The role of the retinoid receptor, RAR/RXR heterodimer, in liver physiology
Activated by retinoids, metabolites of vitamin A, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs) play important roles in a wide variety of biological processes, including embryo development, homeostasis, cell proliferation, differentiation and death. In this review, we summar...
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| Veröffentlicht in: | Biochimica et biophysica acta. Molecular basis of disease 2021-05, Vol.1867 (5), p.166085-166085, Article 166085 |
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| creator | Li, Baixue Cai, Shi-Ying Boyer, James L. |
| description | Activated by retinoids, metabolites of vitamin A, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs) play important roles in a wide variety of biological processes, including embryo development, homeostasis, cell proliferation, differentiation and death. In this review, we summarized the functional roles of nuclear receptor RAR/RXR heterodimers in liver physiology. Specifically, RAR/RXR modulate the synthesis and metabolism of lipids and bile acids in hepatocytes, regulate cholesterol transport in macrophages, and repress fibrogenesis in hepatic stellate cells. We have also listed the specific genes that carry these functions and how RAR/RXR regulate their expression in liver cells, providing a mechanistic view of their roles in liver physiology. Meanwhile, we pointed out many questions regarding the detailed signaling of RAR/RXR in regulating the expression of liver genes, and hope future studies will address these issues.
•RAR/RXR stimulates expression of FGF21 and FGF19, leading to increased fatty acid oxidation and reduced levels of NEFA and TG.•RAR/RXR modulates bile acid homeostasis by regulating the expression of genes involved in bile acid synthesis and transport.•RAR/RXR represses liver fibrosis by blocking hepatic stellate cell activation and proliferation.•RAR/RXR accelerates lipid metabolism in macrophages by stimulating cholesterol transport. |
| doi_str_mv | 10.1016/j.bbadis.2021.166085 |
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•RAR/RXR stimulates expression of FGF21 and FGF19, leading to increased fatty acid oxidation and reduced levels of NEFA and TG.•RAR/RXR modulates bile acid homeostasis by regulating the expression of genes involved in bile acid synthesis and transport.•RAR/RXR represses liver fibrosis by blocking hepatic stellate cell activation and proliferation.•RAR/RXR accelerates lipid metabolism in macrophages by stimulating cholesterol transport.</description><identifier>ISSN: 0925-4439</identifier><identifier>ISSN: 1879-260X</identifier><identifier>EISSN: 1879-260X</identifier><identifier>DOI: 10.1016/j.bbadis.2021.166085</identifier><identifier>PMID: 33497820</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Bile acid hemostasis ; Gene Expression Regulation ; Gene regulation ; Humans ; Lipid metabolism ; Liver - cytology ; Liver - metabolism ; Liver - physiology ; Liver fibrogenesis ; Nuclear receptors ; Protein Multimerization ; Receptors, Retinoic Acid - chemistry ; Receptors, Retinoic Acid - genetics ; Receptors, Retinoic Acid - metabolism ; Retinoic acid receptors ; Retinoid X receptors ; Retinoid X Receptors - chemistry ; Retinoid X Receptors - genetics ; Retinoid X Receptors - metabolism ; Signal Transduction</subject><ispartof>Biochimica et biophysica acta. Molecular basis of disease, 2021-05, Vol.1867 (5), p.166085-166085, Article 166085</ispartof><rights>2021 Elsevier B.V.</rights><rights>Copyright © 2021 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c418t-9603db0bf93bc233f22010d844d2df05f623faf72d3f4d2df5c4b55e3e65537b3</citedby><cites>FETCH-LOGICAL-c418t-9603db0bf93bc233f22010d844d2df05f623faf72d3f4d2df5c4b55e3e65537b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbadis.2021.166085$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33497820$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Baixue</creatorcontrib><creatorcontrib>Cai, Shi-Ying</creatorcontrib><creatorcontrib>Boyer, James L.</creatorcontrib><title>The role of the retinoid receptor, RAR/RXR heterodimer, in liver physiology</title><title>Biochimica et biophysica acta. Molecular basis of disease</title><addtitle>Biochim Biophys Acta Mol Basis Dis</addtitle><description>Activated by retinoids, metabolites of vitamin A, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs) play important roles in a wide variety of biological processes, including embryo development, homeostasis, cell proliferation, differentiation and death. In this review, we summarized the functional roles of nuclear receptor RAR/RXR heterodimers in liver physiology. Specifically, RAR/RXR modulate the synthesis and metabolism of lipids and bile acids in hepatocytes, regulate cholesterol transport in macrophages, and repress fibrogenesis in hepatic stellate cells. We have also listed the specific genes that carry these functions and how RAR/RXR regulate their expression in liver cells, providing a mechanistic view of their roles in liver physiology. Meanwhile, we pointed out many questions regarding the detailed signaling of RAR/RXR in regulating the expression of liver genes, and hope future studies will address these issues.
•RAR/RXR stimulates expression of FGF21 and FGF19, leading to increased fatty acid oxidation and reduced levels of NEFA and TG.•RAR/RXR modulates bile acid homeostasis by regulating the expression of genes involved in bile acid synthesis and transport.•RAR/RXR represses liver fibrosis by blocking hepatic stellate cell activation and proliferation.•RAR/RXR accelerates lipid metabolism in macrophages by stimulating cholesterol transport.</description><subject>Animals</subject><subject>Bile acid hemostasis</subject><subject>Gene Expression Regulation</subject><subject>Gene regulation</subject><subject>Humans</subject><subject>Lipid metabolism</subject><subject>Liver - cytology</subject><subject>Liver - metabolism</subject><subject>Liver - physiology</subject><subject>Liver fibrogenesis</subject><subject>Nuclear receptors</subject><subject>Protein Multimerization</subject><subject>Receptors, Retinoic Acid - chemistry</subject><subject>Receptors, Retinoic Acid - genetics</subject><subject>Receptors, Retinoic Acid - metabolism</subject><subject>Retinoic acid receptors</subject><subject>Retinoid X receptors</subject><subject>Retinoid X Receptors - chemistry</subject><subject>Retinoid X Receptors - genetics</subject><subject>Retinoid X Receptors - metabolism</subject><subject>Signal Transduction</subject><issn>0925-4439</issn><issn>1879-260X</issn><issn>1879-260X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1LI0EQbcRFo-s_EJmjByf298xclCB-LCsshAjempnuatNhMh27J4H8ezs7UdzL1qWKqlevivcQOid4TDCR14tx09TGxTHFlIyJlLgUB2hEyqLKqcSvh2iEKypyzll1jE5iXOAUssBH6JgxXhUlxSP0ezaHLPgWMm-zfldD7zrvTCo0rHofrrLpZHo9fZ1mc-gheOOWkJquy1q3gZCt5tvofOvftj_RD1u3Ec72-RS9PNzP7p7y5z-Pv-4mz7nmpOzzSmJmGtzYijWaMmYpxQSbknNDjcXCSspsbQtqmP3bEpo3QgADKQQrGnaKbgfe1bpZgtHQ9aFu1Sq4ZR22ytdO_Tvp3Fy9-Y0ihAiKS5kYLvcMwb-vIfZq6aKGtq078OuoKC-J5KykJEH5ANXBxxjAft0hWO2MUAs1GKF2RqjBiLR28f3Hr6VP5RPgZgBAUmrjIKioHXQajEvK98p49_8LH1aLm6w</recordid><startdate>20210501</startdate><enddate>20210501</enddate><creator>Li, Baixue</creator><creator>Cai, Shi-Ying</creator><creator>Boyer, James L.</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><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><scope>5PM</scope></search><sort><creationdate>20210501</creationdate><title>The role of the retinoid receptor, RAR/RXR heterodimer, in liver physiology</title><author>Li, Baixue ; Cai, Shi-Ying ; Boyer, James L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-9603db0bf93bc233f22010d844d2df05f623faf72d3f4d2df5c4b55e3e65537b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Bile acid hemostasis</topic><topic>Gene Expression Regulation</topic><topic>Gene regulation</topic><topic>Humans</topic><topic>Lipid metabolism</topic><topic>Liver - cytology</topic><topic>Liver - metabolism</topic><topic>Liver - physiology</topic><topic>Liver fibrogenesis</topic><topic>Nuclear receptors</topic><topic>Protein Multimerization</topic><topic>Receptors, Retinoic Acid - chemistry</topic><topic>Receptors, Retinoic Acid - genetics</topic><topic>Receptors, Retinoic Acid - metabolism</topic><topic>Retinoic acid receptors</topic><topic>Retinoid X receptors</topic><topic>Retinoid X Receptors - chemistry</topic><topic>Retinoid X Receptors - genetics</topic><topic>Retinoid X Receptors - metabolism</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Baixue</creatorcontrib><creatorcontrib>Cai, Shi-Ying</creatorcontrib><creatorcontrib>Boyer, James L.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biochimica et biophysica acta. Molecular basis of disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Baixue</au><au>Cai, Shi-Ying</au><au>Boyer, James L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The role of the retinoid receptor, RAR/RXR heterodimer, in liver physiology</atitle><jtitle>Biochimica et biophysica acta. Molecular basis of disease</jtitle><addtitle>Biochim Biophys Acta Mol Basis Dis</addtitle><date>2021-05-01</date><risdate>2021</risdate><volume>1867</volume><issue>5</issue><spage>166085</spage><epage>166085</epage><pages>166085-166085</pages><artnum>166085</artnum><issn>0925-4439</issn><issn>1879-260X</issn><eissn>1879-260X</eissn><abstract>Activated by retinoids, metabolites of vitamin A, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs) play important roles in a wide variety of biological processes, including embryo development, homeostasis, cell proliferation, differentiation and death. In this review, we summarized the functional roles of nuclear receptor RAR/RXR heterodimers in liver physiology. Specifically, RAR/RXR modulate the synthesis and metabolism of lipids and bile acids in hepatocytes, regulate cholesterol transport in macrophages, and repress fibrogenesis in hepatic stellate cells. We have also listed the specific genes that carry these functions and how RAR/RXR regulate their expression in liver cells, providing a mechanistic view of their roles in liver physiology. Meanwhile, we pointed out many questions regarding the detailed signaling of RAR/RXR in regulating the expression of liver genes, and hope future studies will address these issues.
•RAR/RXR stimulates expression of FGF21 and FGF19, leading to increased fatty acid oxidation and reduced levels of NEFA and TG.•RAR/RXR modulates bile acid homeostasis by regulating the expression of genes involved in bile acid synthesis and transport.•RAR/RXR represses liver fibrosis by blocking hepatic stellate cell activation and proliferation.•RAR/RXR accelerates lipid metabolism in macrophages by stimulating cholesterol transport.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>33497820</pmid><doi>10.1016/j.bbadis.2021.166085</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Bile acid hemostasis Gene Expression Regulation Gene regulation Humans Lipid metabolism Liver - cytology Liver - metabolism Liver - physiology Liver fibrogenesis Nuclear receptors Protein Multimerization Receptors, Retinoic Acid - chemistry Receptors, Retinoic Acid - genetics Receptors, Retinoic Acid - metabolism Retinoic acid receptors Retinoid X receptors Retinoid X Receptors - chemistry Retinoid X Receptors - genetics Retinoid X Receptors - metabolism Signal Transduction |
| title | The role of the retinoid receptor, RAR/RXR heterodimer, in liver physiology |
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