Effects of Pharmacological Thermogenic Adipocyte Activation on Metabolism and Atherosclerotic Plaque Regression
Thermogenic adipocytes burn nutrients in order to produce heat. Upon activation, brown adipose tissue (BAT) clears vast amounts of lipids and glucose from the circulation and thus substantially lowers plasma lipid levels. As a consequence, BAT activation protects from the development of atherosclero...
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| Veröffentlicht in: | Nutrients 2019-02, Vol.11 (2), p.463 |
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| description | Thermogenic adipocytes burn nutrients in order to produce heat. Upon activation, brown adipose tissue (BAT) clears vast amounts of lipids and glucose from the circulation and thus substantially lowers plasma lipid levels. As a consequence, BAT activation protects from the development of atherosclerosis. However, it is unclear if pharmacologic activation of BAT can be exploited therapeutically to reduce plaque burden in established atherosclerotic disease. Here we study the impact of thermogenic adipose tissues on plaque regression in a mouse model of atherosclerosis. Thermogenic adipocytes in atherosclerotic low-density lipoprotein (LDL) receptor (LDLR)-deficient mice were pharmacologically activated by dietary CL316,243 (CL) treatment for 4 weeks and the outcomes on metabolically active tissues, plasma lipids and atherosclerosis were analyzed. While the chronic activation of thermogenic adipocytes reduced adiposity, increased browning of white adipose tissue (WAT), altered liver gene expression, and reduced plasma triglyceride levels, atherosclerotic plaque burden remained unchanged. Our findings suggest that despite improving adiposity and plasma triglycerides, pharmacologic activation of thermogenic adipocytes is not able to reverse atherosclerosis in LDLR-deficient mice. |
| doi_str_mv | 10.3390/nu11020463 |
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Upon activation, brown adipose tissue (BAT) clears vast amounts of lipids and glucose from the circulation and thus substantially lowers plasma lipid levels. As a consequence, BAT activation protects from the development of atherosclerosis. However, it is unclear if pharmacologic activation of BAT can be exploited therapeutically to reduce plaque burden in established atherosclerotic disease. Here we study the impact of thermogenic adipose tissues on plaque regression in a mouse model of atherosclerosis. Thermogenic adipocytes in atherosclerotic low-density lipoprotein (LDL) receptor (LDLR)-deficient mice were pharmacologically activated by dietary CL316,243 (CL) treatment for 4 weeks and the outcomes on metabolically active tissues, plasma lipids and atherosclerosis were analyzed. While the chronic activation of thermogenic adipocytes reduced adiposity, increased browning of white adipose tissue (WAT), altered liver gene expression, and reduced plasma triglyceride levels, atherosclerotic plaque burden remained unchanged. Our findings suggest that despite improving adiposity and plasma triglycerides, pharmacologic activation of thermogenic adipocytes is not able to reverse atherosclerosis in LDLR-deficient mice.</description><identifier>ISSN: 2072-6643</identifier><identifier>EISSN: 2072-6643</identifier><identifier>DOI: 10.3390/nu11020463</identifier><identifier>PMID: 30813320</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Activation ; Adipocytes ; adiposity ; animal models ; Apolipoproteins ; Arteriosclerosis ; Atherosclerosis ; blood lipids ; Body fat ; Body weight ; brown adipose tissue ; Cholesterol ; Cold ; Communication ; Deceleration ; Diet ; Experiments ; Gene expression ; glucose ; heat ; High cholesterol diet ; High fat diet ; Hypercholesterolemia ; Lipids ; Lipoproteins ; Liver ; low density lipoprotein ; Metabolism ; mice ; Nutrient deficiency ; nutrients ; Pharmacology ; Rodents ; Sucrose ; Sugar ; triacylglycerols ; Triglycerides ; white adipose tissue</subject><ispartof>Nutrients, 2019-02, Vol.11 (2), p.463</ispartof><rights>2019. 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>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-56c036f1e8f2c97e0a7153c77e1a71cb13ffc2f5ed221efa3da739954608f45b3</citedby><cites>FETCH-LOGICAL-c439t-56c036f1e8f2c97e0a7153c77e1a71cb13ffc2f5ed221efa3da739954608f45b3</cites><orcidid>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/PMC6412269/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412269/$$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/30813320$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Worthmann, Anna</creatorcontrib><creatorcontrib>Schlein, Christian</creatorcontrib><creatorcontrib>Berbée, Jimmy F P</creatorcontrib><creatorcontrib>Rensen, Patrick C N</creatorcontrib><creatorcontrib>Heeren, Joerg</creatorcontrib><creatorcontrib>Bartelt, Alexander</creatorcontrib><title>Effects of Pharmacological Thermogenic Adipocyte Activation on Metabolism and Atherosclerotic Plaque Regression</title><title>Nutrients</title><addtitle>Nutrients</addtitle><description>Thermogenic adipocytes burn nutrients in order to produce heat. Upon activation, brown adipose tissue (BAT) clears vast amounts of lipids and glucose from the circulation and thus substantially lowers plasma lipid levels. As a consequence, BAT activation protects from the development of atherosclerosis. However, it is unclear if pharmacologic activation of BAT can be exploited therapeutically to reduce plaque burden in established atherosclerotic disease. Here we study the impact of thermogenic adipose tissues on plaque regression in a mouse model of atherosclerosis. Thermogenic adipocytes in atherosclerotic low-density lipoprotein (LDL) receptor (LDLR)-deficient mice were pharmacologically activated by dietary CL316,243 (CL) treatment for 4 weeks and the outcomes on metabolically active tissues, plasma lipids and atherosclerosis were analyzed. While the chronic activation of thermogenic adipocytes reduced adiposity, increased browning of white adipose tissue (WAT), altered liver gene expression, and reduced plasma triglyceride levels, atherosclerotic plaque burden remained unchanged. Our findings suggest that despite improving adiposity and plasma triglycerides, pharmacologic activation of thermogenic adipocytes is not able to reverse atherosclerosis in LDLR-deficient mice.</description><subject>Activation</subject><subject>Adipocytes</subject><subject>adiposity</subject><subject>animal models</subject><subject>Apolipoproteins</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>blood lipids</subject><subject>Body fat</subject><subject>Body weight</subject><subject>brown adipose tissue</subject><subject>Cholesterol</subject><subject>Cold</subject><subject>Communication</subject><subject>Deceleration</subject><subject>Diet</subject><subject>Experiments</subject><subject>Gene expression</subject><subject>glucose</subject><subject>heat</subject><subject>High cholesterol diet</subject><subject>High fat diet</subject><subject>Hypercholesterolemia</subject><subject>Lipids</subject><subject>Lipoproteins</subject><subject>Liver</subject><subject>low density lipoprotein</subject><subject>Metabolism</subject><subject>mice</subject><subject>Nutrient deficiency</subject><subject>nutrients</subject><subject>Pharmacology</subject><subject>Rodents</subject><subject>Sucrose</subject><subject>Sugar</subject><subject>triacylglycerols</subject><subject>Triglycerides</subject><subject>white adipose tissue</subject><issn>2072-6643</issn><issn>2072-6643</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNqFkVFrFDEUhYMottS--AMk4IsIq0luJpl5EZZSbaFikfocspmb3ZTMZE0yhf57U1pr9cUQkgv57iHnHkJec_YBYGAf54VzJphU8IwcCqbFSikJz5_UB-S4lGt2tzTTCl6SA2A9BxDskKRT79HVQpOnlzubJ-tSTNvgbKRXO8xT2uIcHF2PYZ_cbUW6djXc2BrSTNv-itVuUgxlonYe6bq2nlRcbGdtbZfR_lyQfsdtxlJazyvywttY8PjhPiI_Pp9enZytLr59OT9ZX6ychKGuOuUYKM-x98INGpnVvAOnNfJWuQ0H753wHY5CcPQWRqthGDqpWO9lt4Ej8uled79sJhwdzjXbaPY5TDbfmmSD-ftlDjuzTTdGSS6EGprAuweBnJqFUs0UisMY7YxpKUaIXg2sA9n_H-W9ZkJyCQ19-w96nZY8t0kYAc0hZ32vG_X-nnJtliWjf_w3Z-YudfMn9Qa_eer0Ef2dMfwCGeyo0w</recordid><startdate>20190223</startdate><enddate>20190223</enddate><creator>Worthmann, Anna</creator><creator>Schlein, Christian</creator><creator>Berbée, Jimmy F P</creator><creator>Rensen, Patrick C N</creator><creator>Heeren, Joerg</creator><creator>Bartelt, Alexander</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</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>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8455-4988</orcidid></search><sort><creationdate>20190223</creationdate><title>Effects of Pharmacological Thermogenic Adipocyte Activation on Metabolism and Atherosclerotic Plaque Regression</title><author>Worthmann, Anna ; Schlein, Christian ; Berbée, Jimmy F P ; Rensen, Patrick C N ; Heeren, Joerg ; Bartelt, Alexander</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-56c036f1e8f2c97e0a7153c77e1a71cb13ffc2f5ed221efa3da739954608f45b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Activation</topic><topic>Adipocytes</topic><topic>adiposity</topic><topic>animal models</topic><topic>Apolipoproteins</topic><topic>Arteriosclerosis</topic><topic>Atherosclerosis</topic><topic>blood lipids</topic><topic>Body fat</topic><topic>Body weight</topic><topic>brown adipose tissue</topic><topic>Cholesterol</topic><topic>Cold</topic><topic>Communication</topic><topic>Deceleration</topic><topic>Diet</topic><topic>Experiments</topic><topic>Gene expression</topic><topic>glucose</topic><topic>heat</topic><topic>High cholesterol diet</topic><topic>High fat diet</topic><topic>Hypercholesterolemia</topic><topic>Lipids</topic><topic>Lipoproteins</topic><topic>Liver</topic><topic>low density lipoprotein</topic><topic>Metabolism</topic><topic>mice</topic><topic>Nutrient deficiency</topic><topic>nutrients</topic><topic>Pharmacology</topic><topic>Rodents</topic><topic>Sucrose</topic><topic>Sugar</topic><topic>triacylglycerols</topic><topic>Triglycerides</topic><topic>white adipose tissue</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Worthmann, Anna</creatorcontrib><creatorcontrib>Schlein, Christian</creatorcontrib><creatorcontrib>Berbée, Jimmy F P</creatorcontrib><creatorcontrib>Rensen, Patrick C N</creatorcontrib><creatorcontrib>Heeren, Joerg</creatorcontrib><creatorcontrib>Bartelt, Alexander</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Physical Education Index</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>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 Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</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>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nutrients</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Worthmann, Anna</au><au>Schlein, Christian</au><au>Berbée, Jimmy F P</au><au>Rensen, Patrick C N</au><au>Heeren, Joerg</au><au>Bartelt, Alexander</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Pharmacological Thermogenic Adipocyte Activation on Metabolism and Atherosclerotic Plaque Regression</atitle><jtitle>Nutrients</jtitle><addtitle>Nutrients</addtitle><date>2019-02-23</date><risdate>2019</risdate><volume>11</volume><issue>2</issue><spage>463</spage><pages>463-</pages><issn>2072-6643</issn><eissn>2072-6643</eissn><abstract>Thermogenic adipocytes burn nutrients in order to produce heat. Upon activation, brown adipose tissue (BAT) clears vast amounts of lipids and glucose from the circulation and thus substantially lowers plasma lipid levels. As a consequence, BAT activation protects from the development of atherosclerosis. However, it is unclear if pharmacologic activation of BAT can be exploited therapeutically to reduce plaque burden in established atherosclerotic disease. Here we study the impact of thermogenic adipose tissues on plaque regression in a mouse model of atherosclerosis. Thermogenic adipocytes in atherosclerotic low-density lipoprotein (LDL) receptor (LDLR)-deficient mice were pharmacologically activated by dietary CL316,243 (CL) treatment for 4 weeks and the outcomes on metabolically active tissues, plasma lipids and atherosclerosis were analyzed. While the chronic activation of thermogenic adipocytes reduced adiposity, increased browning of white adipose tissue (WAT), altered liver gene expression, and reduced plasma triglyceride levels, atherosclerotic plaque burden remained unchanged. Our findings suggest that despite improving adiposity and plasma triglycerides, pharmacologic activation of thermogenic adipocytes is not able to reverse atherosclerosis in LDLR-deficient mice.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>30813320</pmid><doi>10.3390/nu11020463</doi><orcidid>https://orcid.org/0000-0002-8455-4988</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Activation Adipocytes adiposity animal models Apolipoproteins Arteriosclerosis Atherosclerosis blood lipids Body fat Body weight brown adipose tissue Cholesterol Cold Communication Deceleration Diet Experiments Gene expression glucose heat High cholesterol diet High fat diet Hypercholesterolemia Lipids Lipoproteins Liver low density lipoprotein Metabolism mice Nutrient deficiency nutrients Pharmacology Rodents Sucrose Sugar triacylglycerols Triglycerides white adipose tissue |
| title | Effects of Pharmacological Thermogenic Adipocyte Activation on Metabolism and Atherosclerotic Plaque Regression |
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