N-acetylcysteine attenuates TNF-α induced changes in secretion of interleukin-6, plasminogen activator inhibitor-1 and adiponectin from 3T3-L1 adipocytes

Abstract TNF-α is a key molecule in obesity-related metabolic disturbances. This study was designed to determine whether N -acetylcysteine (NAC), an antioxidant, prevents the activation of nuclear factor-κB (NF-κB) by exogenously administered TNF-α in adipocytes, and whether such change affects the production of adipocytokines. The treatment of well-differentiated 3T3-L1 cells with 20 mM of NAC significantly increased the reduced glutathione concentration up to 150% of control. The treatment with 10 ng/ml of TNF-α decreased antioxidant enzyme levels such as CuZn-superoxide dismutase (SOD), MnSOD and catalase, and activated NF-κB in 3T3-L1 adipocytes. The activation of NF-κB was significantly prevented by the pretreatment with 20 mM of NAC. TNF-α (1–10 ng/ml) dose-dependently increased interleukin (IL)-6 and plasminogen activator inhibitor-1 (PAI-1) secretion from 3T3-L1 adipocytes, while decreased adiponectin secretion. NAC (5–20 mM) attenuated the TNF-α-induced changes in these adipocytokine secretions in a dose-dependent manner. The effect of TNF-α and NAC on the adipocytokine productions was exerted at the m-RNA level, judging from results of the real time RT-PCR analysis. The present study revealed that NAC inhibited the TNF-α-mediated activation of NF-κB and improved the adverse changes in the levels of IL-6, PAI-1 and adiponectin in 3T3-L1 adipocytes. NAC may have the potential to improve the obesity-related abnormal adipocytokine metabolism by attenuating the TNF-α-induced oxidant–antioxidant imbalance in adipocytes.