Eudesmin impairs adipogenic differentiation via inhibition of S6K1 signaling pathway
Eudesmin has been reported to possess diverse therapeutic effects, including anti-tumor, anti-inflammatory, and anti-bacterial activities. However, its molecular action has not been implicated in metabolic disease. In this study, we show that treatment of mesenchymal stem cells (MSCs) with eudesmin...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2018-11, Vol.505 (4), p.1148-1153 |
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| description | Eudesmin has been reported to possess diverse therapeutic effects, including anti-tumor, anti-inflammatory, and anti-bacterial activities. However, its molecular action has not been implicated in metabolic disease. In this study, we show that treatment of mesenchymal stem cells (MSCs) with eudesmin disturbs adipogenesis via suppression of S6K1 signaling pathway. Eudesmin treatment inhibited activation and nuclear translocation of S6K1. Consequently, S6K1-mediated phosphorylation of H2B at serine 36 (H2BS36p) was reduced upon eudesmin treatment, further inducing the expression of Wnt6, Wnt10a, and Wnt10b, which disturbed adipogenic differentiation. Moreover, eudesmin promoted myogenic and osteogenic gene expression in MSCs. Taken together, we found a novel small molecule, eudesmin, to block adipogenesis through down-regulation of S6K1-H2BS36p axis, followed by regulation of cell fate determination genes. This study suggests a promising therapeutic approach with eudesmin to cure obesity and metabolic diseases.
•Eudesmin inhibits activation sand nuclear translocation of S6K1.•Eudesmin promotes Wnt gene expression by reducing S6K1-mediated H2BS36 phosphorylation.•Eudesmin disturbs adipogenic gene expression and de novo adipocyte generation.•Eudesmin enhances myogenic and osteogenic gene expression. |
| doi_str_mv | 10.1016/j.bbrc.2018.09.188 |
| format | Article |
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•Eudesmin inhibits activation sand nuclear translocation of S6K1.•Eudesmin promotes Wnt gene expression by reducing S6K1-mediated H2BS36 phosphorylation.•Eudesmin disturbs adipogenic gene expression and de novo adipocyte generation.•Eudesmin enhances myogenic and osteogenic gene expression.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2018.09.188</identifier><identifier>PMID: 30316515</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Active Transport, Cell Nucleus - drug effects ; Adipogenesis ; Adipogenesis - drug effects ; Animals ; Cell Line ; Eudesmin ; Furans - pharmacology ; Gene Expression - drug effects ; H2BS36 phosphorylation ; Histones - metabolism ; INFLAMMATION ; Lignans - pharmacology ; Mesenchymal Stem Cells - cytology ; Mesenchymal Stem Cells - drug effects ; Mesenchymal Stem Cells - metabolism ; METABOLIC DISEASES ; Mice ; Muscle Cells - cytology ; Muscle Cells - drug effects ; Muscle Cells - metabolism ; NEOPLASMS ; Osteoblasts - cytology ; Osteoblasts - drug effects ; Osteoblasts - metabolism ; PHOSPHORYLATION ; Protein Kinase Inhibitors - pharmacology ; Ribosomal Protein S6 Kinases, 90-kDa - antagonists & inhibitors ; Ribosomal Protein S6 Kinases, 90-kDa - metabolism ; S6K1 ; SERINE ; Signal Transduction - drug effects ; STEM CELLS ; Wnt genes ; Wnt Proteins - genetics</subject><ispartof>Biochemical and biophysical research communications, 2018-11, Vol.505 (4), p.1148-1153</ispartof><rights>2018 Elsevier Inc.</rights><rights>Copyright © 2018 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-47edf913c17b99ad97e3eee3fde4fa0472d270d40c1c66b1703b9beacbc58fa63</citedby><cites>FETCH-LOGICAL-c384t-47edf913c17b99ad97e3eee3fde4fa0472d270d40c1c66b1703b9beacbc58fa63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2018.09.188$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30316515$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/23107749$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Nam, Ki Hong</creatorcontrib><creatorcontrib>Yi, Sang Ah</creatorcontrib><creatorcontrib>Lee, Jaecheol</creatorcontrib><creatorcontrib>Lee, Min Gyu</creatorcontrib><creatorcontrib>Park, Jee Hun</creatorcontrib><creatorcontrib>Oh, Hwamok</creatorcontrib><creatorcontrib>Lee, Jieun</creatorcontrib><creatorcontrib>Park, Jong Woo</creatorcontrib><creatorcontrib>Han, Jeung-Whan</creatorcontrib><title>Eudesmin impairs adipogenic differentiation via inhibition of S6K1 signaling pathway</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Eudesmin has been reported to possess diverse therapeutic effects, including anti-tumor, anti-inflammatory, and anti-bacterial activities. However, its molecular action has not been implicated in metabolic disease. In this study, we show that treatment of mesenchymal stem cells (MSCs) with eudesmin disturbs adipogenesis via suppression of S6K1 signaling pathway. Eudesmin treatment inhibited activation and nuclear translocation of S6K1. Consequently, S6K1-mediated phosphorylation of H2B at serine 36 (H2BS36p) was reduced upon eudesmin treatment, further inducing the expression of Wnt6, Wnt10a, and Wnt10b, which disturbed adipogenic differentiation. Moreover, eudesmin promoted myogenic and osteogenic gene expression in MSCs. Taken together, we found a novel small molecule, eudesmin, to block adipogenesis through down-regulation of S6K1-H2BS36p axis, followed by regulation of cell fate determination genes. This study suggests a promising therapeutic approach with eudesmin to cure obesity and metabolic diseases.
•Eudesmin inhibits activation sand nuclear translocation of S6K1.•Eudesmin promotes Wnt gene expression by reducing S6K1-mediated H2BS36 phosphorylation.•Eudesmin disturbs adipogenic gene expression and de novo adipocyte generation.•Eudesmin enhances myogenic and osteogenic gene expression.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>Active Transport, Cell Nucleus - drug effects</subject><subject>Adipogenesis</subject><subject>Adipogenesis - drug effects</subject><subject>Animals</subject><subject>Cell Line</subject><subject>Eudesmin</subject><subject>Furans - pharmacology</subject><subject>Gene Expression - drug effects</subject><subject>H2BS36 phosphorylation</subject><subject>Histones - metabolism</subject><subject>INFLAMMATION</subject><subject>Lignans - pharmacology</subject><subject>Mesenchymal Stem Cells - cytology</subject><subject>Mesenchymal Stem Cells - drug effects</subject><subject>Mesenchymal Stem Cells - metabolism</subject><subject>METABOLIC DISEASES</subject><subject>Mice</subject><subject>Muscle Cells - cytology</subject><subject>Muscle Cells - drug effects</subject><subject>Muscle Cells - metabolism</subject><subject>NEOPLASMS</subject><subject>Osteoblasts - cytology</subject><subject>Osteoblasts - drug effects</subject><subject>Osteoblasts - metabolism</subject><subject>PHOSPHORYLATION</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Ribosomal Protein S6 Kinases, 90-kDa - antagonists & inhibitors</subject><subject>Ribosomal Protein S6 Kinases, 90-kDa - metabolism</subject><subject>S6K1</subject><subject>SERINE</subject><subject>Signal Transduction - drug effects</subject><subject>STEM CELLS</subject><subject>Wnt genes</subject><subject>Wnt Proteins - genetics</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE2L1EAQhhtR3HH1D3iQgBcviVXpTJIGL7KsH7jgwRW8Nf1Rmalh0h27Myv7702c1aOnouB5X14eIV4iVAjYvj1U1iZX1YB9BarCvn8kNggKyhqheSw2ANCWtcIfF-JZzgcAxKZVT8WFBIntFrcbcXt98pRHDgWPk-GUC-N5ijsK7ArPw0CJwsxm5hiKOzYFhz1b_vPGofjWfsEi8y6YI4ddMZl5_8vcPxdPBnPM9OLhXorvH65vrz6VN18_fr56f1M62Tdz2XTkB4XSYWeVMl51JIlIDp6awUDT1b7uwDfg0LWtxQ6kVZaMs27bD6aVl-L1uTfmmXV2PJPbuxgCuVnXEqHrGrVQb87UlOLPE-VZj5wdHY8mUDxlXeNiUNUocUHrM-pSzDnRoKfEo0n3GkGvzvVBr8716lyD0ovzJfTqof9kR_L_In8lL8C7M0CLizumtE6l4MhzWpf6yP_r_w0rmpNE</recordid><startdate>20181110</startdate><enddate>20181110</enddate><creator>Nam, Ki Hong</creator><creator>Yi, Sang Ah</creator><creator>Lee, Jaecheol</creator><creator>Lee, Min Gyu</creator><creator>Park, Jee Hun</creator><creator>Oh, Hwamok</creator><creator>Lee, Jieun</creator><creator>Park, Jong Woo</creator><creator>Han, Jeung-Whan</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>20181110</creationdate><title>Eudesmin impairs adipogenic differentiation via inhibition of S6K1 signaling pathway</title><author>Nam, Ki Hong ; Yi, Sang Ah ; Lee, Jaecheol ; Lee, Min Gyu ; Park, Jee Hun ; Oh, Hwamok ; Lee, Jieun ; Park, Jong Woo ; Han, Jeung-Whan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-47edf913c17b99ad97e3eee3fde4fa0472d270d40c1c66b1703b9beacbc58fa63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>Active Transport, Cell Nucleus - drug effects</topic><topic>Adipogenesis</topic><topic>Adipogenesis - drug effects</topic><topic>Animals</topic><topic>Cell Line</topic><topic>Eudesmin</topic><topic>Furans - pharmacology</topic><topic>Gene Expression - drug effects</topic><topic>H2BS36 phosphorylation</topic><topic>Histones - metabolism</topic><topic>INFLAMMATION</topic><topic>Lignans - pharmacology</topic><topic>Mesenchymal Stem Cells - cytology</topic><topic>Mesenchymal Stem Cells - drug effects</topic><topic>Mesenchymal Stem Cells - metabolism</topic><topic>METABOLIC DISEASES</topic><topic>Mice</topic><topic>Muscle Cells - cytology</topic><topic>Muscle Cells - drug effects</topic><topic>Muscle Cells - metabolism</topic><topic>NEOPLASMS</topic><topic>Osteoblasts - cytology</topic><topic>Osteoblasts - drug effects</topic><topic>Osteoblasts - metabolism</topic><topic>PHOSPHORYLATION</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Ribosomal Protein S6 Kinases, 90-kDa - antagonists & inhibitors</topic><topic>Ribosomal Protein S6 Kinases, 90-kDa - metabolism</topic><topic>S6K1</topic><topic>SERINE</topic><topic>Signal Transduction - drug effects</topic><topic>STEM CELLS</topic><topic>Wnt genes</topic><topic>Wnt Proteins - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nam, Ki Hong</creatorcontrib><creatorcontrib>Yi, Sang Ah</creatorcontrib><creatorcontrib>Lee, Jaecheol</creatorcontrib><creatorcontrib>Lee, Min Gyu</creatorcontrib><creatorcontrib>Park, Jee Hun</creatorcontrib><creatorcontrib>Oh, Hwamok</creatorcontrib><creatorcontrib>Lee, Jieun</creatorcontrib><creatorcontrib>Park, Jong Woo</creatorcontrib><creatorcontrib>Han, Jeung-Whan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nam, Ki Hong</au><au>Yi, Sang Ah</au><au>Lee, Jaecheol</au><au>Lee, Min Gyu</au><au>Park, Jee Hun</au><au>Oh, Hwamok</au><au>Lee, Jieun</au><au>Park, Jong Woo</au><au>Han, Jeung-Whan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Eudesmin impairs adipogenic differentiation via inhibition of S6K1 signaling pathway</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2018-11-10</date><risdate>2018</risdate><volume>505</volume><issue>4</issue><spage>1148</spage><epage>1153</epage><pages>1148-1153</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Eudesmin has been reported to possess diverse therapeutic effects, including anti-tumor, anti-inflammatory, and anti-bacterial activities. However, its molecular action has not been implicated in metabolic disease. In this study, we show that treatment of mesenchymal stem cells (MSCs) with eudesmin disturbs adipogenesis via suppression of S6K1 signaling pathway. Eudesmin treatment inhibited activation and nuclear translocation of S6K1. Consequently, S6K1-mediated phosphorylation of H2B at serine 36 (H2BS36p) was reduced upon eudesmin treatment, further inducing the expression of Wnt6, Wnt10a, and Wnt10b, which disturbed adipogenic differentiation. Moreover, eudesmin promoted myogenic and osteogenic gene expression in MSCs. Taken together, we found a novel small molecule, eudesmin, to block adipogenesis through down-regulation of S6K1-H2BS36p axis, followed by regulation of cell fate determination genes. This study suggests a promising therapeutic approach with eudesmin to cure obesity and metabolic diseases.
•Eudesmin inhibits activation sand nuclear translocation of S6K1.•Eudesmin promotes Wnt gene expression by reducing S6K1-mediated H2BS36 phosphorylation.•Eudesmin disturbs adipogenic gene expression and de novo adipocyte generation.•Eudesmin enhances myogenic and osteogenic gene expression.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>30316515</pmid><doi>10.1016/j.bbrc.2018.09.188</doi><tpages>6</tpages></addata></record> |
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| subjects | 60 APPLIED LIFE SCIENCES Active Transport, Cell Nucleus - drug effects Adipogenesis Adipogenesis - drug effects Animals Cell Line Eudesmin Furans - pharmacology Gene Expression - drug effects H2BS36 phosphorylation Histones - metabolism INFLAMMATION Lignans - pharmacology Mesenchymal Stem Cells - cytology Mesenchymal Stem Cells - drug effects Mesenchymal Stem Cells - metabolism METABOLIC DISEASES Mice Muscle Cells - cytology Muscle Cells - drug effects Muscle Cells - metabolism NEOPLASMS Osteoblasts - cytology Osteoblasts - drug effects Osteoblasts - metabolism PHOSPHORYLATION Protein Kinase Inhibitors - pharmacology Ribosomal Protein S6 Kinases, 90-kDa - antagonists & inhibitors Ribosomal Protein S6 Kinases, 90-kDa - metabolism S6K1 SERINE Signal Transduction - drug effects STEM CELLS Wnt genes Wnt Proteins - genetics |
| title | Eudesmin impairs adipogenic differentiation via inhibition of S6K1 signaling pathway |
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