Quercetin Lowers Plasma Triglycerides Accompanied by White Adipose Tissue Browning in Diet-Induced Obese Mice
Obesity and dyslipidemia are major risk factors for the development of cardiovascular diseases (CVD). Quercetin, a natural flavonoid, lowers plasma triglycerides (TG) in human intervention studies, and its intake is associated with lower CVD risk. The aim of this study was to elucidate the mechanism...
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| Veröffentlicht in: | International journal of molecular sciences 2018-06, Vol.19 (6), p.1786 |
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| creator | Kuipers, Eline N Dam, Andrea D van Held, Ntsiki M Mol, Isabel M Houtkooper, Riekelt H Rensen, Patrick C N Boon, Mariëtte R |
| description | Obesity and dyslipidemia are major risk factors for the development of cardiovascular diseases (CVD). Quercetin, a natural flavonoid, lowers plasma triglycerides (TG) in human intervention studies, and its intake is associated with lower CVD risk. The aim of this study was to elucidate the mechanism by which quercetin lowers plasma TG levels in diet-induced obesity. C57Bl/6J mice received a high-fat diet (45% of calories derived from fat) with or without quercetin (0.1%
/
) for 12 weeks. Quercetin decreased plasma TG levels from nine weeks onwards (−19%,
< 0.05), without affecting food intake, body composition, or energy expenditure. Mechanistically, quercetin did not reduce intestinal fatty acid (FA) absorption. Rather, quercetin induced a slight reduction in liver
expression (−13%,
< 0.05), which suggests decreased very-low density lipoprotein-TG production. Interestingly, quercetin also markedly increased the uptake of [³H]oleate, which was derived from glycerol tri[³H]oleate-labeled lipoprotein-like particles by subcutaneous white adipose tissue (sWAT, +60%,
< 0.05). Furthermore, quercetin also markedly increased mRNA expression of
(+229%,
< 0.05) and
(+138%,
< 0.05), specifically in sWAT. Accordingly, only quercetin-treated animals showed uncoupling protein-1 protein-positive cells in sWAT, which is fully compatible with increased browning. Taken together, the TG-lowering effect of quercetin may, at least in part, be due to increased TG-derived FA uptake by sWAT as a consequence of browning. |
| doi_str_mv | 10.3390/ijms19061786 |
| format | Article |
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/
) for 12 weeks. Quercetin decreased plasma TG levels from nine weeks onwards (−19%,
< 0.05), without affecting food intake, body composition, or energy expenditure. Mechanistically, quercetin did not reduce intestinal fatty acid (FA) absorption. Rather, quercetin induced a slight reduction in liver
expression (−13%,
< 0.05), which suggests decreased very-low density lipoprotein-TG production. Interestingly, quercetin also markedly increased the uptake of [³H]oleate, which was derived from glycerol tri[³H]oleate-labeled lipoprotein-like particles by subcutaneous white adipose tissue (sWAT, +60%,
< 0.05). Furthermore, quercetin also markedly increased mRNA expression of
(+229%,
< 0.05) and
(+138%,
< 0.05), specifically in sWAT. Accordingly, only quercetin-treated animals showed uncoupling protein-1 protein-positive cells in sWAT, which is fully compatible with increased browning. Taken together, the TG-lowering effect of quercetin may, at least in part, be due to increased TG-derived FA uptake by sWAT as a consequence of browning.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms19061786</identifier><identifier>PMID: 29914151</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adipose tissue ; Adipose Tissue, Brown - drug effects ; Adipose Tissue, Brown - metabolism ; Adipose Tissue, White - drug effects ; Adipose Tissue, White - metabolism ; Animals ; Antioxidants - pharmacology ; Antioxidants - therapeutic use ; Body composition ; Browning ; Calories ; Cardiovascular diseases ; Diet, High-Fat - adverse effects ; Dyslipidemia ; Energy expenditure ; Fatty Acids - metabolism ; Food composition ; Food intake ; Gene expression ; Glycerol ; High fat diet ; Intestinal Absorption ; Intestine ; Liver ; Low density lipoprotein ; Male ; Mice ; Mice, Inbred C57BL ; Obesity ; Obesity - drug therapy ; Obesity - etiology ; Obesity - metabolism ; Proteins ; Quercetin ; Quercetin - pharmacology ; Quercetin - therapeutic use ; Risk analysis ; Risk factors ; Rodents ; Triglycerides ; Triglycerides - blood ; Uncoupling Protein 1 - genetics ; Uncoupling Protein 1 - metabolism</subject><ispartof>International journal of molecular sciences, 2018-06, Vol.19 (6), p.1786</ispartof><rights>2018. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 by the authors. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-6c9c8428f1f8c1eec8c9493b0042b9d23c1af1d19c519291e30982006c72a5663</citedby><cites>FETCH-LOGICAL-c412t-6c9c8428f1f8c1eec8c9493b0042b9d23c1af1d19c519291e30982006c72a5663</cites><orcidid>0000-0003-1360-7525 ; 0000-0002-8455-4988</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032193/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032193/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29914151$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kuipers, Eline N</creatorcontrib><creatorcontrib>Dam, Andrea D van</creatorcontrib><creatorcontrib>Held, Ntsiki M</creatorcontrib><creatorcontrib>Mol, Isabel M</creatorcontrib><creatorcontrib>Houtkooper, Riekelt H</creatorcontrib><creatorcontrib>Rensen, Patrick C N</creatorcontrib><creatorcontrib>Boon, Mariëtte R</creatorcontrib><title>Quercetin Lowers Plasma Triglycerides Accompanied by White Adipose Tissue Browning in Diet-Induced Obese Mice</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Obesity and dyslipidemia are major risk factors for the development of cardiovascular diseases (CVD). Quercetin, a natural flavonoid, lowers plasma triglycerides (TG) in human intervention studies, and its intake is associated with lower CVD risk. The aim of this study was to elucidate the mechanism by which quercetin lowers plasma TG levels in diet-induced obesity. C57Bl/6J mice received a high-fat diet (45% of calories derived from fat) with or without quercetin (0.1%
/
) for 12 weeks. Quercetin decreased plasma TG levels from nine weeks onwards (−19%,
< 0.05), without affecting food intake, body composition, or energy expenditure. Mechanistically, quercetin did not reduce intestinal fatty acid (FA) absorption. Rather, quercetin induced a slight reduction in liver
expression (−13%,
< 0.05), which suggests decreased very-low density lipoprotein-TG production. Interestingly, quercetin also markedly increased the uptake of [³H]oleate, which was derived from glycerol tri[³H]oleate-labeled lipoprotein-like particles by subcutaneous white adipose tissue (sWAT, +60%,
< 0.05). Furthermore, quercetin also markedly increased mRNA expression of
(+229%,
< 0.05) and
(+138%,
< 0.05), specifically in sWAT. Accordingly, only quercetin-treated animals showed uncoupling protein-1 protein-positive cells in sWAT, which is fully compatible with increased browning. Taken together, the TG-lowering effect of quercetin may, at least in part, be due to increased TG-derived FA uptake by sWAT as a consequence of browning.</description><subject>Adipose tissue</subject><subject>Adipose Tissue, Brown - drug effects</subject><subject>Adipose Tissue, Brown - metabolism</subject><subject>Adipose Tissue, White - drug effects</subject><subject>Adipose Tissue, White - metabolism</subject><subject>Animals</subject><subject>Antioxidants - pharmacology</subject><subject>Antioxidants - therapeutic use</subject><subject>Body composition</subject><subject>Browning</subject><subject>Calories</subject><subject>Cardiovascular diseases</subject><subject>Diet, High-Fat - adverse effects</subject><subject>Dyslipidemia</subject><subject>Energy expenditure</subject><subject>Fatty Acids - metabolism</subject><subject>Food composition</subject><subject>Food intake</subject><subject>Gene expression</subject><subject>Glycerol</subject><subject>High fat diet</subject><subject>Intestinal Absorption</subject><subject>Intestine</subject><subject>Liver</subject><subject>Low density lipoprotein</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Obesity</subject><subject>Obesity - drug therapy</subject><subject>Obesity - etiology</subject><subject>Obesity - metabolism</subject><subject>Proteins</subject><subject>Quercetin</subject><subject>Quercetin - pharmacology</subject><subject>Quercetin - therapeutic use</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Triglycerides</subject><subject>Triglycerides - blood</subject><subject>Uncoupling Protein 1 - genetics</subject><subject>Uncoupling Protein 1 - metabolism</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkU2LFDEQhoMo7rp68ywBLx5sTSX9lYswrl8LI6sw4jGkq6tnM3Qns0m3y_x7I7suo6cU5KmHenkZew7ijVJavHW7KYEWNTRt_YCdQillIUTdPDyaT9iTlHZCSCUr_ZidSK2hhApO2fR9oYg0O8_X4YZi4t9GmybLN9FtxwNSdD0lvkIM0956Rz3vDvznlZuJr3q3D4n4xqW0EH8fw413fsuz64Ojubjw_YJ54bKjTH11SE_Zo8GOiZ7dvWfsx6ePm_Mvxfry88X5al1gCXIuatTYlrIdYGgRiLBFXWrVCVHKTvdSIdgBetBYgZYaSAndyhwUG2mrulZn7N2td790E_VIfo52NPvoJhsPJlhn_v3x7spswy9TCyVBqyx4dSeI4XqhNJvJJaRxtJ7CkowUVQNQSWgy-vI_dBeW6HM8I0G0ZdOUWmfq9S2FMaQUabg_BoT506M57jHjL44D3MN_i1O_AVdfmVg</recordid><startdate>20180616</startdate><enddate>20180616</enddate><creator>Kuipers, Eline N</creator><creator>Dam, Andrea D van</creator><creator>Held, Ntsiki M</creator><creator>Mol, Isabel M</creator><creator>Houtkooper, Riekelt H</creator><creator>Rensen, Patrick C N</creator><creator>Boon, Mariëtte R</creator><general>MDPI AG</general><general>MDPI</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>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><orcidid>https://orcid.org/0000-0003-1360-7525</orcidid><orcidid>https://orcid.org/0000-0002-8455-4988</orcidid></search><sort><creationdate>20180616</creationdate><title>Quercetin Lowers Plasma Triglycerides Accompanied by White Adipose Tissue Browning in Diet-Induced Obese Mice</title><author>Kuipers, Eline N ; Dam, Andrea D van ; Held, Ntsiki M ; Mol, Isabel M ; Houtkooper, Riekelt H ; Rensen, Patrick C N ; Boon, Mariëtte R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-6c9c8428f1f8c1eec8c9493b0042b9d23c1af1d19c519291e30982006c72a5663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adipose tissue</topic><topic>Adipose Tissue, Brown - drug effects</topic><topic>Adipose Tissue, Brown - metabolism</topic><topic>Adipose Tissue, White - drug effects</topic><topic>Adipose Tissue, White - metabolism</topic><topic>Animals</topic><topic>Antioxidants - pharmacology</topic><topic>Antioxidants - therapeutic use</topic><topic>Body composition</topic><topic>Browning</topic><topic>Calories</topic><topic>Cardiovascular diseases</topic><topic>Diet, High-Fat - adverse effects</topic><topic>Dyslipidemia</topic><topic>Energy expenditure</topic><topic>Fatty Acids - metabolism</topic><topic>Food composition</topic><topic>Food intake</topic><topic>Gene expression</topic><topic>Glycerol</topic><topic>High fat diet</topic><topic>Intestinal Absorption</topic><topic>Intestine</topic><topic>Liver</topic><topic>Low density lipoprotein</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Obesity</topic><topic>Obesity - drug therapy</topic><topic>Obesity - etiology</topic><topic>Obesity - metabolism</topic><topic>Proteins</topic><topic>Quercetin</topic><topic>Quercetin - pharmacology</topic><topic>Quercetin - therapeutic use</topic><topic>Risk analysis</topic><topic>Risk factors</topic><topic>Rodents</topic><topic>Triglycerides</topic><topic>Triglycerides - blood</topic><topic>Uncoupling Protein 1 - genetics</topic><topic>Uncoupling Protein 1 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kuipers, Eline N</creatorcontrib><creatorcontrib>Dam, Andrea D van</creatorcontrib><creatorcontrib>Held, Ntsiki M</creatorcontrib><creatorcontrib>Mol, Isabel M</creatorcontrib><creatorcontrib>Houtkooper, Riekelt H</creatorcontrib><creatorcontrib>Rensen, Patrick C N</creatorcontrib><creatorcontrib>Boon, Mariëtte R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><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>Kuipers, Eline N</au><au>Dam, Andrea D van</au><au>Held, Ntsiki M</au><au>Mol, Isabel M</au><au>Houtkooper, Riekelt H</au><au>Rensen, Patrick C N</au><au>Boon, Mariëtte R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Quercetin Lowers Plasma Triglycerides Accompanied by White Adipose Tissue Browning in Diet-Induced Obese Mice</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2018-06-16</date><risdate>2018</risdate><volume>19</volume><issue>6</issue><spage>1786</spage><pages>1786-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Obesity and dyslipidemia are major risk factors for the development of cardiovascular diseases (CVD). Quercetin, a natural flavonoid, lowers plasma triglycerides (TG) in human intervention studies, and its intake is associated with lower CVD risk. The aim of this study was to elucidate the mechanism by which quercetin lowers plasma TG levels in diet-induced obesity. C57Bl/6J mice received a high-fat diet (45% of calories derived from fat) with or without quercetin (0.1%
/
) for 12 weeks. Quercetin decreased plasma TG levels from nine weeks onwards (−19%,
< 0.05), without affecting food intake, body composition, or energy expenditure. Mechanistically, quercetin did not reduce intestinal fatty acid (FA) absorption. Rather, quercetin induced a slight reduction in liver
expression (−13%,
< 0.05), which suggests decreased very-low density lipoprotein-TG production. Interestingly, quercetin also markedly increased the uptake of [³H]oleate, which was derived from glycerol tri[³H]oleate-labeled lipoprotein-like particles by subcutaneous white adipose tissue (sWAT, +60%,
< 0.05). Furthermore, quercetin also markedly increased mRNA expression of
(+229%,
< 0.05) and
(+138%,
< 0.05), specifically in sWAT. Accordingly, only quercetin-treated animals showed uncoupling protein-1 protein-positive cells in sWAT, which is fully compatible with increased browning. Taken together, the TG-lowering effect of quercetin may, at least in part, be due to increased TG-derived FA uptake by sWAT as a consequence of browning.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>29914151</pmid><doi>10.3390/ijms19061786</doi><orcidid>https://orcid.org/0000-0003-1360-7525</orcidid><orcidid>https://orcid.org/0000-0002-8455-4988</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Adipose tissue Adipose Tissue, Brown - drug effects Adipose Tissue, Brown - metabolism Adipose Tissue, White - drug effects Adipose Tissue, White - metabolism Animals Antioxidants - pharmacology Antioxidants - therapeutic use Body composition Browning Calories Cardiovascular diseases Diet, High-Fat - adverse effects Dyslipidemia Energy expenditure Fatty Acids - metabolism Food composition Food intake Gene expression Glycerol High fat diet Intestinal Absorption Intestine Liver Low density lipoprotein Male Mice Mice, Inbred C57BL Obesity Obesity - drug therapy Obesity - etiology Obesity - metabolism Proteins Quercetin Quercetin - pharmacology Quercetin - therapeutic use Risk analysis Risk factors Rodents Triglycerides Triglycerides - blood Uncoupling Protein 1 - genetics Uncoupling Protein 1 - metabolism |
| title | Quercetin Lowers Plasma Triglycerides Accompanied by White Adipose Tissue Browning in Diet-Induced Obese Mice |
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