Anthocyanin increases adiponectin secretion and protects against diabetes-related endothelial dysfunction
Adiponectin is an adipose tissue-secreted adipokine with beneficial effects on the cardiovascular system. In this study, we evaluated a potential role for adiponectin in the protective effects of anthocyanin on diabetes-related endothelial dysfunction. We treated db/db mice on a normal diet with ant...
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Veröffentlicht in: | American journal of physiology: endocrinology and metabolism 2014-04, Vol.306 (8), p.E975-E988 |
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description | Adiponectin is an adipose tissue-secreted adipokine with beneficial effects on the cardiovascular system. In this study, we evaluated a potential role for adiponectin in the protective effects of anthocyanin on diabetes-related endothelial dysfunction. We treated db/db mice on a normal diet with anthocyanin cyanidin-3-O-β-glucoside (C3G; 2 g/kg diet) for 8 wk. Endothelium-dependent and -independent relaxations of the aorta were then evaluated. Adiponectin expression and secretion were also measured. C3G treatment restores endothelium-dependent relaxation of the aorta in db/db mice, whereas diabetic mice treated with an anti-adiponectin antibody do not respond. C3G treatment induces adiponectin expression and secretion in cultured 3T3 adipocytes through transcription factor forkhead box O1 (Foxo1). Silencing Foxo1 expression prevented C3G-stimulated induction of adiponectin expression. In contrast, overexpression of Foxo1-ADA promoted adiponectin expression in adipocytes. C3G activates Foxo1 by increasing its deacetylation via silent mating type information regulation 2 homolog 1 (Sirt1). Furthermore, purified anthocyanin supplementation significantly improved flow-mediated dilation (FMD) and increased serum adiponectin concentrations in patients with type 2 diabetes. Changes in adiponectin concentrations positively correlated with FMD in the anthocyanin group. Mechanistically, adiponectin activates cAMP-PKA-eNOS signaling pathways in human aortic endothelial cells, increasing endothelial nitric oxide bioavailability. These results demonstrate that adipocyte-derived adiponectin is required for anthocyanin C3G-mediated improvement of endothelial function in diabetes. |
doi_str_mv | 10.1152/ajpendo.00699.2013 |
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In this study, we evaluated a potential role for adiponectin in the protective effects of anthocyanin on diabetes-related endothelial dysfunction. We treated db/db mice on a normal diet with anthocyanin cyanidin-3-O-β-glucoside (C3G; 2 g/kg diet) for 8 wk. Endothelium-dependent and -independent relaxations of the aorta were then evaluated. Adiponectin expression and secretion were also measured. C3G treatment restores endothelium-dependent relaxation of the aorta in db/db mice, whereas diabetic mice treated with an anti-adiponectin antibody do not respond. C3G treatment induces adiponectin expression and secretion in cultured 3T3 adipocytes through transcription factor forkhead box O1 (Foxo1). Silencing Foxo1 expression prevented C3G-stimulated induction of adiponectin expression. In contrast, overexpression of Foxo1-ADA promoted adiponectin expression in adipocytes. C3G activates Foxo1 by increasing its deacetylation via silent mating type information regulation 2 homolog 1 (Sirt1). Furthermore, purified anthocyanin supplementation significantly improved flow-mediated dilation (FMD) and increased serum adiponectin concentrations in patients with type 2 diabetes. Changes in adiponectin concentrations positively correlated with FMD in the anthocyanin group. Mechanistically, adiponectin activates cAMP-PKA-eNOS signaling pathways in human aortic endothelial cells, increasing endothelial nitric oxide bioavailability. These results demonstrate that adipocyte-derived adiponectin is required for anthocyanin C3G-mediated improvement of endothelial function in diabetes.</description><identifier>ISSN: 0193-1849</identifier><identifier>EISSN: 1522-1555</identifier><identifier>DOI: 10.1152/ajpendo.00699.2013</identifier><identifier>PMID: 24595303</identifier><identifier>CODEN: AJPMD9</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>3T3-L1 Cells ; Adipocytes ; Adiponectin - secretion ; Animals ; Anthocyanins - pharmacology ; Cardiovascular Diseases - metabolism ; Cardiovascular Diseases - physiopathology ; Cardiovascular Diseases - prevention & control ; Cells, Cultured ; Cellular biology ; Cytoprotection ; Diabetes ; Diabetes Mellitus, Experimental - complications ; Diabetes Mellitus, Experimental - metabolism ; Diabetes Mellitus, Experimental - physiopathology ; Diabetic Angiopathies - metabolism ; Diabetic Angiopathies - physiopathology ; Diabetic Angiopathies - prevention & control ; Drug Evaluation, Preclinical ; Endothelium ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - physiopathology ; Humans ; Male ; Mice ; Physiology ; Pigments ; Rats</subject><ispartof>American journal of physiology: endocrinology and metabolism, 2014-04, Vol.306 (8), p.E975-E988</ispartof><rights>Copyright American Physiological Society Apr 15, 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c364t-794ea38ef08b3644ef0250fcfcd676e66ac648b434f22ee3f35b274abc9959193</citedby><cites>FETCH-LOGICAL-c364t-794ea38ef08b3644ef0250fcfcd676e66ac648b434f22ee3f35b274abc9959193</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3039,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24595303$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Yan</creatorcontrib><creatorcontrib>Li, Dan</creatorcontrib><creatorcontrib>Zhang, Yuhua</creatorcontrib><creatorcontrib>Sun, Ruifang</creatorcontrib><creatorcontrib>Xia, Min</creatorcontrib><title>Anthocyanin increases adiponectin secretion and protects against diabetes-related endothelial dysfunction</title><title>American journal of physiology: endocrinology and metabolism</title><addtitle>Am J Physiol Endocrinol Metab</addtitle><description>Adiponectin is an adipose tissue-secreted adipokine with beneficial effects on the cardiovascular system. In this study, we evaluated a potential role for adiponectin in the protective effects of anthocyanin on diabetes-related endothelial dysfunction. We treated db/db mice on a normal diet with anthocyanin cyanidin-3-O-β-glucoside (C3G; 2 g/kg diet) for 8 wk. Endothelium-dependent and -independent relaxations of the aorta were then evaluated. Adiponectin expression and secretion were also measured. C3G treatment restores endothelium-dependent relaxation of the aorta in db/db mice, whereas diabetic mice treated with an anti-adiponectin antibody do not respond. C3G treatment induces adiponectin expression and secretion in cultured 3T3 adipocytes through transcription factor forkhead box O1 (Foxo1). Silencing Foxo1 expression prevented C3G-stimulated induction of adiponectin expression. In contrast, overexpression of Foxo1-ADA promoted adiponectin expression in adipocytes. C3G activates Foxo1 by increasing its deacetylation via silent mating type information regulation 2 homolog 1 (Sirt1). Furthermore, purified anthocyanin supplementation significantly improved flow-mediated dilation (FMD) and increased serum adiponectin concentrations in patients with type 2 diabetes. Changes in adiponectin concentrations positively correlated with FMD in the anthocyanin group. Mechanistically, adiponectin activates cAMP-PKA-eNOS signaling pathways in human aortic endothelial cells, increasing endothelial nitric oxide bioavailability. These results demonstrate that adipocyte-derived adiponectin is required for anthocyanin C3G-mediated improvement of endothelial function in diabetes.</description><subject>3T3-L1 Cells</subject><subject>Adipocytes</subject><subject>Adiponectin - secretion</subject><subject>Animals</subject><subject>Anthocyanins - pharmacology</subject><subject>Cardiovascular Diseases - metabolism</subject><subject>Cardiovascular Diseases - physiopathology</subject><subject>Cardiovascular Diseases - prevention & control</subject><subject>Cells, Cultured</subject><subject>Cellular biology</subject><subject>Cytoprotection</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Experimental - complications</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetes Mellitus, Experimental - physiopathology</subject><subject>Diabetic Angiopathies - metabolism</subject><subject>Diabetic Angiopathies - physiopathology</subject><subject>Diabetic Angiopathies - prevention & control</subject><subject>Drug Evaluation, Preclinical</subject><subject>Endothelium</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - physiopathology</subject><subject>Humans</subject><subject>Male</subject><subject>Mice</subject><subject>Physiology</subject><subject>Pigments</subject><subject>Rats</subject><issn>0193-1849</issn><issn>1522-1555</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kMtOwzAQRS0EoqXwAyxQJNYpfideVoiXVIkNrCPHGVNXqVNsZ9G_x6GF1Yyu750ZH4RuCV4SIuiD3u7Bd8MSY6nUkmLCztA8P9CSCCHO0RwTxUpSczVDVzFuMcaV4PQSzSgXSjDM5sitfNoM5qC984XzJoCOEAvduf3gwaSsRshqcoMvtO-KfRhS1rPlSzsfU9E53UKCWAbodYKumG5KG-id7ovuEO3ozZS-RhdW9xFuTnWBPp-fPh5fy_X7y9vjal0aJnkqK8VBsxosrtss8NxQga2xppOVBCm1kbxuOeOWUgBmmWhpxXVrlBIqf3iB7o9z86XfI8TUbIcx-LyyIYIoSTFlIrvo0WXCEGMA2-yD2-lwaAhuJrrNiW7zS7eZ6ObQ3Wn02O6g-4_84WQ_khZ52A</recordid><startdate>20140415</startdate><enddate>20140415</enddate><creator>Liu, Yan</creator><creator>Li, Dan</creator><creator>Zhang, Yuhua</creator><creator>Sun, Ruifang</creator><creator>Xia, Min</creator><general>American Physiological 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>7QP</scope><scope>7TS</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20140415</creationdate><title>Anthocyanin increases adiponectin secretion and protects against diabetes-related endothelial dysfunction</title><author>Liu, Yan ; Li, Dan ; Zhang, Yuhua ; Sun, Ruifang ; Xia, Min</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c364t-794ea38ef08b3644ef0250fcfcd676e66ac648b434f22ee3f35b274abc9959193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>3T3-L1 Cells</topic><topic>Adipocytes</topic><topic>Adiponectin - secretion</topic><topic>Animals</topic><topic>Anthocyanins - pharmacology</topic><topic>Cardiovascular Diseases - metabolism</topic><topic>Cardiovascular Diseases - physiopathology</topic><topic>Cardiovascular Diseases - prevention & control</topic><topic>Cells, Cultured</topic><topic>Cellular biology</topic><topic>Cytoprotection</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Experimental - complications</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetes Mellitus, Experimental - physiopathology</topic><topic>Diabetic Angiopathies - metabolism</topic><topic>Diabetic Angiopathies - physiopathology</topic><topic>Diabetic Angiopathies - prevention & control</topic><topic>Drug Evaluation, Preclinical</topic><topic>Endothelium</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - physiopathology</topic><topic>Humans</topic><topic>Male</topic><topic>Mice</topic><topic>Physiology</topic><topic>Pigments</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Yan</creatorcontrib><creatorcontrib>Li, Dan</creatorcontrib><creatorcontrib>Zhang, Yuhua</creatorcontrib><creatorcontrib>Sun, Ruifang</creatorcontrib><creatorcontrib>Xia, Min</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>American journal of physiology: endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Yan</au><au>Li, Dan</au><au>Zhang, Yuhua</au><au>Sun, Ruifang</au><au>Xia, Min</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anthocyanin increases adiponectin secretion and protects against diabetes-related endothelial dysfunction</atitle><jtitle>American journal of physiology: endocrinology and metabolism</jtitle><addtitle>Am J Physiol Endocrinol Metab</addtitle><date>2014-04-15</date><risdate>2014</risdate><volume>306</volume><issue>8</issue><spage>E975</spage><epage>E988</epage><pages>E975-E988</pages><issn>0193-1849</issn><eissn>1522-1555</eissn><coden>AJPMD9</coden><abstract>Adiponectin is an adipose tissue-secreted adipokine with beneficial effects on the cardiovascular system. In this study, we evaluated a potential role for adiponectin in the protective effects of anthocyanin on diabetes-related endothelial dysfunction. We treated db/db mice on a normal diet with anthocyanin cyanidin-3-O-β-glucoside (C3G; 2 g/kg diet) for 8 wk. Endothelium-dependent and -independent relaxations of the aorta were then evaluated. Adiponectin expression and secretion were also measured. C3G treatment restores endothelium-dependent relaxation of the aorta in db/db mice, whereas diabetic mice treated with an anti-adiponectin antibody do not respond. C3G treatment induces adiponectin expression and secretion in cultured 3T3 adipocytes through transcription factor forkhead box O1 (Foxo1). Silencing Foxo1 expression prevented C3G-stimulated induction of adiponectin expression. In contrast, overexpression of Foxo1-ADA promoted adiponectin expression in adipocytes. C3G activates Foxo1 by increasing its deacetylation via silent mating type information regulation 2 homolog 1 (Sirt1). Furthermore, purified anthocyanin supplementation significantly improved flow-mediated dilation (FMD) and increased serum adiponectin concentrations in patients with type 2 diabetes. Changes in adiponectin concentrations positively correlated with FMD in the anthocyanin group. Mechanistically, adiponectin activates cAMP-PKA-eNOS signaling pathways in human aortic endothelial cells, increasing endothelial nitric oxide bioavailability. These results demonstrate that adipocyte-derived adiponectin is required for anthocyanin C3G-mediated improvement of endothelial function in diabetes.</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>24595303</pmid><doi>10.1152/ajpendo.00699.2013</doi></addata></record> |
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subjects | 3T3-L1 Cells Adipocytes Adiponectin - secretion Animals Anthocyanins - pharmacology Cardiovascular Diseases - metabolism Cardiovascular Diseases - physiopathology Cardiovascular Diseases - prevention & control Cells, Cultured Cellular biology Cytoprotection Diabetes Diabetes Mellitus, Experimental - complications Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Experimental - physiopathology Diabetic Angiopathies - metabolism Diabetic Angiopathies - physiopathology Diabetic Angiopathies - prevention & control Drug Evaluation, Preclinical Endothelium Endothelium, Vascular - drug effects Endothelium, Vascular - physiopathology Humans Male Mice Physiology Pigments Rats |
title | Anthocyanin increases adiponectin secretion and protects against diabetes-related endothelial dysfunction |
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