Cudratricusxanthone A Inhibits Lipid Accumulation and Expression of Inducible Nitric Oxide Synthase in 3T3-L1 Preadipocytes
Cudratricusxanthone A (CTXA) is a natural bioactive compound extracted from the roots of Bureau and has been shown to possess anti-inflammatory, anti-proliferative, and hepatoprotective activities. However, at present, anti-adipogenic and anti-inflammatory effects of CTXA on adipocytes remain unclea...
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| Veröffentlicht in: | International journal of molecular sciences 2021-01, Vol.22 (2), p.505 |
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| creator | Kwon, Hyo-Shin Jeong, Gil-Saeng Jang, Byeong-Churl |
| description | Cudratricusxanthone A (CTXA) is a natural bioactive compound extracted from the roots of
Bureau and has been shown to possess anti-inflammatory, anti-proliferative, and hepatoprotective activities. However, at present, anti-adipogenic and anti-inflammatory effects of CTXA on adipocytes remain unclear. In this study, we investigated the effects of CTXA on lipid accumulation and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, two known inflammatory enzymes, in 3T3-L1 preadipocytes. Strikingly, CTXA at 10 µM markedly inhibited lipid accumulation and reduced triglyceride (TG) content during 3T3-L1 preadipocyte differentiation with no cytotoxicity. On mechanistic levels, CTXA at 10 µM suppressed not only expression levels of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A, but also phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) and STAT-5 during 3T3-L1 preadipocyte differentiation. In addition, CTXA at 10 µM up-regulated phosphorylation levels of cAMP-activated protein kinase (AMPK) while down-regulating expression and phosphorylation levels of acetyl-CoA carboxylase (ACC) during 3T3-L1 preadipocyte differentiation. Moreover, CTXA at 10 µM greatly attenuated tumor necrosis factor (TNF)-α-induced expression of iNOS, but not COX-2, in 3T3-L1 preadipocytes. These results collectively demonstrate that CTXA has strong anti-adipogenic and anti-inflammatory effects on 3T3-L1 cells through control of the expression and phosphorylation levels of C/EBP-α, PPAR-γ, FAS, ACC, perilipin A, STAT-3/5, AMPK, and iNOS. |
| doi_str_mv | 10.3390/ijms22020505 |
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Bureau and has been shown to possess anti-inflammatory, anti-proliferative, and hepatoprotective activities. However, at present, anti-adipogenic and anti-inflammatory effects of CTXA on adipocytes remain unclear. In this study, we investigated the effects of CTXA on lipid accumulation and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, two known inflammatory enzymes, in 3T3-L1 preadipocytes. Strikingly, CTXA at 10 µM markedly inhibited lipid accumulation and reduced triglyceride (TG) content during 3T3-L1 preadipocyte differentiation with no cytotoxicity. On mechanistic levels, CTXA at 10 µM suppressed not only expression levels of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A, but also phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) and STAT-5 during 3T3-L1 preadipocyte differentiation. In addition, CTXA at 10 µM up-regulated phosphorylation levels of cAMP-activated protein kinase (AMPK) while down-regulating expression and phosphorylation levels of acetyl-CoA carboxylase (ACC) during 3T3-L1 preadipocyte differentiation. Moreover, CTXA at 10 µM greatly attenuated tumor necrosis factor (TNF)-α-induced expression of iNOS, but not COX-2, in 3T3-L1 preadipocytes. These results collectively demonstrate that CTXA has strong anti-adipogenic and anti-inflammatory effects on 3T3-L1 cells through control of the expression and phosphorylation levels of C/EBP-α, PPAR-γ, FAS, ACC, perilipin A, STAT-3/5, AMPK, and iNOS.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms22020505</identifier><identifier>PMID: 33419132</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Accumulation ; Acetyl-CoA carboxylase ; Adipocytes ; Bioactive compounds ; Biocompatibility ; CCAAT/enhancer-binding protein ; Cyclooxygenase-2 ; Cytotoxicity ; Differentiation ; Experiments ; Fatty acids ; Fatty-acid synthase ; Inflammation ; Kinases ; Lipids ; Nitric oxide ; Nitric-oxide synthase ; Obesity ; Peroxisome proliferator-activated receptors ; Phosphorylation ; Preadipocytes ; Protein expression ; Protein kinase ; Proteins ; Stat3 protein ; Stat5 protein ; Transcription ; Transcription factors ; Triglycerides ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α</subject><ispartof>International journal of molecular sciences, 2021-01, Vol.22 (2), p.505</ispartof><rights>2021. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-2332e9ba5b9d7ccf1f84f77c4e73b45af7bd773318cf7428e3c4073bb7b52ce3</citedby><cites>FETCH-LOGICAL-c412t-2332e9ba5b9d7ccf1f84f77c4e73b45af7bd773318cf7428e3c4073bb7b52ce3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825570/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825570/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33419132$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kwon, Hyo-Shin</creatorcontrib><creatorcontrib>Jeong, Gil-Saeng</creatorcontrib><creatorcontrib>Jang, Byeong-Churl</creatorcontrib><title>Cudratricusxanthone A Inhibits Lipid Accumulation and Expression of Inducible Nitric Oxide Synthase in 3T3-L1 Preadipocytes</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Cudratricusxanthone A (CTXA) is a natural bioactive compound extracted from the roots of
Bureau and has been shown to possess anti-inflammatory, anti-proliferative, and hepatoprotective activities. However, at present, anti-adipogenic and anti-inflammatory effects of CTXA on adipocytes remain unclear. In this study, we investigated the effects of CTXA on lipid accumulation and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, two known inflammatory enzymes, in 3T3-L1 preadipocytes. Strikingly, CTXA at 10 µM markedly inhibited lipid accumulation and reduced triglyceride (TG) content during 3T3-L1 preadipocyte differentiation with no cytotoxicity. On mechanistic levels, CTXA at 10 µM suppressed not only expression levels of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A, but also phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) and STAT-5 during 3T3-L1 preadipocyte differentiation. In addition, CTXA at 10 µM up-regulated phosphorylation levels of cAMP-activated protein kinase (AMPK) while down-regulating expression and phosphorylation levels of acetyl-CoA carboxylase (ACC) during 3T3-L1 preadipocyte differentiation. Moreover, CTXA at 10 µM greatly attenuated tumor necrosis factor (TNF)-α-induced expression of iNOS, but not COX-2, in 3T3-L1 preadipocytes. These results collectively demonstrate that CTXA has strong anti-adipogenic and anti-inflammatory effects on 3T3-L1 cells through control of the expression and phosphorylation levels of C/EBP-α, PPAR-γ, FAS, ACC, perilipin A, STAT-3/5, AMPK, and iNOS.</description><subject>Accumulation</subject><subject>Acetyl-CoA carboxylase</subject><subject>Adipocytes</subject><subject>Bioactive compounds</subject><subject>Biocompatibility</subject><subject>CCAAT/enhancer-binding protein</subject><subject>Cyclooxygenase-2</subject><subject>Cytotoxicity</subject><subject>Differentiation</subject><subject>Experiments</subject><subject>Fatty acids</subject><subject>Fatty-acid synthase</subject><subject>Inflammation</subject><subject>Kinases</subject><subject>Lipids</subject><subject>Nitric oxide</subject><subject>Nitric-oxide synthase</subject><subject>Obesity</subject><subject>Peroxisome proliferator-activated receptors</subject><subject>Phosphorylation</subject><subject>Preadipocytes</subject><subject>Protein expression</subject><subject>Protein kinase</subject><subject>Proteins</subject><subject>Stat3 protein</subject><subject>Stat5 protein</subject><subject>Transcription</subject><subject>Transcription factors</subject><subject>Triglycerides</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkctrGzEQh0VpaB7treci6KWHbKqn5b0UjEnagGkK9V3oMVvL7EpbaTfY9J_POkmD29PMMB8fM_wQek_JFec1-Ry2XWGMMCKJfIXOqGCsImSmXh_1p-i8lC0hjDNZv0GnnAtaU87O0J_l6LMZcnBj2Zk4bFIEvMC3cRNsGApehT54vHBu7MbWDCFFbKLH17s-QymHMTUT7UcXbAv4ezio8N0ueMA_95PPFMAhYr7m1YriHxmMD31y-wHKW3TSmLbAu-d6gdY31-vlt2p19_V2uVhVTlA2VIxzBrU10tZeOdfQZi4apZwAxa2QplHWK8U5nbtGCTYH7gSZVlZZyRzwC_TlSduPtgPvIA7ZtLrPoTN5r5MJ-t9NDBv9K91rNWdSKjIJPj0Lcvo9Qhl0F4qDtjUR0lg0E2omZ5w8oh__Q7dpzHH67pGarpzJeqIunyiXUykZmpdjKNGHUPVxqBP-4fiBF_hvivwBl5CfWA</recordid><startdate>20210106</startdate><enddate>20210106</enddate><creator>Kwon, Hyo-Shin</creator><creator>Jeong, Gil-Saeng</creator><creator>Jang, Byeong-Churl</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210106</creationdate><title>Cudratricusxanthone A Inhibits Lipid Accumulation and Expression of Inducible Nitric Oxide Synthase in 3T3-L1 Preadipocytes</title><author>Kwon, Hyo-Shin ; Jeong, Gil-Saeng ; Jang, Byeong-Churl</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-2332e9ba5b9d7ccf1f84f77c4e73b45af7bd773318cf7428e3c4073bb7b52ce3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Accumulation</topic><topic>Acetyl-CoA carboxylase</topic><topic>Adipocytes</topic><topic>Bioactive compounds</topic><topic>Biocompatibility</topic><topic>CCAAT/enhancer-binding protein</topic><topic>Cyclooxygenase-2</topic><topic>Cytotoxicity</topic><topic>Differentiation</topic><topic>Experiments</topic><topic>Fatty acids</topic><topic>Fatty-acid synthase</topic><topic>Inflammation</topic><topic>Kinases</topic><topic>Lipids</topic><topic>Nitric oxide</topic><topic>Nitric-oxide synthase</topic><topic>Obesity</topic><topic>Peroxisome proliferator-activated receptors</topic><topic>Phosphorylation</topic><topic>Preadipocytes</topic><topic>Protein expression</topic><topic>Protein kinase</topic><topic>Proteins</topic><topic>Stat3 protein</topic><topic>Stat5 protein</topic><topic>Transcription</topic><topic>Transcription factors</topic><topic>Triglycerides</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumor necrosis factor-α</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kwon, Hyo-Shin</creatorcontrib><creatorcontrib>Jeong, Gil-Saeng</creatorcontrib><creatorcontrib>Jang, Byeong-Churl</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kwon, Hyo-Shin</au><au>Jeong, Gil-Saeng</au><au>Jang, Byeong-Churl</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cudratricusxanthone A Inhibits Lipid Accumulation and Expression of Inducible Nitric Oxide Synthase in 3T3-L1 Preadipocytes</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2021-01-06</date><risdate>2021</risdate><volume>22</volume><issue>2</issue><spage>505</spage><pages>505-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Cudratricusxanthone A (CTXA) is a natural bioactive compound extracted from the roots of
Bureau and has been shown to possess anti-inflammatory, anti-proliferative, and hepatoprotective activities. However, at present, anti-adipogenic and anti-inflammatory effects of CTXA on adipocytes remain unclear. In this study, we investigated the effects of CTXA on lipid accumulation and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, two known inflammatory enzymes, in 3T3-L1 preadipocytes. Strikingly, CTXA at 10 µM markedly inhibited lipid accumulation and reduced triglyceride (TG) content during 3T3-L1 preadipocyte differentiation with no cytotoxicity. On mechanistic levels, CTXA at 10 µM suppressed not only expression levels of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A, but also phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) and STAT-5 during 3T3-L1 preadipocyte differentiation. In addition, CTXA at 10 µM up-regulated phosphorylation levels of cAMP-activated protein kinase (AMPK) while down-regulating expression and phosphorylation levels of acetyl-CoA carboxylase (ACC) during 3T3-L1 preadipocyte differentiation. Moreover, CTXA at 10 µM greatly attenuated tumor necrosis factor (TNF)-α-induced expression of iNOS, but not COX-2, in 3T3-L1 preadipocytes. These results collectively demonstrate that CTXA has strong anti-adipogenic and anti-inflammatory effects on 3T3-L1 cells through control of the expression and phosphorylation levels of C/EBP-α, PPAR-γ, FAS, ACC, perilipin A, STAT-3/5, AMPK, and iNOS.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33419132</pmid><doi>10.3390/ijms22020505</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Accumulation Acetyl-CoA carboxylase Adipocytes Bioactive compounds Biocompatibility CCAAT/enhancer-binding protein Cyclooxygenase-2 Cytotoxicity Differentiation Experiments Fatty acids Fatty-acid synthase Inflammation Kinases Lipids Nitric oxide Nitric-oxide synthase Obesity Peroxisome proliferator-activated receptors Phosphorylation Preadipocytes Protein expression Protein kinase Proteins Stat3 protein Stat5 protein Transcription Transcription factors Triglycerides Tumor necrosis factor-TNF Tumor necrosis factor-α |
| title | Cudratricusxanthone A Inhibits Lipid Accumulation and Expression of Inducible Nitric Oxide Synthase in 3T3-L1 Preadipocytes |
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