Interruptin B induces brown adipocyte differentiation and glucose consumption in adipose-derived stem cells

Kaewsuwan,Sireewan; Plubrukarn,Anuchit; Utsintong,Maleeruk; Kim,Seok‑Ho; Jeong,Jin‑Hyun; Cho,Jin  Gu; Park,Sang  Gyu; Sung,Jong‑Hyuk

doi:10.3892/mmr.2016.4758

Interruptin B induces brown adipocyte differentiation and glucose consumption in adipose-derived stem cells

Authors:
- Sireewan Kaewsuwan
- Anuchit Plubrukarn
- Maleeruk Utsintong
- Seok‑Ho Kim
- Jin‑Hyun Jeong
- Jin Gu Cho
- Sang Gyu Park
- Jong‑Hyuk Sung
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Affiliations: Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla 90110, Thailand, School of Pharmaceutical Sciences, University of Phayao, Phayao 56000, Thailand, Department of Pharmacy, College of Pharmacy, CHA University, Pocheon 487‑600, Republic of Korea, Department of Pharmaceutics and Institute of Pharmaceutical Science, College of Pharmacy, Yonsei University, Incheon 405‑750, Republic of Korea, Department of Pharmacy, College of Pharmacy, Ajou University, Suwon 16499, Republic of Korea
Published online on: January 12, 2016 https://doi.org/10.3892/mmr.2016.4758
Pages: 2078-2086
Copyright: © Kaewsuwan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Interruptin B has been isolated from Cyclosorus terminans, however, its pharamcological effect has not been fully identified. In the present study, the effects of interruptin B, from C. terminans, on brown adipocyte differentiation and glucose uptake in adipose‑derived stem cells (ASCs) were investigated. The results revealed that interruptin B dose‑dependently enhanced the adipogenic differentiation of ASCs, with an induction in the mRNA expression levels of peroxisome proliferator‑activated receptor (PPAR)‑α and PPAR‑γ. In addition, interruptin B efficiently increased the number and the membrane potential of mitochondria and upregulated the mRNA expression levels of uncoupling protein (UCP)‑1 and cyclooxygenase (COX)‑2, which are all predominantly expressed in brown adipocytes. Interruptin B increased glucose consumption in differentiated ASCs, accompanied by the upregulation in the mRNA expression levels of glucose transporter (GLUT)‑1 and GLUT‑4. The computational analysis of molecular docking, a luciferase reporter assay and surface plasmon resonance confirmed the marked binding affinity of interruptin B to PPAR‑α and PPAR‑γ (KD values of 5.32 and 0.10 µm, respectively). To the best of our knowledge, the present study is the first report to show the stimulatory effects of interruptin B on brown adipocyte differentiation and glucose uptake in ASCs, through its role as a dual PPAR‑α and PPAR‑γ ligand. Therefore, interruptin B could be further developed as a therapeutic agent for the treatment of diabetes.

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