), a lipoamino acid, on 3T3-L1 adipogenesis and to explore the likely mechanisms underlying this process. Lipid accumulation were evaluated using Oil Red O staining and triglyceride content assay. The mRNA expressions of cannabinoid receptors and the protein expressions of adipogenic genes and intracellular signaling pathway were determined by real-time quantitative PCR and western blot, respectively. The results indicated that OLGly itself, but not its degradation products, stimulated lipid accumulation and significantly increased adipogenic genes (PPAR gamma and aP2), in a dose- and time-dependent manner. Additionally, OLGly markedly increased the mRNA expression of CBI receptor (CB1R) and the inhibition of CB1R by its antagonist SR141716 abolished the promotive effects of OLGly on lipid accumulation and the protein expression of PPAR gamma and aP2. Furthermore, OLGly increased the ratio of p-Akt/Akt and p-FoxO1/FoxO1, which could be reversed by SR141716. Moreover, OLGly-induced enhancement of adipogenesis, activation of insulin-mediated Akt signaling pathway and inactivation of FoxO1 were effectively blocked by Wortmannin, a specific PI3K/Akt inhibitor, indicating the essential role of Akt signaling pathway in the process of OLGly-stimulated 3T3-L1 adipogenesis. In conclusion, OLGly, a lipoamino acid, was able to promote 3T3-L1 adipogenesis through the activation of CB1 receptor and the enhancement of insulin-mediated Akt signaling pathway. These findings suggested the potential role of OLGly in increasing insulin sensitivity and suppressing obesity and diabetes. (C) 2015 Elsevier Inc. All rights reserved.