Restoration of adiponectin expression via the ERK pathway in TNFα-treated 3T3-L1 adipocytes

Adiponectin and tumor necrosis factor-α (TNF-α) exert opposite effects on obesity-associated inflammation and insulin signaling. The purpose of the present study was to investigate the effects of chronic TNF-α on adiponectin levels in 3T3-L1 adipocytes, as well as the potential reversal mechanisms. Differentiated 3T3-L1 adipocytes were exposed to TNF-α for three different incubation times and then to various wash-off periods with or without mitogen-activated protein kinase (MAPK) inhibitors. TNF-α significantly reduced adiponectin gene expression in a dose- and time-dependent manner and activated c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinases (ERK) and p38 MAPK. A 16 h restoration period fully reversed the decrease in adiponectin levels following 16 h treatment with TNF-α; however, 16 h withdrawal of TNF-α following 32 or 48 h treatment did not completely reverse the TNF-α-induced decrease in adiponectin levels. In 3T3-L1 adipocytes, 32 or 48 h wash-off periods were required following 32 or 48 h TNF-α treatments, respectively. The pattern of ERK activation following TNF-α exposure and removal was similar to the pattern of adiponectin expression. Furthermore, ERK1/2 inhibition accelerated the recovery of adiponectin levels compared with the levels in the untreated control adipocytes. Therefore, the inhibitory effects of TNF-α on adiponectin levels in differentiated 3T3-L1 cells were fully reversed following a wash-out period equivalent to the TNF-α treatment time, potentially through the ERK 1/2 pathway.