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

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...

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Autores principales: Han, Ga Eun, Kang, Hee-Taik, Chung, Sungkyun, Lim, Changjin, Linton, John A., Lee, Jin-Hee, Kim, Wooki, Kim, Seok-Ho, Lee, Jong Hun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121477/
https://www.ncbi.nlm.nih.gov/pubmed/30060630
http://dx.doi.org/10.3390/ijms19082215
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author Han, Ga Eun
Kang, Hee-Taik
Chung, Sungkyun
Lim, Changjin
Linton, John A.
Lee, Jin-Hee
Kim, Wooki
Kim, Seok-Ho
Lee, Jong Hun
author_facet Han, Ga Eun
Kang, Hee-Taik
Chung, Sungkyun
Lim, Changjin
Linton, John A.
Lee, Jin-Hee
Kim, Wooki
Kim, Seok-Ho
Lee, Jong Hun
author_sort Han, Ga Eun
collection PubMed
description 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.
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spelling pubmed-61214772018-09-07 Novel Neohesperidin Dihydrochalcone Analogue Inhibits Adipogenic Differentiation of Human Adipose-Derived Stem Cells through the Nrf2 Pathway Han, Ga Eun Kang, Hee-Taik Chung, Sungkyun Lim, Changjin Linton, John A. Lee, Jin-Hee Kim, Wooki Kim, Seok-Ho Lee, Jong Hun Int J Mol Sci Article 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. MDPI 2018-07-29 /pmc/articles/PMC6121477/ /pubmed/30060630 http://dx.doi.org/10.3390/ijms19082215 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Han, Ga Eun
Kang, Hee-Taik
Chung, Sungkyun
Lim, Changjin
Linton, John A.
Lee, Jin-Hee
Kim, Wooki
Kim, Seok-Ho
Lee, Jong Hun
Novel Neohesperidin Dihydrochalcone Analogue Inhibits Adipogenic Differentiation of Human Adipose-Derived Stem Cells through the Nrf2 Pathway
title Novel Neohesperidin Dihydrochalcone Analogue Inhibits Adipogenic Differentiation of Human Adipose-Derived Stem Cells through the Nrf2 Pathway
title_full Novel Neohesperidin Dihydrochalcone Analogue Inhibits Adipogenic Differentiation of Human Adipose-Derived Stem Cells through the Nrf2 Pathway
title_fullStr Novel Neohesperidin Dihydrochalcone Analogue Inhibits Adipogenic Differentiation of Human Adipose-Derived Stem Cells through the Nrf2 Pathway
title_full_unstemmed Novel Neohesperidin Dihydrochalcone Analogue Inhibits Adipogenic Differentiation of Human Adipose-Derived Stem Cells through the Nrf2 Pathway
title_short Novel Neohesperidin Dihydrochalcone Analogue Inhibits Adipogenic Differentiation of Human Adipose-Derived Stem Cells through the Nrf2 Pathway
title_sort novel neohesperidin dihydrochalcone analogue inhibits adipogenic differentiation of human adipose-derived stem cells through the nrf2 pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121477/
https://www.ncbi.nlm.nih.gov/pubmed/30060630
http://dx.doi.org/10.3390/ijms19082215
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