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Article

Novel Neohesperidin Dihydrochalcone Analogue Inhibits Adipogenic Differentiation of Human Adipose-Derived Stem Cells through the Nrf2 Pathway

1
Department of Food science and Biotechnology, College of Life Science, CHA University, Seongnam-si 13488, Korea
2
Department of Family Medicine, College of Medicine, Chungbuk National University, Chungbuk 28644, Korea
3
Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam-si 13488, Korea
4
Department of Family Medicine, Severance Hospital, Yonsei University, Seoul 03722, Korea
5
Department of Food Science and Biotechnology, Graduate School of Biotechnology, Kyung Hee University, Yongin 17104, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(8), 2215; https://doi.org/10.3390/ijms19082215
Received: 18 June 2018 / Revised: 12 July 2018 / Accepted: 24 July 2018 / Published: 29 July 2018
(This article belongs to the Special Issue Adipose Stem Cells)
Obesity, characterized by excess lipid accumulation, has emerged as a leading public health problem. Excessive, adipocyte-induced lipid accumulation raises the risk of metabolic disorders. Adipose-derived stem cells (ASCs) are mesenchymal stem cells (MSCs) that can be obtained from abundant adipose tissue. High fat mass could be caused by an increase in the size (hypertrophy) and number (hyperplasia) of adipocytes. Reactive oxygen species (ROS) are involved in the adipogenic differentiation of human adipose-derived stem cells (hASCs). Lowering the level of ROS is important to blocking or retarding the adipogenic differentiation of hASCs. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a transcription factor that mediates various antioxidant enzymes and regulates cellular ROS levels. Neohesperidin dihydrochalcone (NHDC), widely used as artificial sweetener, has been shown to have significant free radical scavenging activity. In the present study, (E)-3-(4-chlorophenyl)-1-(2,4,6-trimethoxyphenyl)prop-2-en-1-one (CTP), a novel NHDC analogue, was synthesized and examined to determine whether it could inhibit adipogenic differentiation. The inhibition of adipogenic differentiation in hASCs was tested using NHDC and CTP. In the CTP group, reduced Oil Red O staining was observed compared with the differentiation group. CTP treatment also downregulated the expression of PPAR-γ and C/EBP-α, adipogenic differentiation markers in hASCs, compared to the adipogenic differentiation group. The expression of FAS and SREBP-1 decreased in the CTP group, along with the fluorescent intensity (amount) of ROS. Expression of the Nrf2 protein was slightly decreased in the differentiation group. Meanwhile, in both the NHDC and CTP groups, Nrf2 expression was restored to the level of the control group. Moreover, the expression of HO-1 and NQO-1 increased significantly in the CTP group. Taken together, these results suggest that CTP treatment suppresses the adipogenic differentiation of hASCs by decreasing intracellular ROS, possibly through activation of the Nrf2 cytoprotective pathway. Thus, the use of bioactive substances such as CTP, which activates Nrf2 to reduce the cellular level of ROS and inhibit the adipogenic differentiation of hASCs, could be a new strategy for overcoming obesity. View Full-Text
Keywords: adipose stem cells; neohesperidin dihydrochalcone; adipogenic differentiation; reactive oxygen species; Nrf2 adipose stem cells; neohesperidin dihydrochalcone; adipogenic differentiation; reactive oxygen species; Nrf2
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MDPI and ACS Style

Han, G.E.; Kang, H.-T.; Chung, S.; Lim, C.; Linton, J.A.; Lee, J.-H.; Kim, W.; Kim, S.-H.; Lee, J.H. Novel Neohesperidin Dihydrochalcone Analogue Inhibits Adipogenic Differentiation of Human Adipose-Derived Stem Cells through the Nrf2 Pathway. Int. J. Mol. Sci. 2018, 19, 2215. https://doi.org/10.3390/ijms19082215

AMA Style

Han GE, Kang H-T, Chung S, Lim C, Linton JA, Lee J-H, Kim W, Kim S-H, Lee JH. Novel Neohesperidin Dihydrochalcone Analogue Inhibits Adipogenic Differentiation of Human Adipose-Derived Stem Cells through the Nrf2 Pathway. International Journal of Molecular Sciences. 2018; 19(8):2215. https://doi.org/10.3390/ijms19082215

Chicago/Turabian Style

Han, Ga E.; Kang, Hee-Taik; Chung, Sungkyun; Lim, Changjin; Linton, John A.; Lee, Jin-Hee; Kim, Wooki; Kim, Seok-Ho; Lee, Jong H. 2018. "Novel Neohesperidin Dihydrochalcone Analogue Inhibits Adipogenic Differentiation of Human Adipose-Derived Stem Cells through the Nrf2 Pathway" Int. J. Mol. Sci. 19, no. 8: 2215. https://doi.org/10.3390/ijms19082215

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