Chrysin Improves Glucose and Lipid Metabolism Disorders by Regulating the AMPK/PI3K/AKT Signaling Pathway in Insulin-Resistant HepG2 Cells and HFD/STZ-Induced C57BL/6J Mice
Natural products with minor side effects have been reported to be an effective adjuvant therapy for glucose and lipid metabolism disorders. Chrysin, a flavone, has a wide range of physiological effects, such as antioxidant, anti-inflammatory, anti-diabetes, anti-hyperlipidemia, and hepatoprotective....
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| Veröffentlicht in: | Journal of agricultural and food chemistry 2021-05, Vol.69 (20), p.5618-5627 |
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| creator | Zhou, Ying-Jun Xu, Nuo Zhang, Xiao-Chen Zhu, Yu-Yan Liu, Shao-Wei Chang, Ya-Ning |
| description | Natural products with minor side effects have been reported to be an effective adjuvant therapy for glucose and lipid metabolism disorders. Chrysin, a flavone, has a wide range of physiological effects, such as antioxidant, anti-inflammatory, anti-diabetes, anti-hyperlipidemia, and hepatoprotective. This study was designed to explore the effects and mechanism of chrysin on metabolic syndrome using insulin-resistant HepG2 cells and HFD/STZ-induced C57BL/6J mice. The results indicated that chrysin significantly decreased insulin resistance, oxidative stress, inflammation, and liver injury. In addition, chrysin improved glycogen synthesis and fatty acid oxidation and inhibited gluconeogenesis and fatty acid synthesis by regulating GSK3β, G6Paes, PEPCK, SREBP1, FAS, and ACC1. Furthermore, the results of western blot and real-time PCR experiments demonstrated that chrysin modulated glucose and lipid metabolism through the AMPK/PI3K/AKT signaling pathway. Treatment with the AMPK inhibitor verified that AMPK activation is positively correlated with chrysin activity on glycolipid metabolism. This study confirms that chrysin is a potential treatment for glucose and lipid metabolism disorders. |
| doi_str_mv | 10.1021/acs.jafc.1c01109 |
| format | Article |
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Chrysin, a flavone, has a wide range of physiological effects, such as antioxidant, anti-inflammatory, anti-diabetes, anti-hyperlipidemia, and hepatoprotective. This study was designed to explore the effects and mechanism of chrysin on metabolic syndrome using insulin-resistant HepG2 cells and HFD/STZ-induced C57BL/6J mice. The results indicated that chrysin significantly decreased insulin resistance, oxidative stress, inflammation, and liver injury. In addition, chrysin improved glycogen synthesis and fatty acid oxidation and inhibited gluconeogenesis and fatty acid synthesis by regulating GSK3β, G6Paes, PEPCK, SREBP1, FAS, and ACC1. Furthermore, the results of western blot and real-time PCR experiments demonstrated that chrysin modulated glucose and lipid metabolism through the AMPK/PI3K/AKT signaling pathway. Treatment with the AMPK inhibitor verified that AMPK activation is positively correlated with chrysin activity on glycolipid metabolism. This study confirms that chrysin is a potential treatment for glucose and lipid metabolism disorders.</description><identifier>ISSN: 0021-8561</identifier><identifier>EISSN: 1520-5118</identifier><identifier>DOI: 10.1021/acs.jafc.1c01109</identifier><identifier>PMID: 33979145</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>AMP-Activated Protein Kinases - genetics ; AMP-Activated Protein Kinases - metabolism ; Animals ; Bioactive Constituents, Metabolites, and Functions ; Flavonoids ; Glucose ; Hep G2 Cells ; Humans ; Insulin - metabolism ; Insulin Resistance ; Lipid Metabolism ; Lipid Metabolism Disorders ; Mice ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases - genetics ; Phosphatidylinositol 3-Kinases - metabolism ; Proto-Oncogene Proteins c-akt - genetics ; Proto-Oncogene Proteins c-akt - metabolism ; Signal Transduction</subject><ispartof>Journal of agricultural and food chemistry, 2021-05, Vol.69 (20), p.5618-5627</ispartof><rights>2021 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a336t-8b332bbbe36da4f35323fbabf59abb615f63ac737f32fc04e1d08675e546cb673</citedby><cites>FETCH-LOGICAL-a336t-8b332bbbe36da4f35323fbabf59abb615f63ac737f32fc04e1d08675e546cb673</cites><orcidid>0000-0003-4415-8064</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.jafc.1c01109$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.jafc.1c01109$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33979145$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Ying-Jun</creatorcontrib><creatorcontrib>Xu, Nuo</creatorcontrib><creatorcontrib>Zhang, Xiao-Chen</creatorcontrib><creatorcontrib>Zhu, Yu-Yan</creatorcontrib><creatorcontrib>Liu, Shao-Wei</creatorcontrib><creatorcontrib>Chang, Ya-Ning</creatorcontrib><title>Chrysin Improves Glucose and Lipid Metabolism Disorders by Regulating the AMPK/PI3K/AKT Signaling Pathway in Insulin-Resistant HepG2 Cells and HFD/STZ-Induced C57BL/6J Mice</title><title>Journal of agricultural and food chemistry</title><addtitle>J. Agric. Food Chem</addtitle><description>Natural products with minor side effects have been reported to be an effective adjuvant therapy for glucose and lipid metabolism disorders. Chrysin, a flavone, has a wide range of physiological effects, such as antioxidant, anti-inflammatory, anti-diabetes, anti-hyperlipidemia, and hepatoprotective. This study was designed to explore the effects and mechanism of chrysin on metabolic syndrome using insulin-resistant HepG2 cells and HFD/STZ-induced C57BL/6J mice. The results indicated that chrysin significantly decreased insulin resistance, oxidative stress, inflammation, and liver injury. In addition, chrysin improved glycogen synthesis and fatty acid oxidation and inhibited gluconeogenesis and fatty acid synthesis by regulating GSK3β, G6Paes, PEPCK, SREBP1, FAS, and ACC1. Furthermore, the results of western blot and real-time PCR experiments demonstrated that chrysin modulated glucose and lipid metabolism through the AMPK/PI3K/AKT signaling pathway. Treatment with the AMPK inhibitor verified that AMPK activation is positively correlated with chrysin activity on glycolipid metabolism. This study confirms that chrysin is a potential treatment for glucose and lipid metabolism disorders.</description><subject>AMP-Activated Protein Kinases - genetics</subject><subject>AMP-Activated Protein Kinases - metabolism</subject><subject>Animals</subject><subject>Bioactive Constituents, Metabolites, and Functions</subject><subject>Flavonoids</subject><subject>Glucose</subject><subject>Hep G2 Cells</subject><subject>Humans</subject><subject>Insulin - metabolism</subject><subject>Insulin Resistance</subject><subject>Lipid Metabolism</subject><subject>Lipid Metabolism Disorders</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Phosphatidylinositol 3-Kinases - genetics</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Proto-Oncogene Proteins c-akt - genetics</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Signal Transduction</subject><issn>0021-8561</issn><issn>1520-5118</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kb1u2zAURomiQeOm3TsVHDtUFimalDy6SmO7tlEjcZcuAkld2gz04-hKDfxOecjKsZMtEwHyfN8l7iHkC2dDziIeaovDe-3skFvGORu_IwMuIxZIzpP3ZMB6Jkik4pfkI-I9YyyRMftALoUYx2M-kgPylO6aA_qKzst9U_8DpNOiszUC1VVOl37vc7qCVpu68FjSa491k0OD1BzoLWy7Qre-2tJ2B3SyWi_C9VwswsliQ-_8ttLF8W2t292jPtDjkAq7_i64BfTY6qqlM9hPI5pCUeDzxNnNdXi3-RvMq7yzkNNUxj-WofpFV97CJ3LhdIHw-XxekT83PzfpLFj-ns7TyTLQQqg2SIwQkTEGhMr1yAkpIuGMNk6OtTGKS6eEtrGInYicZSPgOUtULEGOlDUqFlfk26m3X8lDB9hmpUfb_1FXUHeYRTJSggkViR5lJ9Q2NWIDLts3vtTNIeMsOzrKekfZ0VF2dtRHvp7bO1NC_hp4kdID30_Ac7Tumn6R-Hbff7M4nK8</recordid><startdate>20210526</startdate><enddate>20210526</enddate><creator>Zhou, Ying-Jun</creator><creator>Xu, Nuo</creator><creator>Zhang, Xiao-Chen</creator><creator>Zhu, Yu-Yan</creator><creator>Liu, Shao-Wei</creator><creator>Chang, Ya-Ning</creator><general>American Chemical Society</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><orcidid>https://orcid.org/0000-0003-4415-8064</orcidid></search><sort><creationdate>20210526</creationdate><title>Chrysin Improves Glucose and Lipid Metabolism Disorders by Regulating the AMPK/PI3K/AKT Signaling Pathway in Insulin-Resistant HepG2 Cells and HFD/STZ-Induced C57BL/6J Mice</title><author>Zhou, Ying-Jun ; Xu, Nuo ; Zhang, Xiao-Chen ; Zhu, Yu-Yan ; Liu, Shao-Wei ; Chang, Ya-Ning</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a336t-8b332bbbe36da4f35323fbabf59abb615f63ac737f32fc04e1d08675e546cb673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>AMP-Activated Protein Kinases - genetics</topic><topic>AMP-Activated Protein Kinases - metabolism</topic><topic>Animals</topic><topic>Bioactive Constituents, Metabolites, and Functions</topic><topic>Flavonoids</topic><topic>Glucose</topic><topic>Hep G2 Cells</topic><topic>Humans</topic><topic>Insulin - metabolism</topic><topic>Insulin Resistance</topic><topic>Lipid Metabolism</topic><topic>Lipid Metabolism Disorders</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Phosphatidylinositol 3-Kinases - genetics</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Proto-Oncogene Proteins c-akt - genetics</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Ying-Jun</creatorcontrib><creatorcontrib>Xu, Nuo</creatorcontrib><creatorcontrib>Zhang, Xiao-Chen</creatorcontrib><creatorcontrib>Zhu, Yu-Yan</creatorcontrib><creatorcontrib>Liu, Shao-Wei</creatorcontrib><creatorcontrib>Chang, Ya-Ning</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><jtitle>Journal of agricultural and food chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Ying-Jun</au><au>Xu, Nuo</au><au>Zhang, Xiao-Chen</au><au>Zhu, Yu-Yan</au><au>Liu, Shao-Wei</au><au>Chang, Ya-Ning</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chrysin Improves Glucose and Lipid Metabolism Disorders by Regulating the AMPK/PI3K/AKT Signaling Pathway in Insulin-Resistant HepG2 Cells and HFD/STZ-Induced C57BL/6J Mice</atitle><jtitle>Journal of agricultural and food chemistry</jtitle><addtitle>J. Agric. Food Chem</addtitle><date>2021-05-26</date><risdate>2021</risdate><volume>69</volume><issue>20</issue><spage>5618</spage><epage>5627</epage><pages>5618-5627</pages><issn>0021-8561</issn><eissn>1520-5118</eissn><abstract>Natural products with minor side effects have been reported to be an effective adjuvant therapy for glucose and lipid metabolism disorders. Chrysin, a flavone, has a wide range of physiological effects, such as antioxidant, anti-inflammatory, anti-diabetes, anti-hyperlipidemia, and hepatoprotective. This study was designed to explore the effects and mechanism of chrysin on metabolic syndrome using insulin-resistant HepG2 cells and HFD/STZ-induced C57BL/6J mice. The results indicated that chrysin significantly decreased insulin resistance, oxidative stress, inflammation, and liver injury. In addition, chrysin improved glycogen synthesis and fatty acid oxidation and inhibited gluconeogenesis and fatty acid synthesis by regulating GSK3β, G6Paes, PEPCK, SREBP1, FAS, and ACC1. Furthermore, the results of western blot and real-time PCR experiments demonstrated that chrysin modulated glucose and lipid metabolism through the AMPK/PI3K/AKT signaling pathway. Treatment with the AMPK inhibitor verified that AMPK activation is positively correlated with chrysin activity on glycolipid metabolism. This study confirms that chrysin is a potential treatment for glucose and lipid metabolism disorders.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>33979145</pmid><doi>10.1021/acs.jafc.1c01109</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-4415-8064</orcidid></addata></record> |
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| subjects | AMP-Activated Protein Kinases - genetics AMP-Activated Protein Kinases - metabolism Animals Bioactive Constituents, Metabolites, and Functions Flavonoids Glucose Hep G2 Cells Humans Insulin - metabolism Insulin Resistance Lipid Metabolism Lipid Metabolism Disorders Mice Mice, Inbred C57BL Phosphatidylinositol 3-Kinases - genetics Phosphatidylinositol 3-Kinases - metabolism Proto-Oncogene Proteins c-akt - genetics Proto-Oncogene Proteins c-akt - metabolism Signal Transduction |
| title | Chrysin Improves Glucose and Lipid Metabolism Disorders by Regulating the AMPK/PI3K/AKT Signaling Pathway in Insulin-Resistant HepG2 Cells and HFD/STZ-Induced C57BL/6J Mice |
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