Berberine activates AMPK to suppress proteolytic processing, nuclear translocation and target DNA binding of SREBP-1c in 3T3-L1 adipocytes

Jang,Jaewoong; Jung,Yoonju; Seo,Seong  Jun; Kim,Seok‑Min; Shim,Yae  Jie; Cho,Soo  Hyun; Chung,Sang‑In; Yoon,Yoosik

doi:10.3892/mmr.2017.6513

Berberine activates AMPK to suppress proteolytic processing, nuclear translocation and target DNA binding of SREBP-1c in 3T3-L1 adipocytes

Authors:
- Jaewoong Jang
- Yoonju Jung
- Seong Jun Seo
- Seok‑Min Kim
- Yae Jie Shim
- Soo Hyun Cho
- Sang‑In Chung
- Yoosik Yoon
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Affiliations: Department of Microbiology, Chung‑Ang University College of Medicine, Dongjak‑gu, Seoul 156‑756, Republic of Korea, Department of Dermatology, Chung‑Ang University College of Medicine, Dongjak‑gu, Seoul 156‑756, Republic of Korea, School of Mechanical Engineering, Chung‑Ang University, Dongjak‑gu, Seoul 156‑756, Republic of Korea, College of General Studies, Sangmyung University, Jongno‑gu, Seoul 110‑743, Republic of Korea, Department of Family Medicine, College of Medicine, Chung‑Ang University Hospital, Dongjak‑gu, Seoul 156‑755, Republic of Korea
Published online on: April 26, 2017 https://doi.org/10.3892/mmr.2017.6513
Pages: 4139-4147
Copyright: © Jang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

AMP-activated protein kinase (AMPK) and sterol regulatory element binding protein (SREBP)‑1c are major therapeutic targets in the treatment of metabolic diseases. In the present study, the fat‑reducing mechanisms of berberine (BBR), a natural isoquinoline, was investigated by examining the AMPK‑mediated modulation of SREBP‑1c in 3T3‑L1 adipocytes. BBR activated AMPK in a dose‑ and time‑dependent manner, and increased the phosphorylation of the 125‑kDa precursor form of SREBP‑1c, which suppressed its proteolytic processing into the mature 68‑kDa form and its subsequent nuclear translocation. The binding of nuclear SREBP‑1c to its E‑box motif‑containing target DNA sequence was decreased following treatment with BBR, which led to a decrease in the expression of lipogenic genes and subsequently reduced intracellular fat accumulation. Transfection with AMPKα1 siRNA, and not control siRNA, inhibited BBR‑induced phosphorylation of the 125‑kDa SREBP‑1c, which confirmed that AMPK was responsible for phosphorylating SREBP‑1c. AMPKα1 siRNA transfection rescued the proteolytic processing, nuclear translocation and target DNA binding of SREBP‑1c that had been suppressed by BBR. In addition, BBR‑induced suppression of lipogenic gene expression and intracellular fat accumulation were rescued by AMPKα1 siRNA transfection. In conclusion, the results of the present study demonstrate that BBR activates AMPK to induce phosphorylation of SREBP‑1c, thereby suppressing proteolytic processing, nuclear translocation and target DNA binding of SREBP‑1c, which leads to a reduction in lipogenic gene expression and intracellular fat accumulation. The results of the present study indicate that BBR may be a potential candidate for the development of drugs to treat obesity.

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