Effects of age and soybean isoflavones on hepatic cholesterol metabolism and thyroid hormone availability in acyclic female rats
Soy-food and its isoflavones, genistein (G) and daidzein (D), were reported to exert mild cholesterol-lowering effect, but the underlying mechanism is still unclear. In this research, first we studied age-related alterations in hepatic cholesterol metabolism of acyclic middle-aged (MA) female rats....
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| Veröffentlicht in: | Experimental gerontology 2017-06, Vol.92, p.74-81 |
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| creator | Šošić-Jurjević, Branka Lütjohann, Dieter Jarić, Ivana Miler, Marko Vojnović Milutinović, Danijela Filipović, Branko Ajdžanović, Vladimir Renko, Kostja Wirth, Eva Katrin Janković, Snežana Kӧhrle, Josef Milošević, Verica |
| description | Soy-food and its isoflavones, genistein (G) and daidzein (D), were reported to exert mild cholesterol-lowering effect, but the underlying mechanism is still unclear. In this research, first we studied age-related alterations in hepatic cholesterol metabolism of acyclic middle-aged (MA) female rats. Then we tested if purified isoflavones may prevent or reverse these changes, and whether putative changes in hepatic thyroid hormone availability may be associated with this effect. Serum and hepatic total cholesterol (TChol), bile acid and cholesterol precursors, as well as serum TSH and T4 concentrations, hepatic deiodinase (Dio) 1 enzyme activity and MCT8 protein expression were determined by comparing data obtained for MA with young adult (YA) intact (IC) females. Effects of subcutaneously administered G or D (35mg/kg) to MA rats were evaluated versus vehicle-treated MA females. MA IC females were characterized by: higher (p |
| doi_str_mv | 10.1016/j.exger.2017.03.016 |
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•Age-related hypercholesteremia in middle-aged acyclic female rats (13-month-old) is associated with:(i) lower hepatic cholesterol biosynthesis and(ii) shift from neutral to acydic pathway of cholesterol degradation to bile acid in the liver.(iii) unchanged TSH and total T4 in serum, as well as Dio1 enzyme activity and MCT8 protein expression in the liver•Soy isoflavones reversed only hepatic 27-hydroxycholesterol to the level of young adults.•Only genistein elevated hepatic Dio1 activity, thus indicating local increase in thyroid hormones.]]></description><identifier>ISSN: 0531-5565</identifier><identifier>EISSN: 1873-6815</identifier><identifier>DOI: 10.1016/j.exger.2017.03.016</identifier><identifier>PMID: 28336316</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>Aging ; Animals ; Body Weight - drug effects ; Cholesterol metabolism ; Daidzein ; Female ; Genistein ; Glycine max - chemistry ; Hydroxycholesterols - blood ; Hydroxycholesterols - metabolism ; Isoflavones ; Isoflavones - pharmacology ; Lipid Metabolism - drug effects ; Liver ; Liver - drug effects ; Liver - metabolism ; Organ Size - drug effects ; Phytoestrogens - pharmacology ; Rats ; Rats, Wistar ; Thyroid ; Thyroid Hormones - blood</subject><ispartof>Experimental gerontology, 2017-06, Vol.92, p.74-81</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c359t-225d6f13a6e8ffe98e4c7147e3593dde0c2ed7359f0059942fe9780a2b7d68413</citedby><cites>FETCH-LOGICAL-c359t-225d6f13a6e8ffe98e4c7147e3593dde0c2ed7359f0059942fe9780a2b7d68413</cites><orcidid>0000-0002-0491-9941</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.exger.2017.03.016$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28336316$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Šošić-Jurjević, Branka</creatorcontrib><creatorcontrib>Lütjohann, Dieter</creatorcontrib><creatorcontrib>Jarić, Ivana</creatorcontrib><creatorcontrib>Miler, Marko</creatorcontrib><creatorcontrib>Vojnović Milutinović, Danijela</creatorcontrib><creatorcontrib>Filipović, Branko</creatorcontrib><creatorcontrib>Ajdžanović, Vladimir</creatorcontrib><creatorcontrib>Renko, Kostja</creatorcontrib><creatorcontrib>Wirth, Eva Katrin</creatorcontrib><creatorcontrib>Janković, Snežana</creatorcontrib><creatorcontrib>Kӧhrle, Josef</creatorcontrib><creatorcontrib>Milošević, Verica</creatorcontrib><title>Effects of age and soybean isoflavones on hepatic cholesterol metabolism and thyroid hormone availability in acyclic female rats</title><title>Experimental gerontology</title><addtitle>Exp Gerontol</addtitle><description><![CDATA[Soy-food and its isoflavones, genistein (G) and daidzein (D), were reported to exert mild cholesterol-lowering effect, but the underlying mechanism is still unclear. In this research, first we studied age-related alterations in hepatic cholesterol metabolism of acyclic middle-aged (MA) female rats. Then we tested if purified isoflavones may prevent or reverse these changes, and whether putative changes in hepatic thyroid hormone availability may be associated with this effect. Serum and hepatic total cholesterol (TChol), bile acid and cholesterol precursors, as well as serum TSH and T4 concentrations, hepatic deiodinase (Dio) 1 enzyme activity and MCT8 protein expression were determined by comparing data obtained for MA with young adult (YA) intact (IC) females. Effects of subcutaneously administered G or D (35mg/kg) to MA rats were evaluated versus vehicle-treated MA females. MA IC females were characterized by: higher (p<0.05) serum TChol, lower (p<0.05) hepatic TChol and its biosynthetic precursors, lower (p<0.05) hepatic 7α-hydroxycholesterol but elevated (p<0.05) 27- and 24-hydroxycholesterol in comparison to YA IC. Both isoflavone treatments decreased (p<0.05) hepatic 27-hydroxycholesterol, G being more effective than D, without affecting any other parameter of Chol metabolism. Only G elevated hepatic Dio1 activity (p<0.05). In conclusion, age-related hypercholesteremia was associated with lower hepatic Chol synthesis and shift from main neutral (lower 7α-hydroxycholesterol) to alternative acidic pathway (higher 27-hydroxycholesterol) of Chol degradation to bile acid. Both isoflavones lowered hepatic 27-hydroxycholesterol, which may be considered beneficial. Only G treatment increased hepatic Dio1 activity, thus indicating local increase in thyroid hormones, obviously insufficient to induce prominent cholesterol-lowering effect.
•Age-related hypercholesteremia in middle-aged acyclic female rats (13-month-old) is associated with:(i) lower hepatic cholesterol biosynthesis and(ii) shift from neutral to acydic pathway of cholesterol degradation to bile acid in the liver.(iii) unchanged TSH and total T4 in serum, as well as Dio1 enzyme activity and MCT8 protein expression in the liver•Soy isoflavones reversed only hepatic 27-hydroxycholesterol to the level of young adults.•Only genistein elevated hepatic Dio1 activity, thus indicating local increase in thyroid hormones.]]></description><subject>Aging</subject><subject>Animals</subject><subject>Body Weight - drug effects</subject><subject>Cholesterol metabolism</subject><subject>Daidzein</subject><subject>Female</subject><subject>Genistein</subject><subject>Glycine max - chemistry</subject><subject>Hydroxycholesterols - blood</subject><subject>Hydroxycholesterols - metabolism</subject><subject>Isoflavones</subject><subject>Isoflavones - pharmacology</subject><subject>Lipid Metabolism - drug effects</subject><subject>Liver</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Organ Size - drug effects</subject><subject>Phytoestrogens - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Thyroid</subject><subject>Thyroid Hormones - blood</subject><issn>0531-5565</issn><issn>1873-6815</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1P3DAQhq2Kqiy0v6BS5SOXpP5YO86BA0K0RULqpT1bjj1mvXLixc6uyI2fXsMCx55GnnmfmfE7CH2lpKWEyu_bFh7vIbeM0K4lvK25D2hFVccbqag4QSsiOG2EkOIUnZWyJYRIxukndMoU55JTuUJPN96DnQtOHpt7wGZyuKRlADPhUJKP5pAmqOUJb2Bn5mCx3aQIZYacIh5hNkOKoYwv5LxZcgoOb1IeK4bNwYRohhDDvOAwYWMXG2sLD6OJgLOZy2f00ZtY4MtrPEd_f9z8uf7V3P3-eXt9dddYLvq5YUw46Sk3ElTduFewth1dd1Cr3DkgloHr6sMTIvp-zaqmU8SwoXNSrSk_RxfHvrucHvZ1fz2GYiFGM0HaF02VokzSXvAq5UepzamUDF7vchhNXjQl-tl6vdUv1utn6zXhuuYq9e11wH4Ywb0zb15XweVRAPWbh1DxYgNMFlzI9QTapfDfAf8A-emYNg</recordid><startdate>201706</startdate><enddate>201706</enddate><creator>Šošić-Jurjević, Branka</creator><creator>Lütjohann, Dieter</creator><creator>Jarić, Ivana</creator><creator>Miler, Marko</creator><creator>Vojnović Milutinović, Danijela</creator><creator>Filipović, Branko</creator><creator>Ajdžanović, Vladimir</creator><creator>Renko, Kostja</creator><creator>Wirth, Eva Katrin</creator><creator>Janković, Snežana</creator><creator>Kӧhrle, Josef</creator><creator>Milošević, Verica</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><orcidid>https://orcid.org/0000-0002-0491-9941</orcidid></search><sort><creationdate>201706</creationdate><title>Effects of age and soybean isoflavones on hepatic cholesterol metabolism and thyroid hormone availability in acyclic female rats</title><author>Šošić-Jurjević, Branka ; Lütjohann, Dieter ; Jarić, Ivana ; Miler, Marko ; Vojnović Milutinović, Danijela ; Filipović, Branko ; Ajdžanović, Vladimir ; Renko, Kostja ; Wirth, Eva Katrin ; Janković, Snežana ; Kӧhrle, Josef ; Milošević, Verica</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-225d6f13a6e8ffe98e4c7147e3593dde0c2ed7359f0059942fe9780a2b7d68413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aging</topic><topic>Animals</topic><topic>Body Weight - drug effects</topic><topic>Cholesterol metabolism</topic><topic>Daidzein</topic><topic>Female</topic><topic>Genistein</topic><topic>Glycine max - chemistry</topic><topic>Hydroxycholesterols - blood</topic><topic>Hydroxycholesterols - metabolism</topic><topic>Isoflavones</topic><topic>Isoflavones - pharmacology</topic><topic>Lipid Metabolism - drug effects</topic><topic>Liver</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Organ Size - drug effects</topic><topic>Phytoestrogens - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Thyroid</topic><topic>Thyroid Hormones - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Šošić-Jurjević, Branka</creatorcontrib><creatorcontrib>Lütjohann, Dieter</creatorcontrib><creatorcontrib>Jarić, Ivana</creatorcontrib><creatorcontrib>Miler, Marko</creatorcontrib><creatorcontrib>Vojnović Milutinović, Danijela</creatorcontrib><creatorcontrib>Filipović, Branko</creatorcontrib><creatorcontrib>Ajdžanović, Vladimir</creatorcontrib><creatorcontrib>Renko, Kostja</creatorcontrib><creatorcontrib>Wirth, Eva Katrin</creatorcontrib><creatorcontrib>Janković, Snežana</creatorcontrib><creatorcontrib>Kӧhrle, Josef</creatorcontrib><creatorcontrib>Milošević, Verica</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>Experimental gerontology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Šošić-Jurjević, Branka</au><au>Lütjohann, Dieter</au><au>Jarić, Ivana</au><au>Miler, Marko</au><au>Vojnović Milutinović, Danijela</au><au>Filipović, Branko</au><au>Ajdžanović, Vladimir</au><au>Renko, Kostja</au><au>Wirth, Eva Katrin</au><au>Janković, Snežana</au><au>Kӧhrle, Josef</au><au>Milošević, Verica</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of age and soybean isoflavones on hepatic cholesterol metabolism and thyroid hormone availability in acyclic female rats</atitle><jtitle>Experimental gerontology</jtitle><addtitle>Exp Gerontol</addtitle><date>2017-06</date><risdate>2017</risdate><volume>92</volume><spage>74</spage><epage>81</epage><pages>74-81</pages><issn>0531-5565</issn><eissn>1873-6815</eissn><abstract><![CDATA[Soy-food and its isoflavones, genistein (G) and daidzein (D), were reported to exert mild cholesterol-lowering effect, but the underlying mechanism is still unclear. In this research, first we studied age-related alterations in hepatic cholesterol metabolism of acyclic middle-aged (MA) female rats. Then we tested if purified isoflavones may prevent or reverse these changes, and whether putative changes in hepatic thyroid hormone availability may be associated with this effect. Serum and hepatic total cholesterol (TChol), bile acid and cholesterol precursors, as well as serum TSH and T4 concentrations, hepatic deiodinase (Dio) 1 enzyme activity and MCT8 protein expression were determined by comparing data obtained for MA with young adult (YA) intact (IC) females. Effects of subcutaneously administered G or D (35mg/kg) to MA rats were evaluated versus vehicle-treated MA females. MA IC females were characterized by: higher (p<0.05) serum TChol, lower (p<0.05) hepatic TChol and its biosynthetic precursors, lower (p<0.05) hepatic 7α-hydroxycholesterol but elevated (p<0.05) 27- and 24-hydroxycholesterol in comparison to YA IC. Both isoflavone treatments decreased (p<0.05) hepatic 27-hydroxycholesterol, G being more effective than D, without affecting any other parameter of Chol metabolism. Only G elevated hepatic Dio1 activity (p<0.05). In conclusion, age-related hypercholesteremia was associated with lower hepatic Chol synthesis and shift from main neutral (lower 7α-hydroxycholesterol) to alternative acidic pathway (higher 27-hydroxycholesterol) of Chol degradation to bile acid. Both isoflavones lowered hepatic 27-hydroxycholesterol, which may be considered beneficial. Only G treatment increased hepatic Dio1 activity, thus indicating local increase in thyroid hormones, obviously insufficient to induce prominent cholesterol-lowering effect.
•Age-related hypercholesteremia in middle-aged acyclic female rats (13-month-old) is associated with:(i) lower hepatic cholesterol biosynthesis and(ii) shift from neutral to acydic pathway of cholesterol degradation to bile acid in the liver.(iii) unchanged TSH and total T4 in serum, as well as Dio1 enzyme activity and MCT8 protein expression in the liver•Soy isoflavones reversed only hepatic 27-hydroxycholesterol to the level of young adults.•Only genistein elevated hepatic Dio1 activity, thus indicating local increase in thyroid hormones.]]></abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>28336316</pmid><doi>10.1016/j.exger.2017.03.016</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-0491-9941</orcidid></addata></record> |
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| ispartof | Experimental gerontology, 2017-06, Vol.92, p.74-81 |
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| subjects | Aging Animals Body Weight - drug effects Cholesterol metabolism Daidzein Female Genistein Glycine max - chemistry Hydroxycholesterols - blood Hydroxycholesterols - metabolism Isoflavones Isoflavones - pharmacology Lipid Metabolism - drug effects Liver Liver - drug effects Liver - metabolism Organ Size - drug effects Phytoestrogens - pharmacology Rats Rats, Wistar Thyroid Thyroid Hormones - blood |
| title | Effects of age and soybean isoflavones on hepatic cholesterol metabolism and thyroid hormone availability in acyclic female rats |
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