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New Amphiphilic Squalene Derivative Improves Metabolism of Adipocytes Differentiated From Diabetic Adipose-Derived Stem Cells and Prevents Excessive Lipogenesis

Squalene (Sq) is a natural compound, found in various plant oils, algae, and larger quantity in deep-sea shark liver. It is also known as an intermediate of cholesterol synthesis in plants and animals including humans. Although evidences demonstrated its antioxidant, anticancer, hypolipidemic, and h...

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Autores principales: Ganbold, Munkhzul, Ferdousi, Farhana, Arimura, Takashi, Tominaga, Kenichi, Isoda, Hiroko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672044/
https://www.ncbi.nlm.nih.gov/pubmed/33251210
http://dx.doi.org/10.3389/fcell.2020.577259
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author Ganbold, Munkhzul
Ferdousi, Farhana
Arimura, Takashi
Tominaga, Kenichi
Isoda, Hiroko
author_facet Ganbold, Munkhzul
Ferdousi, Farhana
Arimura, Takashi
Tominaga, Kenichi
Isoda, Hiroko
author_sort Ganbold, Munkhzul
collection PubMed
description Squalene (Sq) is a natural compound, found in various plant oils, algae, and larger quantity in deep-sea shark liver. It is also known as an intermediate of cholesterol synthesis in plants and animals including humans. Although evidences demonstrated its antioxidant, anticancer, hypolipidemic, and hepatoprotective and cardioprotective effects, its biological effects in cellular function might have been underestimated because of the water-insoluble property. To overcome this hydrophobicity, we synthesized new amphiphilic Sq derivative (HH-Sq). On the other hand, adipose-derived stem cells (ASCs) are a valuable source in regenerative medicine for its ease of accessibility and multilineage differentiation potential. Nevertheless, impaired cellular functions of ASCs derived from diabetic donor have still been debated controversially. In this study, we explored the effect of the HH-Sq in comparison to Sq on the adipocyte differentiation of ASCs obtained from subjects with type 2 diabetes. Gene expression profile by microarray analysis at 14 days of adipogenic differentiation revealed that HH-Sq induced more genes involved in intracellular signaling processes, whereas Sq activated more transmembrane receptor pathway-related genes. In addition, more important number of down-regulated and up-regulated genes by Sq and HH-Sq were not overlapped, suggesting the compounds might not only have difference in their chemical property but also potentially exert different biological effects. Both Sq and HH-Sq improved metabolism of adipocytes by enhancing genes associated with energy homeostasis and insulin sensitivity, SIRT1, PRKAA2, and IRS1. Interestingly, Sq increased significantly early adipogenic markers and lipogenic gene expression such as PPARG, SREBF1, and CEBPA, but not HH-Sq. As a consequence, smaller and fewer lipid droplet formation was observed in HH-Sq-treated adipocytes. Based on our findings, we report that both Sq and HH-Sq improved adipocyte metabolism, but only HH-Sq prevented excessive lipogenesis without abrogating adipocyte differentiation. The beneficial effect of HH-Sq provides an importance of synthesized derivatives from a natural compound with therapeutic potentials in the application of cell therapies.
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spelling pubmed-76720442020-11-26 New Amphiphilic Squalene Derivative Improves Metabolism of Adipocytes Differentiated From Diabetic Adipose-Derived Stem Cells and Prevents Excessive Lipogenesis Ganbold, Munkhzul Ferdousi, Farhana Arimura, Takashi Tominaga, Kenichi Isoda, Hiroko Front Cell Dev Biol Cell and Developmental Biology Squalene (Sq) is a natural compound, found in various plant oils, algae, and larger quantity in deep-sea shark liver. It is also known as an intermediate of cholesterol synthesis in plants and animals including humans. Although evidences demonstrated its antioxidant, anticancer, hypolipidemic, and hepatoprotective and cardioprotective effects, its biological effects in cellular function might have been underestimated because of the water-insoluble property. To overcome this hydrophobicity, we synthesized new amphiphilic Sq derivative (HH-Sq). On the other hand, adipose-derived stem cells (ASCs) are a valuable source in regenerative medicine for its ease of accessibility and multilineage differentiation potential. Nevertheless, impaired cellular functions of ASCs derived from diabetic donor have still been debated controversially. In this study, we explored the effect of the HH-Sq in comparison to Sq on the adipocyte differentiation of ASCs obtained from subjects with type 2 diabetes. Gene expression profile by microarray analysis at 14 days of adipogenic differentiation revealed that HH-Sq induced more genes involved in intracellular signaling processes, whereas Sq activated more transmembrane receptor pathway-related genes. In addition, more important number of down-regulated and up-regulated genes by Sq and HH-Sq were not overlapped, suggesting the compounds might not only have difference in their chemical property but also potentially exert different biological effects. Both Sq and HH-Sq improved metabolism of adipocytes by enhancing genes associated with energy homeostasis and insulin sensitivity, SIRT1, PRKAA2, and IRS1. Interestingly, Sq increased significantly early adipogenic markers and lipogenic gene expression such as PPARG, SREBF1, and CEBPA, but not HH-Sq. As a consequence, smaller and fewer lipid droplet formation was observed in HH-Sq-treated adipocytes. Based on our findings, we report that both Sq and HH-Sq improved adipocyte metabolism, but only HH-Sq prevented excessive lipogenesis without abrogating adipocyte differentiation. The beneficial effect of HH-Sq provides an importance of synthesized derivatives from a natural compound with therapeutic potentials in the application of cell therapies. Frontiers Media S.A. 2020-11-04 /pmc/articles/PMC7672044/ /pubmed/33251210 http://dx.doi.org/10.3389/fcell.2020.577259 Text en Copyright © 2020 Ganbold, Ferdousi, Arimura, Tominaga and Isoda. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Ganbold, Munkhzul
Ferdousi, Farhana
Arimura, Takashi
Tominaga, Kenichi
Isoda, Hiroko
New Amphiphilic Squalene Derivative Improves Metabolism of Adipocytes Differentiated From Diabetic Adipose-Derived Stem Cells and Prevents Excessive Lipogenesis
title New Amphiphilic Squalene Derivative Improves Metabolism of Adipocytes Differentiated From Diabetic Adipose-Derived Stem Cells and Prevents Excessive Lipogenesis
title_full New Amphiphilic Squalene Derivative Improves Metabolism of Adipocytes Differentiated From Diabetic Adipose-Derived Stem Cells and Prevents Excessive Lipogenesis
title_fullStr New Amphiphilic Squalene Derivative Improves Metabolism of Adipocytes Differentiated From Diabetic Adipose-Derived Stem Cells and Prevents Excessive Lipogenesis
title_full_unstemmed New Amphiphilic Squalene Derivative Improves Metabolism of Adipocytes Differentiated From Diabetic Adipose-Derived Stem Cells and Prevents Excessive Lipogenesis
title_short New Amphiphilic Squalene Derivative Improves Metabolism of Adipocytes Differentiated From Diabetic Adipose-Derived Stem Cells and Prevents Excessive Lipogenesis
title_sort new amphiphilic squalene derivative improves metabolism of adipocytes differentiated from diabetic adipose-derived stem cells and prevents excessive lipogenesis
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672044/
https://www.ncbi.nlm.nih.gov/pubmed/33251210
http://dx.doi.org/10.3389/fcell.2020.577259
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