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

Chang,Eugene; Choi,Jung  Mook; Kim,Won  Jun; Rhee,Eun-Jung; Oh,Ki  Won; Lee,Won-Young; Park,Se   Eun; Park,Sung  Woo; Park,Cheol-Young

doi:10.3892/mmr.2014.2278

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

Authors:
- Eugene Chang
- Jung Mook Choi
- Won Jun Kim
- Eun-Jung Rhee
- Ki Won Oh
- Won-Young Lee
- Se Eun Park
- Sung Woo Park
- Cheol-Young Park
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Affiliations: Diabetes Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 110-746, Korea, Department of Endocrinology and Metabolism, Gangneung Asan Hospital, Ulsan University School of Medicine, Gangneung 201-711, Korea, Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 110-746, Korea
Published online on: May 28, 2014 https://doi.org/10.3892/mmr.2014.2278
Pages: 905-910

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Abstract

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.

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