In this study, we demonstrated that the two ginger-derived components have a potent and unique pharmacological function in 3T3-L1 adipocytes via different mechanisms. Both pretreatment of 6-shogaol (6S) and 6-gingerol (6G) significantly inhibited the tumor necrosis factor-alpha (TNF-alpha) mediated downregulation of the adiponectin expression in 3T3-L1 adipocytes. Our study demonstrate that (1) 6S functions as a PPAR gamma agonist with its inhibitory mechanism due to the PPAR gamma transactivation, and (2) 6G is not a PPAR gamma agonist, but it is an effective inhibitor of TNF-a induced c-Jun-NH2-terminal kinase signaling activation and thus, its inhibitory mechanism is due to this inhibitory effect. (c) 2008 Elsevier Inc. All rights reserved.